Oxford Handbool< of

Applied Dental Sciences

Oxford University Press makes no representa-tion. 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. .

Oxford Handbool< of

Applied Dental Sciences

.With contributions from: Haytham Al-Bayaty Michael J. Aldred Baruch Arensburg Robert B. Ashman Jeremy Bragg Bill Barrett Agn~s Bloch-Zupan Charlotte Feinmann Sabrina Forcella Brian Henderson Richard Jordan Christopher Lavelle EitanLavon Antonio Mata

Edited by Crispian Scully CBE . University College London

. Robin Matthews Maria Fernanda Mesquita Malcolm M. Musiker Toby Newton-John

Jos~ Luis Relova-Quinteiro Lakshman P. Samaranayake Gregory J. Seymour . Peter M. Smith Guiseppe Spoto Irma Thesleff Michael Wilson Susanne Wish-Baratz Andrew Yeudall

OXFORD UNIVERSITY PRESS

OXFORD UNIVERSITY PRESS Great Clarendon Street. Oxford OX2 6DP 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 in Oxford New York Auckland Cape Town Dar es Salaam Hong Kong Karachi Kuala Lumpur Madrid Melbourne Mexico City Nairobi New Delhi Shanghai Taipei Toronto with offices in Argentina Austria Brazil Chile Czech Republic France Greece Guatemala Hungary Italy Japan South Korea Poland Portugal Singapore Switzerland Thailand TInkey Ukraine Vietnam Oxford is a registered trade mark of Oxford University Press in the UK and in certain other countries Published in the United States by Oxford University Press Inc., New York cc> Oxford University Press, 2002 The moral rights of the author have been asserted Database right Oxford University Press (maker) 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. 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 book in any other binding or cover and you must i.mpose this same condition on any acquirer A catalogue record for this title is available from the British Library : Library of Congress Cataloguing in Publication Data Oxford handbook of applied dental sciences I edited by Crispian Scully.

p.cm. 1. Dentistry-Handbooks. manuals. etc. 2. Dentistry-Examinations. questions. etc. I.

Scully. Crisp ian. RK56 .095 2002 617.6-dc21 2002071532 ISBN 0 198510969 10 9 8 7 6 5 4 3 Typeset by EXPO Holdings, Malaysia Printed in Ita\ybyLegoprint S.p.A. on acid-free paper

Preface

The twentieth century saw impressive advances in science and infor-mation access and transfer, such that not only has the understanding of health and disease increased enormously, but the speed of transfer of the new knowledge into the clinical environment has accelerated in an almost incredible way.

Thirty years ago, when I qualified in biochemistry, having acknowl-edged the growing importance of the understanding of cellular physiology aq.d ~olecular biology to clinical practice, I could not have foreseen the considerable changes ahead. Though there had been recognition of the importance of DNA, and the dawn of DNA tech-nology, few could have imagined the rapid development of immun-ology (and the catastrophic advent of AIDS), the growth of molecular biology, the development of DNA technology, the dawn of informa-tion technology or the Human Genome Project-developments that have opened the way for tremendous leaps in our understanding of the biological sciences, which have (and will continue to) enhanced diagnosis, prevention, and treatment of disease. New words, acronyms, and abbreviations which could not have been foreseen, are now in daily usage. Examples include PCR, IT, ELISA, HIV, HPV, Western blot, CD4, p53, prions, DNA chips, gene therapy, recombi-nants, etc. Who indeed, could have predicted frazzle, or sonic hedge-hogs!?

There have been many significant advances in all fields but none more dramatic and exciting than those in the fields of biochemistry, immunology, molecular biology, and now genomics, and these have overflowed fnto all other aspects of clinical science and changed the face of all disciplines.

The main aim of this handbook is to demonstrate why modern medical science is so"relevant to clinical dental practice. Dental staff are increasingly obliged to understand the language, fundamentals, and applications of these sciences. To this end, this book aims to out-line the preclinical sciences as applied to dentistry, relevant to dental qualifying examinations such as BDS and DDS and, in some coun-tries, to higher examinations such as MFDS.

The authors are an international team of experts, gathered from most continents because of their experience of dental education and research in the applied basic sciences, and their willingness to partici-pate in this project which was carried out solely by electronic mail. For this reason, and the fact that of the 300 million people worldwide who

vi I PREFACE

speak English it is American English that is the major form (Bryson B. (1990). Mother Tongue. Penguin Books. London). we have adopted American spelling in this book.

The information is presented in 58 chapters. assembled in eight parts covering relevant anatomy and development. pain and behav-ioral sciences. biochemistry. genomics. immunology, microbiology, pathology, and physiology. Lack of space has precluded the inclusion of other relevant sciences such as medicine, surgery. informatics. and pharmacology. The advances in the sciences, the changed content of subjects. and the relevance to dental clinical practice are well illus-trated and the reader may be surprised to find that traditional bound-aries between the biological sciences overlap and are increasingly blurred. Inevitably this leads to a certain amount of repetition. which we trust the reader will find useful.

cs London

August 2002

Contents

List of contributors xv List of abbreviations xvii

Part 1 Development and anatomy

1 Craniofacial development 3 Early development 4 Later development 7 Mechanisms of craniofacial growth control 10

2 General anatomy 11 Skin 15 The skeletal system 16 The nervous system 18 The cardiovascular system 22 Bone 26

3 Anatomy of the head and neck 35 Thescalp 36 The face 37 The temporal region 40 Theear 42 Theeye 45 The nasal cavity 48

4 Oral anatomy: the oral cavity, salivary glands, and the tel1lporomandibular joint 51 The palate 54 Floor of the mouth 56 The tongue 57 The salivary glands 60 The temporomandibular joint (TMJ) 63

