Contents Contents Contents Volume 1 List of abbreviations  xxxv List of contributors  xlv SECTION 1 Patients and their treatment Section editors: John D. Firth, Christopher P. Conlon, and Timothy M. Cox 1.1 On being a patient  3 Christopher Booth† 1.2 A young person’s experience of chronic disease  6 1.3 What patients wish you understood  8 Rosamund Snow† 1.4 Why do patients attend and what do they want from the consultation?  14 Des Spence 1.5 Medical ethics  20 Mike Parker, Mehrunisha Suleman, and Tony Hope 1.6 Clinical decision-​making  26 Timothy E.A. Peto and Philippa Peto SECTION 2 Background to medicine Section editors: John D. Firth, Christopher P. Conlon, and Timothy M. Cox 2.1 Science in medicine: When, how, and what  33 William F. Bynum 2.2 Evolution: Medicine’s most basic science  39 Randolph M. Nesse and Richard Dawkins 2.3 The Global Burden of Disease: Measuring the health of populations  43 Theo Vos, Alan Lopez, and Christopher Murray 2.4 Large-​scale randomized evidence: Trials and meta-​analyses of trials  51 Colin Baigent, Richard Peto, Richard Gray, Natalie Staplin, Sarah Parish, and Rory Collins 2.5 Bioinformatics  67 Afzal Chaudhry 2.6 Principles of clinical pharmacology and drug therapy  71 Kevin O’Shaughnessy 2.7 Biological therapies for immune, inflammatory, and allergic diseases  100 John D. Isaacs and Nishanthi Thalayasingam 2.8 Traditional medicine exemplified by traditional Chinese medicine  108 Fulong Liao, Tingliang Jiang, and Youyou Tu 2.9 Engaging patients in therapeutic development  118 Emil Kakkis and Max Bronstein 2.10 Medicine quality, physicians, and patients  124 Paul N. Newton 2.11 Preventive medicine  127 David Mant 2.12 Medical screening  137 Nicholas Wald and Malcolm Law 2.13 Health promotion  152 Evelyne de Leeuw † It is with great regret that we report that Christopher Booth died on 13 July, 2012 and Rosamund Snow died on 2 February, 2017. Contents xiv 2.14 Deprivation and health  157 Harry Burns 2.15 How much should rich countries’ governments spend on healthcare?  161 Allyson M. Pollock and David Price 2.16 Financing healthcare in low-​income developing countries: A challenge for equity in health  168 Luis G. Sambo, Jorge Simões, and Maria do Rosario O. Martins 2.17 Research in the developed world  177 Jeremy Farrar 2.18 Fostering medical and health research in resource-​constrained countries  181 Malegapuru W. Makgoba and Stephen M. Tollman 2.19 Regulation versus innovation in medicine  185 Michael Rawlins 2.20 Human disasters  188 Amartya Sen 2.21 Humanitarian medicine  193 Amy S. Kravitz 2.22 Complementary and alternative medicine  201 Edzard Ernst SECTION 3 Cell biology Section editors: John D. Firth, Christopher P. Conlon, and Timothy M. Cox 3.1 The cell  209 George Banting and Jean Paul Luzio 3.2 The genomic basis of medicine  218 Paweł Stankiewicz and James R. Lupski 3.3 Cytokines  236 Iain B. McInnes 3.4 Ion channels and disease  246 Frances Ashcroft and Paolo Tammaro 3.5 Intracellular signalling  256 R. Andres Floto 3.6 Apoptosis in health and disease  266 Mark J. Arends and Christopher D. Gregory 3.7 Stem cells and regenerative medicine  281 Alexis J. Joannides, Bhuvaneish T. Selvaraj, and Siddharthan Chandran 3.8 The evolution of therapeutic antibodies  296 Herman Waldmann and Greg Winter 3.9 Circulating DNA for molecular diagnostics  299 Y.M. Dennis Lo and Rossa W.K. Chiu SECTION 4 Immunological mechanisms Section editors: John D. Firth, Christopher P. Conlon, and Timothy M. Cox 4.1 The innate immune system  307 Paul Bowness 4.2 The complement system  315 Marina Botto and Matthew C. Pickering 4.3 Adaptive immunity  325 Paul Klenerman and Constantino López-​Macias 4.4 Immunodeficiency  337 Sophie Hambleton, Sara Marshall, and Dinakantha S. Kumararatne 4.5 Allergy  368 Pamela Ewan 4.6 Autoimmunity  379 Antony Rosen 4.7 Principles of transplantation immunology  392 Elizabeth Wallin and Kathryn J. Wood SECTION 5 Principles of clinical oncology Section editors: John D. Firth, Christopher P. Conlon, and Timothy M. Cox 5.1 Epidemiology of cancer  411 Anthony Swerdlow and Richard Peto 5.2 The nature and development of cancer: Cancer mutations and their implications  445 James D. Brenton and Tim Eisen 5.3 The genetics of inherited cancers  456 Rosalind A. Eeles 5.4 Cancer immunity and immunotherapy  471 Charles G. Drake 5.5 Clinical features