1000 Questions & Answers from Kumar & Clark's Clinical Medicine PDF

1000 Questions & Answers from clinical medicine For Elsevier Commissioning Editor: Ellen Green/Pauline Graham Development Editor: Clive Hewat Project Manager: Kerrie-Anne Jarvis Designer: George Ajayi Illustration Manager: Merlyn Harvey 1000 Questions & Answers from Clinical Medicine SECOND EDITION...

1000 Questions & Answers from clinical medicine For Elsevier Commissioning Editor: Ellen Green/Pauline Graham Development Editor: Clive Hewat Project Manager: Kerrie-Anne Jarvis Designer: George Ajayi Illustration Manager: Merlyn Harvey 1000 Questions & Answers from Clinical Medicine SECOND EDITION Professor Parveen J Kumar CBE BSc MD FRCP FRCP (Edin) Professor of Medicine and Education, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, and Honorary Consultant Physician and Gastroenterologist, Barts and The London NHS Trust and the Homerton Hospital NHS Foundation Trust, London, UK Dr Michael L Clark MD FRCP Honorary Senior Lecturer, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, UK Consultant Physician and Gastroenterologist, Princess Grace Hospital, London Edinburgh London New York Oxford Philadelphia St Louis Sydney Toronto 2011 © 2011, Elsevier Limited. All rights reserved. No part of this publication may be reproduced, stored in a retrieval system, or transmitted in any form or by any means, electronic, mechanical, photocopying, recording or otherwise, without the prior permission of the Publishers. Permissions may be sought directly from Elsevier’s Health Sciences Rights Department, 1600 John F. Kennedy Boulevard, Suite 1800, Philadelphia, PA 19103-2899, USA: phone: (⫹1) 215 239 3804; fax: (⫹1) 215 239 3805; or, e-mail: [email protected]. You may also complete your request on-line via the Elsevier homepage (http://www.elsevier.com), by selecting ‘Support and contact’ and then ‘Copyright and Permission’. First published 2008 Second edition published 2011 ISBN: 978-0-7020-4436-6 British Library Cataloguing in Publication Data A catalogue record for this book is available from the British Library Library of Congress Cataloging in Publication Data A catalog record for this book is available from the Library of Congress Notice Knowledge and best practice in this field are constantly changing. As new research and experience broaden our knowledge, changes in practice, treatment and drug therapy may become necessary or appropriate. Readers are advised to check the most current information provided (i) on procedures featured or (ii) by the manufacturer of each product to be administered, to verify the recommended dose or formula, the method and duration of administration, and contraindications. It is the responsibility of the practitioner, relying on their own experience and knowledge of the patient, to make diagnoses, to determine dosages and the best treatment for each individual patient, and to take all appropriate safety precautions. To the fullest extent of the law, neither the Publisher nor the Authors assumes any liability for any injury and/or damage to persons or property arising out or related to any use of the material contained in this book. The Publisher The Publisher’s policy is to use paper manufactured from sustainable forests Printed in China Contents Acknowledgements Preface vi vii 1 Ethics and communication 1 2 Molecular cell biology and genetic disorders 5 3 Clinical immunology 9 4 Infectious diseases, tropical medicine and sexually transmitted infection 13 5 Nutrition 27 6 Gastrointestinal disease 33 7 Liver, biliary tract and pancreatic disease 48 8 Haematological disease 65 9 Malignant disease 79 10 Rheumatology and bone disease 85 11 Renal disease 102 12 Water, electrolytes and acid-base balance 114 13 Cardiovascular disease 120 14 Respiratory disease 156 15 Intensive care medicine 173 16 Drug therapy and poisoning 177 17 Environmental medicine 185 18 Endocrine disease 187 19 Diabetes mellitus and other disorders of metabolism 198 20 The special senses 216 21 Neurological disease 221 22 Psychological medicine 273 23 Skin disease 286 Index 293 v Acknowledgements We would like to thank everyone who has helped in the preparation of this book – especially Ellen Green, who originally commissioned the book from the source questions and answers on the Clinical Medicine website, and other Elsevier staff – Pauline Graham, Clive Hewat, KerrieAnne Jarvis, George Ajayi, and Caroline Cockrell. We are also grateful to Ms Jillian Linton, and Sue Beasley who