5 Theneck 67 Deep fascia 68 The triangles of the neck 73 The cervical nerve plexus 75 Midline structures of the neck 76 The thyroid gland 80 The pharynx 81

vIII I CONTENTS 6 Teeth 85

Tooth structure 87 Enamel 88 Dentin-pulp complex 93 Pulp 98 Dentin sensitivity 99 Cementum 100 Periodontal ligament (PDL) 101 Alveolar process 107

7 Odontogenesis 109 Stages in tooth development 110 Root formation 115 Pulp formation 116

8 Tooth eruption 117 Mechanisms of tooth eruption 121

Part 2 Physiology

9 Cell physiology 125 Introduction 126 The membrane potential 128 Active transport 129 Exocytosis 130 Intracellular signalling 131

10 Neurophysiology 133 Basic mec:hanisms 135 Action potential 136 The synapse 139 Sensory transduction 142 Sensory receptors in oral structures 144

11 Mastication 149 Muscles of mastication 151 Chewing cycles 152 Control of mastication 153 Forces generated by masticatory muscles 156

12 Salivary gland function 157 Saliva 159 Function of saliva 161 Xerostomia 163

13 Swallowing 165 Neural control of swallowing 169 Suckling 170

14 Digestion and absorption 171 Stomach 175 Intestines 178 The exocrine pancreas 181 Bile 183

15 Liver 185 16 Kidneys 189

Ultrafiltration 191 Renal tubular excretion and reabsorption 192 Renal (kidney) functions 193

17 Vitamins 195 18 Blood 199

Hemat~poiesis 201 Red blood ceUs (RBCs) 202 white blood ceUs (leukocytes) 204 Platelets 204 Hemostasis 206 Complement 208

19 Cardiovascular system 209 Cardiac function 211 Cardiac output 212 Cardiac malfunction 213 Blood pressure 214

20 Respiratory system 219 Lung function 220 Oxygen and carbon dioxide transport 221 Neural control of respiration 222

21 Endocrine system 223

CONTENTS I Ix

Growth hormone (GH) (somatotrophin) 225 Adrenocorticotropic hormone (ACTH) (corticotrophin) 226 Luteinizing (LH) and follicle stimulating hormone (FSH) 227 Thyroid stimulating hormone (TSH) 228 Melanocyte stimulating hormone 229 Antidiuretic hormone (ADH) (vasopressin) 230 Oxytocin 231 Melatonin 232 Thyroid hormone (thyroxine. tri-iodothyronine) 233 Parathyroid hormone 234 Vitamin D 235 Calcitonin 236 Epinephrine (adrenaline) and norepinephrine (noradrenaline) 237 Glucocorticoids 238 Mineralocorticoids 239 Insulin 240 Glucagon 241 Somatostatin 242 Estrogen 243 Progesterone 244 Testosterone 245 Gastrin 246 Secretin 247 Cholecystokinin 248

XICONTENTS

22 Bone 249 Bone ceUs 252 Bone formation (osteogenesis) 255 Bone modeling and remodeling 256 Bone fracture repair 256 Bone mineral homeostasis 258 Hormonal control of calcium and bone metabolism 260 Orthodontic tooth movement 262

23 Wound healing 265

Part 3 Biochemistry

24 Molecular architecture 271 Proteins 272 Nucleic acids 274 Carbohydrates 277 Lipids 279 Enzymes 280

25 Protein expression, analysis, and proteomics 283 Amino acid biosynthesis 285 Direction of protein synthesis 286 Genetic code 287 Protein synthesis 289 Protein function 291 Proteins in health and disease 294 Examining protein expression in cells and tissues 295 Expression of exogenous proteins in cultured cells 297 Protein-protein interactions 300 Analysis of protein function in vivo-transgenic approaches 301 Clinical aspects of protein analysis 302 Computer-based analysis of expression patterns--bioinformatics 303 Proteomics 305

26 Metabolism 307 Metabolism of carbohydrates 309 Metabolism of lipids 311 Metabolism of nucleic acids 313 Metabolism of proteins and amino acids 314

27 Cell signaling 317 Features of ceU signaling 319 Types of ceU signaling 320 Types of signal 321 Ceu signaling pathways 322

28 Cells and tissues 325 Epithelial tissues 326 Connective tissue 328 Basement membrane 333

29 Mineralized tissues 335 Metabolism of calcium and phosphorus 337 Biological apatite 338 The mineralization process 339

I 30 Teeth 341 Enamel 342 Dentin 345 Dental pulp 348

31 The periodontal tissues 349 Gingiva 350 Oral mucosa 352 Crevicular fluid 353 Periodontal ligament 354 Cementum 355

32 Thetemporomandibular joint 357 Articular surfaces 359 Interarticular meniscus (TMJ disc) 360 Synovial fluid 361

33 Saliva and the biochemical aspects of oral homeostasis 363 Physicochemical properties of saliva 365 Composition of saliva 366 Functions of saliva 368

34 Dental plaque 369 Formation and properties of dental plaque 370 Properties of mature plaque 372 Plaque metabolism and dental disease 373 Plaque metabolism and periodontal disease 375

Part 4 Genomics

35 Genomics 379 Structural genomics 381 Comparative genomics 383 Functional genomics 384 Bioinformatics 385 Applications of genomics 386 Bioethical questions arising /Tom genomics 388

36 Human genetics 389 Clinical relevance: case study 391 Modes of inheritance 393 Case study continued: finding the cause of the problem 397 The genetic code 404 Genetic counselling 405 Gene therapy and prenatal testing 406