and management  487 Tim Eisen and Martin Gore† 5.6 Systemic treatment and radiotherapy  497 Rajesh Jena and Peter Harper † It is with great regret that we report that Martin Gore died on 10 January, 2019. Contents xv 5.7 Medical management of breast cancer  505 Tim Crook, Su Li, and Peter Harper SECTION 6 Old age medicine Section editor: Finbarr C. Martin 6.1 Ageing and clinical medicine  511 Claire Steves and Neil Pendleton 6.2 Frailty and sarcopenia  521 Andrew Clegg and Harnish Patel 6.3 Optimizing well-​being into old age  532 Steve Iliffe 6.4 Older people and urgent care  539 Simon Conroy and Jay Banerjee 6.5 Older people in hospital  548 Graham Ellis, Alasdair MacLullich, and Rowan Harwood 6.6 Supporting older peoples’ care in surgical and oncological services  563 Jugdeep Dhesi and Judith Partridge 6.7 Drugs and prescribing in the older patient  571 Miles Witham, Jacob George, and Denis O’Mahony 6.8 Falls, faints, and fragility fractures  579 Fiona Kearney and Tahir Masud 6.9 Bladder and bowels  589 Susie Orme and Danielle Harari 6.10 Neurodegenerative disorders in older people  601 John Hindle 6.11 Promotion of dignity in the life and death of older patients  612 Eileen Burns and Claire Scampion SECTION 7 Pain and palliative care Section editor: Bee Wee 7.1 Introduction to palliative care  623 Susan Salt 7.2 Pain management  629 Marie Fallon 7.3 Symptoms other than pain  634 Regina McQuillan 7.4 Care of the dying person  639 Suzanne Kite and Adam Hurlow SECTION 8 Infectious diseases Section editor: Christopher P. Conlon 8.1 Pathogenic microorganisms and the host  651 8.1.1 Biology of pathogenic microorganisms  651 Duncan J. Maskell and James L.N. Wood 8.1.2 Clinical features and general management of patients with severe infections  656 Peter Watkinson and Duncan Young 8.2 The patient with suspected infection  662 8.2.1 Clinical approach  662 Christopher J. Ellis 8.2.2 Fever of unknown origin  664 Steven Vanderschueren 8.2.3 Nosocomial infections  669 Ian C.J.W. Bowler and Matthew Scarborough 8.2.4 Infection in the immunocompromised host  673 Jon Cohen and Elham Khatamzas 8.2.5 Antimicrobial chemotherapy  684 Maha Albur, Alasdair MacGowan, and Roger G. Finch 8.3 Immunization  706 David Goldblatt and Mary Ramsay 8.4 Travel and expedition medicine  713 Susanna Dunachie and Christopher P. Conlon 8.5 Viruses  723 8.5.1 Respiratory tract viruses  723 Malik Peiris 8.5.2 Herpesviruses (excluding Epstein–​Barr virus)  734 J.G.P. Sissons† 8.5.3 Epstein–​Barr virus  754 Alan B. Rickinson and M.A. Epstein 8.5.4 Poxviruses  764 Geoffrey L. Smith 8.5.5 Mumps: Epidemic parotitis  769 B.K. Rima 8.5.6 Measles  772 Hilton C. Whittle and Peter Aaby 8.5.7 Nipah and Hendra virus encephalitides  784 C.T. Tan † It is with great regret that we report that J.G.P. Sissons died on 25 September, 2016. Contents xvi 8.5.8 Enterovirus infections  787 Philip Minor and Ulrich Desselberger 8.5.9 Virus infections causing diarrhoea and vomiting  797 Philip R. Dormitzer and Ulrich Desselberger 8.5.10 Rhabdoviruses: Rabies and rabies-​related lyssaviruses  805 Mary J. Warrell and David A. Warrell 8.5.11 Colorado tick fever and other arthropod-​borne reoviruses  819 Mary J. Warrell and David A. Warrell 8.5.12 Alphaviruses  821 Ann M. Powers, E.E. Ooi, L.R. Petersen, and D.J. Gubler 8.5.13 Rubella  827 Pat Tookey and J.M. Best 8.5.14 Flaviviruses excluding dengue  830 Shannan Lee Rossi and Nikos Vasilakis 8.5.15 Dengue  845 Bridget Wills and Yee-​Sin Leo 8.5.16 Bunyaviridae  852 James W. Le Duc and D.A. Bente 8.5.17 Arenaviruses  862 Jan H. ter Meulen 8.5.18 Filoviruses  870 Jan H. ter Meulen 8.5.19 Papillomaviruses and polyomaviruses  877 Raphael P. Viscidi, Chen Sabrina Tan, and Carole Fakhry 8.5.20 Parvovirus B19  886 Kevin E. Brown 8.5.21 Hepatitis viruses (excluding hepatitis C virus)  889 Matthew Cramp, Ashwin Dhanda, and Nikolai V. Naoumov 8.5.22 Hepatitis C virus  896 Paul Klenerman, Katie J.M. Jeffery, Ellie J. Barnes, and Jane Collier 8.5.23 HIV/​AIDS  901 Sarah Fidler, Timothy E.A. Peto, Philip Goulder, and Christopher P. Conlon 8.5.24 HIV in low-​ and middle-​income countries  933 Alison D. Grant and Kevin M. De Cock 8.5.25 HTLV-​1, HTLV-​2, and associated diseases  941 Kristien Verdonck and Eduardo Gotuzzo 8.5.26 Viruses and cancer  945 Robin A. Weiss 8.5.27 Orf and Milker’s nodule  947 Emma Aarons and