Oxford Textbook of Medicine, 6e (May 6, 2020)_(0198746695)_(Oxford University Press).pdf

Oxford Textbook of Medicine-Volume 1, 6e (May 6, 2020)_(0198746695)_(Oxford University Press) cover Oxford Textbook of Medicine Copyright Foreword Preface Section editors Contents List of abbreviations xxxv List of contributors xlv SECTION 1 Patients and their treatment 1.1 On being a patient 3 1.2 A young person’s experience of chronic disease 6 1.3 What patients wish you understood 8 1.4 Why do patients attend and what do they want from the consultation? 14 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 2.1 Science in medicine: When, how, and what 33 2.2 Evolution: Medicine’s most basic science 39 2.3 The Global Burden of Disease: Measuring the health of populations 43 2.4 Large- scale randomized evidence: Trials and meta- analyses of trials 51 2.5 Bioinformatics 67 2.6 Principles of clinical pharmacology and drug therapy 71 2.7 Biological therapies for immune, inflammatory, and allergic diseases 100 2.8 Traditional medicine exemplified by traditional Chinese medicine 108 2.9 Engaging patients in therapeutic development 118 2.10 Medicine quality, physicians, and patients 124 2.11 Preventive medicine 127 2.12 Medical screening 137 2.13 Health promotion 152 2.14 Deprivation and health 157 2.15 How much should rich countries’ governments spend on healthcare? 161 2.16 Financing healthcare in low- income developing countries: A challenge for equity in health 168 2.18 Fostering medical and health research in resource- constrained countries 181 2.17 Research in the developed world 177 2.19 Regulation versus innovation in medicine 185 2.20 Human disasters 188 2.21 Humanitarian medicine 193 2.22 Complementary and alternative medicine 201 SECTION 3 Cell biology 3.1 The cell 209 3.2 The genomic basis of medicine 218 3.3 Cytokines 236 3.4 Ion channels and disease 246 3.5 Intracellular signalling 256 3.6 Apoptosis in health and disease 266 3.7 Stem cells and regenerative medicine 281 3.8 The evolution of therapeutic antibodies 296 3.9 Circulating DNA for molecular diagnostics 299 SECTION 4 Immunological mechanisms 4.1 The innate immune system 307 4.2 The complement system 315 4.3 Adaptive immunity 325 4.4 Immunodeficiency 337 4.5 Allergy 368 4.6 Autoimmunity 379 4.7 Principles of transplantation immunology 392 SECTION 5 Principles of clinical oncology 5.1 Epidemiology of cancer 411 5.2 The nature and development of cancer: Cancer mutations and their implications 445 5.3 The genetics of inherited cancers 456 5.4 Cancer immunity and immunotherapy 471 5.5 Clinical features and management 487 5.6 Systemic treatment and radiotherapy 497 5.7 Medical management of breast cancer 505 SECTION 6 Old age medicine 6.1 Ageing and clinical medicine 511 6.2 Frailty and sarcopenia 521 6.3 Optimizing well- being into old age 532 6.4 Older people and urgent care 539 6.5 Older people in hospital 548 6.6 Supporting older peoples’ care in surgical and oncological services 563 6.7 Drugs and prescribing in the older patient 571 6.8 Falls, faints, and fragility fractures 579 6.9 Bladder and bowels 589 6.10 Neurodegenerative disorders in older people 601 6.11 Promotion of dignity in the life and death of older patients 612 SECTION 7 Pain and palliative care 7.1 Introduction to palliative care 623 7.2 Pain management 629 7.3 Symptoms other than pain 634 7.4 Care of the dying person 639 SECTION 8 Infectious diseases 8.1 Pathogenic microorganisms and the host 651 8.1.1 Biology of pathogenic microorganisms 651 8.1.2 Clinical features and general management of patients with severe infections 656 8.2 The patient with suspected