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Clinical chemistry principles, techniques, and correlations (7th ed) Clinical chemistry principles, techniques, and correlations (7th ed) Clinical chemistry principles, techniques, and correlations (7th ed) Clinical chemistry principles, techniques, and correlations (7th ed) Clinical chemistry principles, techniques, and correlations (7th ed) Clinical chemistry principles, techniques, and correlations (7th ed)
Acquisitions Editor: David Troy Product Manager: Michael Egolf Marketing Manager: Shauna Kelley Designer: Stephen Druding Compositor: Integra Software Services Copyright © 2013, 2010, 2005, 2000, 1996, 1992, 1985, by Lippincott Williams & Wilkins, a Wolters Kluwer business Two Commerce Square 2001 Market Street Philadelphia, PA 19103 USA LWW.com All rights reserved This book is protected by copyright No part of this book may be reproduced or transmitted in any form or by any means, including as photocopies or scanned-in or other electronic copies, or utilized by any information storage and retrieval system without written permission from the copyright owner, except for brief quotations embodied in critical articles and reviews Materials appearing in this book prepared by individuals as part of their official duties as U.S government employees are not covered by the above-mentioned copyright To request permission, please contact Lippincott Williams & Wilkins at Two Commerce Square, 2001 Market Street, Philadelphia, PA 19103, via email at permissions@lww.com, or via website at lww.com (products and services) 987654321 Printed in China Library of Congress Cataloging-in-Publication Data Clinical chemistry : principles, techniques, and correlations/[edited by] Michael L Bishop, Edward P Fody, Larry E Schoeff.—7th ed p cm ISBN 978-1-4511-1869-8 Clinical chemistry I Bishop, Michael L II Fody, Edward P III Schoeff, Larry E RB40.C576 2013 616.07’56—dc23 2012036179 Care has been taken to confirm the accuracy of the information presented and to describe generally accepted practices However, the authors, editors, and publisher are not responsible for errors or omissions or for any consequences from application of the information in this book and make no warranty, expressed or implied, with respect to the currency, completeness, or accuracy of the contents of the publication Application of this information in a particular situation remains the professional responsibility of the practitioner; the clinical treatments described and recommended may not be considered absolute and universal recommendations The authors, editors, and publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accordance with the current recommendations and practice at the time of publication However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any change in indications and dosage and for added warnings and precautions This is particularly important when the recommended agent is a new or infrequently employed drug Some drugs and medical devices presented in this publication have Health Canada clearance for limited use in restricted research settings It is the responsibility of the health care provider to ascertain the Health Canada status of each drug or device planned for use in his or her clinical practice Visit Lippincott Williams & Wilkins on the Internet: http://www.lww.com Lippincott Williams & Wilkins customer service representatives are available from 8:30 am to 6:00 pm, EST 18698_fm_pi-xxvi.indd 21/11/12 12:55 PM In memory of the University of Vermont Emeritus Professor René C Lachapelle for going the extra mile to ensure his students and colleagues succeeded and In memory of the University of Utah Professor Dr. William Roberts, internationally recognized clinical pathologist and clinical chemist and To my parents, Stewart and Betty Bishop, for their guidance and encouragement and To Sheila, Chris, and Carson for their support and patience MLB 18698_fm_pi-xxvi.indd 21/11/12 12:55 PM 18698_fm_pi-xxvi.indd 21/11/12 12:55 PM Foreword You should not be surprised to learn that the delivery of health care has been undergoing major transformation for several decades The clinical laboratory has been transformed in innumerable ways as well At one time the laboratory students’ greatest asset was motor ability That is not the case any longer Now the need is for a laboratory professional who is well educated, an analytical thinker and problem solver, and one who can add value to the information generated in the laboratory regarding a specific patient This change impacts the laboratory professional in a very positive manner Today the students’ greatest asset is their mental skill; their ability to acquire and apply knowledge The laboratory professional is now considered a knowledge worker, and a student’s ability to successfully become this knowledge worker depends on their instruction and exposure to quality education Herein lies the need for the seventh edition of Clinical Chemistry: Principles, Techniques, and Correlations It contributes to the indispensable solid science foundation in medical laboratory sciences and the application of its principles in improving patient outcomes needed by the laboratory professional of today This edition provides not only a comprehensive understanding of clinical chemistry but also the foundation upon which all the other major laboratory science disciplines can be further understood and integrated It does so by providing a strong discussion of organ function and a solid emphasis on pathophysiology, clinical correlations, and differential diagnosis This information offers a springboard to better understand the many concepts related to the effectiveness of a particular test for a particular patient Reduction of health care costs, while ensuring quality patient care, remains the goal of health care reform efforts Laboratory information is a critical element of such care It is estimated that $65 billion is spent each year to perform more than 4.3 billion laboratory tests This impressive figure has also focused a bright light on laboratory medicine, and appropriate laboratory test utilization is now under major scrutiny The main emphasis is on reducing costly overutilization and unnecessary diagnostic testing; however, the issue of under- and misutilization of laboratory tests must be a cause for concern as well The role of laboratorians in providing guidance to clinicians regarding appropriate test utilization is becoming not only accepted but also welcomed as clinicians try to maneuver their way through an increasingly complex and expensive test menu These new roles lie in the pre- and post-analytic functions of laboratorians The authors of this text have successfully described the importance of these phases as well as the more traditional analytic phase It does not matter how precise or accurate a test is during the analytic phase if the sample has been compromised, or if an inappropriate test has been ordered on the patient In addition, the validation of results with respect to a patient’s condition is an important step in the post-analytic phase Participation with other health care providers in the proper interpretation of test results and appropriate follow-up will be important abilities of future graduates as the profession moves into providing greater consultative services for a patientcentered medical delivery system Understanding these principles is a necessary requirement of the knowledge worker in the clinical laboratory This significant professional role provides effective laboratory services that will improve medical decision making and thus patient safety while reducing medical errors This edition of Clinical Chemistry: Principles, Techniques, and Correlations is a crucial element in graduating such professionals Diana Mass, MA, MT(ASCP) Clinical Professor and Director (Retired) Clinical Laboratory Sciences Program Arizona State University Tempe, Arizona President Associated Laboratory Consultants Valley Center, California Make no mistake: There are few specialties in medicine that have a wider impact on today’s health care than laboratory medicine For example, in the emergency room, a troponin result can not only tell an ER physician if a patient with chest pain has had a heart attack but also assess the likelihood of that patient suffering an acute myocardial infarction in 30 days In the operating room during a parathyroidectomy, a parathyroid hormone assay can tell a surgeon that it is appropriate to close the procedure because he has successfully removed all of the affected glands, or go back and look for more glands to excise In labor and delivery, testing for pulmonary surfactants from amniotic fluid can tell an obstetrician if a child can be safely delivered or if the infant is likely to develop life-threatening respiratory distress syndrome In the neonatal intensive care unit, measurement of bilirubin in a premature infant is used to determine when the ultraviolet lights can be turned off These are just a handful of the thousands of medical decisions that are made each day based on results from clinical laboratory testing v 18698_fm_pi-xxvi.indd 21/11/12 12:55 PM vi foreword Despite our current success, there is still much more to learn and For example, there are no good laboratory tests for the diagnosis of stroke or traumatic brain injury The work on Alzheimer’s and Parkinson’s disease prediction and treatment is in the early stages And when it comes to cancer, while our laboratory tests are good for monitoring therapy, they fail in the detection of early cancer, essential for improving treatment and prolonging survival Finally, personalized medicine including pharmacogenomics will play an increasingly important role in the future Pharmacogenomic testing will be used to select the right drug at the best dose for a particular 18698_fm_pi-xxvi.indd patient in order to maximize efficacy and minimize side effects If you are reading this book, you are probably studying to be a part of the field As a clinical chemist for over 30 years, I welcome you to our profession Alan H B Wu, PhD, DABCC Director, Clinical Chemistry Laboratory, San Francisco General Hospital Professor, Laboratory Medicine, University of California, San Francisco San Francisco, California 21/11/12 12:55 PM Preface Clinical chemistry continues to be one of the most rapidly advancing areas of laboratory medicine Since the publication of the first edition of this textbook in 1985, many changes have taken place New technologies and analytical techniques have been introduced, with a dramatic impact on the practice of clinical chemistry and laboratory medicine In addition, the healthcare system is constantly changing There is increased emphasis on improving the quality of patient care, individual patient outcomes, financial responsibility, and total quality management Now, more than ever, clinical laboratorians need to be concerned with disease correlations, interpretations, problem solving, quality assurance, and cost-effectiveness; they need to know not only the how of tests but more importantly the what, why, and when The editors of Clinical Chemistry: Principles, Techniques, and Correlations have designed the seventh edition to be an even more valuable resource to both students and practitioners Now 35 plus years since the initiation of this effort, the editors have had the privilege of completing the seventh edition with another diverse team of dedicated clinical laboratory professionals In this era of focusing on metrics, the editors would like to share the following information The 295 contributors in the editions represent 65 clinical laboratory science programs, 77 clinical laboratories, 13 medical device companies, government agencies, and professional society One hundred and twenty contributors were clinical laboratory scientists with advanced degrees With today’s global focus, the text has been translated into six languages By definition, a profession is a calling requiring specialized knowledge and intensive academic preparation to define its scope of work and produce its own literature