helped prepare the manuscript, and to the copy-editor Eleanor Flood. vi Preface This book is a compilation of questions, which you, the readers of Clinical Medicine, have sent to us. In this second edition we have replaced some of the older questions with more relevant and up-to-date ones. We have also increased the number of questions in each chapter. We have tried to keep the book as authentic as possible by inserting questions as you have phrased them. It is therefore not a complete coverage of all that is in Clinical Medicine. A number of your questions were quite penetrating and raised issues that were quite unusual. These were quite a challenge to answer! We are told that readers have found the book useful in answering the many intriguing questions that are presented to us by patients every day. We would like to thank all the authors of Clinical Medicine who, with their hard work in producing coherent chapters, made this book possible. The answers to your questions were mainly gleaned from these chapters in Clinical Medicine. We would also like to thank all of you who have sent in questions; these are always extremely helpful in making changes to new editions of Clinical Medicine. Please continue to send in your questions and also your interesting comments to us. We find them all extremely valuable. We hope you find this book helpful and of interest. PJK MLC vii This page intentionally left blank Ethics and communication 1 QUESTIONS Question 1 Regarding medical ethics, if a man is discovered to be hepatitis B or C positive, is it advisable for the physician to inform the wife or sexual contact of the patient? Question 2 Is it unlawful in most countries to limit medical care, particularly by rationing the usage of drugs? Surely rationing must be against the oath we took as doctors to provide the best care available. Question 3 What is meant by QALYs? Is there a difference between quality and quantity of life? Question 4 Are ‘Do not resuscitate’ orders illegal in most countries? Question 5 What is a living will? Question 6 I’ve heard of the Bolam principle but when I mentioned it to my lecturer I was told it was out of date. Could you explain please? Question 7 Why is counselling required before an HIV test can be done on a patient? We don’t counsel patients when we look for a tumour marker to diagnose cancer, which is often more serious for a patient. 1 1 Ethics and communication Question 8 As a junior doctor, I have to attend many multidisciplinary team meetings. I am concerned about the confidentiality of these meetings as they are attended by a diverse group of healthcare workers. Question 9 Is the role of the advocate in a medical interview to help the patient or the doctor? Question 10 We are always asked by our seniors to make sure that the patient has signed the consent form. Isn’t verbal consent enough? Also, for what procedures do I have to get consent, e.g. urinary catheterization in a patient with retention? 2 1 Ethics and communication ANSWERS Answer 1 No. The doctor can only give confidential information to the patient. One would expect, however, that the doctor would counsel the patient, giving advice on his sexual behaviour and safe sex. The patient would hopefully discuss the results with his partner. Answer 2 In all healthcare systems, rationing has become inevitable, partly because of the high costs of modern therapies. To be in line with good medical practice, doctors must acknowledge the obligation that, if rationing is unavoidable, it should be carried out in a responsible and justifiable way. Answer 3 QALYs are Quality Adjusted Life Years. These were developed to place a measurable value to the quality and quantity of life. They were used to try and assess the value of different health measures. More recently, the value of ‘quantity’ over quality has been re-emphasized, i.e. a long life of diminished quality could be as worthwhile as a short life of high quality. Answer 4 It is accepted in most countries that ‘futile’ treatment should not be offered. However, all decisions must be made by senior medical staff after discussion with a patient (if competent), other members of the team and family/carers (if the patient lacks mental capacity). Answer 5 This is a written advanced directive made by competent persons prior to incapacitation, when they would be unable to express their wishes for treatment, resuscitation and terminal care, e.g. to refuse tube feeding if they were to become unconscious from a stroke. Answer 6 Following the Bolam case (Bolam v. Friern Hospital Management Committee 1957), a doctor is not guilty of negligence if he or she has acted in accordance with a practice that is accepted as proper by a responsible body of medical personnel skilled in that particular art. More recently, it was held that for a judge to rely on the opinion of a medical expert, the judge has to be satisfied that the expert’s opinion has a logical basis (Bolitho v. City and Hackney Health Authority 1997). This means that judges can now reach their own conclusions. 