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

Contents xxvi 18.11 Diffuse parenchymal lung diseases  4166

18.11.1 Diffuse parenchymal lung disease: An introduction  4166 F. Teo and A.U. Wells

18.11.2 Idiopathic pulmonary fibrosis  4177 P.L. Molyneaux, A.G. Nicholson, N. Hirani, and A.U. Wells

18.11.3 Bronchiolitis obliterans and cryptogenic
organizing pneumonia  4185 Vasilis Kouranos and A.U. Wells

18.11.4 The lung in autoimmune rheumatic disorders  4191 M.A. Kokosi and A.U. Wells

18.11.5 The lung in vasculitis  4200 G.A. Margaritopoulos and A.U. Wells 18.12 Sarcoidosis  4208 Robert P. Baughman and Elyse E. Lower 18.13 Pneumoconioses  4219 P.T. Reid 18.14 Miscellaneous conditions  4235

18.14.1 Diffuse alveolar haemorrhage  4235 S.J. Bourke and G.P. Spickett

18.14.2 Eosinophilic pneumonia  4238 S.J. Bourke and G.P. Spickett

18.14.3 Lymphocytic infiltrations of the
lung  4241 S.J. Bourke

18.14.4 Hypersensitivity pneumonitis  4244 S.J. Bourke and G.P. Spickett

18.14.5 Pulmonary Langerhans’ cell
histiocytosis  4256 S.J. Bourke

18.14.6 Lymphangioleiomyomatosis  4257 S.J. Bourke

18.14.7 Pulmonary alveolar proteinosis  4259 S.J. Bourke

18.14.8 Pulmonary amyloidosis  4261 S.J. Bourke

18.14.9 Lipoid (lipid) pneumonia  4263 S.J. Bourke

18.14.10 Pulmonary alveolar microlithiasis  4265 S.J. Bourke

18.14.11 Toxic gases and aerosols  4267 Chris Stenton

18.14.12 Radiation pneumonitis  4271 S.J. Bourke

18.14.13 Drug-​induced lung disease  4272 S.J. Bourke 18.15 Chronic respiratory failure  4282 Michael I. Polkey and P.M.A. Calverley 18.16 Lung transplantation  4292 P. Hopkins and A.J. Fisher 18.17 Pleural diseases  4305 D. de Fonseka, Y.C. Gary Lee, and N.A. Maskell 18.18 Disorders of the thoracic cage and diaphragm  4328 John M. Shneerson and Michael I. Polkey 18.19 Malignant diseases  4338

18.19.1 Lung cancer  4338 S.G. Spiro and N. Navani

18.19.2 Pulmonary metastases  4360 S.G. Spiro

18.19.3 Pleural tumours  4361 Y.C. Gary Lee

18.19.4 Mediastinal tumours and cysts  4368 Y.C. Gary Lee and Helen E. Davies SECTION 19 Rheumatological disorders Section editor: Richard A. Watts 19.1 Joints and connective tissue—​structure and function  4379 Thomas Pap, Adelheid Korb-​Pap, Christine Hartmann, and Jessica Bertrand 19.2 Clinical presentation and diagnosis of rheumatological disorders  4386 Christopher Deighton and Fiona Pearce 19.3 Clinical investigation  4395 Michael Doherty and Peter C. Lanyon 19.4 Back pain and regional disorders  4406 Carlo Ammendolia and Danielle Southerst 19.5 Rheumatoid arthritis  4415 Kenneth F. Baker and John D. Isaacs 19.6 Spondyloarthritis and related conditions  4441 Jürgen Braun and Joachim Sieper 19.7 Infection and arthritis  4457 Graham Raftery and Muddassir Shaikh 19.8 Reactive arthritis  4464 Carmel B. Stober and Hill Gaston 19.9 Osteoarthritis  4470 Andrew J. Barr and Philip G. Conaghan

Contents xxvii 19.10 Crystal-​related arthropathies  4482 Edward Roddy and Michael Doherty 19.11 Autoimmune rheumatic disorders and vasculitides  4495

