FIFTH EDITION Clinical Biochemistry AN ILLUSTRATED COLOUR TEXT Content Strategist: Jeremy Bowes Content Development Specialist: Fiona Conn Project Manager: Srividhya Vidhyashankar Design Direction: Christian Bilbow Illustration Manager: Jennifer Rose FIFTH EDITION Clinical Biochemistry AN ILLUSTRATED COLOUR TEXT Allan Gaw MD PhD FRCPath FFPM PGCertMedEd Robert A Cowan BSc PhD Professor and Director Formerly Lecturer in Pathological Biochemistry Northern Ireland Clinical Research Facility Department of Pathological Biochemistry Belfast, UK University of Glasgow Glasgow, UK Michael J Murphy FRCP Edin FRCPath Clinical Reader in Biochemical Medicine Denis St J O’Reilly MSc MD FRCP FRCPath University of Dundee Formerly Consultant Clinical Biochemist Dundee, UK Department of Clinical Biochemistry University of Glasgow Glasgow, UK Rajeev Srivastava MS, FRCS, FRCPath Consultant Clinical Biochemist NHS Greater Glasgow & Clyde, Glasgow, UK Illustrated by Cactus Design and Illustration, Robert Britton, Richard Tibbitts and the authors EDINBURGH LONDON NEW YORK OXFORD PHILADELPHIA ST LOUIS SYDNEY TORONTO 2013 © 2013, Elsevier Ltd. 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First edition 1995 Second edition 1999 Third edition 2004 Fourth edition 2008 Fifth edition 2013 ISBN 978-0-7020-5179-1 e-ISBN 9780702054143 British Library Cataloguing in Publication Data A catalogue record for this book is available from the British Library Library of Congress Cataloging in Publication Data A catalog record for this book is available from the Library of Congress Notices Knowledge and best practice in this feld are constantly changing. As new research and experience broaden our understanding, changes in research methods, professional practices, or medical treatment may become necessary. Practitioners and researchers must always rely on their own experience and knowledge in evaluating and using any information, methods, compounds, or experiments described herein. In using such information or methods they should be mindful of their own safety and the safety of others, including parties for whom they have a professional responsibility. 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The publisher’s policy is to use paper manufactured from sustainable forests Printed in China Preface to the ffth edition Time marches on. As we present the updated, we have, we believe, kept the Srivastava to our team. Rajeev is a ffth edition of our Illustrated Colour essence of the book that has made it Consultant Clinical Biochemist in Text we are reminded that we have such a success with readers around the Glasgow, bringing with him specialist just passed another milestone on world. expertise in nutrition and paediatric a journey that began twenty years Some sections of the book have biochemistry. ago when we were frst invited to received much more attention than Writing this edition of the book has produce a new textbook of Clinical others, with minor adjustments been as challenging and as enjoyable Biochemistry by Churchill Livingstone. on some double page spreads and as all the others. After these frst 20 That book in its various editions and entirely new pages on others, such as years we look forward, with renewed translations has gone on to sell more myocardial infarction, gastrointestinal excitement and vigour, to the than 50, 000 copies. Because of this disorders, osteoporosis, proteinuria, possibilities of the next. success, when it comes to writing a trace metals and paediatrics. new edition we face the combined With this edition we bid farewell to Allan Gaw challenges of preserving what works, two of our original authorship team Michael J Murphy while updating what has become – Professors Jim Shepherd and Mike Rajeev Srivastava outmoded and including for the frst Stewart – who have decided to step Robert A Cowan time important new material. These down and enjoy their retirements. But, Denis St J O’Reilly challenges have been met and while with departures come arrivals, and we every page of this edition has been are delighted to welcome Dr Rajeev  v Prefacetothefrstedition Medical education is changing, so the used by the student to facilitate rapid primarily interested in the subject of educational tools we use must change revision of the text. Clinical Biochemistry from a user’s too. This book was designed and The book is divided into four point of view rather than that of a written for those studying Clinical main sections. Introducing Clinical provider. To this end we have not Biochemistry for the frst time. We biochemistry outlines the background covered analytical aspects except in a have placed the greatest emphasis on to our subject. In Core biochemistry few instances where these have direct the foundations of the subject while we cover the routine