Target Organ Pathology - A Basic Text PDF
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Target Organ Pathology A Basic Text Target Organ Pathology A Basic Text Edited by J.TURTON Department of Toxicology, The School of Pharmacy, University of London and J.HOOSON ITR Laboratories Inc., Montréal This edition published in the Taylor & Francis e-Library, 2005. “To purchase your own copy of this or any of Taylor & Francis or Routledge’s collection of thousands of eBooks please go towww.eBookstore.tandf.co.uk.” UK Taylor & Francis Ltd, 1 Gunpowder Square, London EC4A 3DE USA Taylor & Francis Inc., 1900 Frost Road, Suite 101, Bristol, PA 19007 Copyright © Taylor & Francis Ltd 1998 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, electronic, electrostatic, magnetic tape, mechanical, photocopying, recording or otherwise, without the prior permission of the copyright owner. British Library Cataloguing in Publication Data A catalogue record for this book is available from the British Library ISBN 0-203-48192-5 Master e-book ISBN ISBN 0-203-79016-2 (Adobe eReader Format) ISBN 0-7484-0156-3 (cased) ISBN 0-7484-0157-1 (paperback) Library of Congress Cataloguing in Publication data are available Cover design by Jim Wilkie Contents Foreword page vi Preface vii Contributors ix 1 The Integumentary System 1 Andrew J.Ingram 2 The Digestive System I: The Gastrointestinal Tract and Exocrine Pancreas 27 Graham R.Betton 3 The Digestive System II: The Hepatobiliary System 57 John G.Evans and Brian G.Lake 4 The Urinary System 89 Peter Greaves 5 The Cardiovascular System 126 Kevin R.Isaacs Section A The Heart 126 Section B The Vascular System 142 6 The Haematopoietic System 160 C.Michael Andrews 7 The Immune System 187 Joseph G.Vos, Ian Kimber, C.Frieke Kuper, Henk van Loveren and Henk-Jan Schuurman 8 The Musculoskeletal System 215 Ruth M.Lightfoot Section A Skeletal Muscle 215 Section B Bone, Cartilage and Joints 229 9 The Nervous System 247 Peter Buckley 10 The Endocrine System 281 Mary J.Tucker v 11 The Respiratory System 303 John R.Foster 12 The Male Reproductive System 334 Dianne M.Creasy 13 The Female Reproductive System 366 David J.Lewis and Chirukandath Gopinath 14 The Mammary Gland 386 Jean Hooson 15 Organs of Special Sense I: The Eye 405 Mervyn Robinson 16 Organs of Special Sense II: The Ear 420 Ernest S.Harpur Index 436 Foreword This comprehensive text and reference comprises sixteen chapters dedicated to the main organ systems of the body and their responses to toxic injury. The authors are all practising toxicological pathologists from academia and research laboratories with an international reputation in their field. The adoption of the classical approach to target organ toxicity was influenced by the specific, and sometimes unique, manner in which compounds manifest toxic injury. Each chapter therefore addresses the normal anatomy and physiology of the given organ system before detailing the morphological and pathophysiological events leading to toxic injury. It is this integration of altered form and function that defines the processes of target organ toxicity, the cornerstone of understanding hazard and hence risk and safety assessment. The practising toxicologist needs to receive from the pathologist a lucid appreciation of the likely clinical impact of the toxic changes observed; first in the test species and then, by extrapolation, to man. The information provided in each chapter is directed at understanding the underlying processes of toxicity involved. An appreciation of the significant species differences in the toxic manifestations to these processes is an essential factor in the effective extrapolation of animal test data to the human clinical environment. This synthesis of normality and toxicity states is illustrated by a diverse array of toxic changes induced by natural substances, industrial chemicals, pesticides and pharmaceuticals. Each of these examples illustrates the links between the primarily biochemical approach of classic texts of toxicology and the morphological descriptions of textbooks of pathology. The intended readership—both toxicologists and toxicological pathologists—is given a comprehensive and systematic review of target organ pathology, delivering both basic principles for those in training and learning points as part of the continuous professional development of those working in the field. These concepts are extensively supported by illustrations and key references. These lead the reader into more advanced details, as appropriate, to the practitioner working in academic research, health and safety, chemical and biomedical R&D and contract research. On behalf of the Council of the British Society of Toxicological Pathologists, I can commend this work to both toxicologists and pathologists engaged in all these fields. Dr Graham R.Betton, Senior Vice-President, British Society of Toxicological Pathologists Preface Toxicology is the study of the adverse effects of chemical substances on living systems. It is a relatively new but increasingly important science. Forty or fifty years ago, toxicology was barely recognised as a scientific discipline. However, over the last twenty to thirty years the subject has developed rapidly and there has been a dramatic