CONTENTS I xi

xii I CONTENTS

37 Craniofacial development 407 Sequence of development 408 Regulation of development 409 Genetic basis of development 410 Transcription factors and signaling molecules 411

38 Palate development 413 Primary palate development 414 Secondary palate development 415 Regulation of palate development 417 Genetic basis of abnormal palate development 420

39 Tooth deVelopment 423 Outline of tooth development 424 Regulation of tooth development 426 Genetic basis of abnormal tooth development 428

Part 5 General immunology

40 General immunology 433 Introduction 434 Circulatory system and lymphatic system 435 Cells and tissues of the immune system 436 Innate immunity 439 Generation of diversity 444

41 Humoral and soluble mediators of the immune response 449 Immunolj:lobulins 450 Antibody responses 453 Antigen-antibody interactions 455 Soluble mediators of the Immune response 457 Immunological memory 459

42 Cell-mediated immunity 461 Introduction 462 Natural killer (NK) cells 463 Immunological memory 464 Immunological responses to infectious disease 465

43 Clinical immunology 469 Immunization 470 Hypersensitivity responses 472 Autoimmunity 474 Cancer 475 Immunodeficiency 476 Transplantation immunology 480

Part 6 Pathology

44 Cell and tissue damage 483 Inflammation 484 Responses which mayor may not be preceded by inflammation 490

45 Hemodynamic disorders 493 Edema 494 Thromboembolism 495 Infarction 496 Shock 497

46 Neoplasia 499 Introduction 500 Cancer 501 Oncogenesis 503 Epidemiology of cancer 509

47 Genetic and developmental disorders 513 Terminology 514 Genetic and developmental abnormalities 516

48 Nutritional diseases 519 Protein-energy malnutrition 520 Vitarriin deficiency 522 Obesity 523

Part 7 Microbiology

49 Bacteria 527 Morphology and structure 529 Nutrition. growth. and cultivation 532 Classification of bacteria 534 Bacterial genetics 535

50 Bacteria and disease 537 Normal (commensal) microtlora 538 Diseases caused by the normal bacterial microtlora 540 Diseases caused by exogenous bacterial pathogens 541 Bacterial virulence factors 542 Antimicrobial chemotherapy 543 Diagnostic bacteriology 545

CONTENTS I xiii

51 Major bacteria and the diseases they can cause 547 Gram-positive cocci 548 Gram-negative cocci 551 Gram-positive. spore-forming bacilli 553 Gram-positive. non-spore-forming bacilli 555 Gram-negative. aerobic bacilli 556 Gram-negative. facultative bacilli 559 Gram-negative. curved bacilli 561 MisceUaneous organisms 563

52 Viruses and viral infections 565 Principles of virology 566 . Routes of viiaJ. infection 567 Viral replication 568 Effects of viruses on host cells 569 Laboratory diagnosis of viral infection 570

xiv I CONTENTS

53 Main viral infections 571 Viral hepatitis 572 Retroviruses 576 Hcrpesviruses 579 Othcr rclevant viruses 582 Prions 583

54 Fungi and fungal infections 585 Fungal biology 586 Human mycoses 587

Part 8 Behavioral sciences and pain

55 The dentist-patient relationship 593 Types of relationship 595 Communication skills 596 Principles of behavior change 598 Adherence to treatment 600

56 Personality, mood, and psychiatric disorders 603 Personality 604 Mood 605 Psychoses 608

57 Pain 609 Introduction 610 Perception of pain 613 Control of pain 614

58 Orofacial pain 615 Introduction 616 Chronic idiopathic facial pain 617

Index 619

List of abbreviations

ACh ................ A~~tYi~h~ii~~ ..................................................................... . AcrH ............ Ad~~~~~~~ti~;;t~~pi~ h~~~~~~ ............................................. . ADA~ti~~ti~~d~~~i~ ........................................................... .

AD"C(:~tib;;dy~d~p~~d~~t~~ii~i~~g;t~t~~i~itY ADii""A~tidi~~~ti~h~~~~~~ ...................................................... .

ADi~~i~d~~ti~~ij~~~ti~~ ...................................................... .

ADpAd~~~~i~~diph~~ph~t~ ...................................................... .

XpAik~ii~~ph~~ph~t~~~ ......................................................... .

APcktig~~~p~~;~~ti~g~~ii ........................................................ .

As6T~ti~t~~pt~ly;i~6tit~~ ................................................... .

ASR" .. , .. Ag~~;t~~d~~di~d ~~~t~iitY ~~t~ ................................ . AST&p~~t~t~~~i~;:;t~~~~i~~~~~ .................................................. .

ATLPL ....... Adip~~~ ti;~~~i"ip~p~~t~i~ "jip~~~ ............................. . ~T.~::::::::::::::::::::::~~~:~~~~~~:!~~~~~~~~:~!~::::::::::::::::::::::::::::::::::::::::::::::::::::::::::::: AV Atrioventricular ...........................................................................................................................................

. ~? ....................... ~.i~.~!.~I? .. ~~~~!.~ ........................................................................... .

. ~.~I. ..................... ~.?~r..~~.~~.!.~~~~ .......................................................................... .

. ~.~~ .................... ~.?~~.~~r.l?~?~~~.~~!.':..~~?~~!.~ .................................................. . BMR Basal (resting) metabolic rate ........................................................................................... - .............................................. .

. ~.~!.. ................... ~.?~~.~~.~~~.~.~.~.~.~.~p.~~~~ ........................................................... .

. 0.~.~~ ................. ~r.~~.i.~.~~.~ .. ~!.~.'?~.~ ....................................................................... .