3 1 Ethics and communication Further reading Kumar P, Clark M (2009) Clinical Medicine, 7th edn. Edinburgh, Elsevier Saunders, pp. 1–17. Schwartz L et al. (2002) Medical Ethics. Edinburgh, WB Saunders. Answer 7 In the early days of HIV, AIDS was an inevitably fatal condition. It was therefore thought wise to obtain permission and counsel the patient prior to the test. Highly active antiretroviral therapy (HAART) has changed this but counselling is still thought necessary. Your second point is very valid but opinions might change. Answer 8 Your patients must always be informed about the meeting. It should be emphasized that modern medicine involves people from many disciplines. It must be made clear to patients that their confidentiality will be preserved within the team. Reference Fleissig A et al. (2006) Multidiscplinary teams in cancer care. Lancet Oncology 7: 935–943. Answer 9 Both! However, an advocate represents the values, interests and desires of patients and speaks on their behalf. She or he protects their rights, helps with consent, protects patients’ autonomy and ensures that they receive their fair share of resources. From a doctor’s point of view, it is nice to have someone who can interpret patients’ needs. Answer 10 The law in the UK is clear: touching a patient without prior permission is assault or battery. It is therefore essential that the consent (with an explanation of what will be done) is clearly written down and signed. In view of this, really every procedure should have a written consent. However, the Courts will accept the concept of implied consent for minor procedures, such as venepuncture. The example you give is in a grey area and, if in doubt, always get written consent. Further reading Federation of Royal College of Physicians of the UK (FRCP) (2004) Good Medical Practice for Physicians. London, FRCP. General Medical Council (GMC) (2006) Good Medical Practice. London, GMC. 4 Molecular cell biology and genetic disorders 2 QUESTIONS Question 1 As cells grow and regenerate, what mechanism does the body use to get rid of the continuously dying cells? And what kind of cells can’t be replaced once dead? Question 2 I cannot find out why some of the autosomal dominant diseases have a male or female preponderance, e.g. I have never seen a female Marfans. I was attributing it to imprinting but on reading about imprinting in detail it cannot be the case. Question 3 We have been told that some tumours in the colon are associated with microsatellite instability. What does this mean? Question 4 I understand that microarrays are being used to define the molecular abnormality and the prognosis in some patients with leukaemia. What are microarrays? Question 5 Why do mitochondrial diseases cause a myopathy? Question 6 Why do successive generations of patients with some genetic disorders present earlier and with progressively worse symptoms. 5 2 Molecular cell biology and genetic disorders Question 7 Does a normal serum uric acid level exclude the diagnosis of Lesch–Nyhan syndrome? Question 8 How is retinoblastoma an autosomal dominant disease if the mutation of both RB genes is required to express the disease? 6 2 Molecular cell biology and genetic disorders ANSWERS Answer 1 Cells are continually dying by a process of apoptosis (programmed cell death). These cells (or their fragments) are phagocytosed by macrophages or neutrophils where they undergo autolysis within these phagosomes. Brain cells cannot be replaced when dead, although recent evidence challenges this view. Further reading Voss H. V. et al (2006) Journal of Clinical Investigation 116: 2005–2011. Answer 2 By definition, the genes responsible for autosomal dominant diseases must be located on the 22 autosomes; thus both males and females are affected. Males and females are affected in equal proportions except in sex-limited disorders, e.g. ovarian cancer with BRCA1 locus. Answer 3 Microsatellites are short sequences of randomly