CLINICAL BIOCHEMISTRY - Enpab

1 CLINICAL BIOCHEMISTRY & METABOLIC MEDICINEEIGHTH EDITIONThis page intentionally left blank CLINICAL BIOCHEMISTRY & METABOLIC MEDICINEEIGHTH EDITIONP rofessor Martin Andrew Crook BSc MB BS MA PhD FRCPath FRCPI FRCPC onsultant in Chemical Pathology and Metabolic MedicineGuy s, St Thomas and University Hospital Lewisham, London, UK, and Visiting Professor, School of Science, University of Greenwich, UKFirst published in Great Britain in 1971 by Lloyd-Luke (Medical Books) LtdSecond edition 1975 Third edition 1979 Fourth edition 1984 Fifth edition published in 1988 by Edward Arnold (Publishers) LtdSixth edition published in 1994 Seventh edition published in 2006 by Hodder ArnoldThis eighth edition published in 2012 by Hodder Arnold, an imprint of Hodder Education, Hodder and Stoughton Ltd, a division of Hachette UK,338 Euston Road, London, NW1 3 2012 Hodder & Stoughton LtdAll rights reserved.

2 Apart from any use permitted under UK copyright law, this publication may only be reproduced, stored or transmitted in any form or by any means with prior permission in writing of the publishers or in the case of reprographic production in accordance with the terms of licences issued by the Copyright Licensing Agency. In the United Kingdom such licences are issued by the Copyright Licensing Agency: Saffron House, 6 10 Kirby Street, London EC1N the advice and information in this book are believed to be true and accurate at the date of going to press, neither the author nor the publisher can accept any legal responsibility or liability for any errors or omissions that may be made. In particular (but without limiting the generality of the preceding disclaimer), every effort has been made to check drug dosages; however, it is still possible that errors have been missed. Furthermore, dosage schedules are constantly being revised and new side effects recognized.

3 For these reasons the reader is strongly urged to consult the drug companies printed instructions, and their websites, before administering any of the drugs recommended in this Library Cataloguing in Publication DataA catalogue record for this book is available from the British LibraryLibrary of Congress Cataloging-in-Publication DataA catalog record for this book is available from the Library of CongressISBN-13 978-1-4441-4414-7 ISBN-13 [ISE] 978-1-4441-4416-11 2 3 4 5 6 7 8 9 10In order that we can ensure that students continue to benefit from the availability of our special editions, if you have purchased your copy in an un-authorized country, please email letting us know where, when and from which organization or individual you made the Editor: Joanna KosterProject Editor: Jenny WrightProduction Controller: Francesca WardellCover Designer: Amina Dudhia Indexer: Laurence ErringtonCover: PASIEKA/SCIENCE PHOTO LIBRARYT ypeset in 11/13 pt Minion by Phoenix Photosetting, Chatham, KentPrinted and bound in IndiaWhat do you think about this book?

4 Or any other Hodder Arnold title? Please send your comments to viiList of abbreviations viii1 Requesting laboratory tests and interpreting the results 12 Water and sodium 63 The kidneys 364 Acid base disturbances 595 Potassium 836 Calcium, phosphate and magnesium 957 The hypothalamus and pituitary gland 1168 The adrenal cortex 1299 The reproductive system 14610 Pregnancy and infertility 15711 Thyroid function 16412 Carbohydrate metabolism 17613 Plasma lipids and lipoproteins 20014 Nutrition 21615 Vitamins, trace elements and metals 22416 The gastrointestinal tract 23517 Liver disorders and gallstones 25218 Plasma enzymes in diagnosis ( CLINICAL enzymology) 27019 Proteins in plasma and urine 28220 Purine and urate metabolism 30321 Disorders of haem metabolism: iron and the porphyrias 31022 Cardiovascular disease 325 Contentsvi23 Cerebrospinal, pleural and ascitic fl uids 33224 Metabolic effects of tumours 33825 Therapeutic drug monitoring and poisoning 34726 CLINICAL BIOCHEMISTRY at the extremes of age 35827 Inborn errors of metabolism 37128 Genetics and deoxyribonucleic acid-based technology in CLINICAL BIOCHEMISTRY 38429 Patient sample collection and use of the laboratory 39130 Point-of-care testing 397 Appendix 1: Units in CLINICAL chemistry 401 Index 403 COMPANION WEBSITEThis book has a companion website available website contains downloadable images from the book as well as self assessment access these resources please register on the website using the following access details:Serial number.