. ~.p. .................. ~r.~!.~~.~~.~~.?~!~~.~~~.?p.~.'?~p.~~~~ ........................................ . CCK Cholecystokinin ...........................................................................................................................................

g9.~ .................... ~?~.~~.r~.~!~e..~~~?~.~

xvi I MAJOR CONTRIBUTORS Robin Matthews, The University of the West Indies, Trinidad Maria Fernanda Mesquita, University of Lisbon, Portugal Malcohn 'M. Musiker, North Coast Dental Group, University of

Rochester, New York 14167, USA Toby Newton-John, Behavioural Sciences and Dentistry, Eastman

Dental Hospital, London WCIX BLD, UK Jose Luis Relova-Quinteiro, Departmento de Fisiologia, Facultad de

Medicina y Odontologia, University of Santiago de Compostela, Spain .

Lakshman P. Samaranayake, Oral Biosciences, Faculty of Dentistry, The University of Hong Kong, China

Gregory J. Seymour, University of Quee~sland, Brisbane, Australia Peter M. Smith, University of Liverpool, UK Giuseppe Spoto, Department of Applied Sciences of Oral and Dental

Diseases, University of Chieti 66013, Italy Irma Thesleff, Developmental Biology Program, Institute of

Biotechnology, University of Helsinki, 00014 Helsinki, Finland Michael Wilson, Microbiology, Eastman Dental Institute, University

College London, London WCIX BLD, UK Susanne Wish-Baratz, Department of Anatomy and Anthropology,

Sadder Faculty of Medicine, Tel Aviv University, Ramat Aviv, Tel Aviv, Israel 69-97B

Andrew Yeudall, Molecular Carcinogenesis Group, Head and Neck Cancer Program, Guy's King's and St Thomas' School of Medicine and Dentistry, King's College London, Guy's Hospital, St Thomas Street, London SEI 9RT, UK

List of contributors

Editor Professor Crispian Scully CBE. MD. PhD. MDS. MRCS. FDSRCPS.

FDSRCS. FFDRCSI. FDSRCSE. FRCPath. FmedSci. Eastman Dental Institute for Oral Health Care Sciences. University College London. London WC1X SLD. UK.

Contributors Haytham Al-Bayaty. The University of the West Indies. Trinidad Michaei J. Aldred. Department of Dentistry. Royal Children's

Hospital. Murdoch Children's Research Institute and Department of Paediatrics. University of Melbourne. Australia

Baruch Arensburg. Department of Anatomy and Anthropology. Sadder Faculty of Medicine. Tel Aviv University. Ramat Aviv. Tel Aviv. Israel 69-97S

Robert B. Ashman. University of Queensland. Brisbane. Australia Jeremy Bagg. Department of Clinical Microbiology. Glasgow Dental

Hospital and School. 37S Sauchiehall Street. Glasgow G2 3JZ. UK Bill Barrett. Oral and Maxillofacial Pathology. Eastman Dental

Institute. University College London. London WCIX SLD. UK Agnes Bloch-Zupan. Paediatric Dentistry. Eastman Dental Institute.

University College London. London WC1X 8LD. UK Charlotte Feinmann, Behavioural Sciences and Dentistry, Eastman

Dental Institute, University College London, London WC1X SLD, UK

Sabrina Forcella, Department of Applied Sciences of Oral and Dental Diseases, University of Chieti 66013 Italy

Brian Henderson. Cellular Microbiology. Eastman Dental Institute, University College London, London WC1X SLD, UK

Richard Jordan, Department of Stomatology and Pathology, University of San Francisco. California, USA

Christopher Lavelle. University of Manitoba, Canada Eitan Lavon. Department of Anatomy and Anthropology, Sadder

Faculty of Medicine, Tel Aviv University, Ramat Aviv. Tel Aviv. Israel 69-97S

Antonio Mata. University of Lisbon. Portul!>Al

xviii I LIST OF ABBREVIATIONS

.~~ ...................... ~~r.~~.r~~.l?i.~~~.~.~i.~ ............................... ? .................................... .

. ~~!' ...................... ~?~?~Y..~~~~ll.~~~?~.~a.~t~r. ....................................................... .

. 0.:~ ..................... ~?~.~?~.~e.~.~~.~~ll.~ .. ~i.?!? ......................................................... .

. ~y.~ ...................... ~~~~.~?~~~.~~.I.~~.~.r.~.~~~ ............................................................... .

. ~~9 ..................... ~~.';l:~r.~!?~r.~~~?~ .............................................................................. ..

. ~~! ....................... ?~.~~~~.?:?~~.e.~}~~.~.~~.~? .......................................................... .

. ~.~~.~~?~~.~ ...... ~.~~.~~~.~~r.~~?~~~?!.~.~';l:~~~.~~r.?~ ................................................ . P~~~.~ ............. p:.~y.~r.~~~!?:r?~~~.~!r~~.?~~.?r!.~.~~.i.?: ................................... . . ~~.~ .................... ~:':':~~~?~! .. ~.~.?~~.~!.~ .. ~.';l:ll.~!.~?~.r~ .. ".l.~~~~~ .................................... . EBP Elastin binding protein ECM .. E:,ct~~~~ii;;i~~~~t~~ ....................................................... . ...........................................................................................................................................