repeated segments of DNA, two to five nucleotides in length. These regions are inherently unstable and susceptible to mutations. They have been found in tumours, notably colonic, particularly in individuals with hereditary nonpolyposis colorectal cancer (HNPCC). Answer 4 Microarrays are, as you say, used to analyse gene expression. The technique is a significant advance because thousands of genes can be screened at any one time. The assays work by using a fluorescently tagged known mRNA, binding to the specific DNA template from which it originated. The amount of bound mRNA can be measured accurately. Answer 5 Muscles derive energy via oxidative phosphorylation. Mutations in mitochrondrial DNA impair oxidative phosphorylation. Answer 6 This process is called ‘genetic anticipation’ and is due to expansion of the trinucleotide repeat within the disease gene with each generation. It has been shown in, for example, Huntington’s disease (CAG) and dystrophia myotonica (CTG). 7 2 Molecular cell biology and genetic disorders Answer 7 A raised serum uric acid level is usually, but not always, present. The urate to creatinine concentration ratio in urine is elevated. The diagnosis is confirmed by measuring hypoxanthine-guanine-phosphoribosyl transferase (HGPRT) enzyme in cultured cells. Answer 8 Retinoblastoma (RB) is due to a mutational inactivation of both alleles of the RB gene. A ‘two-hit’ model has been proposed involving a second somatic mutation later in development. 8 Clinical immunology 3 QUESTIONS Question 1 Please could you explain how lymphocytes (especially B) can maintain receptors on their surfaces? Is this genetically related? If so, when the lymphocytes are first exposed to the antigens, how could the antigen receptor be synthesized? Is there a mutation within the nuclei of these lymphocytes when they learn to make the receptors? If there is, can you explain how this occurs? Question 2 I understand how nuclear factor-κB (NFκB) works in the inflammatory response but what is the mechanism by which it causes cancer? Question 3 What are the diseases associated with hypocomplementaemia and which complement deficiency in particular? Question 4 What is meant by ‘B lymphocytes are sensitive to clonal deletion’? Question 5 What are the immunological implications of ‘bare lymphocyte syndrome’/MHC deficiency? Question 6 Please explain oligoclonal and monoclonal. Question 7 I was wondering if there is any study regarding cell culture techniques of CD4 helper cells (stem cell culturing) and, if so, is it of any benefit to HIV-infected patients? 9 3 Clinical immunology Question 8 How do you define autoimmune disease? Question 9 1. Why is dexamethasone not routinely used instead of prednisolone, which is almost universally used routinely in autoimmune diseases, or other indications for steroids? Is it because dexamethasone lacks the mineralocorticoid activity seen with prednisolone and therefore does not cause salt/water retention and hypertension? 2. Can high doses of dexamethasone be used in acute relapses of multiple sclerosis (MS) in place of pulse methylprednisolone? If so, what is the recommended dosage? Question 10 What is meant by ‘pus cell’ and is this term synonymous with neutrophils? Question 11 Can dendritic cells migrate into lymph nodes? Immunology textbooks state that these initial blood monocytes infiltrate inflamed tissue. Is the professional antigen-presenting cell the dendritic cell that enters lymph nodes? Question 12 1. How often should treatment with azathioprine be monitored with liver enzymes and a full blood count? 2. What is the most specific liver enzyme or function test for monitoring azathioprine therapy? Question 13 Do you agree or disagree that the dose of azathioprine should be adjusted according to the dose that lowers lymphocytes to 0.8 × 109/L? 10 3 Clinical immunology ANSWERS Answer 1 B cells differentiate from lymphoid cells in the bone marrow in a way that allows them to express an antigen receptor on the surface permanently. The expression of the receptor is a definition of B cells and is a result of the differentiation pathway. The antigen receptor varies from one immature B cell to another. There are billions of different receptors, but any B cell will express only one type of receptor. The antigen does not ‘design’ the receptor; rather, a clonal B cell that recognizes the antigen (very few B cells will recognize a given antigen) will proliferate in response to the antigen and signals from T cells. As the