The profession of Clinical Laboratory Science has evolved significantly over the past four decades Like the previous six editions, the seventh edition of Clinical Chemistry: Principles, Techniques, and Correlations is comprehensive, up-to-date, and easy to understand for students at all levels It is also intended to be a practically organized resource for both instructors and practitioners The editors have tried to maintain the book’s readability and further improve its content Because clinical laboratorians use their interpretative and analytic skills in the daily practice of clinical chemistry, an effort has been made to maintain an appropriate balance between analytic principles, techniques, and the correlation of results with disease states In this seventh edition, the editors have made several significant changes in response to requests from our readers, students, instructors, and practitioners Key Terms and Chapter Objectives have been introduced at the beginning of each chapter Ancillary materials have been updated and expanded Chapters now include current, more frequently encountered case studies and practice questions or exercises To provide a thorough, up-to-date study of clinical chemistry, all chapters have been updated and reviewed by professionals who practice clinical chemistry and laboratory medicine on a daily basis The basic principles of the analytic procedures discussed in the chapters reflect the most recent or commonly performed techniques in the clinical chemistry laboratory Detailed procedures have been omitted because of the variety of equipment and commercial kits used in today’s clinical laboratories Instrument manuals and kit package inserts are the most reliable reference for detailed instructions on current analytic procedures All chapter material has been updated, improved, and rearranged for better continuity and readability ,a web site with additional case studies, review questions, teaching resources, teaching tips, additional references, and teaching aids for instructors and students is available from the publisher to assist in the use of this textbook Michael L Bishop Edward P Fody Larry E Schoeff vii 18698_fm_pi-xxvi.indd 21/11/12 12:55 PM 18698_fm_pi-xxvi.indd 21/11/12 12:55 PM Acknowledgments A project as large as this requires the assistance and support of many individuals The editors wish to express their appreciation to the contributors of this seventh edition of Clinical Chemistry: Principles, Techniques, and Correlations—the dedicated laboratory professionals and educators whom the editors have had the privilege of knowing and exchanging ideas with over the years These individuals were selected because of their expertise in particular areas and their commitment to the education of clinical laboratorians Many have spent their professional careers in the clinical laboratory, at the bench, teaching students, or consulting with clinicians In these frontline positions, they have developed a perspective of what is important for the next generation of clinical laboratorians We extend appreciation to our students, colleagues, teachers, and mentors in the profession who have helped shape our ideas about clinical chemistry practice and education Also, we want to thank the many companies and professional organizations that provided product information and photographs or granted permission to reproduce diagrams and tables from their publications Many Clinical and Laboratory Standards Institute (CLSI) documents have also been important sources of information These documents are directly referenced in the appropriate chapters The editors would like to acknowledge the contribution and effort of all individuals to previous editions Their efforts provided the framework for many of the current chapters We also want to thank Dr Özgür Aydin for reviewing the manuscript of this edition for accuracy Finally, we gratefully acknowledge the cooperation and assistance of the staff at Lippincott Williams & Wilkins for their advice and support The editors are continually striving to improve future editions of this book We again request and welcome our readers’ comments, criticisms, and ideas for improvement ix 18698_fm_pi-xxvi.indd 21/11/12 12:55 PM www.ebook777.com 18698_fm_pi-xxvi.indd 10 21/11/12 12:55 PM 738 PART n SPECIALTY AREAS OF CLINICAL CHEMISTRY white blood cells, enabling confirmation to be made on a blood sample Enzymic confirmation can be difficult to establish in small babies because large blood samples are frequently required for diagnostic testing Small-Molecule Diseases Small-molecule diseases result from defects in metabolic pathways of intermediary metabolism Usually, the abnormal compounds that are present in these diseases are low-molecular-weight compounds that are readily excreted in body fluids; the types of pathways involved are listed in Table 35-16 Initially, the clinical chemistry laboratory had few diagnostic tools capable of identifying the large number of metabolic intermediates that may accumulate in these diseases, and a number of simple, colorimetric urine tests, such as the dinitrophenylhydrazine test for ketoacids, were developed to establish diagnosis These methods lack both sensitivity and specificity and have no role to play in the modern clinical chemistry laboratory They have been superseded by assays with greater sensitivity and specificity, often based on separation technology and mass spectrometry Small-molecule diseases have a variable clinical presentation and could present to almost any medical subspecialty with any organ system involved (Table 35-16 lists certain pathways that may be involved) Biochemical testing for these diseases is usually described in two phases First, it is important to recognize the degree of tissue compromisation at presentation This requires routine chemistry evaluation for blood gas status, if Case Study 35-4 A normal appearing infant was identified with a positive newborn screen Prior to the introduction of tandem mass spectrometry into the newborn screening program, a sibling had been born who, in association with a viral illness, developed profound hypoglycemia, liver failure leading to coma, and subsequent irreparable brain damage The sibling was subsequently shown by clinical testing to have the same disorder that the newborn screened positively for Questions What is the most likely diagnosis? What biomarker would confirm this on the newborn screening process? What is the likelihood that the newborn will follow the same clinical course as the older sibling? What group of genetic diseases are likely to be incorporated into whole population screens next? Table 35-16 Pathways Involved with Small-Molecule Metabolic Disease and Examples Amino acids—phenylketonuria Fatty acids—medium-chain acyl-CoA dehydrogenase deficiency Organic acids—propionic acidemia Urea cycle—citrullinemia Oxidative phosphorylation—mitochondrial DNA diseases Vitamin metabolism—pyridoxine responsive seizures Steroid biosynthesis and breakdown—21-hydroxylase deficient congenital adrenal hyperplasia Cholesterol synthesis—Smith-Lemli-Opitz syndrome Purine and pyrimidine metabolism—adenosine deaminase form of severe combined immunodeficiency Neurotransmitter metabolism—4-hydroxybutyric aciduria Plasmalogen synthesis—Zellweger syndrome Glutathione metabolism—pyroglutamic aciduria Oxalate metabolism—hyperoxaluria types and Creatine metabolism—guanidinoacetic acidemia acidotic; anion gap measurement; liver function testing; analysis of skeletal and cardiac muscle markers, such as creatine kinase or troponin levels; lactic acid; and ammonia measurement All of these analyses should be available stat and used to monitor management once a diagnosis is established The second phase of analysis should be to look for metabolic markers that pinpoint the site of a defect These tests involve a form of separation technology, such as ion-exchange chromatography or ultra-performance liquid chromatography for amino acids The preferred material for amino acid analysis is serum because the renal tubules have efficient transport systems for reabsorbing filtered amino acids It is possible to miss an amino acid abnormality if only urine is analyzed Urine amino acid analysis is of value if a tubular defect such as cystinuria is suspected The most useful test for detecting abnormal metabolic intermediates is organic acid analysis This test is performed on urine and should only be performed using the technique of gas chromatography–mass spectrometry It is a method that is capable of identifying metabolic markers for up to 200 genetic diseases As mentioned earlier, tandem mass spectrometry is another technique seeing rapid growth in the metabolic disease diagnosis field This technique is being applied to newborn screening and is playing an increasing role in analysis of multiple different metabolites, many of which were not easily measurable prior to the introduction of this technology www.ebook777.com 18698_ch35_p720-742.indd 738 10/11/12 2:54 PM CHAPTER 35 n CLINICAL CHEMISTRY AND THE PEDIATRIC PATIENT 739 Table 35-17 Drugs with Well-Defined Therapeutic Indices Drug Therapeutic Range Toxicity Phenytoin 10–20 mg/L (39.6–79.3 μmol/L) >40 (159) causes seizures, ataxia Phenobarbital 10–40 mg/L (43–172 μmol/L) >40 (172) causes drowsiness; >60 (258) coma Carbamazepine 4–10 mg/L (16.9–42.3 μmol/L) >10 (42.3) causes drowsiness Theophyllinea 5–15 mg/L (27.8–83.3 μmol/L) >20 (111) can cause cardiac arrhythmia Caffeinea 5–15 mg/L (26–77 μmol/L) Less toxic than theophylline Methotrexate 61 Depends on therapy High levels cause myelosuppression Gentamicin 5–10 mg/L (peak)b (10.5–20.9 μmol/L) >12 (25.1) ototoxic; renal toxicity aTheophylline bPeak is metabolized to caffeine in neonates but not in adults Used to treat apnea level should be drawn 30 after last dose for aminoglycoside drugs Children are particularly prone to hearing loss at toxic levels Drug Metabolism and Pharmacokinetics There are several important differences in the way that infants and children handle pharmacologic agents compared with adults.1 This area of pediatric laboratory medicine provides many good examples of why children should not be regarded as “small adults.” It is not clinically appropriate to prorate the amount of drug prescribed to a child based on relative body weight compared with an adult dose Drug metabolism depends on the following factors: absorption, circulation and volume of distribution, and metabolism and clearance Often, the medium in which a drug is provided to a child differs from that in which an adult may take the same drug Syrups, for instance, provide a more rapid release of a drug and greater availability for gastrointestinal absorption than tablets, which have the drug trapped in a solid matrix that requires digestion Children are more likely to be given medication in a palatable form, such as syrup, and to require lower doses The pH of gastric secretions differs in infants At birth, the gastric pH is nearly neutral, not reaching the adult level of acidity for several years This pH difference can affect the absorption of certain drugs, including some frequently prescribed penicillins The distribution of drugs often differs between adults and children Lipid-soluble drugs are taken up into lipid reserves and only slowly released into the circulation Because infants have relatively little adipose tissue, these drugs are not stored as efficiently The overall effect is that lipid-soluble drugs reach a higher level more quickly than in individuals with sizable fat stores; however, the drug is also cleared more rapidly It becomes appropriate for drugs to be provided in smaller, more frequent doses to optimize the effect Hepatic metabolism of many drugs is immature in young infants This may delay the metabolic conversion to an active drug or increase the time in 18698_ch35_p720-742.indd 739 which an active drug is circulating Good hepatic function is important for clearing those drugs metabolized by the liver, as good renal function is important for clearing drugs that have water-soluble end products Therapeutic Drug Monitoring