19.11.1 Introduction  4495 David A. Isenberg and Ian Giles

19.11.2 Systemic lupus erythematosus and related disorders  4499 Anisur Rahman and David A. Isenberg

19.11.3 Systemic sclerosis (scleroderma)  4513 Christopher P. Denton and Carol M. Black

19.11.4 Sjögren’s syndrome  4532 Wan-​Fai Ng

19.11.5 Inflammatory myopathies  4537 Ingrid E. Lundberg, Hector Chinoy, and
Robert Cooper

19.11.6 Large vessel vasculitis  4546 Raashid Luqmani and Cristina Ponte

19.11.7 ANCA-​associated vasculitis  4556 David Jayne

19.11.8 Polyarteritis nodosa  4569 Loïc Guillevin

19.11.9 Small vessel vasculitis  4573 Richard A. Watts

19.11.10 Behçet’s syndrome  4579 Sebahattin Yurdakul, Izzet Fresko, and
Hasan Yazici

19.11.11 Polymyalgia rheumatica  4584 Bhaskar Dasgupta and Eric L. Matteson

19.11.12 Kawasaki disease  4590 Brian W. McCrindle 19.12 Miscellaneous conditions presenting to the rheumatologist  4598 Stuart Carter, Lisa Dunkley, and Ade Adebajo SECTION 20 Disorders of the skeleton Section editor: Cyrus Cooper 20.1 Skeletal disorders—​general approach and clinical conditions  4615 B. Paul Wordsworth and M.K. Javaid 20.2 Inherited defects of connective tissue:
Ehlers–​Danlos syndrome, Marfan’s syndrome, and pseudoxanthoma elasticum  4670 N.P. Burrows 20.3 Osteomyelitis  4688 Martin A. McNally and Anthony R. Berendt 20.4 Osteoporosis  4696 Nicholas C. Harvey, Juliet Compston, and Cyrus Cooper 20.5 Osteonecrosis, osteochondrosis, and osteochondritis dissecans  4703 Gavin Clunie 20.6 Bone cancer  4709 Helen Hatcher SECTION 21 Disorders of the kidney and
urinary tract Section editor: John D. Firth 21.1 Structure and function of the kidney  4717 Steve Harper and Robert Unwin 21.2 Electrolyte disorders  4729

21.2.1 Disorders of water and sodium homeostasis  4729 Michael L. Moritz and Juan Carlos Ayus

21.2.2 Disorders of potassium homeostasis  4748 John D. Firth 21.3 Clinical presentation of renal disease  4764 Richard E. Fielding and Ken Farrington 21.4 Clinical investigation of renal disease  4781 Andrew Davenport 21.5 Acute kidney injury  4807 John D. Firth 21.6 Chronic kidney disease  4830 Alastair Hutchison 21.7 Renal replacement therapy  4861

21.7.1 Haemodialysis  4861 Robert Mactier

21.7.2 Peritoneal dialysis  4874 Simon Davies

21.7.3 Renal transplantation  4879 Nicholas Torpey and John D. Firth 21.8 Glomerular diseases  4909

21.8.1 Immunoglobulin A nephropathy and IgA
vasculitis (HSP)  4909 Jonathan Barratt and John Feehally

21.8.2 Thin membrane nephropathy  4918 Peter Topham and John Feehally

Contents xxviii

21.8.3 Minimal-​change nephropathy and focal segmental glomerulosclerosis  4919 Moin Saleem and Lisa Willcocks

21.8.4 Membranous nephropathy  4928 An S. De Vriese and Fernando C. Fervenza

21.8.5 Proliferative glomerulonephritis  4933 Alan D. Salama and Mark A. Little

21.8.6 Membranoproliferative glomerulonephritis  4937 Tabitha Turner-​Stokes and Mark A. Little

21.8.7 Antiglomerular basement membrane
disease  4943 Mårten Segelmark and Thomas Hellmark 21.9 Tubulointerstitial diseases  4951

21.9.1 Acute interstitial nephritis  4951 Simon D. Roger

21.9.2 Chronic tubulointerstitial nephritis  4956 Marc E. De Broe, Channa Yamasumana,
Patrick C. D’Haese, Monique M. Elseviers, and
Benjamin Vervaet 21.10 The kidney in systemic disease  4975