. r.:9.~ ...................... E..I?!.~~r.'?~! .. ~r.?~t!?:f';l:~t~r. ......................................................... .. ?~~.~~ .................. r.:.?~~.e. .~i.?~.e.~ .. i.~~ll.?~~.?~~.~~.~. ~.s~~y" ... ............................. . . ~.~! .................... r.:.I?!~~.~.~!~~~~~~.~~Y..~.';l:I.~~.';l:~.~~.~!.~~ ......................................... .. . r.:~~.J> .................... r.:.~~!~~~.~r.Y..??s~~.r.:?';l:p.~!~ . .I??~:?~.i~~ .......................................... . . J? ........................ r.:.~.?.~y.~~.~~.s.t.e.~., .......................................... ,' ............................ .. . ~.~ ...................... r.:.~r.t~.r.?T.:.~~~!~.~.?~~~.~?~.~~~e. ............................................. . FAK Focal adhesion kinases ...........................................................................................................................................

. F.9.F. ...................... F.i.?~??!.~.s.t.?~?~t.~ .. ~~~~?~ ........................................................... . FITC Fluorescein isothiocyanate ..........................................................................................................................................

. F.~!: ...................... ~?~~~.~~~.~~i.~ll.~~t.i~.~.~.?~'?'?~.e. ................................................ .

.

LIST OF ABBREVIATIONS I X

.~~0.: ................. ~.e.~.~~r.()i~.~~~ .. s.t~~. ~~~. ~.~.~.rl~?.l~~~ ...................................... . I CAMs Intercellular cell adhesion molecules ...........................................................................................................................................

. ~?~ ....................... ~~~.~.~.~e.?~~t.~.~~~~.~.~o/..~~:P.~.r.~~.~~~.rl .......................................... .

. ~~~ ....................... I~~~r..~~.~~~l. ~:p.~.tl1.e.I~.~~ .......................................................... .

. ~~ ......................... J~.~.~~~.~~~.~~~~.rl ......................................................................... . IL-I Interleukin 1

.~!::lg.~ ................... ~~~?~~~.~~.9.: .~.~~.~~.~.~~~.~.~.r.?~?.~.~ .............. ....................... . InsP3 Inositoll,4,5-trisphosphate

:~~~::::::::::::::::::::::::~~i.~~~i.~:~~~p~i.?~~~~~::::: ::::::::::::::::::::::::::::::::::::::::::::::::::::::::::::: .~~~.~ ................... J~?~?~~2". :P.~.~.~~.r.?~r.~~~ .. I?~.~~~~.~?.~ .......................................... . . ~~!.9. .................... ~~~g~~.I?Y..~~?~?~~~~.c:~~.~~e. .......................................................... . IV Intervertebral (intravenous) ...........................................................................................................................................

. ~~~ ....................... ~~.rl~.~ .. ~~~.~~?~e.~ .. ~.rl?~~ ................................................................ .

. ~~ .......................... ~?l':':~~.~io/..~?~.~~?~~ ...................................................................... .

. ~?~ ...................... ~?~~~.~rl~~.o/.~~?.():P.r.()~e.~~ ........................................................... .

. ~~ ........................ ~':':~.~!.rl.~~~~~.?~.~~.()~~ ................................................................. .

. ~?~ ..................... ~?~~.r~.~~.~.~.~.~.~~.~()~.~~.rl~~~~ ................................................ .

. ~?.~ ..................... ~~.~ .. ()~.h..e.t~~().~~~.s!.o/. ............................................................... .

. ~~~ ....................... ~~g~r.()Iy"~~.~.C:~~.~~?~ ..................................................................... .

. ~~ .................... ~~~~r.~~.e..~~.~?~~.~()~.I?I~.~ ...................................................... .

. ~ ..................... ~r.~??~.c:~~~i.u.~ .. ~~':':~~i~~.~.~~~~~.l?~~ ................................. .. ~T ................. ~l:':c:()~~~?~s.().~.i~t.~.~.~.E?.~~~~.~.~~.~~~ ..................................... . . ~~ ................. ~~.~~.~e.~ .. ~~~~~?~~~ . .1?.~~.~~i.rl .. ~~~~~~ ........................................ . . ~~y. ................... ~~?~.~~.~.I?':':~.~~~~r..~~.~~.~.e. ....................................................... . . ~~.~ ................... ~':':lt.i~.~~l:':~.~~~~~t.~.?t ................................................................... . . ~~~ ................... ~~!.()~.~~~~?~~.~P~~!~~~.i.o/..c:()~:P.~~ ....................................... . . ~~.~ ................... ~?~r.~ .. ~.e.t~.I.I~.I?~~.~~!.rl~~~~ ....................................................... . . ~.~~ ................ ~~~~~~.~~~.~J\: ........................................................................... . NAD Nicotinamide adenine dinucleotide ..........................................................................................................................................

NADH Nicotinamide adenine dinucleotide (reduced form) ..........................................................................................................................................

. ~~.I?~ ................. ~~.~?~~~~~!.~~.~.~~~~~~.~~~~.c:~~~.~~.~~.:P.?()~?.~~.~~ ............... . NADPH Nicotinamide adenine dinucleotide phosphate .............................. S~~~~C:~.?.~().~.~) ............................................................................. . . ~~~~ ................. ~.~~~.tr.l.?~.u.~~~i.?~c:.?~~.~ .......................................................... . . ~~~~~ ............. ~?rl.~~.~.?()~~.~ .. ?~.p.?~~~.~~ ............................................................ . NO Nitric oxide

. :~!.~:::::::::::::::::::~~~.~:t~~~~~~~~:~i.~~~:~~~~:~~~: :::::::::::::::::::::::::::::::::::::::::::::::: g~~ .................... g~~.e.~ .. e.?~.~~~.~:P.~~~.~.I.!':':~ ......................................................... .

xx I LIST OF ABBREVIATIONS

.~ ............................ ~.??~.I?~~~.~ .. g;~~.~p' ........................................................ .