infection 662 8.2.1 Clinical approach 662 8.2.2 Fever of unknown origin 664 8.2.3 Nosocomial infections 669 8.2.4 Infection in the immunocompromised host 673 8.2.5 Antimicrobial chemotherapy 684 8.3 Immunization 706 8.4 Travel and expedition medicine 713 8.5 Viruses 723 8.5.1 Respiratory tract viruses 723 8.5.2 Herpesviruses (excluding Epstein– Barr virus) 734 8.5.3 Epstein– Barr virus 754 8.5.4 Poxviruses 764 8.5.5 Mumps: Epidemic parotitis 769 8.5.6 Measles 772 8.5.7 Nipah and Hendra virus encephalitides 784 8.5.8 Enterovirus infections 787 8.5.9 Virus infections causing diarrhoea and vomiting 797 8.5.10 Rhabdoviruses: Rabies and rabies- related lyssaviruses 805 8.5.11 Colorado tick fever and other arthropod- borne reoviruses 819 8.5.12 Alphaviruses 821 8.5.13 Rubella 827 8.5.14 Flaviviruses excluding dengue 830 8.5.15 Dengue 845 8.5.16 Bunyaviridae 852 8.5.17 Arenaviruses 862 8.5.18 Filoviruses 870 8.5.19 Papillomaviruses and polyomaviruses 877 8.5.20 Parvovirus B19 886 8.5.21 Hepatitis viruses (excluding hepatitis C virus) 889 8.5.22 Hepatitis C virus 896 8.5.23 HIV/ AIDS 901 8.5.24 HIV in low- and middle- income countries 933 8.5.25 HTLV- 1, HTLV- 2, and associated diseases 941 8.5.26 Viruses and cancer 945 8.5.27 Orf and Milker’s nodule 947 8.5.28 Molluscum contagiosum 949 8.5.29 Newly discovered viruses 951 8.6 Bacteria 958 8.6.1 Diphtheria 959 8.6.2 Streptococci and enterococci 965 8.6.3 Pneumococcal infections 975 8.6.4 Staphylococci 991 8.6.5 Meningococcal infections 1010 8.6.6 Neisseria gonorrhoeae 1025 8.6.7 Enterobacteria and bacterial food poisoning 1032 8.6.8 Pseudomonas aeruginosa 1041 8.6.9 Typhoid and paratyphoid fevers 1044 8.6.10 Intracellular klebsiella infections (donovanosis and rhinoscleroma) 1051 8.6.11 Anaerobic bacteria 1055 8.6.12 Cholera 1060 8.6.13 Haemophilus influenzae 1066 8.6.14 Haemophilus ducreyi and chancroid 1071 8.6.15 Bordetella infection 1073 8.6.16 Melioidosis and glanders 1076 8.6.17 Plague: Yersinia pestis 1081 8.6.18 Other Yersinia infections: Yersiniosis 1086 8.6.19 Pasteurella 1088 8.6.20 Francisella tularensis infection 1091 8.6.21 Anthrax 1094 8.6.22 Brucellosis 1102 8.6.23 Tetanus 1109 8.6.24 Clostridium difficile 1115 8.6.25 Botulism, gas gangrene, and clostridial gastrointestinal infections 1120 8.6.26 Tuberculosis 1126 8.6.27 Disease caused by environmental mycobacteria 1150 8.6.28 Leprosy (Hansen’s disease) 1154 8.6.29 Buruli ulcer: Mycobacterium ulcerans infection 1167 8.6.30 Actinomycoses 1170 8.6.31 Nocardiosis 1176 8.6.32 Rat bite fevers (Streptobacillus moniliformis and Spirillum minus infection) 1179 8.6.33 Lyme borreliosis 1181 8.6.34 Relapsing fevers 1188 8.6.35 Leptospirosis 1198 8.6.36 Nonvenereal endemic treponematoses: Yaws, endemic syphilis (bejel), and pinta 1204 8.6.37 Syphilis 1210 8.6.38 Listeriosis 1223 8.6.39 Legionellosis and Legionnaires’ disease 1226 8.6.40 Rickettsioses 1230 8.6.41 Scrub typhus 1252 8.6.42 Coxiella burnetii infections (Q fever) 1257 8.6.43 Bartonellas excluding B. bacilliformis 1262 8.6.44 Bartonella bacilliformis infection 1272 8.6.45 Chlamydial infections 1278 8.6.46 Mycoplasmas 1295 8.6.47 A checklist of bacteria associated with infection in humans 1307 8.7 Fungi (mycoses) 1338 8.7.1 Fungal infections 1338 8.7.2 Cryptococcosis 1359 8.7.3 Coccidioidomycosis 1361 8.7.4 Paracoccidioidomycosis 1364 8.7.5 Pneumocystis jirovecii 1371 8.7.6 Talaromyces (Penicillium) marneffei infection 1375 8.7.7 Microsporidiosis 1378 8.8 Protozoa 1384 8.8.1 Amoebic infections 1384 8.8.2 Malaria 1395 8.8.3 Babesiosis 1414 8.8.4 Toxoplasmosis 1416 8.8.5 Cryptosporidium and cryptosporidiosis 1424 8.8.6 