5 145jw76mc8fwOnce you have registered you will not need the serial number but can log in using the username and password that you will create during your it not for the textbook CLINICAL Chemistry in Diagnosis and Treatment by Joan Zilva and Peter Pannall, I would not be a chemical pathologist. As a medical student, I was so struck by its clarity, depth and CLINICAL relevance that I decided that theirs was the medical field I wished to work the years, the fi eld of CLINICAL BIOCHEMISTRY has changed radically. Confusingly, there is no consensus on the name for this fi eld of medicine, which is known variously as CLINICAL chemistry, chemical pathology or CLINICAL BIOCHEMISTRY , to name but a few. Additionally, the fi eld now overlaps with that of metabolic medicine, a CLINICAL specialty involved with the management and treatment of patients with disorders of metabolism. CLINICAL BIOCHEMISTRY laboratories have become further automated, molecular biology technologies have entered the diagnostic arena, and chemical pathologists have become more clinically orientated towards running out-patient clinics for a variety of biochemical disturbances.

6 This book aims to address these new changes. Indeed, it is diffi cult to imagine a branch of medicine that does not at some time require CLINICAL BIOCHEMISTRY tests, which may not be too surprising, given the fact that every body cell is composed of chemicals!Unfortunately, there have been some diffi culties in recent times, with a relative shortage of graduates entering the specialty, which has not been helped by some people s attitude that CLINICAL BIOCHEMISTRY is merely a laboratory factory churning out results that anyone can interpret. There are also concerns that medical student CLINICAL BIOCHEMISTRY teaching may become diluted as part of an expanding curriculum. It is hoped that this book will excite a new generation to enter this fascinating and essential fi eld, as well as benefi t patients as their doctors learn more about their biochemical and metabolic am most grateful to Dr Sethsiri Wijeratne, Dr Alam Garrib (particularly for molecular biology expertise) and Dr Paul Eldridge for constructive criticism of the text.

7 I am also grateful to Professor Philip Mayne for his earlier contributions and the anonymous medical student reviewer(s) who commented on the text. The book has also greatly benefi ted from the wise, helpful and experienced input of Dr Andrew Day many thanks. Although every effort has been made to avoid inaccuracies and errors, it is almost inevitable that some may still be present, and feedback from readers is therefore CrookLondon, 2012 PrefaceDisclaimer The publishers and author accept no responsibility for errors in the text or misuse of the material presented. Drugs and their doses should be checked with a pharmacy, and the investigation protocols with an appropriate CLINICAL laboratory. Dynamic test protocols should be checked with an accredited CLINICAL investigation unit and may require different instructions in the elderly, children and the adenosine triphosphate-binding cassette protein 1 ACE angiotensin-converting enzymeACP acid phosphataseACR albumin to creatinine ratioACTH adrenocorticotrophic hormone (corticotrophin)ADH antidiuretic hormone (arginine vasopressin)A&E accident and emergency (department)AFP a-fetoproteinAIDS acquired immunodeficiency syndromeAIS autoimmune insulin syndromeAKI acute kidney injuryALA 5-aminolaevulinic acidALP alkaline phosphataseALT alanine aminotransferase (also known as glutamate pyruvate aminotransferase, GPT)

8 AMC arm muscle circumferenceANA antinuclear antibodyANCA antineutrophil cytoplasmic antibodyANP atrial natriuretic peptideAPA aldosterone-producing adenomaapo apolipoproteinAPRT adenine phosphoribosyl transferaseAPUD amine precursor uptake and decarboxylationARA angiotensin II receptor antagonistARB angiotensin II receptor blockerARMS amplification refractory mutation systemAST aspartate aminotransferase (also known as glutamate oxaloacetate aminotransferase, GOT)ATPase adenosine triphosphataseATP adenosine triphosphateBJP Bence Jones proteinBMD bone mineral densityBMI body mass indexBMR basal metabolic rateBNP brain natriuretic peptideBPH benign prostatic hyperplasiaCA carbohydrate antigenCaE calcium excreted per litre of glomerular filtrateCAH congenital adrenal hyperplasiacAMP cyclic adenosine monophosphateCaSR calcium-sensing receptorCAT computerized axial tomographyCBG cortisol-binding globulin (transcortin)CD carbonate dehydratase (carbonic anhydrase)