analyses that relevance to the interpretation of covering all those topics found in a would form the basic repertoire biochemical tests. What we have tried medical undergraduate course on of most hospital laboratories. The to do is present Clinical Biochemistry Clinical Biochemistry. The format is Endocrinology section covers as a subject intimately connected to not that of a traditional textbook. thyroid, adrenal, pituitary and gonadal Clinical Medicine, placing emphasis By arranging the subject in double- function testing, and in Specialized on the appropriate use of biochemical page learning units we offer the investigations we discuss less tests and their correct interpretation in student a practical and effcient way to commonly requested, but important a clinical setting. assimilate the necessary facts, while analyses. presenting opportunities for problem This book relies on illustrations and Glasgow solving and self-testing with case diagrams to make many of its points 1995 Allan Gaw, histories. Clinical notes present and these should be viewed as integral RobertA Cowan channels for lateral thinking about to the text. The reader is assumed to DenisStJ O’Reilly each learning unit, and boxes have a basic knowledge of anatomy, MichaelJ Stewart summarizing the key points may be physiology and biochemistry and to be James Shepherd vi Acknowledgements The following have helped in many Roy Fisher Heather Murray different ways in the preparation Alan Foulis Brian Neilly of the various editions of this book: Callum Fraser John Paterson in providing illustrations, in Moira Gaw Nigel Rabie discussions, and in suggesting Dairena Gaffney Margaret Rudge improvements to the manuscript. Brian Gordon Naveed Sattar Christina Gray Heather Stevenson Bryan Adamson Helen Gray Ian Stewart Bill Bartlett David Halls Judith Strachan Sally Beard John Hinnie Mike Wallace Graham Beastall Fiona Jenkinson Janet Warren Iain Boyle Jennie Johnston Philip Welsby Sharon Boyle Witsanu Kumthornthip Peter H. Wise Kimberley Brown Kim Lim Helen Wright Louise Brown Grace Lindsay Alesha Zeschke John Card Greig Louden Sam Chakraverty Tom MacDonald Special mention must also be made Brain Cook Jean McAllister of our editorial and design team at Ellie Dow Neil McConnell Elsevier without whose encouragement Frances Dryburgh Derek McLean and wise counsel this book would not Andy Duncan Ellen Malcolm have been written. Gordon Fell Hazel Miller 2 1 INTRODUCING CLINICAL BIOCHEMISTRY 1 The clinical biochemistry laboratory Clinical biochemistry, chemical pathol- laboratory is often involved in research diseases, there may be just one or two ogy and clinical chemistry are all into the biochemical basis of disease and laboratories in the country offering the names for the subject of this book, that in clinical trials of new drugs. service. branch of laboratory medicine in which chemical and biochemical methods are Core biochemistry Urgent samples applied to the study of disease (Fig 1.1). While in theory this embraces all non- Biochemical facilities are provided in All clinical biochemistry laboratories morphological studies, in practice it is every hospital, although not necessarily provide facilities for urgent tests, and usually, though not exclusively, con- to the same extent. All biochemistry can expedite the analysis of some fned to studies on blood and urine laboratories provide the ‘core analyses’, samples more quickly than others. Labo- because of the relative ease in obtaining commonly requested tests that are of ratories also offer an ‘out of hours’ such specimens. Analyses are made on value in many patients, on a frequent service, in those cases where analyses other body fuids, however, such as basis (Table 1.1). The clinician will often gastric aspirate and cerebrospinal fuid. request specifc groupings of tests, and Clinical biochemical tests comprise over clinical biochemistry assumes a cryptic Table 1.1 The clinical biochemistry one-third of all hospital laboratory language of its own as request forms repertoire investigations. arrive at laboratory reception for ‘U & Core biochemical tests Es’ (urea and electrolytes), ‘LFTs’ (liver n Sodium, potassium and bicarbonate function tests) or ‘blood gases’. n Urea and creatinine The use of biochemical n Calcium and phosphate tests n Total protein and albumin Specialized tests n Bilirubin and alkaline phosphatase Biochemical investigations are involved, n Alanine aminotransferase (ALT) and aspartate to varying degrees, in every branch of There are a variety of specialties within aminotransferase (AST) clinical medicine. The results of bio- clinical biochemistry (Table 1.1). Not n Free thyroxine (FT4) and Thyroid Stimulating Hormone (TSH) chemical tests may be of use in diagno- every laboratory is equipped to carry out n γ-glutamyl