David A. Warrell 8.5.28 Molluscum contagiosum  949 David A. Warrell and Christopher P. Conlon 8.5.29 Newly discovered viruses  951 Susannah J.A. Froude and Harriet C. Hughes 8.6 Bacteria  958 8.6.1 Diphtheria  959 Delia B. Bethell and Tran Tinh Hien 8.6.2 Streptococci and enterococci  965 Dennis L. Stevens and Sarah Hobdey 8.6.3 Pneumococcal infections  975 Anthony Scott 8.6.4 Staphylococci  991 Kyle J. Popovich, Robert A. Weinstein, and Bala Hota 8.6.5 Meningococcal infections  1010 Petter Brandtzaeg 8.6.6 Neisseria gonorrhoeae  1025 Jackie Sherrard and Magnus Unemo 8.6.7 Enterobacteria and bacterial food poisoning  1032 Hugh Pennington 8.6.8 Pseudomonas aeruginosa  1041 G.C.K.W. Koh and Sharon J. Peacock 8.6.9 Typhoid and paratyphoid fevers  1044 Christopher M. Parry and Buddha Basnyat 8.6.10 Intracellular klebsiella infections (donovanosis and rhinoscleroma)  1051 John Richens and Nicole Stoesser 8.6.11 Anaerobic bacteria  1055 Anilrudh A. Venugopal and David W. Hecht 8.6.12 Cholera  1060 Aldo A.M. Lima and Richard L. Guerrant 8.6.13 Haemophilus influenzae  1066 Esther Robinson 8.6.14 Haemophilus ducreyi and chancroid  1071 Nigel O’Farrell 8.6.15 Bordetella infection  1073 Cameron C. Grant 8.6.16 Melioidosis and glanders  1076 Sharon J. Peacock 8.6.17 Plague: Yersinia pestis  1081 Michael Prentice 8.6.18 Other Yersinia infections: Yersiniosis  1086 Michael Prentice 8.6.19 Pasteurella  1088 Marina S. Morgan 8.6.20 Francisella tularensis infection  1091 Petra C.F. Oyston Contents xvii 8.6.21 Anthrax  1094 Arthur E. Brown 8.6.22 Brucellosis  1102 Juan D. Colmenero and Pilar Morata 8.6.23 Tetanus  1109 C. Louise Thwaites and Lam Minh Yen 8.6.24 Clostridium difficile  1115 David W. Eyre and Mark H. Wilcox 8.6.25 Botulism, gas gangrene, and clostridial gastrointestinal infections  1120 Dennis L. Stevens, Michael J. Aldape, and Amy E. Bryant 8.6.26 Tuberculosis  1126 Richard E. Chaisson and Jean B. Nachega 8.6.27 Disease caused by environmental mycobacteria  1150 Jakko van Ingen 8.6.28 Leprosy (Hansen’s disease)  1154 Diana N.J. Lockwood 8.6.29 Buruli ulcer: Mycobacterium ulcerans infection  1167 Bouke de Jong, Françoise Portaels, and Wayne M. Meyers 8.6.30 Actinomycoses  1170 Klaus P. Schaal 8.6.31 Nocardiosis  1176 Roderick J. Hay 8.6.32 Rat bite fevers (Streptobacillus moniliformis and Spirillum minus infection)  1179 Andrew F. Woodhouse 8.6.33 Lyme borreliosis  1181 Gary P. Wormser, John Nowakowski, and Robert B. Nadelman 8.6.34 Relapsing fevers  1188 David A. Warrell 8.6.35 Leptospirosis  1198 Nicholas P.J. Day 8.6.36 Nonvenereal endemic treponematoses: Yaws, endemic syphilis (bejel), and pinta  1204 Michael Marks, Oriol Mitjà, and David Mabey 8.6.37 Syphilis  1210 Phillip Read and Basil Donovan 8.6.38 Listeriosis  1223 Herbert Hof 8.6.39 Legionellosis and Legionnaires’ disease  1226 Diego Viasus and Jordi Carratalà 8.6.40 Rickettsioses  1230 Karolina Griffiths, Carole Eldin, Didier Raoult, and Philippe Parola 8.6.41 Scrub typhus  1252 Daniel H. Paris and Nicholas P.J. Day 8.6.42 Coxiella burnetii infections (Q fever)  1257 Thomas J. Marrie 8.6.43 Bartonellas excluding B. bacilliformis  1262 Bruno B. Chomel, Henri-​Jean Boulouis, Matthew J. Stuckey, and Jean-​Marc Rolain 8.6.44 Bartonella bacilliformis infection  1272 A. Llanos-​Cuentas and C. Maguiña-​Vargas 8.6.45 Chlamydial infections  1278 Patrick Horner, David Mabey, David Taylor-​Robinson, and Magnus Unemo 8.6.46 Mycoplasmas  1295 Jørgen Skov Jensen and David Taylor-​Robinson 8.6.47 A checklist of bacteria associated with infection in humans  1307 John Paul 8.7 Fungi (mycoses)  1338 8.7.1 Fungal infections  1338 Roderick J. Hay 8.7.2 Cryptococcosis  1359 William G. Powderly, J. William Campbell, and Larry J. Shapiro 8.7.3 Coccidioidomycosis  1361 Gregory M. Anstead 8.7.4 Paracoccidioidomycosis  1364 M.A. Shikanai-​Yasuda 8.7.5 Pneumocystis jirovecii  1371 Robert F. Miller and Christopher P. Eades 8.7.6 Talaromyces (Penicillium) marneffei infection  1375 Romanee Chaiwarith, Khuanchai Supparatpinyo, and Thira Sirisanthana 8.7.7 Microsporidiosis  1378 Louis M. Weiss 8.8 Protozoa  1384 8.8.1 Amoebic infections  1384 Richard Knight 8.8.2 Malaria  1395 Nicholas J. White and Arjen M. Dondorp 8.8.3 Babesiosis  1414 Philippe Brasseur 8.8.4 Toxoplasmosis  1416 Oliver Liesenfeld and Eskild Petersen 8.8.5 Cryptosporidium and cryptosporidiosis  