The principles of therapeutic drug monitoring remain the same in adult and pediatric clinical chemistry It is important to measure the blood levels of various drugs if that information can provide important guidance to the physician with regard to optimal dosing This is most important if a drug has a well-defined therapeutic index This means that the drug is known to be ineffective if the blood level is below a certain value, that there is a well-defined therapeutic range over which the drug is effective, and that there is a higher level at which the drug becomes toxic It is important to monitor levels of drugs with these characteristics Table 35-17 lists drugs for which the importance of therapeutic monitoring is established Toxicologic Issues in Pediatric Clinical Chemistry Issues related to the provision of a toxicologic service can be divided into two distinct groups in pediatrics The first group involves infants and young children who unknowingly consume pharmacologic and other chemical agents This usually involves the child finding access to medication belonging to another individual in the household and consuming the medication as if it were candy It is relatively easy for the investigator to ascertain the nature of the medication by identifying what is available in the household Toxicologic investigation can usually be restricted to a few specific tests A rare, but potentially dangerous condition is that of Munchausen syndrome by proxy In this condition, mental 10/11/12 2:54 PM 740 PART n SPECIALTY AREAS OF CLINICAL CHEMISTRY illness in a caregiver causes them to give unnecessary and illness-causing drugs to an otherwise well child This can go unrecognized and result in multiple hospitalizations and even death of the child Clinical suspicion of this form of child abuse should involve performing a comprehensive drug screen to identify causative agents Because of the intermittent nature of clinical presentation of Munchausen syndrome by proxy, it can often be confused with metabolic disease Metabolic studies, in addition to comprehensive toxicologic studies, may be necessary Because the likelihood of self-ingestion of street drugs of abuse is present in older children, pediatric clinical chemistry laboratories should make assays available for street drugs similar to those in adult practice For additional student resources please visit thePoint at http://thepoint.lww.com QUESTIONS All of the following represent normal physiology of the newborn except a Weight of 2.4 kg b Immature liver function and inability to eliminate excess bilirubin c Closure of the ductus arteriosus and a shift of blood flow through the heart d to months for the infant’s body weight to double Which of the following choices is false concerning blood obtained by heel stick (capillary) and venipuncture (venous)? a The chemical composition of the sera derived from each is identical b The capillary specimen is likely contaminated with interstitial fluid and tissue debris c Venous blood contains higher bilirubin and calcium concentrations d Capillary blood contains less concentrated proteins due to mixing with interstitial fluid Under normal conditions, what is the maximum amount of blood that should be drawn from a 30-kg child during a single blood draw? a 60 mL b 80 mL c 40 mL d 20 mL When choosing a chemistry analyzer for a pediatric laboratory, it is necessary to a Incorporate total laboratory automation b Be able to analyze from small volumes c Have a rapid turnaround time d Ensure a minimum specimen dead volume Which of the following is true regarding POCT? a Results are generally available more rapidly than with traditional laboratory tests b POCT is usually less expensive than traditional laboratory measurements c The device cannot be linked to the hospital information system d Quality control samples are not needed Which of the following conditions are related to acidosis in the newborn? a Anoxia and trauma during delivery b Respiratory distress syndrome c Hyperammonemia caused by liver disease d Hyperventilation Which of the following are characteristics of renal development and function during the neonatal period? a Control the rate of salt and water loss and retention b GFR about 50% of the rate seen in older children c Completely developed by 24 weeks of gestation d Have a maximum solute concentrating power of approximately 30% of an adult kidney Which of the following statements about the neonatal thyroid system is true? a Secondary hypothyroidism is usually diagnosed by measuring a low TSH level b Thyroid hormones (T4 and T3) are less than 50% bound to thyroid-binding globulins c CH is a very rare and untreatable disorder d A low measured TSH level may be due to a global pituitary gland dysfunction (panhypopituitarism) Cystic fibrosis a Is diagnosed by the measurement of elevated chloride concentration in sweat following iontophoresis b Is a very uncommon genetic disease c Is caused by only a single type of mutation in the CF transmembrane regulator (CFTR) gene d Is characterized by thin, watery mucous secretions in the lungs and pancreatic ducts www.ebook777.com 18698_ch35_p720-742.indd 740 10/11/12 2:54 PM CHAPTER 35 n CLINICAL CHEMISTRY AND THE PEDIATRIC PATIENT References Green A, Morgan I, Gray J Neonatology and Laboratory Medicine London: ACB Venture Publications; 2003 Soldin SJ, Rifai N, Hicks JMB, eds Biochemical Basis of Pediatric Disease Washington, DC: American Association for Clinical Chemistry; 1992 Rautenberg MW, van Solinge WW, Heunks JJ, et al Pediatric tube direct sampling by the Abbott Architect Integrated ci8200 Chemistry/Immunochemistry Analyzer Clin Chem 2006;52: 768-770 Demir AY, van Solinge WW, Kemperman H Handling of and direct sampling from primary barcode-labeled pediatric tubes on Vitros clinical chemistry analyzers integrated into an enGen work cell Clin Chem 2005;51:920-921 Gill FN, Bennett MJ Point of care testing in pediatrics In: Price CP, St John A, Hicks JM, eds Point of Care Testing 2nd ed Washington, DC: American Association for Clinical Chemistry; 2004:341-352 Honest H, Bachmann LM, Gupta JK, Kleijnen J, Khan KS Accuracy of cervicovaginal fetal fibronectin test in predicting risk of spontaneous preterm birth: systematic review BMJ 2002;325: 301-311 Goldenberg RL, Mercer BM, Iams JD The preterm prediction study: patterns of cervicovaginal fetal fibronectin as predictors of spontaneous preterm delivery Am J Obstet Gynecol 1997;177:8-12 Polak M, Van Vliet G Disorders of the thyroid gland In: Sargoglou K, Hoffman G, Roth K, eds Pediatric Endocrinology and Inborn Errors of Metabolism New York: McGraw-Hill; 2009: 353-382 9 Summary of the Revisions for the 2010 Clinical Practice Recommendations Diabetes Care 2010;33(suppl 1):S3 10 Hannon TS, Rao G, Arslanian SA Childhood obesity and type diabetes mellitus Pediatrics 2005;116(2):299-306 11 Zimmet P, Alberti K, George MM, et al.; IDF Consensus Group The metabolic syndrome in children and adolescents—an IDF consensus report Pediatr Diabetes 2007;8:299-306 12 Levey AS, Coresh J, Greene T, et al Chronic Kidney Disease Epidemiology Collaboration Using standardized serum creatinine values in the modification of diet in renal disease study equation for estimating glomerular filtration rate Ann Intern Med August 2006;145(4):247-254 18698_ch35_p720-742.indd 741 741 13 Schwartz GJ, Work DF Measurement and estimation of GFR in children and adolescents J Am Soc Nephrol November 2009;4(11):1832-1843 14 Newman DJ Cystatin C Ann Clin Biochem 2002;39:89-104 15 Schwartz GJ, Munoz A, Schneider MF, et al New equations to estimate GFR in children with CKD J Am Soc Nephrol 2009;20:629-637 16 Wagner C, Greer FR Prevention of rickets and vitamin D deficiency in infants, children, and adolescents Pediatrics 2008;122:1142 17 Austin A, Finkielstain GP Adrenal disorders In: Dietzen DJ, Bennett MJ, Wong ECC, eds Biochemical and Molecular Basis of Pediatric Disease 4th ed Washington, DC: AACC Press; 2010: 135-153 18 Winter WE, Rosenbloom AL Disorders of growth In: Dietzen DJ, Bennett MJ, Wong ECC, eds Biochemical and Molecular Basis of Pediatric Disease 4th ed Washington, DC: AACC Press; 2010; 171-194 19 Loechelt BJ Primary immunodeficiency diseases In: Dietzen DJ, Bennett MJ, Wong ECC, eds Biochemical and Molecular Basis of Pediatric Disease 4th ed Washington, DC: AACC Press; 2010: 409-427 20 Valle D, Beaudet AL, Vogelstein B, Kinzler KW, Antonarakis SE, Ballabio A, eds Online Metabolic and Molecular Bases of Inherited Disease (OMMBID) http://www.ommbid.com/ Accessed July 30, 2012 21 Sargoglou K, Hoffman G, Roth K, eds Pediatric Endocrinology and Inborn Errors of Metabolism New York: McGraw-Hill; 2009 22 Hommes FA, ed Techniques in Diagnostic Human Biochemical Genetics New York: Wiley-Liss; 1991 23 American College of Obstetricians & Gynecologists, American College of Medical Genetics Preconception and Prenatal Carrier Screening for Cystic Fibrosis: Clinical and Laboratory Guidelines Washington, DC: American College of Obstetricians & Gynecologists; 2001 24 Dietzen, DJ, Rinaldo P, Whitley RJ, et al National Academy of Clinical Biochemistry Laboratory Medicine Practice Guidelines: follow-up testing for metabolic diseases identified by expanded newborn screening using tandem mass spectrometry; executive summary Clin Chem 2009;55:1615-1626 http://www.aacc.org/ Accessed July 30, 2012 members/nacb/lmpg/onlineguide/publishedguidelines/newborn/pages/default.aspx# Accessed July 30, 2012 10/11/12 2:54 PM www.ebook777.com 18698_ch35_p720-742.indd 742 10/11/12 2:54 PM INDEX Index Note: Locators followed by ‘f ’ and ‘t’ refer to figures and tables respectively A Absolute specificity, 265 Absorption, 627–628, 712–713 ACC/AHA/Heart Failure Society of America and the European Society of Cardiology, 554–556, 555t Accreditation, 193–194 Accuracy, 53, 64, 196, 337–338 Acetaminophen, 657–658 Acid, 376 Acid-base balance, 376–378, 574 ammonia (NH3), reaction with, 574 bicarbonate ions, regeneration of, 574 buffer systems: regulation of H+, 377, 377f excretion of metabolic acids, 574 lungs and kidneys, regulation of, 377–378 maintenance of H+, 376 monohydrogen phosphate (HPO4–2), reaction with, 574 Acid–base homeostasis, 378–382 acidosis and alkalosis, 380–382 bicarbonate buffering system, 378–380 Henderson-Hasselbalch equation, 378–380 Acidemia, 380 α1-Acid glycoprotein, 221–222 Acidosis, 376, 380–382 Acid phosphatase (ACP), 281–282 Acromegaly, 443–444 Activation energy, 265 Activators, 263 Active transport, 347 Actual percent oxyhemoglobin (O2Hb), 385 Acute and chronic toxicity, 647–648 Acute coronary syndrome (ACS), 546 Acute kidney injury (AKI), therapy for, 586–588 dialysis, 586–587 therapy for kidney failure, 587–588 Acute myocardial infarction (AMI), 714 Acute renal failure, 577 Addison’s disease See Adrenal insufficiency (Addison’s disease) Adenohypophysis, 439 Adenoma, toxic, 498 Adiponectin, 229 Adrenal androgens, 464–465 Adrenal cortex by zone, 454–457 congenital adrenal hyperplasia, 456–457 cortex steroidogenesis, 455–456 Adrenal gland, 454, 454f Adrenal “incidentaloma,” 469 Adrenal insufficiency (Addison’s disease), 459–460 diagnosis of, 459 treatment of, 459–460 Adrenal medulla, 465–469 biosynthesis and storage of catecholamines, 465–466 catecholamine degradation, 466 causes of sympathetic hyperactivity, 467 development, 465 diagnosis of pheochromocytoma, 467–468 outcome and prognosis, 468–469 treatment of pheochromocytoma, 468 urine and plasma catecholamine measurements, 466–467 Adrenocorticotropic hormone (ACTH), 297, 455, 455f, 458f, 459f, 731 Adsorption, 122–123, 171 Aerobic pathway, 295 Affinity, 161 chromatography, 308 Agammaglobulinemia, 735 Ag capture assay See Sandwich assays Age on laboratory testing, effects of, 708–710, 708t bone, 709 endocrine system, 709–710 decreased hormone level, 710 increased hormone level, 710 gastrointestinal system, 709 glucose metabolism, 710 immune system, 709 muscle, 709 sex hormones, 710 urinary system, 709 Aging and medical science, 705–706 age-specific changes, 705–706, 706t diminished physiological reserve, 705 gerontology, 705 heterogeneous, 705 Aging of