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Neil Herring Robert Wilkins BASIC SCIENCES FOR CORE MEDICAL TRAINING AND THE MRCP Basic Sciences for Core Medical Training and the MRCP Basic Sciences for Core Medical Training and the MRCP Edited by Neil Herring Associate Professor and BHF Intermediate Fellow, University of Oxford, UK Tutor and Fellow, Keble College, University of Oxford, UK Consultant Cardiologist, John Radcliffe Hospital, Oxford, UK Robert Wilkins Associate Professor of Epithelial Physiology, University of Oxford, UK American Fellow in Physiology, St Edmund Hall, Oxford, UK 1 3 Great Clarendon Street, Oxford, OX2 6DP, United Kingdom Oxford University Press is a department of the University of Oxford. It furthers the University’s objective of excellence in research, scholarship, and education by publishing worldwide. Oxford is a registered trade mark of Oxford University Press in the UK and in certain other countries © Oxford University Press 2015 The moral rights of the authors have been asserted Impression: 1 All rights reserved. No part of this publication may be reproduced, stored in a retrieval system, or transmitted, in any form or by any means, without the prior permission in writing of Oxford University Press, or as expressly permitted by law, by licence or under terms agreed with the appropriate reprographics rights organization. Enquiries concerning reproduction outside the scope of the above should be sent to the Rights Department, Oxford University Press, at the address above You must not circulate this work in any other form and you must impose this same condition on any acquirer Published in the United States of America by Oxford University Press 198 Madison Avenue, New York, NY 10016, United States of America British Library Cataloguing in Publication Data Data available Library of Congress Control Number: 2015949661 ISBN 978–0–19–959967–7 Printed in Great Britain by Ashford Colour Press Ltd, Gosport, Hampshire Oxford University Press makes no representation, express or implied, that the drug dosages in this book are correct. Readers must therefore always check the product information and clinical procedures with the most up-to-date published product information and data sheets provided by the manufacturers and the most recent codes of conduct and safety regulations. The authors and the publishers do not accept responsibility or legal liability for any errors in the text or for the misuse or misapplication of material in this work. Except where otherwise stated, drug dosages and recommendations are for the non-pregnant adult who is not breast-feeding Links to third party websites are provided by Oxford in good faith and for information only. Oxford disclaims any responsibility for the materials contained in any third party website referenced in this work. Foreword I was honoured and delighted to be asked by Neil and Robert this is more likely to reflect basic educational experience to write a foreword to this book. Honoured because two within those schools than academic qualifications on entry great scientists who have co-edited an excellent book asked to medicine. me to do so, but delighted because I thus read the book, Students and trainees appreciate the importance of basic including chapters relevant to specialities other than my science but sometimes their inquisitiveness and thirst for a own, which is something I might otherwise not have done. It better understanding only comes later in their training when is so easy to forget some basic principles and so often they they try to disentangle what is going on in difficult clinical transcend disciplines. However, when starting one’s career cases. It is almost impossible to understand why a pregnant the task can seem insurmountable and breaking principles lady has an increased heart rate and a quiet heart murmur down and applying them to one system at a time produces without understanding the normal physiological response to more manageable challenges. pregnancy, and one will not be able to differentiate between We live in changing times. Access to information is now normality and abnormality without such understanding. almost instantaneous. Rote learning of facts may never have Similarly, an understanding of the variability in carbohy- been appropriate but is even less sensible now. However, drate metabolism and insulin kinetics between individuals the ability to use knowledge to solve problems remains of is essential if we are to truly offer personalized prescribing paramount importance and, as medicine becomes more for those with diabetes, and why one intervention is pre- complex, the scientific underpinning of the practice of ferred to another in complex cardiac rhythm disturbances medicine is of increasing rather than lessening importance. necessitates a firm understanding of electrophysiology. As the provision of healthcare is shared with more fellow Understanding mechanisms is thus crucial—mechanisms in health professionals a doctor’s especial responsibilities for health, mechanisms giving rise to disease, and mechanisms diagnosis, prescribing and the explanation of risk can only by which medication can cure or ameliorate the underlying be done adequately with such an underlying understanding. disorders. During a 40-year