1424 Simone M. Cacciò 8.8.6 Cyclospora and cyclosporiasis  1432 Paul Kelly and Ralph Lainson† † It is with great regret that we report that Ralph Lainson died on 5 May, 2015. Contents xviii 8.8.7 Cystoisosporiasis  1436 Louis M. Weiss 8.8.8 Sarcocystosis (sarcosporidiosis)  1438 John E. Cooper 8.8.9 Giardiasis and balantidiasis  1440 Lars Eckmann and Martin F. Heyworth 8.8.10 Blastocystis infection  1449 Richard Knight 8.8.11 Human African trypanosomiasis  1451 Reto Brun and Johannes Blum 8.8.12 Chagas disease  1459 Michael A. Miles 8.8.13 Leishmaniasis  1467 Antony D.M. Bryceson and Diana N.J. Lockwood 8.8.14 Trichomoniasis  1475 Jane Schwebke 8.9 Nematodes (roundworms)  1478 8.9.1 Cutaneous filariasis  1478 Gilbert Burnham 8.9.2 Lymphatic filariasis  1487 Richard Knight 8.9.3 Guinea worm disease (dracunculiasis)  1495 Richard Knight 8.9.4 Strongyloidiasis, hookworm, and other gut strongyloid nematodes  1500 Michael Brown 8.9.5 Gut and tissue nematode infections acquired by ingestion  1506 Peter L. Chiodini 8.9.6 Angiostrongyliasis  1516 Richard Knight 8.10 Cestodes (tapeworms)  1520 8.10.1 Cestodes (tapeworms)  1520 Richard Knight 8.10.2 Cystic hydatid disease (Echinococcus granulosus)  1529 Pedro L. Moro, Hector H. Garcia, and Armando E. Gonzalez 8.10.3 Cysticercosis  1533 Hector H. Garcia and Robert H. Gilman 8.11 Trematodes (flukes)  1540 8.11.1 Schistosomiasis  1540 David Dunne and Birgitte Vennervald 8.11.2 Liver fluke infections  1551 Ross H. Andrews, Narong Khuntikeo, Paiboon Sithithaworn, and Trevor N. Petney 8.11.3 Lung flukes (paragonimiasis)  1558 Udomsak Silachamroon and Sirivan Vanijanonta 8.11.4 Intestinal trematode infections  1562 Alastair McGregor 8.12 Nonvenomous arthropods  1568 John Paul 8.13 Pentastomiasis (porocephalosis, linguatulosis/​linguatuliasis, or tongue worm infection)  1582 David A. Warrell SECTION 9 Sexually transmitted diseases Section editor: Jackie Sherrard 9.1 Epidemiology of sexually transmitted infections  1589 David Mabey and Anita Vas-​Falcao 9.2 Sexual behaviour  1597 Catherine H. Mercer and Anne M. Johnson 9.3 Sexual history and examination  1600 Gary Brook, Jackie Sherrard, and Graz A. Luzzi 9.4 Vaginal discharge  1603 Paul Nyirjesy 9.5 Urethritis  1606 Patrick Horner 9.6 Genital ulceration  1610 Patrick French and Raj Patel 9.7 Anogenital lumps and bumps  1613 Henry J.C. de Vries and Charles J.N. Lacey 9.8 Pelvic inflammatory disease  1622 Jonathan D.C. Ross 9.9 Principles of contraception  1626 Zara Haider Index Contents xix Volume 2 List of abbreviations  xxxv List of contributors  xlv SECTION 10 Environmental medicine, occupational medicine, and poisoning Section editor: Jon G. Ayres 10.1 Environmental medicine, occupational medicine, and poisoning—​Introduction  1637 Jon G. Ayres 10.2 Occupational health  1638 10.2.1 Occupational and environmental health  1638 Raymond Agius and Debasish Sen 10.2.2 Occupational safety  1652 Lawrence Waterman 10.2.3 Aviation medicine  1656 Michael Bagshaw 10.2.4 Diving medicine  1664 David M. Denison and Mark A. Glover 10.2.5 Noise  1671 David Koh and Tar-​Ching Aw† 10.2.6 Vibration  1673 Tar-​Ching Aw† 10.3 Environment and health  1677 10.3.1 Air pollution and health  1677 Om P. Kurmi, Kin Bong Hubert Lam, and Jon G. Ayres 10.3.2 Heat  1687 Michael A. Stroud 10.3.3 Cold  1689 Michael A. Stroud 10.3.4 Drowning  1691 Peter J. Fenner 10.3.5 Lightning and electrical injuries  1696 Chris Andrews 10.3.6 Diseases of high terrestrial altitudes  1701 Tyler Albert, Erik R. Swenson, Andrew J. Pollard, Buddha Basnyat, and David R. Murdoch 10.3.7 Radiation  1709 Jill Meara 10.3.8 Disasters: Earthquakes, hurricanes, floods, and volcanic eruptions  1713 Peter J. Baxter 10.3.9 Bioterrorism  1718 Manfred S. Green 10.4 Poisoning  1725 10.4.1 Poisoning by drugs and chemicals  1725 John A. Vale, Sally M. Bradberry, and D. Nicholas Bateman 10.4.2 Injuries, envenoming, poisoning, and allergic reactions caused by animals  1778 David A. Warrell 10.4.3 Poisonous fungi  1817 Hans Persson and David A. Warrell 10.4.4 Poisonous plants  1828 Michael Eddleston and Hans Persson 10.5 Podoconiosis (nonfilarial elephantiasis)  1833 Gail Davey SECTION 11 Nutrition Section editor: Katherine Younger 11.1 Nutrition: Macronutrient metabolism  1839 Keith N. Frayn and Rhys D. Evans 11.2 Vitamins  1855 Tom R. Hill and David A. Bender 11.3 Minerals