America, 703–705 age/gender structure of the population, 704f first “baby boomers,” 704 immigration trends, 704 population 65 years and older, 704f projected population by age and sex, 705f Airborne pathogens, 42–43 Air-displacement pipets, 15 ALA dehydratase (ALAD) deficiency, 417 Alanine (Ala), 206 Alanine aminotransferase (ALT), 278–279 Albumin, 218, 220, 233, 234t, 682–683 Alcohol, 648–650, 649t Aldosterone, 456, 571 Aldosterone-producing adenoma (APA), 458 Alkalemia, 380 Alkaline, 580–581 Alkaline phosphatase (ALP), 279–281, 531–532 Alkalosis, 376, 380–382 Alkaptonuria, 209–210 Aluminum, 401 Alzheimer’s disease (AD), 712 Amenorrhea, 481 classification, by WHO, 482 etiologies of, 481t primary/secondary, 481, 481f runner’s, 482 American Thyroid Association Guidelines for Hypothyroidism Screening, 496 Aminoacidopathies, 207–212 alkaptonuria, 209–210 argininosuccinic aciduria (ASA), 211–212 citrullinemia, 211 cystinuria, 212 homocystinuria, 210–211 isovaleric acidemia, 210 maple syrup urine disease (MSUD), 210 phenylketonuria (PKU), 207–209 tyrosinemia, 209 Amino acids, 203–213 aminoacidopathies, 207–212 analysis of, 212–213 basic structure, 203, 203f charged states of, 216f essential, 205–206 metabolism, 203–205 new, 207 nonessential, 206–207 in protein synthesis, 204t Aminoglycosides, 635–636 δ-Aminolevulinic acid synthase (ALAS), 416 Aminostat-FLM, 609 Aminotransferases, 531 Amiodarone-induced thyroid disease, 498 Ammonia, 247, 257 analytical methods, 257–259, 258t biochemistry, 257 clinical application, 257 interconversion of, 257f pathophysiology, 259 Amniocentesis, 605, 605f Amniotic fluid (AF), 604–609 fetal lung maturity, 606–609, 607f fluorescence polarization, 609 FSI determination, 608t hemolytic disease of newborn, 606, 606f, 607f lamellar body counts, 609 neural tube defects (NTDs), 604–606 phosphatidylglycerol, 609 thin-layer chromatogram, 608f Amphetamines, 658–659 Ampholytes, 238 Amplicons, 185 Amylase (AMY), 283–285 Amyloid, 230 Amyloid β42 (Aβ42), 230 Anabolic steroids, 659–660 Analyte fluctuations, 710 Analytes, Analytic measurement range (AMR), 62 Analytic performance goals, 338 Analytic phase (chemical analyses) in total laboratory automation, 156 Analytic reagent (AR), Analytic specificity, 62 Analytic techniques, 100–118 electrochemistry, 111–115 electrophoresis, 115–118 osmometry, 118 spectrophotometry, 101–111 Androgen hormone, 474, 480 Andropause, 708 Angina pectoris (chest pain), 546 Angina, stable, 546, 546t Angiogenesis, 671 Angiotensin-converting enzyme (ACE), 456 Anhydrous compounds, 17 Anion gap (AG), 371 Anions, 346 Anneals, 182 Anode, 386 Anodic stripping voltammetry, 114–115 Anterior pituitary hormones, 441, 442t Antibiotics, 635–636 aminoglycosides, 635–636 vancomycin, 636 Antibody, 161 Antibody (Ab)–antigen (Ag) reactions, 163f α1-Antichymotrypsin, 222 Antidiuretic hormone (ADH), 439, 458, 571, 572f Antiepileptic drugs, 636–640 Antigen, 161 Antineoplastics, 642 methotrexate, 642 α1-Antitrypsin, 221 Apathetic hyperthyroidism, 714 Apoenzyme, 263 Apolipoprotein (apo), 315–317, 316f, 317t methods, 336 Apoptosis, 671 Arachnoid villi, 610 Arginine (Arg), 205 Argininosuccinic aciduria (ASA), 211–212 743 18698_index_p743-758.indd 743 12/11/12 6:40 PM 744 index Arrhythmias, 548t, 555t Arsenic, 402, 652–653 Arterial blood, 28 Arteriosclerosis, 324–328 Ascites, 619 Ascitic fluid, 619 Ascorbic acid, 693–694 Asparagine (Asn), 206 Aspartate aminotransferase (AST), 277–278 Aspartic Acid (Asp), 206 Atherosclerosis, 546 arteries, 548f LDL deposition and oxidation, 549, 549f pathophysiology of, 548–550 T cells and foam cells, 550, 549f Atmospheric pressure chemical ionization (APCI), 129 Atomic absorption (AA), 101, 397–398 spectrophotometer, 106–108 basic components, 106–107, 107f electrodeless discharge lamps, 107 flameless atomic absorption, 107–108 inductively coupled plasma (ICP), 108 single-beam, 107f Atomic absorption spectroscopy (AAS), 397–398, 398f Atomic emission spectroscopy (AES), 397 Atrial natriuretic peptide (ANP), 454 Atypical pituitary tumors, 442 Automated analyzers history of, 140 selection of, 153 Automatic Clinical Analyzer (ACA), 140 Automatic pipets, 14–15, 14f Automation, 139–157 analyzers in history of, 140 selection of, 153 approaches to, 141–142 forces towards more, 140–141 future trends in, 157 steps in analysis, 142–153 chemical reaction phase, 148–149 measurement phase, 149–151 reagent systems and delivery, 147–148 signal processing and data handling, 151–153 specimen measurement and delivery, 142–147 specimen preparation and identification, 142 total laboratory, 153–157, 154f analytic phase (chemical analyses), 156 postanalytic phase (data management), 156–157 preanalytic phase (sample processing), 153–156 Average See Mean Avidity, 161 Azotemia, 248 B Balances, 17–18, 17f Bar code, 142 Barrier-layer cell, 104 Basal and maximal secretory tests, 598 Base, 376 Base excess, 386 Basic units, Beer’s law, 26–28, 101–103 absorptivity, 103 layers of light-absorbing solution, 102, 102f percent transmittance (%T) and absorbance (A), 101–102 Bell curve See Gaussian distribution Bias, 58, 76 Bicarbonate, 358–359 buffering system, 378–380 clinical applications, 358–359 determination of CO2, 359 reference ranges, 359 regulation of, 358 Bicarbonate–carbonic acid system, 377, 379f Bile, 327, 520, 521, 531 Bilirubin, 521, 522f, 528–530 analysis of, 528–529 Jendrassik-Grof method, 529–530 Malloy-Evelyn procedure, 529 methods, 529 reference ranges, 530t specimen collection and storage, 529 Bioaccumulation, 653 Bioavailability, 627 Biochemical markers macronutrients, 682–685 micronutrients, 686–700 miscellaneous, 685–686 Biochips, 184 Biohazardous waste, 49 Biological fluids, Biologic safety, 42–43 Biosafety cabinets (BSCs), 40, 41t Biotin, 693 Bisphosphonates, 509 Bloodborne pathogens, OSHA standard for, 37, 42 Blood–brain barrier, 610 Blood gas analysis quality assurance cycle, 390f Blood gases, 375–393 and PH in neonates and infants, 724–725 acidosis in newborn, 724 amniotic fluid lecithin/sphingomyelin (L/S), 724 blood gas and acid–base measurement, 724–725 causes of acidosis and alkalosis, 724t fetal fibronectin (fFN) test, 724 Body burden, 653 Body fluid analysis, 604–621 amniotic fluid, 604–609 cerebrospinal fluid (CSF), 609–613 serous fluids, 616–621 sweat, 613–615 synovial fluid, 615–616 Body mass index (BMI), 681 Bond specificity, 265 Bone resorption, 364 Bone turnover or “remodeling,” 505 Bowman’s capsule, 569, 570f Brain natriuretic peptide (BNP) and N-terminal–BNP, 228–229 Branched chain DNA (bDNA), 188, 188f Buffer systems, 9–10, 375–393 Burets, 16 Bypassing ultracentrifugation, 335–336 C CABG or “bypass surgery,” 554 Cadmium, 402–403, 653 Calcitonin, 363–364, 489 Calcium, 363–367, 574 clinical applications, 364–366 determination of, 366 distribution, 364 physiology, 363 reference ranges, 367, 367t regulation, 363–364 Calcium analyzer, 367f Calcium and bone metabolism, in pediatric patient, 729–730 bone growth, 730 causes of hypocalcemia, 730t hypocalcemia and hypercalcemia, 730 vitamin D deficiency, 729–730 Calcium homeostasis, 502–517 hormonal regulation of, 503–504 parathyroid hormone, 504–504, 504f vitamin D, 503–504, 503f hypercalcemia, 507–511 hypocalcemia, 512–513 metabolic bone diseases, 513–516 organ system regulation, 505–507, 506f bone physiology, 505–507 GI regulation, 505 role of kidneys, 505 secondary hyperparathyroidism, 516–517 Calcium-sensing receptors (CSRs), 509, 510f Calibration, 113, 113f Cancer, 664, 665t, 666f, 669t Cancer antigen 125 (CA-125), 673–674 Cannabinoids, 660 Capillary electrophoresis (CE), 117, 117f, 238 electro-osmotic flow (EOF), 117, 117f Caraway method, 250 Carbamazepine, 637–638 Carbohydrates, 293–298 aldose and ketose, 293f chemical properties, 294–295 Haworth projection of sucrose, 295f classification of, 293 Fisher projection of glucose, 293, 293f Haworth projection of glucose, 293, 293f pathways in, 293f description of, 293–298 fate of glucose, 295–297 glucose metabolism, 295 hyperglycemia, 298–303 hypoglycemia, 303–304 monosaccharides, disaccharides, and polysaccharides, 294 regulation of carbohydrate metabolism, 297–298 stereoisomers, 293–294 Carbonic acid, 388, 390 Carbon monoxide, 651–652 Carboxyhemoglobin (COHb), 383–384, 651, 651t Carcinoembryonic antigen (CEA), 674 Carcinogenic chemicals, 45 Cardiac damage, markers of, 550–553, 562t cardiac troponins, 551–552 heart-type fatty acid–binding protein, 552, 553 initial markers, 550–551 ischemia-modified albumin, 552, 553 myoglobin, 552, 553 novel markers of plaque instability, 552, 553 Cardiac insults, 555f Cardiac markers, 546 Cardiac troponin (cTn), 228, 551–552 Cardioactive drugs, 633–635 digoxin, 633–634 disopyramide (Norpace), 635 procainamide, 634–635 quinidine, 634 Carnitine, 694 Catabolism, 214–215 Catalytic mechanism, of enzymes, 265 Catecholamines biosynthesis and storage of, 465–466 degradation, 466 Catechol methyltransferase, 466 Cathode, 386 Cations, 346 Caustic agents, 652 CDC Cholesterol Reference Method Laboratory Network, 338 Cell cycle, 671 Cellular breakdown, 354 Cellulose acetate hemoglobin electrophoresis, 430 Centrifugal analysis, 142 Centrifugation, 18–19, 18f, 19f Cerebrospinal fluid (CSF), 29, 609–613, 610f biochemical (chemical) analysis, 612 collection, 611f comparison of, 612f CSF/serum albumin index, 613 decreased CSF glucose levels, 612 functions of, 610 laboratory investigation, 611 major pathways, 610f myelin basic protein (MBP), 606 protein levels in, 613 specimens of, 611 Cerebrovascular disease (CVD), 325 Ceruloplasmin, 223 Channel, 140 Charge and isoelectric point, 215–216 Chemically pure (CP) reagent, Chemicals, handling, 44 hazard communication, 43 www.ebook777.com 18698_index_p743-758.indd 744 12/11/12 6:40 PM Index hazardous, 43 hygiene plan, 43 OSHA Laboratory Standard, 43–44 precipitation, 334 reactions in automated analysis, 148–149 safety, 43–45 safety data sheet, 43 storage, 44, 44t Chemiluminescence, 101, 110, 110f Chloride, 357–358, 573 clinical applications, 358 determination of, 358 reference ranges, 358, 358t Chloride shift, 357, 357f, 377 Cholecystokinin, 592 Cholesterol, 315 enzymatic assay sequence, 332f measurement of, 331–332 Chromatography, 122–128 gas, 127–128 HPLC, 124–126 modes of separation, 122–124 adsorption, 122–123 ion-exchange chromatography, 123–124 partition, 123 steric exclusion, 123, 123f procedures, 124 retention factor (Rf), 124 thin-layer chromatography (TLC), 124, 124f Chromium, 403–404 Chronic kidney disease (CKD), 576 etiology of, 585t increasing incidence of, 584–585 pathophysiology of, 584f renal hypertension, 585 systematic classification of, 585t Chronic Kidney Disease Epidemiology Collaboration equation (CKD EPI), 713 Chronic lymphocytic thyroiditis, 493 Chronic obstructive pulmonary disease (COPD), 381 Chylomicrons, 317 Cinacalcet, 509 Circulating tumor markers, 664–677 carbohydrate and cancer antigen tumor markers, 669t detection, applications of, 667–669 prognosis, 669 screening and susceptibility testing, 668–669 therapy and disease recurrence, 669 endocrine tumor markers, 668t enzyme tumor markers, 667t frequently ordered tumor markers, 672–677 laboratory considerations for measurement, 669–672 receptor tumor markers, 670t serum protein tumor markers, 667t types of tumor markers, 665–667, 667t Cirrhosis, 526 Citrate agar electrophoresis, 430, 430f Citrullinemia, 211 type I, 211 type II, 211 CKD-EPI equation, 254 CKD-EPI formula, 576 Clarke electrodes, 386 Class A pipets, 15–16 Clean Water Act, 38 Clinical and Laboratory Standards Institute (CLSI), Clinical Laboratory Improvement Amendments (CLIA), 60, 67, 336 Clinical laboratory reagent water (CLRW), Clinically reportable range (CRR), 62 Clinical toxicology, 646 Cloned enzyme donor immunoassays (CEDIAs), 173 Closed tube sampling, 146 Cocaine, 660 Cockcroft-Gault formula, 576 Coenzyme, 263 Cofactor, 263 Cold vapor AAS, 409 18698_index_p743-758.indd 745 Collecting duct, 572 Colligative property, Combined hyperlipoproteinemia, 329–330 Compact analyzers, 336 Comparison-of-methods (COM) studies, 65–67 statistical analysis, 66–67 Compensation, 380 Competitive immunoassays, 