Cyclospora and cyclosporiasis 1432 8.8.7 Cystoisosporiasis 1436 8.8.9 Giardiasis and balantidiasis 1440 8.8.8 Sarcocystosis (sarcosporidiosis) 1438 8.8.10 Blastocystis infection 1449 8.8.11 Human African trypanosomiasis 1451 8.8.12 Chagas disease 1459 8.8.13 Leishmaniasis 1467 8.8.14 Trichomoniasis 1475 8.9 Nematodes (roundworms) 1478 8.9.1 Cutaneous filariasis 1478 8.9.2 Lymphatic filariasis 1487 8.9.3 Guinea worm disease (dracunculiasis) 1495 8.9.4 Strongyloidiasis, hookworm, and other gut strongyloid nematodes 1500 8.9.5 Gut and tissue nematode infections acquired by ingestion 1506 8.9.6 Angiostrongyliasis 1516 8.10 Cestodes (tapeworms) 1520 8.10.1 Cestodes (tapeworms) 1520 8.10.2 Cystic hydatid disease (Echinococcus granulosus) 1529 8.10.3 Cysticercosis 1533 8.11 Trematodes (flukes) 1540 8.11.1 Schistosomiasis 1540 8.11.2 Liver fluke infections 1551 8.11.3 Lung flukes (paragonimiasis) 1558 8.11.4 Intestinal trematode infections 1562 8.12 Nonvenomous arthropods 1568 8.13 Pentastomiasis (porocephalosis, linguatulosis/ linguatuliasis, or tongue worm infection) 1582 SECTION 9 Sexually transmitted diseases 9.1 Epidemiology of sexually transmitted infections 1589 9.2 Sexual behaviour 1597 9.3 Sexual history and examination 1600 9.4 Vaginal discharge 1603 9.5 Urethritis 1606 9.6 Genital ulceration 1610 9.7 Anogenital lumps and bumps 1613 9.8 Pelvic inflammatory disease 1622 9.9 Principles of contraception 1626 Index Oxford Textbook of Medicine-Volume 2, 6e (May 6, 2020)_(0198746695)_(Oxford University Press) cover Oxford Textbook of Medicine Copyright Foreword Preface Section editors Contents List of abbreviations List of contributors SECTION 10 Environmental medicine, occupational medicine, and poisoning 10.1 Environmental medicine, occupational medicine, and poisoning— Introduction 1637 10.2 Occupational health 1638 10.2.1 Occupational and environmental health 1638 10.2.2 Occupational safety 1652 10.2.3 Aviation medicine 1656 10.2.4 Diving medicine 1664 10.2.5 Noise 1671 10.2.6 Vibration 1673 10.3 Environment and health 1677 10.3.1 Air pollution and health 1677 10.3.2 Heat 1687 10.3.3 Cold 1689 10.3.4 Drowning 1691 10.3.5 Lightning and electrical injuries 1696 10.3.6 Diseases of high terrestrial altitudes 1701 10.3.7 Radiation 1709 10.3.8 Disasters: Earthquakes, hurricanes, floods, and volcanic eruptions 1713 10.3.9 Bioterrorism 1718 10.4 Poisoning 1725 10.4.1 Poisoning by drugs and chemicals 1725 10.4.2 Injuries, envenoming, poisoning, and allergic reactions caused by animals 1778 10.4.3 Poisonous fungi 1817 10.4.4 Poisonous plants 1828 10.5 Podoconiosis (nonfilarial elephantiasis) 1833 SECTION 11 Nutrition 11.1 Nutrition: Macronutrient metabolism 1839 11.2 Vitamins 1855 11.3 Minerals and trace elements 1871 11.4 Severe malnutrition 1880 11.5 Diseases of affluent societies and the need for dietary change 1891 11.6 Obesity 1903 11.7 Artificial nutrition support 1914 SECTION 12 Metabolic disorders 12.1 The inborn errors of metabolism: General aspects 1929 12.2 Protein- dependent inborn errors of metabolism 1942 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 12.4 Disorders of purine and pyrimidine metabolism 2015 12.5 The porphyrias 2032 Timothy M. Cox 12.6 Lipid disorders 2055 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 12.8 Lysosomal disease 2121 12.9 Disorders of peroxisomal metabolism in adults 2157 12.10 Hereditary disorders of oxalate metabolism: The primary hyperoxalurias 2174 12.11 A physiological approach to acid– base disorders: The roles of ion transport and body fluid compartments 2182 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 12.12.2 Hereditary