. ~i ......................... J~?~.s.~Il.i~. p.~.?~p.J:t~.t~ .~.r?~p' ..................................... .

. ~.~! ........................ ~.~?~.I?~Il.~~.p.r.~?p.??~p..?~.t': ......................................................... . PCF Peri-implant crevicular fluid ............................................................................................................................

. ~g.~ ........ " ............ I>.'!:~':!.'!!.o.cr.st!~. c.ti'.i.,!:ii, .I?~~ll:~~.~i.a ........... " .................. " .......... .

. ~~.~ .......... " ......... ~?~?:??e.~.~.~~ .. ~?.~.~Il .. ~.~.~~~.~?~ ................................................ " ..... .

. ~.~?F. .... " ............ ~.~~~.~.~~~.~?~~~::~.cl.~.~?~.~~ .. ~~~.t~.~ ............................................... .

. ~?!':-...................... ~~~~.

Part 1 Development and anatomy relevant to the head, necl

1 Cranofacial development

Chistopher Lavelle

Early development 4 Later development 7 Mechanism of cranofacial growth control 10

l I

41 CRANOFACIAL DEVELOPMENT

Early development (see also Chapter 37)

After fertilization, rapid cell proliferation and migration lead to the forma-tion of a germ disk by the eighth day. with ectodermal and mesodermal component cell layers.

The axis of the embryo is established by the second week. with slight enlargement at the head (rostral) region and the formation of the prochordal plate.

The bilaminar embryonic disk is converted to a trilaminar structure by the third week, with the inclusion of a mesodermal layer. so that anomalies may occur in these crucial processes before the pregnancy is apparent.

By the end of the third week, the embryo has flexed around the anterior end of the notochord. The nervous system then develops as a thickening within the ectodermal layer (the neural plate), which folds to become a distinct neural tube leading to the formation of the brain and spinal cord.

A group of distinct neuroectodermal cells separate from the lateral aspect of the neural plate. These undergo a period of rapid proliferation and migration to give rise to such diverse structures as the sensory ganglia. sym-pathetic neurons, Schwann cells. pigment cells. cartilage of the branchial arches. and most of the connective tissues of the craniofacial region (Table 1.1).

Further development gives rise to the stomatodeum (primitive mouth cavity), which comprises a slit-like space bounded by the brain capsule above, the

Table 1.1 Principal neural crest-derived tissues of the head and neck Derivative Example Neural .~.':!"!~~~r. .g.~~~.I!~ .?~ .~~~~.i.a!. ~':~.':'~.~ .'I!.'!. ~!!. !.~!. ~~.d .. ~ ............ .

. ~ ~~.-.':'~~~.~!~~. ~.~lT!p.?ne.~t.s .~~. p.~~~~~.'!1p.~t.~~tlc. ~~n.~~~~ ....... . ............................ . S.~~-:V~~.~. ~~.~. ~.~p.P.~~Y.':'~. ~.~~.~!~I .. ~~~:'.':. ~.':~ ~~ ..................... . Skeletal Branchial arch cartilages

...................................................................................

. ~?~~.~ .?!. ~.~~ .. '!1~~!I.I:~! .~.~~.~!~I.':~ p'~I.~~~,. ~~~~'. ~':'.~ .~.~~~i.~!. :,~u.I.~ Chondrocranlal cartilages and otic capsule and their

............................. ':!"!~.~~.~.'?~~.~~" . .':,:p.~~.~~.'!1~.~~.~ ........................................... . Connective tissue Cranial vascular tissue

...................................................................................

Dermal smooth muscles Connective tissue components of cranial and lingual muscles, adenohypophysis, salivary, thyroid and .'='.~~.~~~~.':~!~ .~!~~~.~'. ~~.~. ~.~~.'!1~~ ...................................... . . ~.':!~':'.'?~.~~~. ~,:,.d. ~.,:!~n.~p'~.,?~.':~ ...................................... .

............................ P7.':'!1!~ .. ~~~. ~~I.,=,~~~ y~~.~e.~. ?~ .~~.': .~~~~'. !~-:V~!. ~~.~. !"!7~~ ....... . Secretory cells .~~.'?~~?~!~~~.~ .~.~~ .,=,.~!p.~". ~7! !~ ......................................... .

CalCitonin-producing cells of ultimobranchlal body Carotid type-l cells

DEVELOPMENT AND ANATOMY 15

Table 1.2 Principal stages of craniofacial embryology Stage 1

Developments Germ layer formation and Initial structural

Days postfertilization Related syndromes 17 Fetal alcohol

syndrome .............. ~.~~.~~I.~~~~~I~ ............................................................................... . . ~ ............ ~ ~~~~!. ~.~?7. !~~~.':I.t".~~ ... ~~-::~:~ ......................... ~.~~~.~~.~~':I".~ ........... . 3 Cell population origin, 19-28

migration, and interaction

Mandibulofacial dysostosis. Hemifacial microsomia

...............................................................................................................

4 Organ system formation 28-38 C left lip and/or palate, cleft palate

Primary palate 42-55 .............. ~.~~?~~':I.~r. P'~I.':I.t~ ............................ '" .............................. '" ........ . 5 Final tissue

differentiation 50-birth Achondroplasia.

Cranial synostosis syndromes

pericardial sac below, and laterally by the mandibular and maxillary processes derived from the first branchial arch: The stomatodeum is separated from the foregut by the buccopharyngeal

membrane at this time. An ectodermal ingrowth (Rathke's pouch), formed just anterior to this membrane attachment, then migrates towards the base of the developing brain. With apoptosis (programmed cell death) of this stoma to deal attachment, this pouch is detached to become transformed to the anterior lobe of the pituitary.