168–169, 168t, 169f Complement system, 224–225 Concentration, of solutions, 20–23 conversions, 23 molarity, 21–22 normality, 22 percent solution, 21–22 specific gravity, 22–23 Conductivity, of solutions, Confidence interval, 76 Congenital adrenal hyperplasia, 456–457, 456t hyperaldosteronism, 457 isolated hypoaldosteronism, 457 Congestive heart failure, 557 Conjugated bilirubin, 522 Conjugated proteins, 218 Connectivity, 197 Constant error, 59, 62 Constant systematic error, 59 Continuous flow, 141 Control limits, 68 Control material, 68 Copper, 404–405, 697 Coproporphyrin (COPRO), 416 Coronary artery disease (CAD), 318 Coronary heart disease (CHD), 313, 323t, 556–559 Corpus luteum, 479 Corrosive chemicals, 45 Cortex steroidogenesis, 455–456 Corticotropin-releasing hormone (CRH), 441, 455 Cortisol, 727, 728 Coulometric chloridometers, 114–115 Countercurrent multiplier system, 571 Counterimmunoelectrophoresis, 164 Coupled enzymatic methods, 251, 255, 268 “Coupling,” process of, 505 C-reactive protein (CRP), 225–226, 552, 553, 556–558, 685 Creatine, 252–257 analytical methods, 256 biochemistry, 253, 253f clinical application, 253–254 pathophysiology, 256–257 Creatine kinase (CK), 271–275, 253f, 550–551 isoenzymes, 272t, 273f CK-BB, 273–274, 272t CK-MB, 273–274, 272t CK-Mi, 274 CK-MM, 272–273, 272t macro-CK, 274 Creatine kinase MB (CK-MB), 551 Creatinine, 252–257, 572 analytical methods, 254–255, 255t biochemistry, 253, 253f clinical application, 253–254 pathophysiology, 256 Creatinine clearance (CrCl), 253–254, 575–576 Creutzfeldt-Jakob disease, 712 Crigler-Najjar syndrome, 524 Cross-linked C-telopeptides (CTXs), 229 Cross-reactivity, 162 Cryogenic materials hazards, 48 Cumulus cells, 479 Current Procedural Terminology (CPT) codes, 32 Cushing’s syndrome, 460–464, 463f algorithm for suspected, 463 CRH stimulation tests, 462–463 diagnosis of, 461–462 endogenous, 460 inferior petrosal sinus sampling, 461 localization procedures, 463 pituitary versus ectopic ACTH secretion, 460–461 treatment, 464 workup, 463f 745 Cyanide, 652 “Cycle sequencing,” 183 Cyclosporine, 641 Cylinder, graduated, 12 Cystatin C, 229, 576–577 biologic variation, 576–577 Cysteine (Cys), 206 Cystic fibrosis, 592–593 Cystinuria, 212 Cytochromes, 416 Cytokines, 685 D Data handling in automated analysis, 151–153 D-Dimer detection in PE, 560 Dead space air, 382 Dehydroepiandrosterone (DHEA), 454 Dehydroepiandrosterone sulfate (DHEAS), 454 Deionized water, Deliquescent substances, 17 Delta absorbance, 27 Delta bilirubin, 525 Dementia, 712 Dementia with Lewy bodies (DLB), 712 Deming plot, 65 Deming regression analysis, 65 Denaturation, 215 Densitometer, 116, 116f Density, 22–23 11-Deoxycortisol, 459 Deoxyhemoglobin (HHb), 383 Deoxyribonucleic acid (DNA), 179 De Quervain’s thyroiditis, 499 De Ritis ratio, 527 Derived units, Descriptive statistics, 53 of groups of paired observations, 57–59 measures of center, 53–55, 53f, 54f measures of shape, 53f, 55–57, 56f Gaussian curve, 56, 56f “68–95–99 Rule,” 56, 56f measures of spread, 54f Descriptive toxicology, 645–646 Desiccants, 17 Desiccators, 17 Detoxification and drug metabolism, 523 Diabetes Control and Complications Trial (DCCT), 308 Diabetes insipidus, 348 Diabetes mellitus, 298–303, 577 classification, 299t criteria for diagnosis, 302 diagnostic criteria, 300t GDM, 299–303 criteria for testing and diagnosis, 302–303 pathophysiology of, 300 testing for prediabetes and, 301–302 type diabetes, 298–299 type diabetes, 299 Dialysis, 19, 586–587 Dideoxynucleotides, 183 Dietary molybdenum deficiency, 410 Dietary Reference Intake (DRI), 682 Diffusion, 347 Digene’s Hybrid Capture assay, 183 Digoxin, 74t, 633–634 1,25-Dihydroxy vitamin D3, 575 1,25-Dihydroxy vitamin D (1,25(OH)2D), 503, 729 Dilutions, 23–26 factor, 23 serial, 25–26, 25f Dilutor/dispensers, 15, 15f Dimension RxL analyzer, 141 Direct effectors, 441 Direct immunofluorescence (DIF), 175 Disaccharides, 294 Discrete analysis, 142 Disopyramide (Norpace), 635 Dispensers, 15, 15f Dispersion of data, 53 12/11/12 6:40 PM 746 index Disposal of hazardous materials, 48–49 biohazardous waste, 49 chemical waste, 48–49 medical waste, 49 radioactive waste, 49 Dissociation-enhanced lanthanide fluoroimmunoassay (DELFIA), 174 Distal convoluted tubule, 571–572 Distilled water, Distribution, drug, 628 Diurnal rhythms, 439 DMAIC (Define, Measure, Analyze, Improve, and Control) methodology, 91–92 DNA chip technology, 184 DNA molecule, 180, 180f DNA sequencing, 183–184 Dopamine, 445 Dose-response relationship, 645 Dot-blot hybridization assays, 182 Double-stranded DNA (dsDNA), 180, 185f Drug- and alcohol-related disorders, 527–528 Drug metabolism and pharmacokinetics, 739–740 lipid-soluble drugs, 739 therapeutic drug monitoring, 739 toxicologic issues in pediatric clinical chemistry, 739–740 Drug-metabolizing enzymes, 287–288, 288t–289t Drugs of abuse, toxicology of, 658–653 amphetamines, 658–659 anabolic steroids, 659–660 cannabinoids, 660 cocaine, 660 opiates, 660–661 phencyclidine (PCP), 661 sedatives-hypnotics, 661 Dry chemistry slide, 147 Dual energy x-ray absorptiometry (DEXA), 515 Dubin-Johnson syndrome, 524–525 Duplicate assays, 392 d-xylose absorption test, 599–600 Dye-binding methods, 233, 240 Dyshemoglobins, 385–386 Dyslipidemia, 313 E Effusion, 617 Electrical hazards, 47 Electrochemical cell, 111, 111f, 386 Electrochemistry, 111–115 anodic stripping voltammetry, 114–115 coulometric chloridometers, 114–115 enzyme electrodes, 114 galvanic and electrolytic cells, 111, 111f gas-sensing electrodes, 114 half-cells, 111–112 ion-selective electrodes, 112 pH electrodes, 112–114 Electrodeless discharge lamps, 107 Electroendosmosis, 116 Electrolytes, 346–372, 686 anion gap, 370 balance, 573–574 chloride, 573 phosphate, calcium, and magnesium, 574 potassium, 573 sodium, 573 bicarbonate, 358–359 calcium, 363–367 chloride, 357–358 hyperkalemia, 686 lactate, 368–370 magnesium, 359–363 osmotic regulation, 686 phosphate, 367–368 potassium, 353–357 and renal function, 371–372, 371f sodium, 349–353 sodium regulation, 686 water, 347–349 Electro-osmotic flow (EOF), 117, 117f Electrophoresis, 115–118, 234 capillary electrophoresis (CE), 117, 117f components, 115, 115f detection and quantitation, 116 electroendosmosis, 116 isoelectric focusing, 117 procedure, 115 buffers, 115 power supply, 115 support materials, 116 agarose gel, 116 cellulose acetate, 116 polyacrylamide gel, 116 starch gel, 116 treatment and application of sample, 116 two-dimensional electrophoresis, 117–118, 118f values, 222t Electrophoretic methods, 333–334 Electrophoretic mobility, 238 Elemental speciation, 400 Elimination, 713–714 CKD EPI, 713 decline in GFR, 713 diazepam, 714 drug, 629–631, 630f exponential rate of, 629, 630f first-order drug elimination, 629–630, 630f MDRD, 713 morphine sulfate, 714 rate of, 627 Embden-Meyerhof pathway, 295, 296f Endocrine function, 574–575 1,25-dihydroxy vitamin D3, 574 erythropoietin, 574–575 in pediatrics, 730–733 causes of hypercalcemia, 730t endocrine control of sexual maturation, 733 growth factors, 732–733 hormone secretion, 730–731 hypothalamic–pituitary-adrenal cortex system, 731–732 hypothalamic–pituitary-thyroid system, 731 prostaglandins, 574–575 renin, 574–575 Endocrine system, 709–710, 731 norepinephrine secretion, 707–708 protection from free radicals, 707 thyroid hormone levels, 708 Endogenous pathway, 319, 320–321 Endpoint (Mancini) method, 164 Environmental toxicology, 646 Enzyme-linked immunosorbent assays (ELISAs), 172–173, 173f Enzymemultiplied immunoassay technique (EMIT), 173 Enzymes, 262–288, 531–532 assays, 672 classification and nomenclature, 263–265, 264t of clinical significance, 270–288, 270t acid phosphatase (ACP), 281–282 alanine aminotransferase (ALT), 278–279 alkaline phosphatase (ALP), 279–281 amylase (AMY), 283–285 aspartate aminotransferase (AST), 277–278 creatine kinase, 271–275 drug-metabolizing enzymes, 287–288, 288t–289t γ-glutamyltransferase (GGT), 282–283 glucose-6-phosphate dehydrogenase (G-6-PD), 286–287 lactate dehydrogenase (LD), 275–277 lipase (LPS), 285–286 CYP 450 enzymes, 288t–289t electrodes, 114 factors influencing, 265–267 cofactors, 267 enzyme concentration, 266 inhibitors, 267 Lineweaver-Burk transformation, 266f Michaelis-Menten curve, 266, 266f pH, 266 substrate concentration, 265–266 temperature, 266–267 general properties and definitions, 263 kinetics, 265–270 calculation of enzyme activity, 269 catalytic mechanism, 265 enzymes as reagents, 269–270 factors influencing, 265–267 measurement of enzyme activity, 268–269 measurement of enzyme mass, 269 labels, 167 Enzyme–substrate (ES) complex, 265 Epinephrine (EPI), 297, 454 Epitope, 161 Equivalent weight, Ergonomic hazards, 47 Erlenmeyer flasks, 12 Error, 58 Erythropoietin, 574, 575 Essential amino acids, 205–206 arginine (Arg), 205 histidine (His), 205 isoleucine (Ile), 205 leucine (Leu), 205 lysine (Lys), 205 methionine (Met), 205 phenylalanine (Phe), 205 threonine (Thr), 205 tryptophan (Trp), 205–206 valine (Val), 206 Essential element, 396 Essential nutrients, 688 Estimated GFR, 576 CKD-EPI formula, 576 Cockcroft-Gault formula, 576 modification of diet in renal disease (MDRD), 576 Estimated glomerular filtration rate (eGFR), 254 Estrogen, 479 Estrogen replacement therapy, 485–486 Ethosuximide, 638 Excretion, 378 Exogenous pathway, 319–320 Extracellular fluid (ICF), 347 Exudate, 617 Ezetimibe, 327 F Familial hypocalciuric hypercalcemia (FHH), 509–510 Families of Structurally Similar Proteins (FSSP), 217 Fasting blood glucose (FBG), 302t, 305 Fat, 685 Fat-soluble vitamins, 687 vitamin D, 687–688 vitamin E, 688 vitamin K, 689–690 Fatty acids, 313–314 measurement, 337 Fecal fat analysis, 595–596 Feedback loops, 439, 440f Felbamate, 638 Ferritin, 406 Fetal fibronectin (fFN) test, 724 Fetal lung maturity, 606–609 α-Fetoprotein (AFP), 221, 672–673 Fibric acid derivatives, 327 Fibrinogen, 225 Fibronectin, 229, 684 Filter fluorometers, 108–109, 109f Filtrate, 19 Filtration, 19, 19f Fire extinguishers, 46–47, 47f Fire safety, 46–47 Fire tetrahedron, 46, 46f First “baby boomers,” 704 First-generation AEDs, 636–640 First-order kinetics, 265 First pass, 523 Fisher projection of glucose, 293f Fish oil, 327 Fixed-time method, 268–269 www.ebook777.com 18698_index_p743-758.indd 746 12/11/12 6:40 PM Index Flameless atomic absorption, 107–108 Flame photometry, 108 Flammable chemicals, 44 Flow cytometry, 176 Fluorescence excitation transfer immunoassay, 173 Fluorescence polarization, 609 Fluorescence polarization immunoassay (FPIA), 173–174 Fluorescence resonance energy transfer (FRET), 186 Fluorescent labels, 167 Fluorometry, 108 advantages, 109–110 disadvantages, 109–110 Folate, 691 Follicle-stimulating hormone (FSH), 440, 473 Follicular cells, 490 Follicular phase, 479 Forensic toxicology, 646 Fractional (or percent) oxyhemoglobin (FO2Hb), 384 Fractionation proteins, 233–234 salt, 233 Fraction of inspired oxygen (FiO2), 383 Fragility fracture, 515 Free radical, 707 Free T4 and free T3, 491 Free vs bound drugs, 628 Friedewald equation, 319 Frontotemporal dementia, 712 Fume hoods, 40 G Gabapentin, 638 Galactosemia, 304 Galvanic and electrolytic cells, 111 Gas chromatography, 127–128 columns, 127 detectors, 127–128, 127f Gas chromatography–mass spectrometry (GC/MS), 209 Gas discharge lamps, 109 Gas-sensing electrodes, 114 pCO2 electrode, 114, 114f Gastric function, tests of, 598 Gastrin, 597 Gastrointestinal function, 590–601, 706–707 atrophic gastritis, 706 clinical aspects of, 597–598 clinicopathologic aspects of, 599 intestinal physiology, 598–599, 599f physiology and biochemistry, 597 tests of, 599–601 D-xylose absorption test, 599–600 lactose tolerance test, 599 other tests of intestinal malabsorption, 600–601 serum carotenoids, 600 vitamin B12 deficiency, 706 Gaussian distribution, 55, 56f Gc-globulin, 222 “Gender-specific” reference ranges/“age-specific” reference ranges, 710 GeneChips, 184 Genetic diseases, 735–738 cystic fibrosis (CF), 736 diagnosis of metabolic disease, 736t, 737 large-molecule diseases, 737, 737t small-molecule diseases, 738, 738t newborn screening for whole populations MCAD deficiency, 