increase in the number of books and publications on toxicology, the number of learned societies devoted to the subject, and the number of establishments, departments and units involved in toxicological investigations. Similarly, there has been a great expansion in the number of courses teaching toxicology and in the number of individuals describing themselves as toxicologists. This volume is intended as an introductory text. It covers the essentials of target organ pathology that all toxicologists should know. The book is aimed at undergraduate and postgraduate students of toxicology and its allied sciences, and at toxicologists, particularly those in non-pathological branches of the subject, in the early stages of their careers. The objective is to provide a basic understanding of the pathological reactions of the various organs of the body in response to toxic injury induced by chemical substances. Furthermore, the text should help all toxicologists understand the language of toxicological pathology. There is a lack of student texts in the area of target organ pathology. The concept for the book arose from the involvement of both editors in teaching on various courses in toxicology at the undergraduate and postgraduate level. Although there are several volumes now available on the subject of toxicological pathology which include coverage of target organ effects, these books are generally specialist and comprehensive reference texts aimed at the trained pathologist. There are no suitable books to recommend to students, or to the toxicologist who does not have an extensive background in pathology. For these reasons this book is intended primarily as a teaching and basic reference text which will allow the reader to progress, when necessary, to the more specialised volumes of toxicological pathology which are currently available, for example, Toxicologic Pathology, edited by W.M.Haschek and C.G.Rousseau, 1991, Academic Press, San Diego. We have attempted to make this book comprehensive and user friendly. All the major organ systems of the body are covered, with each chapter written by an eminent authority in the field. A systematic approach has been taken for each organ system, with each of the sixteen chapters having a similar outline, including, Introduction; Anatomy, Histology and Physiology; Biochemical and Cellular Mechanisms of Toxicity; Morphological Responses to Injury; Testing for Toxicity; Conclusions. Chapter length is weighted according to the toxicological importance of each organ system. This repeatable format allows the reader to move from chapter to chapter and find the contents organised in a similar way. This arrangement also permits the reader to progress through the book in a systematic way, or consult each chapter, or part of a chapter, in isolation. It goes without saying that we are deeply indebted to our twenty-one authors, without whom this book would not exist. We would also like to take the opportunity of acknowledging the many students we have viii taught, both at the undergraduate and postgraduate level. These students were unknowingly the stimulus for the concept of the book, and for defining the approach and direction of the editorial policy. We also wish to thank Mary Fagg who has dealt with the very large amount of correspondence and word processing necessary in the editing of such a volume; it is her diligent work which made the book possible. Finally we wish to thank the members of staff at Taylor and Francis who have been involved with the publication. Their professionalism, advice, guidance and encouragement, ensured that the book saw the light of day. The editors wish to thank Astra Charnwood, Unilever Environmental Safety Laboratory, and Shell Research Limited for assistance towards the editorial costs of this book. John Turton, London Jean Hooson, Montreal Contributors C.Michael Andrews Glaxo Wellcome Research and Development, Park Road, Ware, Hertfordshire, SG12 ODP, UK Graham R.Betton Zeneca Pharmaceuticals, Mereside, Alderley Park, Macclesfield, Cheshire, SK10 4TG, UK Peter Buckley Unilever Research, Environmental Safety Laboratory, Colworth House, Sharnbrook, Bedfordshire, MK44 1LQ, UK Dianne M.Creasy Huntingdon Life Sciences, Eye, Suffolk, IP23 7BR, UK John G.Evans Astra Charnwood, Bakewell Road, Loughborough, Leicestershire, LE11 ORH, UK John R.Foster Zeneca Central Toxicology Laboratory, Mereside, Alderley Park, Macclesfield, Cheshire, SK10 4TJ, UK Chirukandath Gopinath Huntingdon Life Sciences, PO Box 2, Huntingdon, Cambridgeshire, PE18 6ES, UK Peter Greaves Zeneca Pharmaceuticals, Mereside, Alderley Park, Macclesfield, Cheshire, SK10 4TG, UK Ernest S.Harpur Sanofi Research Division, Alnwick Research Centre, Willowburn Avenue, Alnwick, Northumberland, NE66 2JH, UK Jean Hooson ITR Laboratories Canada Inc., 19601 Boul. Clark Graham, Baie d’ Urfé (Montreal), Quebec, Canada, H9X 3T1 Andrew J.Ingram Ingram Pathology and Toxicology Services (IPTS), 31 Esher Avenue, Walton-on-Thames, Surrey, KT12 2SZ, UK Kevin R. Isaacs 14 Rossett Park Road, Harrogate, North Yorkshire, HG2 9NP, UK Ian Kimber Zeneca Central Toxicology Laboratory, Mereside, Alderley Park, Macclesfield, Cheshire, SK10 4TJ, UK
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