professional career new diseases and new A system approach can thus be justified as a basis for interventions will bring new challenges to all, but a sound our learning but such an approach needs to also respect understanding of the science of health and disease makes the importance of the science of population health, epide- such challenges easier to tackle. Unfortunately current miology, genetics, statistics, and clinical pharmacology and assessment methods can appear to involve rather bland this fusion of approaches is particularly well done in Basic assessment of competency in discrete domains rather than Sciences for Core Medical Training and the MRCP. necessarily assessing overall ability to solve the often complex challenges of modern medicine. Published data sug- Martyn R Partridge gests that performance in postgraduate examinations does Professor of Respiratory Medicine vary between graduates from different medical schools and Imperial College London Preface Medical education, like medical science, is constantly evolv- bullet point format with simple concise explanations. It ing. Traditional courses often start by focusing on the basic makes extensive use of tables, lists, and diagrams, with each sciences such as physiology, cell biology, biochemistry, and chapter also containing multiple-choice questions aimed at anatomy, studying each in isolation. However, medical school consolidating the material covered and highlighting topics teaching is moving to a more systems based approach, often that are frequently examined. No book of this length cover- based around the clinical specialties. From the first year of ing such a wide area can be completely comprehensive. For study, students may learn about the basic science, pathology, the busy junior doctor or medical student, we hope it will diagnosis, and treatments related to a particular specialty provide a coherent starting point for improving their under- whilst also seeing patients in the clinical setting. Old-style standing of medical science before turning to other texts textbooks, which focus on a particular medical science, that focus more on pathology, diagnosis, and management. are therefore not always ideal for this structure for learn- Although we have structured the chapters around the ing. Similarly post-graduate medical examinations, such as syllabus for the MRCP (UK) Part 1 examination, we hope those for Membership of the Royal College of Physicians that the specialty-based approach makes it a useful text (MRCP) in the UK, require a detailed knowledge of core for undergraduate medical education and other post- medical science, and yet examine it in a way that focuses on graduate examinations, such as the US Medical Licensing its relevance to clinical practice. Examinations. This concise text provides an up-to-date and easily read- Neil Herring able explanation of the relevant basic science behind each Robert Wilkins of the medical specialties. The text is often presented in Oxford 2015 Acknowledgements We are particularly grateful to our contributing authors: We are also grateful to our medical consultant colleagues Dr Hussein Al-Mossawi, Dr Sophie Anwar, Dr Chris for their valuable critique and advice. In particular: Dr Sue Duncan, Dr Brad Hillier, Dr James Kolasinski, Dr David Burge, Dr Niki Karavitaki, Dr Annabel Nichols, Prof Chris McCartney, Dr Niki Meston, Dr Joel Meyer, Dr Michal Pugh, and Dr John Reynolds. Rolinski, and Dr Susanne Hodgson. Dedication This book is dedicated to our late fathers, our teachers, and the students we have taught. Contents Contributors xiii Abbreviations xv 1 Genetics 1 2 Cellular, molecular, and membrane biology 15 3 Biochemistry and metabolism 27 4 Immunology 51 5 Infectious diseases 73 6 Statistics and epidemiology 113 7 Haematology 123 8 Clinical pharmacology 135 9 Rheumatology 145 10 Cardiology 163 11 Respiratory medicine 187 12 Neurology 201 13 Psychiatry 235 14 Gastroenterology 253 15 Endocrinology 271 16 Nephrology 289 17 Dermatology 303 Appendix: Answers to multiple choice questions 313 Index 315 Contributors Dr Hussein Al-Mossawi Dr David McCartney Department of Rheumatology, Nuffied Department of Primary Care Health Sciences, Southmead Hospital, University of Oxford, UK Bristol, UK Dr Niki Meston Dr Sophie Anwar Department of Newborn Screening, The Oxford Clinic, St Helier Hospital, Littlemore Mental Health Centre, Carshalton, UK Oxford, UK Dr Joel Meyer Dr Christopher J. A. Duncan Centre for Clinical Vaccinology and Tropical Medicine, Department of Infection & Tropical Medicine, Churchill Hospital, Royal Victoria Infirmary, University of Oxford, UK University of Newcastle, Newcastle-Upon-Tyne, UK Dr Michal Rolinski Nuffield Department of Clinical Neurosciences, Prof Neil Herring University of Oxford, UK Oxford Heart Centre, John Radcliffe Hospital, Department of Physiology, Anatomy and Genetics, Dr Susanne H. Hodgson University of Oxford, Oxford, UK The Jenner Institue, University of Oxford, UK Dr Bradley Hillier Prof Robert Wilkins Shaftesbury Clinic, South West London Forensic Psychiatry Service, Springfield University Hospital, London, UK Department of Physiology, Anatomy and Genetics, University of Oxford, Oxford, UK Dr James Kolasinski Oxford Centre for fMRI of the Brain, University of Oxford, UK