737 tandem mass spectrometric analysis, 736 pseudomonas, 736 Geriatric patient age-associated changes in drug metabolism, 712–714 aging and medical science, 705–706 aging of America, 703–704 atypical presentations of common diseases, 714 clinical laboratory results, 707t 18698_index_p743-758.indd 747 diseases prevalent in elderly, 711–712, 711t effects of age on laboratory testing, 708–710, 708t impact of exercise and nutrition, 715 leading causes of death, 711t physiologic changes, 706–708 reference intervals, 710 Geriatric syndromes, 714, 714t Gerontology, 705 Gilbert’s disease, 524 Glasgow score, 527 Glassware, 11–17, 17f burets, 16 laboratory vessels, 12 pipets, 12–16 syringes, 16–17 Globulins, 218, 220–221 α1-acid glycoprotein, 221–222 α1-antichymotrypsin, 222 α1-antitrypsin, 221 ceruloplasmin, 223 complement system, 224–225 C-reactive protein (CRP), 225–226 α1-fetoprotein (AFP), 221 fibrinogen, 225 Gc-globulin, 222 haptoglobin (Hp), 222–223 hemopexin, 224 high-sensitivity CRP (hsCRP), 226 immunoglobulins, 226–227 inter-α-trypsin inhibitors (ITIs), 222 lipoproteins, 224 α2-macroglobulin, 223 β2-microglobulin (β2M), 224 transferrin (siderophilin), 223–224 Glomerular filtrate, 570 Glomerular filtration rate (GFR), 252, 570, 707 Glomerulonephritis, 578 Glomerulus, 569 Glucagon, 297 Glucocorticoids, 297 Gluconeogenesis, 295, 370, 523 Glucose metabolic alterations, 304–310 glucose tolerance and 2-hour postprandial tests, 306 glycated hemoglobin measurement, 308t glycosylated hemoglobin/HbA1c, 307–308 islet autoantibody and insulin testing, 310 ketones, 309 methods of glucose measurement, 305–310 microalbuminuria, 309 pathways in, 297t self-monitoring of blood glucose, 306 Glucose-6-phosphate dehydrogenase (G-6-PD), 286–287 Glutamic acid (Glu), 206 Glutamine (Gln), 206 γ-Glutamyltransferase (GGT), 282–283, 532 Glycated (or glycosylated) albumin, 220 Glycine (Gly), 206–207 Glycogen, 295 Glycogenesis, 296, 523 Glycogenolysis, 296, 523 Glycolysis, 295 Glycosylated hemoglobin/HbA1c, 307–309 Goiter, multinodular, 498 Gonadal function, 474–486 ovaries, 478–486 testes, 472–478 Gonadotrophs, 474 Gonadotropin-releasing hormone (GnRH), 440, 474, 733 Gout, 250 Graafian follicle, 479 Granulations, 610 Graphing, Beer’s law and, 26–28 Graves’ disease, 493, 497–498 Gravimetric pipet calibration, 16 Griffin beakers, 12 Growth, 721 Growth hormone (GH), 298, 442 acromegaly, 443–444 actions of, 442–443 747 GH deficiency, 444–445 testing, 443 Growth hormone–releasing hormone (GHRH), 442 Günther’s disease, 418 Guthrie assay, 208, 210 Gynecomastia, 476 H Half-cells, 111–112, 111t Hapten (Hp), 161 Haptoglobin (Hp), 222–223 Hashimoto’s thyroiditis, 493 Haworth projection of glucose, 293f of sucrose, 295f Hazard communication, OSHA standard for, 37, 43 Hazardous material, 43 HbA1c, 307–308, 307t Healthcare Common Procedure Coding System (HCPCS) test, 32 Health Insurance Portability and Accountability Act (HIPAA), 32 Heart-type fatty acid–binding protein (H-FABP), 552–553 Hemiketal or hemiacetal ring, 293f Hemodialysis, 586 Hemofiltration, 587 Hemoglobin, 421–432 clinical significance and disease correlation, 423–429 DNA technology, 431–432 electrophoretic patterns, 426f methodology, 429–431 qualitative defects (hemoglobinopathies), 423–425 quantitative defects (thalassemias), 425–429 role in the body, 421 structure of, 421–422, 422f synthesis and degradation, 422–423, 423f synthesis of heme, 417f Hemoglobin A or A1, 422 Hemoglobin A2, 422, 430 Hemoglobin C, 425 Hemoglobin D, 425 Hemoglobin E, 425 Hemoglobin F, 422, 431 Hemoglobinopathies, 415, 423–424 Hemoglobin-oxygen dissociation, 384, 385, 385f Hemoglobin S, 423–424 Hemoglobin SC, 425 Hemolysis, 28 Hemopexin, 224 Henderson-Hasselbalch equation, 10, 377, 378–380 Hepatic synthetic ability, tests measuring, 532 Hepatitis, 533–540 chronic, 533 Hepatitis A (HAV), 533–534, 533t Hepatitis B (HBV), 533t, 534–538, 539t chronic infection, 536, 537t core antigen (HBcAg), 534 HB e antigen (HBeAg), 535–536, 536f serologic markers of, 534, 537t surface antigen (HBsAg), 534, 536f treatment and prevention, 537–538 Hepatitis C (HCV), 533t, 538 chronic infection, 538 laboratory tests for, 538 Hepatitis D (HDV), 533t, 538–539, 539t Hepatitis E (HEV), 533t, 540 Heterogeneous assays, 170 Heterophile or human anti-mouse interference, 172f Hexokinase method, 306 Hexose monophosphate (HMP) shunt, 295 High-complexity test, 194 High-density lipoproteins (HDL), 313, 318, 334–335 High-efficiency particulate air (HEPA) filter, 41 12/11/12 6:40 PM 748 index High-performance liquid chromatography (HPLC), 6, 124–126, 209 columns, 124–125 detectors, 125–126 pumps, 124 recorders, 126 sample injectors, 125 High-resolution electrophoretic (HRE), 237f High-resolution mass spectrometers, 399 High-resolution protein electrophoresis, 237–238 High-sensitivity CRP (hsCRP), 226 Hirsutism, 480, 485 androgen levels in, 485t causes of, 485t classification of, 485t Histidine (His), 205 Histogram, 57, 77f Holoenzyme, 263 Homocysteine, 549, 558–559 Homocystinuria, 210–211 Homogeneous assays, 170 Homovanillic acid, 465 Hook effect, 172, 172f, 671, 671f Hormonogenesis, 473–474 Human chorionic gonadotropin, 675 Huntington’s disease, 712 Hybridization techniques, 181–183 nucleic acid probe, 181 solid support hybridization, 182, 182t solution hybridization, 182–183 Hydrate, 17 Hydrocephalus, 712 Hydrolase, 281 17-Hydroxycorticosteroid excretion, 461 25-Hydroxy vitamin D, 505 Hygroscopic compounds, 17 Hyperbilirubinemia, 526f Hypercalcemia, 366, 505, 507–509 biochemical differential diagnosis, 508t causes of, 507 medications causing, 510–511 symptoms of, 366 treatment of, 366 Hypercarbia, 378 Hyperchloremia, 358 Hypercholesterolemia, 328–329 Hypercortisolism, 460 Hyperglycemia, 297, 298–303, 299t Hypergonadotropic hypogonadism, 475–476, 483 5α-reductase deficiency, 476 myotonic dystrophy, 476 sertoli cell–only syndrome, 476 testicular feminization syndrome, 476 testicular injury and infection, 476 Hyperkalemia, 300, 353, 355–356 Hyperlipoproteinemia, 328 Hypermagnesemia, 362 causes of, 362t symptoms of, 362, 362t treatment of, 362 Hypernatremia, 350t, 352–353 chronic, 352 symptoms of, 352 treatment of, 353 urine osmolality, 352, 352t Hyperosmolality, 354 Hyperphenylalaninemia, 208 Hyperphosphatemia, 368 Hyperprolactinemia, 446 Hyperproteinemia, 230 Hypertension (HTN), 456f Hyperthyroidism, 496, 510 Hypertriglyceridemia, 329 Hyperuricemia, 251 Hyperventilation, 381 Hypervitaminosis, 688 Hypoalphalipoproteinemia, 331 Hypobetalipoproteinemia, 331 Hypocalcemia, 364–366, 365, 512–513 causes of, 512–513 neonatal monitoring, 365 organ system causes of, 513 surgery and intensive care, 365 symptoms of, 365 treatment of, 366 Hypochloremia, 358 Hypoglycemia, 297, 303–304 Hypoglycorrhachia, 612 Hypogonadism, 474, 477–478 Hypogonadotropic hypogonadism, 476–477, 481–483 age, 477 hyperprolactinemia, 476 Kallmann’s syndrome, 476 male hypogonadism, evaluation of, 477f pituitary disease, 477 type diabetes, 477 Hypokalemia, 355 Hypomagnesemia, 359–361 causes of, 360t symptoms of, 361, 361t treatment of, 361 Hyponatremia, 350–352, 350t increased Na+ loss, 350 increased water retention, 350 by osmolality, 351, 351t pseudohyponatremia, 351 symptoms of, 351 treatment of, 351–352 water imbalance, 351 Hypophosphatemia, 368 Hypophysiotropic hormones, 441T Hypophysis, 439 Hypopituitarism, 446–448 etiology of, 447–448 treatment of panhypopituitarism, 448 Hypoproteinemia, 230 Hypothalamic and pituitary function, 438–449 anterior pituitary hormones, 441 embryology and anatomy, 439 functional aspects of hypothalamic–hypophyseal unit, 439–441 growth hormone, 442–445 hypophysiotropic or hypothalamic hormones, 441 hypopituitarism, 446–448 pituitary tumors, 440f, 441–442 posterior pituitary hormones, 448–449 prolactin, 445–446 Hypothalamic–hypophyseal unit, 439–441 Hypothalamic–pituitary–thyroid axis, 492, 492f Hypothalamus, 439 Hypothyroidism, 490, 495–496 causes of, 496t measurement of TSH, 496 primary, 731 secondary, 731 signs and symptoms, 495 types of, 495 Hypouricemia, 252 Hypoventilation, 381 Hypovitaminosis, 687 Hypovitaminosis D, 513 Hypovolemia, 348 Hypoxemia, 381 Hypoxia, 369, 369f I ICP-MS, 398–399, 399f Icterus, 30 Idiopathic galactorrhea, 440 Idiopathic hyperaldosteronism, 452 Idiopathic type diabetes, 299 IGF-binding proteins, 732 Immobilized enzymes, 269–270 Immune precipitation in gel, 163t Immune system, 707, 733–735 autoimmune antibody, 707 basic concepts of immunity, 733 components of acute-phase proteins, 734 antibody production, 734 B Cells, 734 natural killer cells, 734 phagocytes, 733–734 properties of Ig classes, 734t skin, 733 declining cellular immunity, 707 herpes varicella zoster virus (HVZ), 707 immunity disorders, 735 neonatal and infant antibody production, 735 Immunity, 735 Immunoassays, 161–176, 670, 672 future directions, 176 general considerations, 161–162 heterophile antibodies, 669 hook effect, 671 labeled, 166–176 linearity, 671–672 tumor marker immunoassays, 671–672 unlabeled, 162–166 Immunoblots (Western blot), 175, 175f Immunochemical methods, 238 Immunochemical techniques, 160–176 Immunocytochemistry, 175–176 Immunoelectrophoresis (IEP), 164–165, 164f Immunofixation electrophoresis (IFE), 160–165, 238f Immunofluorescence, 672 Immunoglobulins, 226–227 Immunohistochemistry, 175–176, 672 Immunometric assays See Noncompetitive immunoassays Immunophenotyping, 176 Immunosuppressive drugs, 641–642 cyclosporine, 641 mycophenolic acid, 641–642 sirolimus, 641 tacrolimus, 641 Imprecision, 61–62, 62f measurement of, 62–64 Inaccuracy, 61–62 Indicator electrode, 112 Indirect immunofluorescence (IIF), 175 Individual dose–response relationship, 647 Inductively coupled plasma atomic emission spectroscopy (ICP-AES), 396 Inductively coupled plasma (ICP), 108 Inductively coupled plasma mass spectrometry (ICP-MS), 396 Inferential statistics, 59–60 Inferior petrosal sinus sampling, 461 Infertility, causes of, 482t Infundibulum or pituitary stalk, 439 Inhibin, 474 In situ hybridization, 183 Insulin, 297, 297t Insulin-dependent diabetes mellitus (IDDM), 298 Insulin-like growth factor (IGF), 443 Insulin, measurement of, 161 Inter-α-trypsin inhibitors (ITIs), 222 Interferences, 399–400 Intermediate-density lipoproteins (IDL), 318 International Classification of Diseases (ICD), 32 International Federation of Clinical Chemistry and Laboratory Medicine (IFCC), 308 International unit (IU), 27, 269 Intracellular fluid (ICF), 347 Intrinsic factor, 597 Ion-exchange chromatography, 123–124, 274, 738 Ionic strength, 10 Ion-selective electrodes (ISE), 110, 140 Iron, 405–406, 695–696 Ischemia-modified albumin (IMA), 552, 553 Islet cell tumors, 593 Islets of Langerhans, 591 Isoelectric focusing (IEF), 117, 238 Isoelectric point (pI), 216 Isoenzyme, 263 Isoenzymes, 276t, 277 Isoform, 263 Isoleucine (Ile), 205 Isovaleric acidemia, 210 IUB system, 263 recommended name, 263 systematic name, 263 www.ebook777.com 18698_index_p743-758.indd 748 12/11/12 6:40 PM Index J Jaundice, 524–525 concentration of bilirubin, 525t physiologic, 525 posthepatic, 524–525 prehepatic, 524 K Ketones, 309, 309f Kidney stones, types of, 582t Kidney/urinary system, 707 glomerular filtration rate (GFR), 707 renal responsiveness, 707 Kinetic assays, 269 Kinetic (Fahey-McKelvey) method, 164 Kodak Ektachem (now Vitros) Analyzer, 140 Kupffer cells, 521 Kussmaul-Kien respiration (deep respirations), 300 Kuvan®, 208 Kwashiorkor, 683 L Labeled immunoassays, 166–176 assay design, 168–174 examples of, 172–174 general considerations, 166 immunoblots, 175 immunocytochemistry and immunohistochemistry, 175–176 immunophenotyping, 176 labels, 166–167, 166t rapid immunoassay, 174–175 separation techniques, 170–172 Labels, 166–167, 166t enzyme, 167 fluorescent, 167 luminescent, 167 radioactive, 166–167 Laboratory information system (LIS), 195 Laboratory markers of cardiac damage and function, 545–562 cardiac injury, 554 cardiac ischemia, angina, and heart attacks, 546–548, 546t markers of cardiac damage, 550–554 markers of CHD risk, 556–559 markers of pulmonary embolism, 559–561 pathophysiology of atherosclerosis, 548–550 use of