and trace elements  1871 Katherine Younger 11.4 Severe malnutrition  1880 Alan A. Jackson 11.5 Diseases of affluent societies and the need for dietary change  1891 J.I. Mann and A.S. Truswell 11.6 Obesity  1903 I. Sadaf Farooqi 11.7 Artificial nutrition support  1914 Jeremy Woodward † It is with great regret that we report that Tar-Ching Aw died on 18 July, 2017. Contents xx SECTION 12 Metabolic disorders Section editor: Timothy M. Cox 12.1 The inborn errors of metabolism: General aspects  1929 Timothy M. Cox and Richard W.E. Watts† 12.2 Protein-​dependent inborn errors of metabolism  1942 Georg F. Hoffmann and Stefan Kölker 12.3 Disorders of carbohydrate metabolism  1985 12.3.1 Glycogen storage diseases  1985 Robin H. Lachmann and Timothy M. Cox 12.3.2 Inborn errors of fructose metabolism  1993 Timothy M. Cox 12.3.3 Disorders of galactose, pentose, and pyruvate metabolism  2003 Timothy M. Cox 12.4 Disorders of purine and pyrimidine metabolism  2015 Anthony M. Marinaki, Lynette D. Fairbanks, and Richard W.E. Watts† 12.5 The porphyrias  2032 Timothy M. Cox 12.6 Lipid disorders  2055 Jaimini Cegla and James Scott 12.7 Trace metal disorders  2098 12.7.1 Hereditary haemochromatosis  2098 William J.H. Griffiths and Timothy M. Cox 12.7.2 Inherited diseases of copper metabolism: Wilson’s disease and Menkes’ disease  2115 Michael L. Schilsky and Pramod K. Mistry 12.8 Lysosomal disease  2121 Patrick B. Deegan and Timothy M. Cox 12.9 Disorders of peroxisomal metabolism in adults  2157 Anthony S. Wierzbicki 12.10 Hereditary disorders of oxalate metabolism: The primary hyperoxalurias  2174 Sonia Fargue, Dawn S. Milliner, and Christopher J. Danpure 12.11 A physiological approach to acid–​base disorders: The roles of ion transport and body fluid compartments  2182 Julian Seifter 12.12 The acute phase response, hereditary periodic fever syndromes, and amyloidosis  2199 12.12.1 The acute phase response and C-​reactive protein  2199 Mark B. Pepys 12.12.2 Hereditary periodic fever syndromes  2207 Helen J. Lachmann, Stefan Berg, and Philip N. Hawkins 12.12.3 Amyloidosis  2218 Mark B. Pepys and Philip N. Hawkins 12.13 α1-​Antitrypsin deficiency and the serpinopathies  2235 David A. Lomas SECTION 13 Endocrine disorders Section editor: Mark Gurnell 13.1 Principles of hormone action  2245 Rob Fowkes, V. Krishna Chatterjee, and Mark Gurnell 13.2 Pituitary disorders  2258 13.2.1 Disorders of the anterior pituitary gland  2258 Niki Karavitaki and John A.H. Wass 13.2.2 Disorders of the posterior pituitary gland  2277 Niki Karavitaki, Shahzada K. Ahmed, and John A.H. Wass 13.3 Thyroid disorders  2284 13.3.1 The thyroid gland and disorders of thyroid function  2284 Anthony P. Weetman and Kristien Boelaert 13.3.2 Thyroid cancer  2302 Kristien Boelaert and Anthony P. Weetman 13.4 Parathyroid disorders and diseases altering calcium metabolism  2313 R.V. Thakker 13.5 Adrenal disorders  2331 13.5.1 Disorders of the adrenal cortex  2331 Mark Sherlock and Mark Gurnell 13.5.2 Congenital adrenal hyperplasia  2360 Nils P. Krone and Ieuan A. Hughes 13.6 Reproductive disorders  2374 13.6.1 Ovarian disorders  2374 Stephen Franks, Kate Hardy, and Lisa J. Webber 13.6.2 Disorders of male reproduction and male hypogonadism  2386 P.-​M.G. Bouloux 13.6.3 Benign breast disease  2406 Gael M. MacLean † It is with great regret that we report that Richard W.E. Watts died on 11 February, 2018. Contents xxi 13.6.4 Sexual dysfunction  2408 Ian Eardley 13.7 Disorders of growth and development  2416 13.7.1 Normal growth and its disorders  2416 Gary Butler 13.7.2 Normal puberty and its disorders  2428 Fiona Ryan and Sejal Patel 13.7.3 Normal and abnormal sexual differentiation  2435 S. Faisal Ahmed and Angela K. Lucas-​Herald 13.8 Pancreatic endocrine disorders and multiple endocrine neoplasia  2449 B. Khoo, T.M. Tan, and S.R. Bloom 13.9 Diabetes and hypoglycaemia  2464 13.9.1 Diabetes  2464 Colin Dayan and Julia Platts 13.9.2 Hypoglycaemia  2531 Mark Evans and Ben Challis 13.10 Hormonal manifestations of nonendocrine disease  2541 Thomas M. Barber and John A.H. Wass 13.11 The pineal gland and melatonin  2553 J. Arendt and Timothy M. Cox SECTION 14 Medical disorders in pregnancy Section editor: Catherine Nelson-​Piercy 14.1 Physiological changes of normal pregnancy  2563 David J. Williams 14.2 Nutrition in pregnancy  2568 David J. Williams 14.3 