21.10.1 Diabetes mellitus and the kidney  4975 Rudolf Bilous

21.10.2 The kidney in systemic vasculitis  4988 David Jayne

21.10.3 The kidney in rheumatological
disorders  5001 Liz Lightstone and Hannah Beckwith

21.10.4 The kidney in sarcoidosis  5012 Ingeborg Hilderson and Jan Donck

21.10.5 Renal involvement in plasma cell dyscrasias, immunoglobulin-​based amyloidoses, and fibrillary glomerulopathies, lymphomas, and leukaemias  5016 Pierre Ronco, Frank Bridoux, and Arnaud Jaccard

21.10.6 Haemolytic uraemic syndrome  5027 Edwin K.S. Wong and David Kavanagh

21.10.7 Sickle cell disease and the kidney  5032 Claire C. Sharpe

21.10.8 Infection-​associated nephropathies  5034 A. Neil Turner

21.10.9 Malignancy-​associated renal disease  5041 A. Neil Turner

21.10.10 Atherosclerotic renovascular disease  5044 Philip A. Kalra and Diana Vassallo 21.11 Renal diseases in the tropics  5049 Vivekanand Jha 21.12 Renal involvement in genetic disease  5065 D. Joly and J.P. Grünfeld 21.13 Urinary tract infection  5074 Charles Tomson and Neil Sheerin 21.14 Disorders of renal calcium handling, urinary stones, and nephrocalcinosis  5093 Christopher Pugh, Elaine M. Worcester, Andrew P. Evan, and Fredric L. Coe 21.15 The renal tubular acidoses  5104 John A. Sayer and Fiona E. Karet 21.16 Disorders of tubular electrolyte handling  5112 Nine V.A.M. Knoers and Elena N. Levtchenko 21.17 Urinary tract obstruction  5124 Muhammad M. Yaqoob and Kieran McCafferty 21.18 Malignant diseases of the urinary tract  5136 Tim Eisen, Freddie C. Hamdy, and Robert A. Huddart 21.19 Drugs and the kidney  5150 Aine Burns and Caroline Ashley Index Volume 4 List of abbreviations  xxxv List of contributors  xlv SECTION 22 Haematological disorders Section editors: Chris Hatton and Deborah Hay 22.1 Introduction to haematology  5169 Chris Hatton 22.2 Haematopoiesis  5172

22.2.1 Cellular and molecular basis of haematopoiesis  5172 Paresh Vyas and N. Asger Jakobsen

22.2.2 Diagnostic techniques in the assessment of haematological malignancies  5181 Wendy N. Erber

Contents xxix 22.3 Myeloid disease  5189

22.3.1 Granulocytes in health and disease  5189 Joseph Sinning and Nancy Berliner

22.3.2 Myelodysplastic syndromes  5197 Charlotte K. Brierley and David P. Steensma

22.3.3 Acute myeloid leukaemia  5205 Nigel Russell and Alan Burnett

22.3.4 Chronic myeloid leukaemia  5213 Mhairi Copland and Tessa L. Holyoake†

22.3.5 The polycythaemias  5227 Daniel Aruch and Ronald Hoffman

22.3.6 Thrombocytosis and essential thrombocythaemia  5239 Daniel Aruch and Ronald Hoffman

22.3.7 Primary myelofibrosis  5247 Evan M. Braunstein and Jerry L. Spivak

22.3.8 Eosinophilia  5254 Peter F. Weller

22.3.9 Histiocytosis  5259 Chris Hatton 22.4 Lymphoid disease  5263

22.4.1 Introduction to lymphopoiesis  5263 Caron A. Jacobson and Nancy Berliner

22.4.2 Acute lymphoblastic leukaemia  5269 H. Josef Vormoor, Tobias F. Menne, and
Anthony V. Moorman

22.4.3 Hodgkin lymphoma  5280 Vijaya Raj Bhatt and James O. Armitage

22.4.4 Non-​Hodgkin lymphoma  5288 Vijaya Raj Bhatt and James O. Armitage

22.4.5 Chronic lymphocytic leukaemia  5302 Clive S. Zent and Aaron Polliack

22.4.6 Plasma cell myeloma and related monoclonal gammopathies  5310 S. Vincent Rajkumar and Robert A. Kyle 22.5 Bone marrow failure  5325