The face develops between the 24th and 38th days and apoptosis of the buc-copharyngeal membrane during the fourth week leads to contiguity between the stomatodeum and the foregut. Further craniofacial morphogenesis may be subdivided into five compo-

nent stages, which helps the understanding of the origin of various congenital anomalies (Table 1.2): Some craniofacial abnormalities originate as early as the first and second

stages (for example fetal alcohol syndrome), although most arise in the third stage from anomalous migrations of neural crest cells due mainly to either chromosomal (10%) or genetic (20%) factors. Complex polygenetidenviron-mental interactions are more commonly (70%) involved with anomalous sig-nal tranduction pathways linked to disrupted cell-cell and cell-matrix interactions. Such developmental complexities may be illustrated by mandibulofacial !iysostosis (Treacher-Collins' syndrome), where excessive apoptosis in the trigeminal ganglion leads to anomalous migration patterns of neural crest cells and maxillary and mandibular underdevelopment.

Congenital craniofacial defects also arise during the fourth and fifth devel-opmental stages, when morphogenesis of the neural crest-derived facial prominences (i.e. maxillary, mandibular, and frontonasal prominences) is the predominant developmental feature.

These initial morphogenetic events are controlled by a diverse array of sig-o nal transduction pathways that affect local thickenings of the surface ecto-

6 I CRANOFACIAL DEVELOPMENT derm to form the nasal (olfactory) placodes. whereas invagination of the region to form nasal pits is inductively influenced by signals derived from the forebrain. The subsequent formation of the lateral nasal prominence on the outer edge of the pits and the medial nasal prominences on the inner edge in the fifth week of life underscores the complex signal transductions associated with early craniofacial morphogenesis.

As the maxillary prominences grow in size. their medial expansion com-presses the median nasal prominences toward the midline to induce their fusion. i.e. lip c1efting follows failure of fusion between the medial nasal and maxillary prominences during the sixth week of development. Since such fusion is also linked with primary palate formation to create both the lip and the alveolar ridge containing the incisors. this may be denoted by a bilateral notch in the maxillary alveolus.

Closure of the secondary palate occurs by elevation of the palatal shelves following primary palate formation. so that interference with lip closure may also impact on subsequent palatal development (i.e. 60% of those with cleft lip also have a cleft palate). By contrast. the lower lip and mandible are derived from the mandibular prominences that merge across the midline.

Initially. the maxillary and lateral nasal prominences are separated by the nasolacrimal groove which forms a solid epithelial cord. later canalized to form the naso lacrimal duct. These structures become detached from the overlying ectoderm to allow the lateral nasal and maxillary prominences to merge. whereas enlargement of the maxillary prominences forms the max-illae and cheeks. The shape of the face is thus not only a function of expan-sion of craniofacial skeletal structures derived from the neural crest (Table 1.3). but also development of teeth from the neural crest-derived dental lamina at the sixth week of life. Dentofacial anomalies (for example peg-shaped maxillary lateral incisors) are therefore derived from more localized neural crest defects (i.e. the dental lamina) and are more prevalent than more generalized neural crest anomalies. although their impact may be masked or exacerbated by subsequent changes in craniofacial growth. Another major group of craniofacial malformations arises during the final

fetal stages from premature closure of the sutures between the craniofacial bones (craniofacial synostosis). emphasizing their contributions to cranial growth. For instance. Crouzon's syndrome arises from premature fusion of the superior and posterior sutures of the maxilla and the walls of the orbit. leading to variably distorted growth of both facial and orbital regions depend-ing on the specific suture affected.

Table 1.3 Embryonic contributions to craniofacial form Craniofacial prominence Structure(s) formed Frontonasal Forehead, bridge of nose, medial and lateral .......................................... ':l~~~~ .r;>.~,:,.~~ ~.~~.~~~ .......................................... . . ~.~~I.I.I.~!,y' .............................

DEVELOPMENT AND ANATOMY 17

Later development Organogenesis of the facial tissues and organs is virtually complete by the third trimester. so that localized patterns of endochondral and intramembra-nous osteogenesis then predominate in the component regions.

Tile neurocranium Calvarial (neurocranial) development begins at the seventh to eighth week of gestation. with the unique aggregation of collagen fibers in the dura mater that preconfigure future sutures and fontanelles in the mesodermal tissues around the developing brain: + Intramembranous osteogenesis begins at discrete centres that subsequently

develop into the component calvarial bones. Their growth entirely results from periosteal activity at the bone surfaces. augmented by mesodermal development at the intervening sutures and fontanelles.

+ Separation of these flat cranial bones at birth by sutures and fontanelles principally serves to: + facilitate molding of the relatively large neurocranium at parturition accommodate brain growth and intracranial fluid expansion. i.e. sutures

and fontanelles have little inherent growth potential of their own. The calvarial bones are then encased by periosteal and endosteal mesoder-

mal tissues . After birth. intramembranous osteogenesis along the edges of the

fontenelles eliminates these 'open' spaces fairly quickly. although the adja-cent bones remain separated by thin periosteal-lined sutures for many years (Fig. 1.1). They fuse sequentially during adulthood: a feature with impor-tant forensic connotations.

+ Despite their small size. intramembranous osteogenesis at these sutures is a major mechanism for calvarial growth. This is augmented by surface

Frontal -----,,,!:... Coronal suture

---"",---- Parietal Posterior fontanelle Occipital

Nasal '-....A;, ..... ".;:;::;:::=""" ..... ,--...{jr---:;r- !-:t~~dOid

Squamous temporal

Greater --""'.J-~oZ,J wing sphenoid

L-___ Thu nll~ cartilage L------MaKllla

IIgamentl~~~: Fig.l.l Craniofacial skeleton at birth. 'See p. 83.