periodic fever syndromes 2207 12.12.3 Amyloidosis 2218 12.13 a1- Antitrypsin deficiency and the serpinopathies 2235 SECTION 13 Endocrine disorders 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 13.3 Thyroid disorders 2284 13.3.1 The thyroid gland and disorders of thyroid function 2284 13.3.2 Thyroid cancer 2302 13.4 Parathyroid disorders and diseases altering calcium metabolism 2313 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 13.6.3 Benign breast disease 2406 13.6.4 Sexual dysfunction 2408 13.7 Disorders of growth and development 2416 13.7.1 Normal growth and its disorders 2416 13.7.2 Normal puberty and its disorders 2428 13.7.3 Normal and abnormal sexual differentiation 2435 13.8 Pancreatic endocrine disorders and multiple endocrine neoplasia 2449 13.9 Diabetes and hypoglycaemia 2464 13.9.1 Diabetes 2464 13.9.2 Hypoglycaemia 2531 13.10 Hormonal manifestations of nonendocrine disease 2541 13.11 The pineal gland and melatonin 2553 SECTION 14 Medical disorders in pregnancy 14.1 Physiological changes of normal pregnancy 2563 14.2 Nutrition in pregnancy 2568 14.3 Medical management of normal pregnancy 2575 14.4 Hypertension in pregnancy 2583 14.5 Renal disease in pregnancy 2589 14.6 Heart disease in pregnancy 2597 14.7 Thrombosis in pregnancy 2606 14.8 Chest diseases in pregnancy 2613 14.9 Liver and gastrointestinal diseases of pregnancy 2619 14.10 Diabetes in pregnancy 2627 14.11 Endocrine disease in pregnancy 2638 14.12 Neurological conditions in pregnancy 2642 14.13 The skin in pregnancy 2648 14.14 Autoimmune rheumatic disorders and vasculitis in pregnancy 2655 14.15 Maternal infection in pregnancy 2671 14.16 Fetal effects of maternal infection 2678 14.17 Blood disorders in pregnancy 2687 14.18 Malignant disease in pregnancy 2696 14.19 Maternal critical care 2701 14.20 Prescribing in pregnancy 2706 14.21 Contraception for women with medical diseases 2711 SECTION 15 Gastroenterological disorders 15.1 Structure and function of the gastrointestinal tract 2721 15.2 Symptoms of gastrointestinal disease 2727 15.3 Methods for investigation of gastroenterological disease 2734 15.3.1 Colonoscopy and flexible sigmoidoscopy 2734 15.3.2 Upper gastrointestinal endoscopy 2740 15.3.3 Radiology of the gastrointestinal tract 2748 15.3.4 Investigation of gastrointestinal function 2757 15.4 Common acute abdominal presentations 2765 15.4.1 The acute abdomen 2765 15.4.2 Gastrointestinal bleeding 2771 15.5 Immune disorders of the gastrointestinal tract 2783 15.6 The mouth and salivary glands 2797 15.7 Diseases of the oesophagus 2828 15.8 Peptic ulcer disease 2849 15.9 Hormones and the gastrointestinal tract 2862 15.9.1 Hormones and the gastrointestinal tract 2862 15.9.2 Carcinoid syndrome 2870 15.10 Malabsorption 2875 15.10.1 Differential diagnosis and investigation of malabsorption 2875 15.10.2 Bacterial overgrowth of the small intestine 2879 15.10.3 Coeliac disease 2884 15.10.4 Gastrointestinal lymphomas 2892 15.10.5 Disaccharidase deficiency 2902 15.10.6 Whipple’s disease 2909 15.10.7 Effects of massive bowel resection 2911 15.10.8 Malabsorption syndromes in the tropics 2916 15.11 Crohn’s disease 2925 15.12 Ulcerative colitis 2937 15.13 Irritable bowel syndrome 2951 15.14 Colonic diverticular disease 2960 15.15 Congenital abnormalities of the gastrointestinal tract 2967 15.16 Cancers of the gastrointestinal tract 2977 15.17 Vascular disorders of the gastrointestinal tract 2997 15.18 Gastrointestinal infections 3008 15.19 Miscellaneous disorders of the bowel 3025 15.20 Structure and function of the liver, biliary tract, and pancreas 3032 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 