B cells proliferate and differentiate further, the DNA region that codes for the antigen receptor undergoes mutation, and cells with mutations that recognize the antigen better are selected for further development, while those that do not recognize the antigen die. Answer 2 NFκB is a transcription factor that alters cell behaviour. It inhibits apoptosis and increases cell proliferation by increasing the production of tumour necrosis factor (TNF-α). Answer 3 The following are the major patterns of deficiency: C3, C1q and factors H and I: susceptibility to capsulated bacteria, also systemic lupus erythematosus (SLE)-like syndrome C5-9: susceptibility to disseminated neisserial infections C1 esterase deficiency: hereditary angio-oedema. (See K&C 7e, p. 71 for a discussion of complement deficiency.) Answer 4 Clonal deletion occurs during the development of immune tolerance. Clonal deletion occurs when lymphocytes of a particular specificity are lost when in contact with ‘self’ or an extrinsic antigen. Answer 5 In the bare lymphocyte syndrome, a rare recessive condition, major histocompatibility complexes are not expressed. The clinical manifestation is of severe combined immune deficiency (SCID). Patients present in infancy with viral, bacterial, fungal and protozoal infections that are difficult to control because of poor immunity. Answer 6 ‘Oligoclonal’ antibodies are produced by more than one clone (family) of cells, but not by as many as are involved in the production of polyclonal 11 3 Clinical immunology antibodies. ‘Monoclonal’ indicates that the antibodies are produced by a single clone of cells. Answer 7 Cell culture techniques of CD4 helper cells are available but we are unaware of their use in HIV-infected patients. Answer 8 In autoimmune disorders, the body generates immune responses against its own tissues, producing autoreactive T cells and autoantibodies. In normal development, T and B lymphocytes that recognize ‘self’ antigens are deleted in the thymus and bone marrow (central tolerance). Those that escape are suppressed by regulatory T cells in the circulation. Further reading Clinical Medicine (2006) July/Aug: 337–360 CME section on clinical immunology. Answer 9 1 Dexamethasone has very high glucocorticoid activity and therefore needs careful monitoring to avoid side-effects. Most trials on the use of corticosteroids have been performed with prednisolone, hence its common use. 2. All trials in MS are with methylprednisolone (1 g daily for 3 days), so it is better to use this agent. Answer 10 Yes; the pus cell is a neutrophil. Answer 11 Dendritic cells can change their expression of chemokine receptors and migrate from the mucosa to the lymph nodes. Dendritic cells are of several types and are similar to monocytes (myeloid dendritic cells), plasma cells (plasmacytoid) and follicular cells, which are probably not of haemopoeitic origin. Answer 12 1. Many advocate monthly monitoring, but on long-term azathioprine 3-monthly will often suffice. 2. Serum transferases: measurement of thiopurine methyltransferase (TPMT) levels before starting therapy can predict patients who will have a toxic reaction to azathioprine. Answer 13 12 We normally use a dose of 2 mg/kg and stick to it unless there are problems. Infectious diseases, tropical medicine and sexually transmitted infection 4 QUESTIONS Question 1 Which haematogenous infections (bacterial, fungal and protozoal) can give rise to positive findings in the urine? What are the appropriate microbiological investigations for each infection? Question 2 Could you please explain the term ‘zoonosis’. Question 3 What are soil transmitters? Question 4 Please explain the difference between bacteraemia and septicaemia. Can the presence of toxins, fungi or viruses in the blood also be called septicaemia? Question 5 I want to know about the safety of antibiotics used in pregnancy in different trimesters. Question 6 What are the uses and the side-effects of the antibiotic lincomycin? Question 7 I have a question that keeps troubling me. Is there any drug taken orally that prevents penicillin hypersensitivity reactions? Question 8 Is there any replacement intravenous antibiotic for those patients who have hypersensitivity to penicillin? 