22.5.1 Inherited bone marrow failure syndromes  5325 Irene Roberts and Inderjeet S. Dokal

22.5.2 Acquired aplastic anaemia and pure red cell aplasia  5336 Judith C.W. Marsh, Shreyans Gandhi,
and Ghulam J. Mufti

22.5.3 Paroxysmal nocturnal haemoglobinuria  5348 Lucio Luzzatto 22.6 Erythroid disorders  5354

22.6.1 Erythropoiesis  5354 Vijay G. Sankaran

22.6.2 Anaemia: pathophysiology, classification, and clinical features  5359 David J. Weatherall† and Chris Hatton

22.6.3 Anaemia as a challenge to world health  5366 David J. Roberts and David J. Weatherall†

22.6.4 Iron metabolism and its disorders  5371 Timothy M. Cox and John B. Porter

22.6.5 Anaemia of inflammation  5402 Sant-​Rayn Pasricha and Hal Drakesmith

22.6.6 Megaloblastic anaemia and miscellaneous deficiency anaemias  5407 A.V. Hoffbrand

22.6.7 Disorders of the synthesis or function of haemoglobin  5426 Deborah Hay and David J. Weatherall†

22.6.8 Anaemias resulting from defective maturation
of red cells  5450 Stephen J. Fuller and James S. Wiley

22.6.9 Disorders of the red cell membrane  5456 Patrick G. Gallagher

22.6.10 Erythrocyte enzymopathies  5463 Alberto Zanella and Paola Bianchi

22.6.11 Glucose-​6-​phosphate dehydrogenase deficiency  5472 Lucio Luzzatto

22.6.12 Acquired haemolytic anaemia  5479 Amy Powers and Leslie Silberstein 22.7 Haemostasis  5490

22.7.1 The biology of haemostasis and
thrombosis  5490 Gilbert C. White, II, Harold R. Roberts,
and Nigel S. Key

22.7.2 Evaluation of the patient with a bleeding tendency  5509 Trevor Baglin

22.7.3 Thrombocytopenia and disorders of platelet function  5520 Nicola Curry and Susie Shapiro

22.7.4 Genetic disorders of coagulation  5532 Eleanor S. Pollak and Katherine A. High

22.7.5 Acquired coagulation disorders  5546 T.E. Warkentin † It is with great regret that we report that Tessa L. Holyoake died on 30 August, 2017. † It is with great regret that we report that David J. Weatherall died on 8 December, 2018.

Contents xxx 22.8 Transfusion and transplantation  5563

22.8.1 Blood transfusion  5563 D.S. Giovanniello and E.L. Snyder

22.8.2 Haemopoietic stem cell transplantation  5579 E.C. Gordon-​Smith and Emma C. Morris SECTION 23 Disorders of the skin Section editor: Roderick J. Hay 23.1 Structure and function of skin  5591 John A. McGrath 23.2 Clinical approach to the diagnosis of skin disease  5596 Vanessa Venning 23.3 Inherited skin disease  5602 Thiviyani Maruthappu and David P. Kelsell 23.4 Autoimmune bullous diseases  5612 Kathy Taghipour and Fenella Wojnarowska 23.5 Papulosquamous disease  5621 Christopher E.M. Griffiths 23.6 Dermatitis/​eczema  5630 Peter S. Friedmann, Michael J. Arden-​Jones, and Roderick J. Hay 23.7 Cutaneous vasculitis, connective tissue diseases, and urticaria  5639 Volha Shpadaruk and Karen E. Harman 23.8 Disorders of pigmentation  5677 Eugene Healy 23.9 Photosensitivity  5688 Hiva Fassihi and Jane McGregor 23.10 Infections of the skin  5695 Roderick J. Hay 23.11 Sebaceous and sweat gland disorders  5699 Alison M. Layton 23.12 Blood and lymphatic vessel disorders  5709 Peter S. Mortimer and Roderick J. Hay 23.13 Hair and nail disorders  5724 David de Berker 23.14 Tumours of the skin  5732 Edel O’Toole 23.15 Skin and systemic diseases  5743 Clive B. Archer and Charles M.G. Archer 23.16 Cutaneous reactions to drugs  5752 Sarah Walsh, Daniel Creamer, and Haur Yueh Lee 23.17 Management of skin disease  5761 Rod Sinclair SECTION 24 Neurological disorders Section editor: Christopher Kennard 24.1 Introduction and approach to the patient with neurological disease  5775 Alastair Compston and Christopher Kennard 24.2 Mind and brain: Building bridges
between neurology, psychiatry, and psychology  5778 Adam Zeman 24.3 Clinical investigation of neurological disease  5781