8 I CRANOFACIAL DEVELOPMENT

remodeling, which leads to differential development of the inner and outer compact layers separated by cancellous bone. Changes in size and contour are then achieved by differential resorption and apposition on the inner and outer surfaces. Growth and development of the pneumatized (e.g. paranasal sinuses) and muscle attachment areas (e.g. temporal and nuchal crests, supraorbital ridges, etc.) involve more complex remodeling patterns, although the actual mechanisms result from the release of specific growth factors rather than differential tissue tensions arising from attachments of muscle or connective tissue to the periosteal or endosteal tissues.

These morphogenic changes are more complex than traditionally envis-aged, since the calvarium incorporates squamous parts of complex bones that serve different functions (e.g the squamous and petrous regions of the temporal bone) and follow distinct growth patterns.

The cranial base In contrast to the calvarium, the bones of the cranial base are initially formed in cartilage (the chondrocranium) on the ventral surface of the brain: Endochondral osteogenesis then leads to the deVelopment of the ethmoid,

the body of the sphenoid, the basiocciput, and the petrous temporal bones, although cartilaginous tissue remains between the body of the sphenoid and ethmoid anteriorly and the occipital posteriorly, in addition to inter-sphenoid synchondrosis between the two parts of the sphenoid bone.

Endochondral cell proliferation then continues at these synchondroses, although they tend to fuse by birth. The intersphenoidal and spheno-occipital synchondroses are exceptions, since they persist .until the age of 7 years and late adolescence respectively, therefore contributing significant-ly to skull growth. Their growth patterns appear largely immune to extra-neous influences.

The length and growth of the cranial base has an important impact on craniofacial development. For instance, the upper facial skeleton articulates with the anterior cranial fossa, whereas the mandible articulates with the midcranial fossa through the temporomandibular joint. Growth at the syn-chondroses therefore affects their morphogenetic development. For instance, growth at the spheno-occipital synchondrosis carries the maxilla upwards and forwards relative to the mandible and thereby contributes to increased facial height and depth. Furthermore, deficiencies in growth of the cranial base (e.g. achondroplasia) lead to retarded maxillary growth, whereas a long cranial base may contribute to mandibular prognathism.

The mandible Migrations of neural crest cells are not the only factor in iniJ:ial mandibular development; growth factors derived from the largely vestigial Meckel's carti-lage control early morphogenesis of both the mandible and maxilla: Mandibular growth is principally attributed to intramembranous osteoge-

nesis, augmented by focal endochondral ossification at the condylar head, mandibular angle, and coronoid process.

The subsequent complex growth patterns include synchronized 'cortical drifting' at the lateral and medial periosteal surfaces leading to forward and downward mandibular rotation and expansion.

DEVELOPMENT AND ANATOMY 19

Mandibular growth is also dependent on muscle attachments (e.g. tempo-ralis, masseter, and pterygoid muscles), where tooth development and eruption influence alveolar development.

These dynamic influences are superimposed on differential surface remod-eling patterns. For instance, growth in mandibular length results from sur-face apposition on the posterior surface of the ramus and resorption at the anterior surface (i.e. the mandible essentially grows longer as the ramus moves away from the chin).

The classic view holds that that the mandible grows downwards and for-wards relative to the cranial base, although more recent evidence indicates rather downward and forward rotational movements dictated by very com-plex patterns of differential surface remodeling. In fact, both forms of mor-phogenetic change occur, with rotation being more pronounced in the anterior than the posterior of the mandible, whereas compensatory tooth movements are required to maintain the appropriate relationships between the maxillary and mandibular teeth. The mandible then does not grow as an isolated entity, since normal skeletal and dental relationships require linkages to the the development of the face, lips, and tongue.

The maxilla: Whereas initial mandibular development depends on differential migrations of neural crest cells, initial maxillary development functionally depends on signals from the largely vestigial Meckel's cartilage: The maxilla arises from intramembranous osteogenesis at two centers lat-

eral to the nasal capsule. Since there is no cartilage replacement, growth pri-marily occurs by apposition at sutures that connect the maxilla to the cranium and cranial base, augmented by complex differential surface appo-sitional and resorptive patterns.

Bony development in the infraorbital and alveolar regions, in addition to the frontal, zygomatic, and palatal processes, largely appears to reflect the differential functions of vision, respiration, olfaction, mastication, degluti-tion, and speech, where the face progressively grows 'out from under the

cranium~ As the maxilla moves through a considerable distance downward and for-

ward relative to the cranium and cranial base, such complex growth pat-terns are facilitated by intramembranous osteogenesis at sutures posterior and superior to the back of the maxilla.

These growth patterns are superimposed by simultaneous surface remodel-ing of the anterior surface of the maxilla, augmented by differential surface apposition and resorption of the parana"al processes of the nasal capsule and the alveolar border of the zygomatic processes.

Maxillary growth is further complicated by the attachment to the neurocra-nium (cranial vault). For instance, the neurocranial attachment follows a neural growth pattern, whereas the maxilla per se follows a general somatic pattern. These patterns are also variably modified by forces from the adja-cent soft tissues. in addition to the erupting teeth. Such growth patterns are inherently robust; however. the temporary arrest of downward and forward growth movements by orthopedic forces is generally followed by variable catch-up phases to reassert the original pattern after the removal of such a temporary force .

.............................. ~