13 4 Infectious diseases, tropical medicine and STI Question 9 Is it correct to perform an intradermal skin sensitivity test before administering penicillin or a cephalosporin? Question 10 Why are antibiotics not allowed in the treatment of rotaviruses? Question 11 Does aciclovir prevent the chances of developing herpes zoster (shingles) when given during primary infection? Question 12 How long does it take after vaccination to become immunized against chickenpox and therefore safe to work in infectious areas? Question 13 Is meticillin-resistant Staphylococcus aureus (MRSA) the only major hospital-acquired infection? Question 14 Do you have to have antibiotics to get Clostridium difficile infection? Question 15 Why do some patients with rheumatic fever later progress to chronic rheumatic heart disease? Question 16 What is the World Health Organization recommendation for the prophylaxis of rheumatic fever after a streptococcal throat infection? Question 17 Does rheumatic fever have an infectious or an immunological aetiology? Question 18 Why is migratory polyarthritis found in rheumatic heart disease? Question 19 Are penicillins still the drug of choice in streptococcal infections (particularly Strep. Pneumoniae)? Question 20 14 1. How long can the antistreptolysin-O (ASO) titre remain positive after a streptococcal infection? 2. What is the effect of a suitable antibiotic on the ASO titre, if any? 4 Infectious diseases, tropical medicine and STI Question 21 What is the correct method of diagnosis of meningococcal septicaemia: cerebrospinal fluid culture or blood culture? Question 22 Can Escherichia coli 0157 be spread by foods other than meats? Question 23 I have a question about a patient with brucellosis in whom, after 6 weeks of treatment with 600 mg rifampicin +200 mg doxycycline, the agglutination test still shows a 1/320 titre. If, after stopping the treatment, the patient begins to experience identical symptoms as previously, how should treatment proceed? What is the best laboratory test to show relapse? Question 24 Do steroids have a role in the treatment of dengue haemorrhagic fever, in particular to prevent the further fall in the platelet count? Question 25 Please give me the mechanism of thrombocytopenia in dengue and malaria. Question 26 What is the recommended procedure for the treatment of a case of dengue fever? Question 27 What diseases can you get from tick bites? Question 28 Why has severe acute respiratory syndrome (SARS) not spread as widely as was predicted? Question 29 Please explain the relation between recurrent typhoid fever and chronic carrier, and the recommended treatment for both. Question 30 What is the single most confirmatory diagnostic test for typhoid? Question 31 Has human-to-human transmission of the H5N1 avian influenza virus been described? 15 4 Infectious diseases, tropical medicine and STI Question 32 In brucellosis, is it possible to see a brucella agglutination test of more than 1/160 even for years after specific and successful therapy of brucellosis? Question 33 Please define the terms holoendemic, mesoendemic, and hyperendemic in relation to malaria. Question 34 You only recommend malarone for malarial prophylaxis when there is a significant chlorquine resistance. Isn’t malarone now widely used in travellers going to areas with low resistance. Question 35 Parenteral vaccination with a killed suspension of Vibrio cholerae is recommended by some – isn’t an oral vaccine better? Question 36 Please suggest possible reasons why Entamoeba histolytica infection associated with bloody diarrhoea is not relieved by treatment with ciprofloxacin and metronidazole 400 mg × 2 daily over a 3-week period. Question 37 Is there a basis for treating patients for filariasis according to the eosinophil count (except for cases of tropical pulmonary eosinophils; TPE)? Filariasis is everywhere in my part of the world; a fluorescent antibody test (FAT) might not be very useful – except when there are very high values. Question 38 Why do patients who ingest eggs from a tapeworm in contaminated food not develop tapeworms? Question 39 I have a query about one of the details in the book. You mention that perihepatitis is a feature of gonorrhoeal infection, but other books say that perihepatitis (Fitz-Hugh–Curtis syndrome) is a complication of chlamydial infections. Is there a possibility of perihepatitis in gonorrhoea? Thank you. Question 40 16 In the 7th edition of Kumar and Clark Clinical Medicine, you indicate that there is no benefit in treating the male partner of a woman diagnosed 4 Infectious diseases, tropical medicine and STI with bacterial vaginosis (BV). As many physicians use the 2 g × 1 metronidazole dose, is this unwarranted? Does it differ in women experiencing frequent recurrences of infection? Question 41 Why is a caesarean section recommended for the delivery of HIV-positive women? Question 42 Why is HIV not transmitted when delivering a baby through caesarean section? Question 43 1. Is HIV transmitted from mother to child during breastfeeding? 