15.22.2 Cirrhosis and ascites 3058 15.22.3 Portal hypertension and variceal bleeding 3068 15.22.4 Hepatic encephalopathy 3080 15.22.5 Liver failure 3089 15.22.6 Liver transplantation 3100 15.23 Hepatitis and autoimmune liver disease 3108 15.23.1 Hepatitis A to E 3108 15.23.2 Autoimmune hepatitis 3119 15.23.3 Primary biliary cholangitis 3127 15.23.4 Primary sclerosing cholangitis 3135 15.24 Other liver diseases 3142 15.24.1 Alcoholic liver disease 3142 15.24.2 Nonalcoholic fatty liver disease 3147 15.24.3 Drug- induced liver disease 3155 15.24.4 Vascular disorders of the liver 3166 15.24.5 The liver in systemic disease 3169 15.24.6 Primary and secondary liver tumours 3178 15.24.7 Liver and biliary diseases in infancy and childhood 3191 15.25 Diseases of the gallbladder and biliary tree 3196 15.26 Diseases of the pancreas 3209 15.26.1 Acute pancreatitis 3209 15.26.2 Chronic pancreatitis 3218 15.26.3 Tumours of the pancreas 3227 Index Oxford Textbook of Medicine- Volume 3, 6e (May 6, 2020)_(0198746695)_(Oxford University Press) cover Oxford Textbook of Medicine Copyright Foreword Preface Section editors Contents Abbreviations Contributors 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 Andrew R. Houghton and David Gray 16.3.2 Echocardiography 3314 James D. Newton, Adrian P. Banning, and Andrew R.J. Mitchell Andrew R.J. Mitchell 16.3.3 Cardiac investigations: Nuclear, MRI, and CT 3326 Nikant Sabharwal, Andrew Kelion, Theodoros Karamitos, and Stefan Neubauer 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 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, 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 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 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 Oliver P. Guttmann and Perry Elliott 16.7.3 Specifific 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 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 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 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 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 Chronic peripheral oedema and lymphoedema 3811 Peter S. Mortimer Peter S. Mortimer 16.19 Idiopathic oedema of women 3823 John D. Firth 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 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 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 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 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 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 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 rheumatologist 4598 SECTION 20 Disorders of the skeleton 20.1 Skeletal disorders— general approach and conditions 4615 Inherited defects of connective tissue: Ehlers– Danlos syndrome, Marfan’s syndrome, and pseudoxanthoma elasticum 4670 N.P. Burrows 20.3 Osteomyelitis 4688 20.4 Osteoporosis 4696 Nicholas C. Harvey, Juliet Compston, and Osteonecrosis, osteochondrosis, and osteochondritis dissecans 4703 20.6 Bone cancer 4709 Helen Hatcher SECTION 21 Disorders of the kidney and urinary tract 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 Michael L. Moritz and Juan Carlos Ayus 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 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 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 21.2.2 Disorders of potassium homeostasis 4748 John D. Firth 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 21.10The kidney in systemic disease CONTENTS 21.10.1 Diabetes mellitus andthe kidney ESSENTIALS Aetiology and pathology— Staging and natural history— Clinical features— Preventi