Table Of Content

Basic Pathology This page intentionally left blank Fourth edition Basic Pathology An introduction to the mechanisms of disease Sunil R Lakhani BSc MBBS MD FRCPath FRCPA Professor and Head, Molecular and Cellular Pathology, School of Medicine, University of Queensland, Mayne Medical School, Brisbane, Australia Susan A Dilly BSc MBBS FRCPath Professor and Institute Director, Institute of Health Sciences Education, Barts and The London, Queen Mary’s School of Medicine and Dentistry, London, UK Caroline J Finlayson MBBS FRCPath Honorary Senior Lecturer and Consultant in Histopathology, St George’s Hospital Medical School, London, UK First published in Great Britain in 1993 Second edition 1998 Third edition 2003 This fourth edition published in 2009 by Hodder Arnold, an imprint of Hodder Education, an Hachette UK Company, 338 Euston Road, London NW1 3BH http://www.hoddereducation.com © 2009 Sunil R Lakhani, Susan A Dilly, Caroline J Finlayson All rights reserved. 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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. For these reasons the reader is strongly urged to consult the drug companies’ printed instructions before administering any of the drugs recommended in this book. 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 ISBN 978 0 340 95003 6 2 3 4 5 6 7 8 9 10 Commissioning Editor: Sara Purdy Production Editor: Jane Tod Production Controller: Karen Dyer Cover Designer: Helen Townson Indexer: John Sampson Typeset in 10.5 Perpetua by Macmillan Publishing Solutions Printed and bound in Italy What do you think about this book? Or any other Hodder Arnold title? Please visit our website: www.hoddereducation.com CONTENTS Preface vii Acknowledgements ix PART 1 Introduction: what is a disease? 1 Prologue: What is a disease? 3 Chapter 1: Causes and mechanisms – general principles 7 Chapter 2: What causes disease? 29 PART 2 Defence against disease 75 Introduction: The role of epidemiology in disease 77 Chapter 3: The body’s response to infection 79 Chapter 4: The acute inflammatory response 89 Chapter 5: Chronic and granulomatous inflammation, healing and repair 115 Chapter 6: The immune defence against infection 139 PART 3 Circulatory disorders 163 Introduction: Features of circulatory disorders 165 Chapter 7: Vascular occlusion and thrombosis 169 Chapter 8: Atherosclerosis and hypertension 189 Chapter 9: Circulatory failure 211 PART 4 Cell growth and its disorders 239 Introduction: A brief history of cancer 241 Chapter 10: Benign grown disorders 243 Chapter 11: Malignant neoplasms 251 Chapter 12: What causes cancer? 263 Chapter 13: Molecular genetics of cancer 273 Chapter 14: The behaviour of tumours 291 Chapter 15: The clinical effects of tumours 297 Epilogue 307 Index 309 This page intentionally left blank vii CPROENFATCEENTS What is the use of a book’, thought Alice, ‘without students reading the book will be able to shed the dull, pictures or conversations’. dreary image of histopathology that they all seem to be Lewis Carroll born with. Pathology is one of the most fascinating and fun subjects students are likely to encounter during Any artist will tell you that in drawing objects, you their undergraduate training. If you understand the basic cannot ignore the spaces in between.The picture ceases principles then the interpretation of clinical symptoms to exist when only one aspect is viewed in isolation. and signs, the rationale behind investigation and Musical pieces composed entirely of notes and without treatment and the unravelling of complex cases pauses would be nothing more than a noise and an becomes more logical.Time spent building a framework irritation. Yet when it comes to teaching, we may of mechanisms will assist your clinical practice. ignore this fact and fail to put our own specialty into To help you with this, we have produced a companion the context of the whole curriculum. volume called Pathology in Clinical Practice: 50 Case Over the last decade, there has been a trend towards Studies. These are designed to help you to use your a more integrated approach to medical education. We pathology knowledge in clinical settings by taking a are delighted that such an approach, which we have clinical presentation, such as you might come across on always used in our teaching, is now widely adopted in the wards or in a case-based learning tutorial, and to the UK and abroad. pose you a number of questions, then guide you with Our aim in this book has been to create a tutorial on the answers. This is divided into sections based on the mechanisms of disease over a background of history, symptoms, signs, investigation, patient management and science and clinical relevance. The goal is to give the complex cases. It helps you to add clinical information student a sense of belonging to a movement, the on to the basic science and to recognize some of the movement from past to present and from laboratory to processes of clinical reasoning that you must master.We patient. hope that you will also find it stimulating and fun. This book has been written in the hope that the This pair of books is primarily intended for student will read the text fully and at leisure. This not undergraduate medical students, but should also be only contains detail about the disease processes but also useful to students of dentistry, human biology and historical anecdotes and clinical scenarios.The cartoons other health professions. Postgraduate students are intended to amuse as well as illustrate the studying for pathology or surgical exams may also wish importance of certain topics, and we sincerely hope that to consult these books. To access the image library on the website www.hodderplus.co.uk/basicpathology please register using the serial number student09. Once you have registered you will not need the serial number but can log in using the username and password you will create during registration. This page intentionally left blank PARCEKFANCOEWLEDGEMENTS When we set out 15 years ago to write a textbook in aspects have to be taught side by side, not instead of, which we would take the students on a journey, from the mechanisms of disease. past to present and from patient to the cell and back Our endeavours to produce this fourth edition have again, the phrase ‘integrated curriculum’ was not in been considerably aided by help, comments and common usage. Today, most medical schools have constructive criticism from a number of people and we switched to the new style curriculum in which would like to acknowledge their time and effort.They pathology is supposedly taught as an integrated subject include Professor Philip Butcher, Professor Mike with other disciplines. We have always believed that Davies and Dr Grant Robinson at St George’s Hospital pathology should be taught in the context of the clinical who helped us with the second edition and whose situation and hope that this has been reflected by the efforts are still included in the current work. Dr Ahmet content of this and the previous editions. It is a shame, Dogan, one of our co-authors from the third edition, however, that in many schools, pathology rather than had to withdraw due to other work commitments but being integrated with clinical work has been dis- has kindly agreed to let us use his previous integrated and lost as it is not deemed as important as contributions. We are grateful for his generosity and clinical training for the new generation of doctors, continued support.We would like to acknowledge the nurses and disciplines allied to medicine. work that Drs Pria Pakkiri, Leonard Da Silva and Pathology is the study of the mechanism of disease. Professor Frederique Penault-Llorca have put in to read It has therefore been, and hopefully will remain, at the and review the changes and the images kindly provided heart of anybody’s desire to understand and manage by Dr Mitesh Gandhi. disease. It is the core discipline of medical education Finally and most importantly, we would like to thank and the very fabric that underpins clinical medical our families for their encouragement and support. But practice. That is not intended to imply that the non- for their understanding, it would be difficult to get biomedical aspects–ethics, communication, developing away with the disproportionate amount of time that empathy and understanding–are not important. These such projects consume. SRL SAD CJF 2009