2. Is it possible to be infected with HIV through the ingestion of food and drinks contaminated with the virus? Question 44 Is it true that some patients are resistant to HIV infection despite repeated exposure to the virus? Question 45 With regard to live vaccination and HIV, can MMR be given to an HIV-positive baby? Question 46 In a patient with meningitis: can the development of digital gangrene of the thumbs and sudden dyspnoea with a respiratory rate of 40/min, with intercostal, subcostal and suprasternal withdrawal, be attributed to disseminated intravascular coagulation (DIC)? Question 47 1. What are the causes of anaemia in HIV infection? 2. What are the measures necessary to prevent the transfusion of HIV-infected blood to an individual (please explain in light of the window period)? Question 48 What is the recommended treatment for pulmonary anthrax? Question 49 What primary or specific tests should be performed before giving a patient primaquine for the treatment of relapsing malaria? 17 4 Infectious diseases, tropical medicine and STI Question 50 How sensitive is the polymerase chain reaction (PCR) test for herpes simplex virus 1 (HSV-1) in the cerebrospinal fluid (CSF) for confirming the diagnosis of HSV-1 encephalitis? And is herpes simplex virus 2 (HSV-2) usually tested for as well? Question 51 Herpes simplex is usually not associated with chronic infections such as tuberculosis or typhoid fever. Why is this? Question 52 In my country, now that we know that the pin in the percussion reflex hammer bottom and the pinwheel can transmit infections such as hepatitis B from patient to patient, we prefer the use of wooden or dispersible metal pins. Do the authors agree? Question 53 Can scorpion bite be complicated by ischaemic stroke? If so, how does this occur? 18 4 Infectious diseases, tropical medicine and STI ANSWERS Answer 1 Haematogenous infections seldom give rise to positive findings in the urine. However, infections such as infective endocarditis do produce red cells in the urine. On the whole, microbiological investigations of the urine are not useful in haematogenous infections. Answer 2 Zoonoses are infections that can be transmitted from wild or domestic animals to man. Infections are acquired in various ways, e.g. direct contact (rabies from a dog bite), ingestion of animal products (campylobacter from chickens) and via an arthropod vector (tick bite, Lyme disease). Answer 3 These are helminth infections and the main ones are ascariasis, trichuriasis and hookworm. Answer 4 ‘Bacteraemia’ means viable bacteria in the blood, e.g. viable bacteria can be found after tooth extraction. The term ‘septicaemia’ is difficult to define and is being replaced by ‘systemic inflammatory response syndrome’ (SIRS) (see K&C 7e, p. 899). By definition, this implies that at least two of the following are abnormal: temperature (>38°C or 90 beats per min) respiratory rate (>20 /min or PaCO2 12 or 10% immature forms). SIRS has many causes; bacterial infection is the most common. Answer 5 Antibiotics, like all drugs, should be avoided in pregnancy if possible. Co-trimoxazole is thought to be a teratogenic risk in the first trimester and produces neonatal haemolysis in the third trimester. Quinolones should also not be used in pregnancy. Whenever one is prescribing an antibiotic it is always wise to check local antibiotic policy, and this is even more so in pregnancy. Some drugs are not known to be harmful in pregnancy, e.g. penicillin. Answer 6 Lincomycin is not available in the UK; its uses and side-effects are similar to those of clindamycin (see K&C 7e, p. 99). Its main use is in osteomyelitis because it is concentrated in bone. 19 4 Infectious diseases, tropical medicine and STI Answer 7 In the rare situation that no other antibiotic is available, steroid therapy would be the best measure to prevent hypersensitivity reactions. Penicillins, cephalosporins or any other beta-lactam antibiotic should not be used in patients with a history of penicillin allergy. Answer 8 Yes, erythromycin is a good IV alternative, e.g. in severe respiratory tract infections. Vancomycin is used IV in serious infections caused by Gram-positive bacteria. These are some examples but which