cardiac biomarkers in heart failure, 554–556 use of natriuretic peptides and troponins, 556 Laboratory safety, 36–50 accident documentation and investigation, 49–50 biologic safety, 42–43 chemical safety, 43–44 compressed gases hazards, 47–48 control of other hazards, 47–48 cryogenic materials hazards, 48 disposal of hazardous materials, 48–49 biohazardous waste, 49 chemical waste, 48–49 radioactive waste, 49 electrical hazards, 47 equipment, 39–42 ergonomic hazards, 48 fire safety, 46–47 chemistry of fire, 46 classification of fires, 46 fire extinguishers, 46–47, 47f mechanical hazards, 48 OSHA, 37–38 radiation safety, 45 regulations and guidelines, 38 responsibility, 38 signage and labeling, 38–39, 39f Laboratory standard, 43 18698_index_p743-758.indd 749 Lactate, 362–364 biochemistry and physiology, 368–370 clinical applications, 370 determination of, 370 reference ranges, 370, 370t regulation, 369–370 Lactate dehydrogenase (LD), 275–277, 532 Lactose tolerance test, 599 Lamellar body counts, 608 Lamotrigine, 638–639 Laser applications, 111 Laurell technique or electroimmunoassay See Rocket technique LD50, 647 LD flipped pattern, 276 LDL-related receptor protein, 320 Lead, 407–408, 653–655 Lean Six Sigma Methodology, 90–97 adoption and implementation, 90–91 applications in laboratory and greater health-care system, 93f, 94–95 major improvements, 94t integration of, 91f measurements of success, 92–94 practical application of six sigma metrics, 95–97 choosing appropriate Westgard rules, 97, 97t defining sigma performance of an assay, 96–97 detecting laboratory errors, 95–96, 95t “OPSpecs” chart, 96, 96f process improvement, 91–92 analyze phase, 92 control phase, 92 define phase, 91 DMAIC methodology, 91–92 measure phase, 92 quality improvement, 91f Lecithin–sphingomyelin ratio (L/S ratio), 608, 724 Leucine (Leu), 205 Levetiracetam, 639 Levey–Jennings control chart, 68 Leydig cells, 474 Ligandin, 522 Ligase chain reaction (LCR), 188 Limit of detection (LoD), 62, 80 Linearity, 106 Linear regression, 57, 57f Lipase (LPS), 285–286 Lipemia, 30 Lipids, 312–339 absorption, 319–320 analyses of, 331–337 chemistry, 313–315 diagnosis and treatment of disorders, 323–331 measurement, 331 population distributions, 321–323 reference ranges, 322t standardization of assays, 337–339 structures of, 314f Lipoprotein (a) (Lp(a)), 317, 318 Lipoproteins, 224, 312–339 analyses of, 331–337 characteristics of major, 316t methods, 333–334 physiology and metabolism, 319–321, 319f standardization of assays, 337–339 structure of, 315–319, 316f Lipoprotein X, 319 Liquid junctions, 112–113 Lithium carbonate, 511 Liver function, 519–540 alterations during disease, 524–528 cirrhosis, 526 drug- and alcohol-related disorders, 527–528 Jaundice, 524–525 Reye syndrome, 527 tumors, 526 anatomy, 520–521 gross, 520, 520f microscopic, 521, 521f biochemical functions, 521–523 detoxification and drug metabolism, 523 excretory and secretory, 521–523, 521f metabolism, 523 749 and liver function tests, assessment of, 528–540 bilirubin, 528–530 enzymes, 531–532 hepatitis, 533–540 serum bile acids, 531 tests measuring hepatic synthetic ability, 532 tests measuring nitrogen metabolism, 532–533 urobilinogen in urine and feces, 530–531 in pediatric patient, 726–729 biochemical pathways, 727t diabetes mellitus, 727–728 energy metabolism, 727 liver function tests, 729 nitrogen metabolism, 728 nitrogenous end products, 728–729 physiologic jaundice, 726 Lobules, 521 Logarithms, 20 Long feedback loop, 440 Loop of Henle, 571 Low-density lipoproteins (LDL), 313, 318 methods, 335–336 Lp(a) elevation, 330 Luminescent labels, 167 Luteal phase, 479 Luteinization, 479 Luteinizing hormone (LH), 440, 473 Lysine (Lys), 205 M Macroelectrode sensors, 388 α2-Macroglobulin, 223 Macronutrients, 682–685 carbohydrate, 685 fat, 685 protein, 682–685 Macro pipets, 15 Magnesium, 359–363, 574 clinical applications, 359–362 determination of, 362–363 physiology, 359 reference ranges, 363, 363f regulation of, 359 Male reproductive tract, 473 Malnutrition, 681 Manganese, 409–410 Mantissa, 20 Maple syrup urine disease (MSUD), 210 Marasmus, 683 Masculinization, 480 Mass analyzer, 129–132 high-resolution MS, 132 ion trap, 130–131 quadrupole, 130 tandem mass spectrometry, 131 Mass spectrometry (MS), 128–137, 128f applications in clinical laboratory, 132–134 definition, 122 detector, 132 mass analyzer, 129–132 high-resolution MS, 132 ion trap, 130–131 quadrupole, 130 tandem mass spectrometry, 131 in proteomics and pathogen identification, 134–137 MALDI-TOF and SELDI-TOF MS, 134–135, 137f pathogen identification, 136–137 sample introduction and ionization, 129 APCI, 129 atmospheric pressure ionization, 129 electron ionization (EI), 129 electrospray ionization, 129 small molecule analysis, 132–134 Mass-to-charge ratio, 398 Material Safety Data Sheet (MSDS), Matrix, 64, 64f, 338 Mean, 53 12/11/12 6:40 PM 750 index Measurement, 385–390 in automated analysis, 149–151 blood gas analyzers: pH, pCO2, and pO2, 386 calculated parameters, 390 calibration, 389–390 correction for temperature, 390 optical sensors, 388–389 of pH and pCO2, 387–388 of pO2, 386–387 of specimen in automated analysis, 142–147 spectrophotometric (co-oximeter) determination, 385–386 types of electrochemical sensors, 388 Measuring pipet, 13–14 Mechanical hazards, 48 Mechanistic toxicology, 645 Median, 54 Median eminence, 439 Medical decision level, 74 Medical waste, 49 Medium-chain acyl-CoA dehydrogenase (MCAD) deficiency, 737 Menopause, 483, 706, 711 Menorrhagia, 481 Menstrual cycle, 480 abnormalities, 481–485 amenorrhea, 481 hypergonadotropic hypogonadism, 483 hypogonadotropic hypogonadism, 481–483 polycystic ovary syndrome, 484–485 follicular phase, 480 luteal phase, 480 Mercury, 408–409, 655 Messenger RNA (mRNA), 180 Metabolic bone diseases, 513–516 osteoporosis, 514–516 rickets and osteomalacia, 513–514 Metabolic syndrome, 682 Metalloenzyme, 396 Metalloprotein, 396 Metals and metalloids, 652–656 Methemoglobin (MetHb), 384 Methionine (Met), 205 Method evaluation, 52–87 acceptance criteria, 68 allowable analytic error, 67–68 COM studies, 65–67 descriptive statistics, 53–59 determination imprecision and inaccuracy, 61–62 diagnostic efficiency, 80–85 imprecision measurement, 62–64 inferential statistics, 59–60 interference studies, 64–65 method selection, 60–61 practice problems, 85–87 quality control (QC), 53, 68–72 reference interval studies, 72–79 regulation aspects of (Alphabet Soup), 60 Methotrexate, 642 Methylenedioxymethylamphetamine (MDMA), 659 MFO system, 629 Michaelis-Menten constant (Km), 266 Microalbumin, 577 Microalbuminuria, 309 Micro-ammeter, 386 Microarrays See Biochips, 184 Microelectrodes, 388 Microfluorometric assay, 209 β2-Microglobulin (β2-M), 224, 577 Micronutrients conditionally essential nutrients, 694–696 minerals, 695–696 trace elements, 697–700 vitamins, 686–694 Microparticle capture enzyme immunoassay (MEIA), 173 Micro pipets, 14, 15 Milk alkali syndrome, 510 Minerals calcium/phosphorus, 695, 695t iron, 695–696 Mixed hemoglobinopathy, 425 Mode, 54 Model for End-Stage Liver Disease (MELD) score, 527 Moderately complex test, 194 Modification of diet in renal disease (MDRD), 576, 713 Modular analyzer, 140 Modular chemistry/immunoassay analyzers, 141 Mohr pipet, 14 Molality, Molarity, 8, 21–22 Molybdenum, 410 Molybdopterin, 410 Monoamine oxidase (MAO), 466 Monochromator fluorometers, 109 Monoclonal antibody, 161 Monoclonal immunoglobulin disease, 237 Monosaccharides, 294, 294f Morphine sulfate, 714 Moving boundary electrophoresis, 234 MRP-8/14, 553 Multirule procedure, 68 Munchausen syndrome, 739 Mycophenolic acid, 641–642 Myeloperoxidase (MPO), 552, 553 Myocardial infarction (MI) (heart attack), 546, 547t, 548t Myocarditis, 552 Myoglobin, 227–228, 415–416, 432, 552, 553, 577 causes of elevations, 432t clinical significance, 432 elevations, 228t methodology, 432 structure and role in the body, 432 N National Formulary (NF), Natriuretic peptides, 556 cardiac troponins, 556 NCEP, 323t, 324t, 325t Neoplasm, 664, 671 Nephelometry, 110–111, 110f, 165 Nephron, 570 Nephrotic syndrome, 580, 581f Nernst equation, 113 Neural tube defects (NTDs), 605–606 Neurohypophysis, 439 Neutrophil gelatinase–associated lipocalin (NGAL), 577 Niacin or nicotinic acid, 327, 690–691 Nitisinone (NTBC), 209 Nitrogen, 231 Nitrogen balance, 214–215, 684–685 Nitrogen content, 215 Nitrogen metabolism, tests measuring, 532–533 Noncompetitive immunoassays, 169–170, 169f Nonessential amino acids, 206–207 alanine (Ala), 206 asparagine (Asn), 206 aspartic Acid (Asp), 206 cysteine (Cys), 206 glutamic acid (Glu), 206 glutamine (Gln), 206 glycine (Gly), 206–207 proline (Pro), 207 serine (Ser), 207 tyrosine (Tyr), 207 Nonessential element, 396 Non–HDL cholesterol, 330–331 Non–insulin-dependent diabetes mellitus (NIDDM), 298 Nonparametric method, 76 Nonprotein nitrogen compounds (NPN), 246–259, 572–573 ammonia, 257 creatinine, 572 creatinine/creatine, 252–257 urea, 247–250, 572 uric acid, 250–252, 572–573 Nonrespiratory acidosis, 380–381, 390 Nonrespiratory alkalosis, 381, 390 Nonrespiratory disorder, 380 Nonsurrogate QC, 392–393 Norepinephrine (NE), 465 Normality, 8, 22 Normal range, 74 Northern blot, 182 Nucleic acid–based techniques, 179–189 Nucleic acid chemistry, 180–181 Nucleic acid extraction, 181 Nucleic acid probe, 181, 189 Nucleic acid sequence–based amplification (NASBA), 184 5′-Nucleotidase (5NT), 532 Nutrient, 681 Nutrition assessment assessment, 681–382 biochemical assessment, 681 biochemical markers macronutrients, 682–685 micronutrients, 686–700 miscellaneous, 685–686 clinical component, 681 dietary component, 682 environmental assessment, 682 nutrition care process, 680–681 nutrition, definition, 680 O “Occam’s razor,” 714 Occupational exposure to hazardous chemicals in laboratories, 37–38 Occupational Safety and Health Act (OSHA), 37–38 OGTT, 306 Oligoclonal bands, 613 Oligomenorrhea, 481 Oligosaccharides, 294 Oncofetal antigens, 665 Oncogenes, 664, 671 One-point calibration, 26–27 Open-loop negative feedback system, 440 Opiates, 660–661 Opsonization, 225 Optical immunoassay (OIA), 174 Oral glucose tolerance, 302, 302t Organ function, 686 OSHA Laboratory Standard, 43–44 Osmolal gap, 349 Osmolality, 347–349 clinical significance of, 347–348 determination of, 348–349 reference ranges, 349t regulation of blood volume, 348 Osmolarity, 347 Osmometers, 348–349 Osmometry, 118 freezing point, 118, 118f Osmotic pressure, Osteoblasts, 504 Osteoclast, 504 Osteomalacia, 513–514 Osteoporosis, 514–516, 711–712 diagnosis of, 515 treatment of, 515–516 Otorrhea, 613 Ovaries, 478–486 early ovarian development, 478–479 estrogen replacement therapy, 485–486 functional anatomy, 479 Hirsutism, 485 hormonal control of ovulation, 480 hormonal production, 479–480 menstrual cycle, 480 abnormalities, 481–485 precocious sexual development, 481 pubertal development in female, 480–481 Tanner staging of breast and pubic hair, 481t Ovulation, hormonal control of, 480 Oxcarbazepine, 639 Oxidation, 386 Oxidizing agent, www.ebook777.com 18698_index_p743-758.indd 750 12/11/12 6:40 PM Index Oxidoreductase, 286 Oxygen, 382–385 and carbon dioxide, 382–383 content, 384 hemoglobin–oxygen dissociation, 385 patient’s status, assessment of, 384 transport, 383–384 Oxygen saturation (SO2), 384 Oxytocin, 439, 448 P Painful thyroiditis, 499 Pancreatic carcinoma, 593 Pancreatic function diseases of pancreas, 592–594 physiology of, 591–592, 591f, 592f tests of, 594–595 fecal fat analysis, 595–596 secretin/CCK test, 594–595 serum enzymes, 596–597 sweat electrolyte determinations, 596 Pancreatitis, 593 Panhypopituitarism, 448 Pantothenic acid, 693 PAPP-A, 553 Paracentesis of abdominal cavity, 620f Parametric method, 76 Parathyroid glands, 490 Parathyroid hormone (PTH), 504–505, 504f, 508, 706 Parathyroid hormone-related protein (PTHrP), 511, 511f Parenteral nutrition, 685–686 Partial pressure of oxygen dissolved in plasma (pO2), 384 Particle concentration fluorescence immunoassay, 173 Partition, 123 Peak drug level, 631 Pediatric patient calcium and bone metabolism, 729–730 developmental changes from neonate to adult, 