Medical management of normal pregnancy  2575 David J. Williams 14.4 Hypertension in pregnancy  2583 Fergus McCarthy 14.5 Renal disease in pregnancy  2589 Kate Wiles 14.6 Heart disease in pregnancy  2597 Catherine E.G. Head 14.7 Thrombosis in pregnancy  2606 Peter K. MacCallum and Louise Bowles 14.8 Chest diseases in pregnancy  2613 Meredith Pugh and Tina Hartert 14.9 Liver and gastrointestinal diseases of pregnancy  2619 Michael Heneghan and Catherine Williamson 14.10 Diabetes in pregnancy  2627 Bryony Jones and Anne Dornhorst 14.11 Endocrine disease in pregnancy  2638 David Carty 14.12 Neurological conditions in pregnancy  2642 Pooja Dassan 14.13 The skin in pregnancy  2648 Gudula Kirtschig and Fenella Wojnarowska 14.14 Autoimmune rheumatic disorders and vasculitis in pregnancy  2655 May Ching Soh and Catherine Nelson-​Piercy 14.15 Maternal infection in pregnancy  2671 Rosie Burton 14.16 Fetal effects of maternal infection  2678 Lawrence Impey 14.17 Blood disorders in pregnancy  2687 David J. Perry and Katharine Lowndes 14.18 Malignant disease in pregnancy  2696 Robin A.F. Crawford 14.19 Maternal critical care  2701 Rupert Gauntlett 14.20 Prescribing in pregnancy  2706 Lucy MacKillop and Charlotte Frise 14.21 Contraception for women with medical diseases  2711 Aarthi R. Mohan SECTION 15 Gastroenterological disorders Section editor: Jack Satsangi 15.1 Structure and function of the gastrointestinal tract  2721 Michael E.B. FitzPatrick and Satish Keshav† 15.2 Symptoms of gastrointestinal disease  2727 Jeremy Woodward 15.3 Methods for investigation of gastroenterological disease  2734 15.3.1 Colonoscopy and flexible sigmoidoscopy  2734 James E. East and Brian P. Saunders † It is with great regret that we report that Satish Keshav died on 23 January, 2019. Contents xxii 15.3.2 Upper gastrointestinal endoscopy  2740 James E. East and George J. Webster 15.3.3 Radiology of the gastrointestinal tract  2748 Fiachra Moloney and Michael Maher 15.3.4 Investigation of gastrointestinal function  2757 Jervoise Andreyev 15.4 Common acute abdominal presentations  2765 15.4.1 The acute abdomen  2765 Simon J.A. Buczacki and R. Justin Davies 15.4.2 Gastrointestinal bleeding  2771 Vanessa Brown and T.A. Rockall 15.5 Immune disorders of the gastrointestinal tract  2783 Joya Bhattacharyya and Arthur Kaser 15.6 The mouth and salivary glands  2797 John Gibson and Douglas Robertson 15.7 Diseases of the oesophagus  2828 Rebecca C. Fitzgerald and Massimiliano di Pietro 15.8 Peptic ulcer disease  2849 Joseph Sung 15.9 Hormones and the gastrointestinal tract  2862 15.9.1 Hormones and the gastrointestinal tract  2862 Rebecca Scott, T.M. Tan, and S.R. Bloom 15.9.2 Carcinoid syndrome  2870 B. Khoo, T.M. Tan, and S.R. Bloom 15.10 Malabsorption  2875 15.10.1 Differential diagnosis and investigation of malabsorption  2875 Alastair Forbes and Victoria Mulcahy 15.10.2 Bacterial overgrowth of the small intestine  2879 Stephen J. Middleton and Raymond J. Playford 15.10.3 Coeliac disease  2884 Peter D. Mooney and David S. Sanders 15.10.4 Gastrointestinal lymphomas  2892 Kikkeri N. Naresh 15.10.5 Disaccharidase deficiency  2902 Timothy M. Cox 15.10.6 Whipple’s disease  2909 Florence Fenollar and Didier Raoult 15.10.7 Effects of massive bowel resection  2911 Stephen J. Middleton, Simon M. Gabe, and Raymond J. Playford 15.10.8 Malabsorption syndromes in the tropics  2916 Vineet Ahuja and Govind K. Makharia 15.11 Crohn’s disease  2925 Miles Parkes and Tim Raine 15.12 Ulcerative colitis  2937 Jeremy Sanderson and Peter Irving 15.13 Irritable bowel syndrome  2951 Adam D. Farmer and Qasim Aziz 15.14 Colonic diverticular disease  2960 Nicolas C. Buchs, Roel Hompes, Shazad Q. Ashraf, and Neil J.McC. Mortensen 15.15 Congenital abnormalities of the gastrointestinal tract  2967 Holm H. Uhlig 15.16 Cancers of the gastrointestinal tract  2977 Peter L. Labib, J.A. Bridgewater, and Stephen P. Pereira 15.17 Vascular disorders of the gastrointestinal tract  2997 Ray Boyapati 15.18 Gastrointestinal infections  3008 Sarah O’Brien 15.19 Miscellaneous disorders of the bowel  3025 Alexander Gimson 15.20 Structure and function of the liver, biliary tract, and pancreas  3032 William Gelson and Alexander Gimson 15.21 Pathobiology of chronic liver disease  3043 Wajahat Z. Mehal 15.22 Presentations and management of liver disease  3049 15.22.1 Investigation