24.3.1 Lumbar puncture  5781 R. Rhys Davies and Andrew J. Larner

24.3.2 Electrophysiology of the central and peripheral nervous systems  5785 Christian Krarup

24.3.3 Imaging in neurological diseases  5802 Andrew J. Molyneux, Shelley Renowden, and
Marcus Bradley

24.3.4 Investigation of central motor pathways:
Magnetic brain stimulation  5817 K.R. Mills 24.4 Higher cerebral function  5821

24.4.1 Disturbances of higher cerebral function  5821 Peter J. Nestor

24.4.2 Alzheimer’s disease and other dementias  5830 Jonathan M. Schott 24.5 Epilepsy and disorders of consciousness  5860

24.5.1 Epilepsy in later childhood and adulthood  5860 Arjune Sen and M.R. Johnson

24.5.2 Narcolepsy  5882 Matthew C. Walker

24.5.3 Sleep disorders  5886 Paul J. Reading

24.5.4 Syncope  5896 Andrew J. Larner

24.5.5 The unconscious patient  5901 David Bates

Contents xxxi

24.5.6 Brainstem death and prolonged disorders of consciousness  5908 Ari Ercole, Peter J. Hutchinson, and John D. Pickard 24.6 Disorders of the special senses  5913

24.6.1 Visual pathways  5913 Sara Ajina and Christopher Kennard

24.6.2 Eye movements and balance  5922 Michael Strupp and Thomas Brandt

24.6.3 Hearing loss  5931 Linda Luxon 24.7 Disorders of movement  5937

24.7.1 Subcortical structures: The cerebellum, basal ganglia, and thalamus  5937 Mark J. Edwards and Penelope Talelli

24.7.2 Parkinsonism and other extrapyramidal diseases  5946 Elisaveta Sokolov, Vinod K. Metta, and K. Ray Chaudhuri

24.7.3 Movement disorders other than Parkinson’s disease  5956 Bettina Balint and Kailash Bhatia

24.7.4 Ataxic disorders  5976 Nicholas Wood 24.8 Headache  5987 Peter J. Goadsby 24.9 Brainstem syndromes  6006 David Bates 24.10 Specific conditions affecting the central nervous system  6010

24.10.1 Stroke: Cerebrovascular disease  6010 J. van Gijn (revised by Peter M. Rothwell)

24.10.2 Demyelinating disorders of the central nervous system  6026 Alasdair Coles and Siddharthan Chandran

24.10.3 Traumatic brain injury  6042 Tim Lawrence and Laurence Watkins

24.10.4 Intracranial tumours  6048 Jeremy Rees

24.10.5 Idiopathic intracranial hypertension  6054 Alexandra Sinclair 24.11 Infections of the central nervous system  6060

24.11.1 Bacterial infections  6060 Diederik van de Beek and Guy E. Thwaites

24.11.2 Viral infections  6082 Fiona McGill, Jeremy Farrar, Bridget Wills, Menno
De Jong, David A. Warrell, and Tom Solomon

24.11.3 Intracranial abscesses  6097 Tim Lawrence and Richard S.C. Kerr

24.11.4 Neurosyphilis and neuro-​AIDS  6100 Hadi Manji

24.11.5 Human prion diseases  6109 Simon Mead and R.G. Will 24.12 Disorders of cranial nerves  6120 Robert D.M. Hadden 24.13 Disorders of the spinal cord  6127

24.13.1 Diseases of the spinal cord  6127 Anu Jacob and Andrew J. Larner

24.13.2 Spinal cord injury and its management  6135 Wagih El Masri(y) and Michael Barnes 24.14 Diseases of the autonomic nervous system  6150 Christopher J. Mathias and David A. Low 24.15 The motor neuron diseases  6166 Tom Jenkins, Alice Brockington, and Pamela J. Shaw 24.16 Diseases of the peripheral nerves  6176 Robert D.M. Hadden 24.17 Inherited neurodegenerative diseases  6197 Swati Sathe 24.18 Disorders of the neuromuscular junction  6295 David Hilton-​Jones and Jacqueline Palace 24.19 Disorders of muscle  6304