transpeptidase (γGT) sis and in the monitoring of treatment. all possible biochemistry requests. Large n Creatine kinase (CK) Biochemical tests may also be of value departments may act as reference n H+, PCO2 and PO2 (blood gases) in screening for disease or in assessing centres where less commonly asked for n Glucose the prognosis once a diagnosis has been tests are performed. For some tests that n Amylase Specialized tests made (Fig 1.2). The biochemistry are needed in the diagnosis of rare n Hormones n Specifc proteins n Trace elements n Vitamins n Drugs n Lipids and lipoproteins History n Intermediary metabolites n DNA analyses Diagnosis Treatment Clinical examination Diagnostic services Physiological tests: Imaging ECG, EEG, lung function Laboratory services Haematology Genetics Screening Histopathology Immunology Microbiology Screening Prognosis Clinical biochemistry Emergency Core Specialized services biochemistry tests Fig 1.1 The place of clinical biochemistry in medicine. Fig 1.2 How biochemical tests are used. K.........5 mmol/L Cl .......95 mmol/L Biochemistry Report Na......140 mmol/L 1 The clinical biochemistry laboratory 3 (a) (b) (c) Fig 1.3 Analysing the samples: (a) the automated analyser, (b) ‘kit’ analysis and (c) manual methods. are required during the night or at This book describes how the results Test repertoire weekends. The rationale for performing of biochemistry analyses are interpreted, such tests is based on whether the test There are over 400 different tests that rather than how the analyses are per- result is likely to infuence the immedi- may be carried out in clinical biochem- formed in the laboratory. An important ate treatment of the patient. istry laboratories. They vary from the function of many biochemistry depart- Some larger hospitals have laboratory very simple, such as the measurement ments is research and development. facilities away from the main laboratory, of sodium, to the highly complex, such Advances in analytical methodology and such as in the theatre suite or adjacent as DNA analysis, screening for drugs, in our understanding of disease con- to the diabetic clinic (see pp. 8–9). identifcatication of intermediary metab- tinue to change the test repertoire of the olites or differentiation of lipoprotein biochemistry department as the value of variants. Many high-volume tests are new tests is appreciated. Automation and done on large automated machines. Less computerization frequently performed tests may be con- Laboratory personnel Most laboratories are now computer- veniently carried out by using commer- ized, and the use of bar-coding of speci- cially prepared reagents packaged in ‘kit’ As well as performing the analyses, the mens and automated methods of form. Some analyses are carried out clinical biochemistry laboratory also analysis allows a high degree of produc- manually (Fig 1.3). Assays that are per- provides a consultative service. The labo- tivity and improves the quality of service. formed infrequently may be sent to ratory usually has on its staff both Links to computer terminals on wards another laboratory where the test is medical and scientifc personnel who and in General Practices allow direct carried out regularly. This has both cost are familiar with the clinical signifcance access to results by the requesting and reliability benefts. and the analytical performance of the clinician. Dynamic tests require several speci- test procedures, and they will readily mens, timed in relation to a biochemical give advice on the interpretation of the stimulus, such as a glucose load in the results. Do not be hesitant to take advan- glucose tolerance test for the diagnosis tage of this advice, especially where a of diabetes mellitus. Some tests provide case is not straightforward. a clearcut answer to a question; others are only a part of the diagnostic jigsaw. Clinical note The clinical biochemistry laboratory plays only a part in the overall assessment and management of the patient. For The clinical biochemistry laboratory some patients, biochemical analyses may have little or no part in their n Biochemical tests are used in diagnosis, monitoring treatment, screening and for prognosis. diagnosis or the management of n Core biochemical tests are carried out in every biochemistry laboratory. Specialized tests their illness. For others, many tests may be referred to larger departments. All hospitals provide for urgent tests in the may be needed before a diagnosis is ‘emergency laboratory’. made, and repeated analyses may n Laboratory personnel will readily give advice, based on their knowledge and experience, on be required to monitor treatment the use of the biochemistry laboratory, on the appropriate selection of tests, and about the over a long period. interpretation of results.