and management of jaundice  3049 Jane Collier 15.22.2 Cirrhosis and ascites  3058 Javier Fernández and Vicente Arroyo 15.22.3 Portal hypertension and variceal bleeding  3068 Marcus Robertson and Peter Hayes 15.22.4 Hepatic encephalopathy  3080 Paul K. Middleton and Debbie L. Shawcross 15.22.5 Liver failure  3089 Jane Macnaughtan and Rajiv Jalan 15.22.6 Liver transplantation  3100 John G. O’Grady 15.23 Hepatitis and autoimmune liver disease  3108 15.23.1 Hepatitis A to E  3108 Graeme J.M. Alexander and Kate Nash Contents xxiii 15.23.2 Autoimmune hepatitis  3119 G.J. Webb and Gideon M. Hirschfield 15.23.3 Primary biliary cholangitis  3127 Jessica K. Dyson and David E.J. Jones 15.23.4 Primary sclerosing cholangitis  3135 Kate D. Lynch and Roger W. Chapman 15.24 Other liver diseases  3142 15.24.1 Alcoholic liver disease  3142 Ewan Forrest 15.24.2 Nonalcoholic fatty liver disease  3147 Quentin M. Anstee and Christopher P. Day 15.24.3 Drug-​induced liver disease  3155 Guruprasad P. Aithal 15.24.4 Vascular disorders of the liver  3166 Alexander Gimson 15.24.5 The liver in systemic disease  3169 James Neuberger 15.24.6 Primary and secondary liver tumours  3178 Graeme J.M. Alexander, David J. Lomas, William J.H. Griffiths, Simon M. Rushbrook, and Michael E.D. Allison 15.24.7 Liver and biliary diseases in infancy and childhood  3191 Richard J. Thompson 15.25 Diseases of the gallbladder and biliary tree  3196 Colin Johnson and Mark Wright 15.26 Diseases of the pancreas  3209 15.26.1 Acute pancreatitis  3209 R. Carter, Euan J. Dickson, and C.J. McKay 15.26.2 Chronic pancreatitis  3218 Marco J. Bruno and Djuna L. Cahen 15.26.3 Tumours of the pancreas  3227 James R.A. Skipworth and Stephen P. Pereira Index Volume 3 List of abbreviations  xxxv List of contributors  xlv SECTION 16 Cardiovascular disorders Section editor: Jeremy Dwight 16.1 Structure and function  3241 16.1.1 Blood vessels and the endothelium  3241 Keith Channon and Patrick Vallance 16.1.2 Cardiac physiology  3253 Rhys D. Evans, Kenneth T. MacLeod, Steven B. Marston, Nicholas J. Severs, and Peter H. Sugden 16.2 Clinical presentation of heart disease  3276 16.2.1 Chest pain, breathlessness, and fatigue  3276 Jeremy Dwight 16.2.2 Syncope and palpitation  3284 K. Rajappan, A.C. Rankin, A.D. McGavigan, and S.M. Cobbe 16.3 Clinical investigation of cardiac disorders  3294 16.3.1 Electrocardiography  3294 Andrew R. Houghton and David Gray 16.3.2 Echocardiography  3314 James D. Newton, Adrian P. Banning, and Andrew R.J. Mitchell 16.3.3 Cardiac investigations: Nuclear, MRI, and CT  3326 Nikant Sabharwal, Andrew Kelion, Theodoros Karamitos, and Stefan Neubauer 16.3.4 Cardiac catheterization and angiography  3339 Edward D. Folland 16.4 Cardiac arrhythmias  3350 Matthew R. Ginks, D.A. Lane, A.D. McGavigan, and Gregory Y.H. Lip 16.5 Cardiac failure  3390 16.5.1 Epidemiology and general pathophysiological classification of heart failure  3390 Theresa A. McDonagh and Kaushik Guha 16.5.2 Acute cardiac failure: Definitions, investigation, and management  3397 Andrew L. Clark and John G.F. Cleland 16.5.3 Chronic heart failure: Definitions, investigation, and management  3407 John G.F. Cleland and Andrew L. Clark Contents xxiv 16.5.4 Cardiorenal syndrome  3421 Darren Green and Philip A. Kalra 16.5.5 Cardiac transplantation and mechanical circulatory support  3428 Jayan Parameshwar and Steven Tsui 16.6 Valvular heart disease  3436 Michael Henein 16.7 Diseases of heart muscle  3459 16.7.1 Myocarditis  3459 Jay W. Mason and Heinz-​Peter Schultheiss 16.7.2 The cardiomyopathies: Hypertrophic, dilated, restrictive, and right ventricular  3468 Oliver P. Guttmann and Perry Elliott 16.7.3 Specific heart muscle disorders  3489 Oliver P. Guttmann and Perry Elliott 16.8 Pericardial disease  3501 Michael Henein 16.9 Cardiac involvement in infectious disease  3509 16.9.1 Acute rheumatic fever  3509 Jonathan R. Carapetis 16.9.2 Endocarditis  3519 James L. Harrison, John L. Klein, William A. Littler, and Bernard D. Prendergast 16.9.3 Cardiac disease in HIV infection  3534 Peter F. Currie 16.9.4 Cardiovascular syphilis  3539 Krishna Somers 16.10 Tumours of the heart  3544 Thomas A. Traill 16.11 Cardiac involvement in genetic disease  3551 Thomas A. Traill 16.12 Congenital heart disease in the adult  3559 S.A. Thorne 16.13 Coronary heart disease  3596 16.13.1 Biology