9 CEA carcinoembryonic antigenCETP cholesterol ester transfer proteinCK creatine kinaseCKD chronic kidney diseaseCNP C-type natriuretic peptideCNS central nervous systemCoA coenzyme ACOPD chronic obstructive pulmonary diseaseCRH corticotrophin-releasing hormoneCRP C-reactive proteinCSF cerebrospinal fluidCT computerized tomographyCV coefficient of variationCys C cystatin C2,3-DPG 2,3-diphosphoglycerateDDAVP 1-desamino-8-D-arginine vasopressin (desmopressin acetate)DHEA dehydroepiandrosteroneDHEAS dehydroepiandrosterone sulphateDIT di-iodotyrosineDNA deoxyribonucleic acidDPP-4 dipeptidyl peptidase-4 DVT deep vein thrombosisECF extracellular fluidECG electrocardiogramEDTA ethylenediamine tetra-acetic acideGFR estimated glomerular filtration rateENA extractable nuclear antigenENT ear, nose and throat (department)ERCP endoscopic retrograde cholangiopancreatographyESR erythrocyte sedimentation rateList of abbreviationsList of abbreviationsixEUS endoscopic ultrasonographyFAD flavine adenine dinucleotideFCH familial combined hyperlipidaemiaFDH familial dysalbuminaemic hyperthyroxinaemiaFENa% fractional excretion of sodiumFEPi% fractional excretion of phosphateFH familial hypercholesterolaemiaFMN flavine mononucleotideFSH follicle-stimulating hormonefT4 free T4fT3 free T3 GAD glutamic decarboxylaseGDM gestational diabetes mellitusGFR glomerular filtration rateGGT g-glutamyl transferaseGH growth hormoneGHRH growth hormone-releasing hormoneGIP gastric inhibitory peptideGLP-1 glucagon-like peptide 1 GnRH gonadotrophin-releasing hormoneG6P glucose-6-phosphateG6PD glucose-6-phosphate dehydrogenaseGRA glucocorticoid remediable aldosteronismHAV hepatitis A virusHb haemoglobinHbA1c glycated

10 HaemoglobinHBsAg viral surface antigenHBD hydroxybutyrate dehydrogenaseHBV hepatitis B virushCG human chorionic gonadotrophinHCV hepatitis C virusHDL high-density lipoproteinHELP heparin extracorporeal low-density lipoprotein precipitationHFE human haemochromatosis proteinHGPRT hypoxanthine guanine phosphoribosyl transferase5-HIAA 5-hydroxyindole acetic acidHIV human immunodeficiency virusHLA human leucocyte antigenHMG-CoA 3-hydroxy-3-methyl glutaryl coenzyme AHMMA 4-hydroxy-3-methoxymandelic acidHNF hepatocyte nuclear factorHONK hyperosmolal non-ketotic (coma)HRT hormone replacement therapyhs-CRP high-sensitivity C-reactive protein5-HT hydroxytryptamine (serotonin)5-HTP hydroxytryptophanHVA homovanillic acidIAH idiopathic adrenal hyperplasiaIDL intermediate-density lipoproteinIDMS isotope dilution mass spectrometryIEM inborn errors of metabolismIFG impaired fasting glucoseIFN interferonIg immunoglobulinIGF insulin-like growth factorIGT impaired glucose toleranceIL interleukinINR international normalized ratioLADA latent autoimmune diabetes of adultsLCAT lecithin cholesterol acyltransferaseLDH lactate dehydrogenaseLDL low-density lipoproteinLH luteinizing hormoneLR likelihood ratioMCADD medium-chain acyl coenzyme A dehydrogenase deficiencyMCH mean corpuscular haemoglobinMCV mean corpuscular volumeMDRD modification of diet in renal disease (formula)