24.19.1 Structure and function of muscle  6304 Michael G. Hanna and Enrico Bugiardini

24.19.2 Muscular dystrophy  6310 Kate Bushby and Chiara Marini-​Bettolo

24.19.3 Myotonia  6328 David Hilton-​Jones

24.19.4 Metabolic and endocrine disorders  6334 David Hilton-​Jones and Richard Edwards

24.19.5 Mitochondrial disease  6343 Patrick F. Chinnery and D.M. Turnbull 24.20 Developmental abnormalities of the central nervous system  6350 Chris M. Verity, Jane A. Hurst, and Helen V. Firth 24.21 Acquired metabolic disorders and the nervous system  6368 Neil Scolding 24.22 Neurological complications of systemic disease  6376 Neil Scolding

Contents xxxii 24.23 Paraneoplastic neurological syndromes  6384 Jeremy Rees 24.24 Autoimmune encephalitis and Morvan’s syndrome  6393 Camilla Buckley and Angela Vincent SECTION 25 Disorders of the eye Section editor: Christopher P. Conlon 25.1 The eye in general medicine  6399 Tasanee Braithwaite, Richard W.J. Lee, and Peng T. Khaw SECTION 26 Psychiatric and drug-​related disorders Section editor: Michael Sharpe 26.1 General introduction  6445 Michael Sharpe 26.2 The psychiatric assessment of the medical patient  6447 Jane Walker, Roger Smyth, and Michael Sharpe 26.3 Common psychiatric presentations in medical patients  6454

26.3.1 Confusion  6454 Bart Sheehan and Thomas Jackson

26.3.2 Self-​harm  6457 Kate E.A. Saunders and Keith Hawton

26.3.3 Medically unexplained symptoms  6460 Michael Sharpe

26.3.4 Low mood  6462 Jane Walker 26.4 Psychiatric treatments in the medically ill  6465

26.4.1 Psychopharmacology in medical practice  6465 Philip J. Cowen

26.4.2 Psychological treatments  6470 Michael Sharpe and Simon Wessely 26.5 Specific psychiatric disorders  6475

26.5.1 Delirium  6475 Bart Sheehan

26.5.2 Dementia  6478 Bart Sheehan

26.5.3 Organic psychoses  6482 Curtis McKnight and Jason Caplan

26.5.4 Alcohol misuse  6486 Jonathan Wood

26.5.5 Substance misuse  6490 Stephen Potts

26.5.6 Depressive disorder  6493 Joseph Cerimele and Lydia Chwastiak

26.5.7 Bipolar disorder  6498 Kate E.A. Saunders and John Geddes

26.5.8 Anxiety disorders  6501 Ted Liao and Steve Epstein

26.5.9 Acute stress disorder, adjustment disorders,
and post-​traumatic stress disorder  6506 Jonathan I. Bisson

26.5.10 Eating disorders  6509 Christopher G. Fairburn

26.5.11 Schizophrenia  6513 Stephen M. Lawrie

26.5.12 Somatic symptom and related
disorders  6517 Michael Sharpe

26.5.13 Personality disorders  6520 Iain Jordan 26.6 Changing unhealthy behaviours  6524

26.6.1 Brief interventions for excessive alcohol consumption  6524 Amy O’Donnell, Eileen Kaner, and Nick Heather

26.6.2 Obesity and weight management  6529 Susan Jebb and Paul Aveyard

26.6.3 Smoking cessation  6533 Paul Aveyard 26.7 Psychiatry, liaison psychiatry, and
psychological medicine  6536 Michael Sharpe SECTION 27 Forensic medicine Section editor: John D. Firth 27.1 Forensic and legal medicine  6541 Jason Payne-​James, Paul Marks, Ralph Bouhaidar, and
Steven B. Karch

Contents xxxiii SECTION 28 Sport and exercise medicine Section editor: John D. Firth 28.1 Sport and exercise medicine  6565 Cathy Speed SECTION 29 Biochemistry in medicine Section editor: Christopher P. Conlon 29.1 The use of biochemical analysis for diagnosis
and management  6577 Brian Shine and Nishan Guha SECTION 30 Acute medicine Section editor: John D. Firth 30.1 Acute medical presentations  6591 Sian Coggle, Elaine Jolly, and John D. Firth 30.2 Practical procedures  6644 Elaine Jolly, Sian Coggle, and John D. Firth Index