and pathology of atherosclerosis  3596 Robin P. Choudhury, Joshua T. Chai, and Edward A. Fisher 16.13.2 Coronary heart disease: Epidemiology and prevention  3603 Goodarz Danaei and Kazem Rahimi 16.13.3 Management of stable angina  3616 Adam D. Timmis 16.13.4 Management of acute coronary syndrome  3626 Rajesh K. Kharbanda and Keith A.A. Fox 16.13.5 Percutaneous interventional cardiac procedures  3655 Edward D. Folland 16.13.6 Coronary artery bypass and valve surgery  3666 Rana Sayeed and David Taggart 16.14 Diseases of the arteries  3674 16.14.1 Acute aortic syndromes  3674 James D. Newton, Andrew R.J. Mitchell, and Adrian P. Banning 16.14.2 Peripheral arterial disease  3680 Janet Powell and Alun Davies 16.14.3 Cholesterol embolism  3688 Christopher Dudley 16.15 The pulmonary circulation  3691 16.15.1 Structure and function of the pulmonary circulation  3691 Nicholas W. Morrell 16.15.2 Pulmonary hypertension  3695 Nicholas W. Morrell 16.16 Venous thromboembolism  3711 16.16.1 Deep venous thrombosis and pulmonary embolism  3711 Paul D. Stein, Fadi Matta, and John D. Firth 16.16.2 Therapeutic anticoagulation  3729 David Keeling 16.17 Hypertension  3735 16.17.1 Essential hypertension: Definition, epidemiology, and pathophysiology  3735 Bryan Williams and John D. Firth 16.17.2 Essential hypertension: Diagnosis, assessment, and treatment  3753 Bryan Williams and John D. Firth 16.17.3 Secondary hypertension  3778 Morris J. Brown and Fraz A. Mir 16.17.4 Mendelian disorders causing hypertension  3796 Nilesh J. Samani and Maciej Tomaszewski 16.17.5 Hypertensive urgencies and emergencies  3800 Gregory Y.H. Lip and Alena Shantsila 16.18 Chronic peripheral oedema and lymphoedema  3811 Peter S. Mortimer 16.19 Idiopathic oedema of women  3823 John D. Firth Contents xxv SECTION 17 Critical care medicine Section editor: Simon Finfer 17.1 The seriously ill or deteriorating patient  3829 Carole Foot and Liz Hickson 17.2 Cardiac arrest  3839 Gavin D. Perkins, Jasmeet Soar, Jerry P. Nolan, and David A. Gabbott 17.3 Anaphylaxis  3849 Anthony F.T. Brown 17.4 Assessing and preparing patients with medical conditions for major surgery  3860 Tom Abbott and Rupert Pearse 17.5 Acute respiratory failure  3867 Susannah Leaver, Jeremy Cordingley, Simon Finney, and Mark Griffiths 17.6 Circulation and circulatory support in the critically ill  3881 Michael R. Pinsky 17.7 Management of raised intracranial pressure  3892 David K. Menon 17.8 Sedation and analgesia in the ICU  3898 Michael C. Reade 17.9 Metabolic and endocrine changes in acute and chronic critical illness  3906 Eva Boonen and Greet Van den Berghe 17.10 Palliative and end-​of-​life care in the ICU  3914 Phillip D. Levin and Charles L. Sprung 17.11 Diagnosis of death and organ donation  3918 Paul Murphy 17.12 Persistent problems and recovery after critical illness  3925 Mark E. Mikkelsen and Theodore J. Iwashyna SECTION 18 Respiratory disorders Section editor: Pallav L. Shah 18.1 Structure and function  3933 18.1.1 The upper respiratory tract  3933 Pallav L. Shah, J.R. Stradling, and S.E. Craig 18.1.2 Airways and alveoli  3937 Peter D. Wagner and Pallav L. Shah 18.2 The clinical presentation of respiratory disease  3947 Samuel Kemp and Julian Hopkin 18.3 Clinical investigation of respiratory disorders  3956 18.3.1 Respiratory function tests  3956 G.J. Gibson 18.3.2 Thoracic imaging  3970 Susan J. Copley and David M. Hansell 18.3.3 Bronchoscopy, thoracoscopy, and tissue biopsy  3992 Pallav L. Shah 18.4 Respiratory infection  4004 18.4.1 Upper respiratory tract infections  4004 P. Little 18.4.2 Pneumonia in the normal host  4008 Wei Shen Lim 18.4.3 Nosocomial pneumonia  4022 Wei Shen Lim 18.4.4 Mycobacteria  4026 Hannah Jarvis and Onn Min Kon 18.4.5 Pulmonary complications of HIV infection  4031 Julia Choy and Anton Pozniak 18.5 The upper respiratory tract  4040 18.5.1 Upper airway obstruction  4040 James H. Hull and Matthew Hind 18.5.2 Sleep-​related breathing disorders  4048 Mary J. Morrell, Julia Kelly, Alison McMillan, and Matthew Hind 18.6 Allergic rhinitis  4059 Stephen R. Durham and Hesham A. Saleh 18.7 Asthma  4067 Alexandra Nanzer-​Kelly, Paul Cullinan, and Andrew Menzies-​Gow 18.8 Chronic obstructive pulmonary disease  4098 Nicholas S. Hopkinson 18.9 Bronchiectasis  4142 R. Wilson and D. Bilton 18.10 Cystic fibrosis  4151 Andrew Bush and Caroline Elston