721 development of immune system, 733–735 development of liver function, 726–729 drug metabolism and pharmacokinetics, 739–740 endocrine function, 730–733 genetic diseases, 735–738 phlebotomy and choice of instrumentation, 721–723 point-of-care analysis, 723–724 regulation of blood gases and PH, 724–725 regulation of electrolytes and water: renal function, 725–726 Pepsin, 597 Peptide bond, 203, 203f Percent saturation, 406 Percent solution, 8, 21 Pericardial fluid, 619, 619f, 619t Peripheral vascular disease (PVD), 318 Peritoneal fluid, 619–621 Pesticides, 656 pH, 9, 20, 375–393 Pharmacogenomics, 628, 633 Pharmacokinetics, 631–632 pH electrodes, 112–114 calibration, 113, 113f components, 112, 112f indicator electrode, 112 liquid junctions, 112–113 Nernst equation, 113 pH combination electrode, 113–114 readout meter, 113 reference electrode, 112 Phencyclidine (PCP), 661 Phenobarbital, 636–637 Phenylalanine (Phe), 205, 208f Phenylethanolamine N-methyltransferase, 465 Phenylketonuria (PKU), 207–209 tests for, 208–209 18698_index_p743-758.indd 751 Phenytoin, 637 Pheochromocytomas, 465, 467–468 Phlebotomy and choice of instrumentation, 721–723, 722t Phosphatases, 531–532 Phosphate, 367–368, 574 clinical applications, 368 determination of inorganic phosphorus, 368 distribution of, 368 physiology, 367 reference ranges, 368, 368t regulation of, 367–368 Phosphatidylglycerol, 609 Phospholipids, 315 measurement, 336–337 Photocell, 104 Photodetectors, 104–106 barrier-layer cell or photocell, 104 photodiode array spectrophotometer, 105–106, 105f photomultiplier (PM) tube, 105, 105f phototube, 104–105, 105f single-/double-beam spectrophotometers, 106, 106f Photodiode array spectrophotometer, 105–106, 105f Photomultiplier (PM) tube, 105, 105f Phototube, 104–105, 105f Pick’s disease, 712 Pipets, 12–16 automatic, 14–15, 14f blowout, 13 classification, 13t correct and incorrect positions, 13, 13f graduated, 13–14 measuring, 13–14 micropipets, 14 Mohr, 14 pipetting technique, 13, 13f serologic, 14 transfer, 14 type of bulbs, 14 volume indication, 14f Pituitary stalk, 439 Planck’s formula, 101 Plasma gastrin, 598 Plasma proteins, 218–227 albumin, 220 characteristics of, 218t, 219t globulins, 220–227 prealbumin (transthyretin), 220 Plasticwares, 11–17, 17f burets, 16 laboratory vessels, 12 pipets, 12–16 syringes, 16–17 Pleural fluid, 618–619 POCT coordinator (POCC), 196 Point-of-care (POC) analyzers, 140 Point-of-care testing (POCT), 192–198, 723–724, 723t advantages and disadvantages, 192–193, 193t analyzers, types of, 197 checklist, 195 implementation, 194–195 establishing need, 194 personnel requirements, 196 POCT Implementation Protocol, 195 informatics and, 198 laboratory regulations, 193–194 accreditation, 193–194 POCT complexity, 194 POC applications, 197–198 quality management, 196–197 accuracy requirements, 196 QC and proficiency testing, 196–197 Poisons, 646 Polyclonal antibody, 162 Polycystic ovary syndrome, 484–485 Polydipsia, 348 Polymerase chain reaction (PCR), 182, 186 Polypeptide, 203 Polysaccharides, 294 751 Porphyrias, 415, 418T Porphyrinogens, 416 Porphyrins, 415–521 chemistry of, 416 clinical significance and disease correlation, 416–420 methods of analyzing porphyrins, 420–421 tests for porphyrins, 421 tests for urinary PBG and ALA, 420 role in the body, 416 structure, 416F synthesis, 416 Porphyrinurias (secondary porphyrias), 419 Positive-displacement pipets, 15 Postanalytic phase (data management) in total laboratory automation, 156–157 Posterior pituitary hormones, 448–449 or neurohypophysis, 439 oxytocin, 448 vasopressin, 448–449 Posthepatic jaundice, 524 Postpartum thyroiditis, 499 Postrenal, 248 Postzone, 162 Potassium, 353–357, 573 clinical applications of, 355–356 collection of samples, 356–357 determination of, 357 reference ranges, 357, 357t regulation of, 354 32P radionuclide, 181 Prealbumin (transthyretin), 220 Preanalytic errors, 390 Preanalytic phase (sample processing) in total laboratory automation, 153–156, 155f Precipitation techniques, 171 Precipitin curve, 162f Precision study, 62, 63f, 337 Precocious sexual development, 481 Predictive value, 80 Prehepatic Jaundice, 524 Primary aldosteronism, 458 Primary hyperparathyroidism (PHPT), 505, 508–509 biochemical findings, 509 management of, 509 Primary hypothyroidism, 731 Primary respiratory acidosis or alkalosis, 380 Primary standards, Primers, 185t Principal fetal protein, 218 Prism, 104 Probe, 146 amplification, 188 Problem–cause–solution methodology, 91 Procainamide, 634–635 Process Sigma, 93, 93t Proenzyme or zymogen, 263 Proficiency samples, 71 Proficiency testing, 67, 71, 392–393 in QC, 196–197 Progesterone, 479–480 Prolactin, 441 clinical evaluation of hyperprolactinemia, 446 idiopathic galactorrhea, 446 management of prolactinoma, 446 other causes of hyperprolactinemia, 446 prolactinoma, 445–446 Prolactin inhibitory factor (PIF), 445 Prolactinoma, 445–446 Proline (Pro), 207 Proportional error, 59, 62 Prostaglandins, 574, 575 Prostate-specific antigen (PSA), 675–676, 677t Prosthetic group, 263 Protein-free filtrate, 250 Proteins, 213–218, 682–685 abnormalities case study, 230–231 hyperproteinemia, 230 hypoproteinemia, 230 adiponectin, 229 albumin, 682–683 12/11/12 6:40 PM 752 index Proteins (Continued) amyloid, 230 analysis, methods of, 233–238 BNP and N-terminal–BNP, 228–229 β–trace protein (BTP), 229 cardiac troponin (cTn), 228 case study, 239 catabolism and nitrogen balance, 214–215 charge and isoelectric point, 215–216 classification, 216–218 by protein functions, 216–217 by protein structure, 217–218 C-reactive protein, 685 cross-linked C-telopeptides (CTXs), 229 cystatin C, 229 cytokines, 685 electrophoresis, 236f fibronectin, 229, 684 fractionation, identification, and quantitation of, 233–234 functions of, 217t importance, 213 molecular size, 213 myoglobin, 227–228 nitrogen balance, 684–685 nitrogen content, 215 in other body fluids, 239 CSF proteins, 240–242 urinary proteins, 239–240 plasma, 218–227 plasma proteins of nutritional interest, 683t retinol-binding protein, 684 solubility, 216 structure, 215, 215f synthesis, 204t, 213–214, 214f total, 231–233 Biuret, 232–233 dye-binding methods, 233 Kjeldahl, 231–232 methods, 232t transferrin, 683 transthyretin, 683–684 Proteinuria, 217 Protoporphyrin (PROTO), 416 Provider-performed microscopy procedures (PPMPs), 194 Proximal convoluted tubule, 570–571 Prozone, 162 Pseudohypoparathyroidism, 364, 513 Psychoactive drugs, 640–641 clozapine, 640 lithium, 640 olanzapine, 640–641 tricyclic antidepressants (TCAs), 640 Pubertal development in the female, 480–481 Pulmonary embolism, markers of, 559–561 use of D-Dimer detection in PE, 560 value of assaying troponin and BNP in acute PE, 561 Pulsatile secretions, 439 Pulse oximetry (SpO2), 384 Pyridoxine (vitamin B6), 690 Pyrosequencing, 184 Pyrrole rings, 416 Pyrrolysine (Pyl), 207 Q QIAamp/DNeasy kits, 181 Quadrupole mass spectrometers, 399 Quality assurance (QA), 106, 390–393 interpretation of results, 393 linearity, 106 preanalytic considerations, 390–392 quality control and proficiency testing, 392–393 stray light, 106 wavelength accuracy, 106 Quality control (QC), 53, 68–72, 90, 338, 392–393 charts, 69 Multirules RULE!, 70–71, 70t operation of system of, 69–70 and proficiency testing, 196–197 proficiency testing in, 71–72 Quality management, 196–197 Quantal dose–response relationships, 647 Quantitation of proteins, 233–234 Quaternary structure, 215 Quinidine, 634 R Radial immunodiffusion (RID), 163 Radiation safety, 45 environmental protection, 45 nonionizing radiation, 45, 46t personal protection, 45 Radioactive iodine uptake (RAIU), 494 Radioactive labels, 166–167 Radioactive material, 45 Radioactive waste, 49 Radiommunoassay (RIA), 161 Random access, 140 Random error, 58, 62 Rapid immunoassay, 174–175 Reabsorption, 250, 378 Reactive chemicals, 45 Readout meter, 113 Reagents, 5–10 chemicals, grade water, reference materials, 6–7 solution properties, 8–10 systems and delivery in automated analysis, 147–148 water specifications, 7–8 Recovery studies, 64 Redox potential, Reference electrode, 112 Reference interval studies, 56, 72, 74t CAP checklist questions, 73 data analysis, 77–79, 79f establishment of reference interval, 73, 76 “normal ranges,” 73 preanalytic and analytic considerations, 76 selection of, 75–76, 75t verification of, 73, 74 Reference method, 57, 57f Regulatory toxicology, 646 Renal function, 568–588, 569t analytic procedures, 575–581 β2-microglobulin (β2-M), 577 creatinine clearance, 575–576 cystatin C, 576–577 estimated GFR, 576 microalbumin, 577 myoglobin, 577 neutrophil gelatinase–associated lipocalin (NGAL), 577 urinalysis (UA), 578–581 anatomy, 569–570, 569f pathophysiology, 581–588 glomerular diseases, 581 renal calculi, 582 renal failure, 583–588 tubular diseases, 582 urinary tract infection/obstruction, 582 physiology, 570–575 elimination of NPN compounds, 572–573 endocrine function, 574–575 glomerular filtration, 570 tubular function, 570–572 water, electrolyte, and acid–base homeostasis, 573–574 Renal threshold, 571 Renin, 574–575 Renin–angiotensin system (RAS), 456, 571 Resource Conservation and Recovery Act (RCRA), 38 Respiratory acidosis, 381 Respiratory component, 378 Respiratory distress syndrome (RDS), 607 Restriction fragment length polymorphism (RFLP), 182 Retention factor (Rf), 124 Retinol-binding protein, 684 Reverse cholesterol transport pathway, 321 Reverse transcriptase–polymerase chain reaction (RT-PCR), 184t, 185 Reye’s syndrome, 257, 527 Rhabdomyolysis, 577 Rhinorrhea, 613 Riboflavin (vitamin B2), 690 Ribonucleic acid (RNA), 180 Rickets, 514–515 Robotics, 142 Roche MODULAR ANALYTICS system, 156f Rocket technique, 165 RO (reverse osmosis) water, Rotor syndrome, 524–252 Rumack-Matthew nomogram, 657f S Safety data sheet (SDS), 43 Salicylates, 657 Salt fractionation, 233 Sample collection and processing, 396–397 Sandwich assays, 170, 170f, 182 Sandwich immunoassays, 171–172 Sanger dideoxy DNA sequencing, 183, 183f Schiff base reaction, 305 Secondary hyperparathyroidism, 516–517 Secondary hypothyroidism, 731 Secondary standard, “Second messenger” pathway, 505 Secretagogues, 597 Secretin, 592 Secretin/CCK test, 594–595 Secretion, 252, 378 Sedatives–hypnotics, 661 Selenium, 410–411, 698–700 Selenocysteine (Sec), 207 Sella turcica, 439 Sensitivity, 62, 80, 81f, 83f diagnostic, 80 predictive values, positive/negative, 81, 82f Separation techniques, 18–19, 170–172 adsorption, 171 centrifugation, 18–19 dialysis, 19 filtration, 19 precipitation, 171 sandwich immunoassays, 171–172 solid phase, 171 Serial dilution, 25–26 Serine (Ser), 207 Serologic pipet, 14 Serous fluids, 616–621, 617f pericardial fluid, 619 peritoneal fluid, 619–621 pleural fluid, 618–619 Sertoli cells, 474 Serum, 28, 29f Serum bile acids, 531 Serum carotenoids, 600 Serum enzymes, 596–597 Serum glutamic oxaloacetic transaminase (SGOT, or GOT), 277 Serum hepatitis or long-incubation hepatitis See Hepatitis B (HBV) Serum myoglobin testing, 432 Serum protein electrophoresis, 235, 235f Serum protein electrophoresis (SPE), 235–237 Serum T4 and T3, 492 Severe combined immune deficiency (SCID), 735 Severinghaus electrode, 388 Sexual development disorders, 475–477 Sexual maturation, 721 Shifts trends, 79 Shipping, of biohazardous materials, 43 Short feedback loop, 440 Sickling hemoglobins, screening test for, 429–430 Signal amplification, 188–189 Signal processing in automated analysis, 151–153 Significant figures, 19–20 www.ebook777.com 18698_index_p743-758.indd 752 12/11/12 6:40 PM ... what, why, and when The editors of Clinical Chemistry: Principles, Techniques, and Correlations have designed the seventh edition to be an even more valuable resource to both students and practitioners... previous six editions, the seventh edition of Clinical Chemistry: Principles, Techniques, and Correlations is comprehensive, up-to-date, and easy to understand for students at all levels It is also... will improve medical decision making and thus patient safety while reducing medical errors This edition of Clinical Chemistry: Principles, Techniques, and Correlations is a crucial element in