antibiotic is used depends on the type of bacteria. Note that 10% of penicillinsensitive patients will also be allergic to cephalosporins. Answer 9 No, it is unhelpful. Answer 10 Rotavirus is a virus and therefore is not sensitive to antibiotics, which are used for bacterial diseases. Answer 11 There is no evidence that giving aciclovir during the primary infection (chicken pox) has any effect on the subsequent development of shingles. Answer 12 To ensure safety for healthcare workers in this situation, antibody levels should be checked 1–2 weeks post-vaccination. Answer 13 No. Vancomycin-insensitive Staphylococcus aureus (VISA), vancomycinresistant Staphylococcus aureus (VRSA) and glycopeptide-resistant enterococci (GRE) are also problems. Clostridium difficile is another problem and occurs mainly after taking antibiotics. Answer 14 20 Usually. Clostridium difficile is normally carried by approximately 5% of the healthy population. It can cause diarrhoea after other normal bowel commensals have been eliminated by antibiotics. In addition, debilitated patients not on antibiotics can be infected by the faecal–oral route. Patients and healthcare workers can spread the organism through hand contact, hence the importance of hand washing. 4 Infectious diseases, tropical medicine and STI Answer 15 Antibodies to streptococcal polysaccharides are substantially elevated and can cross-react with some myocardial tissue antigens. The pathogenesis is, however, far from clear. Answer 16 Phenoxymethylpenicillin 250 mg twice daily until the age of 20 years or for 5 years after the latest attack. This prevents recurrence and further cardiac damage. Answer 17 Both. Rheumatic fever starts with a streptococcal sore throat. It is followed by an immunological response, which is the result of molecular mimicry between the M proteins of the infecting Streptococcus pyogenes and cardiac myosin and laminin. This causes the cardiac lesions. Also, see next answer. Answer 18 Migratory polyarthritis found in rheumatic fever is due to the reaction of the circulating M protein of Streptococcus pyogenes and the synovial membrane. It is therefore migratory. There is no long-term damage to the joints. Answer 19 Penicillin (usually amoxicillin) is the drug of choice for streptococcal infections. However, resistance to Streptococcus pneumoniae is increasing (up to 25% in some studies) and you should check your hospital’s antibiotic policy for the appropriate antibiotic. Answer 20 1. The ASO titre peaks 4–5 weeks after infection. The levels then fall rapidly with a slower decline after 6 months. 2. Antibiotics have no effect on the levels. Answer 21 Blood culture for meningococcal septicaemia. For treatment and vaccination see Box 4.1. Box 4.1 Meningococcal septicaemia Minutes count! Give IV penicillin immediately. Meningococcal vaccination: travellers to Saudi Arabia for the Hajj and Umrah pilgrimages must receive the polysaccharide vaccine (A, C, W 135 and Y serogroups). 21 4 Infectious diseases, tropical medicine and STI Answer 22 Yes. The reservoir for Escherichia coli 0157 is mainly the intestines of cattle. Thus, pasture land can become contaminated and organisms can be found on vegetables, e.g. sprouts and lettuce; unpasteurized milk is another source. Answer 23 Significantly raised agglutination titres can remain for 2 years so these are not useful in diagnosing a relapse. Blood culture (positive in 50%) or polymerase chain reaction (PCR) should be used. Answer 24 Two randomized, controlled trials (RCTs) in children have shown no benefit in children with dengue haemorrhagic fever. No effect was observed on bleeding episodes, other complications or mortality. Fluid replacement is vital. Further reading Wills BD et al. (2005) Comparison of three fluid solutions for resuscitation in Dengue shock syndrome. New England Journal of Medicine 353: 924. Answer 25 Dengue: platelet destruction due to virus/antibody immune complexes binding to the platelet surface. There is also a direct toxic effect on bone marrow. Malaria: cytokine suppression of haemopoiesis. Answer 26 Mild cases need no active treatment. Dengue haemorrhagic fever requires urgent treatment, the key element being fluid replacement. Further reading Kumar P, Clark M (2009) Clinical Medicine, 7th edn, p. 115. Plus online appendix: http://www.studentconsult.com Wills BA et al. (2005) Comparison of three fluid solutions for resuscitation in dengue shock syndrome. New England Journal of Medicine 353: 877–889. Answer 27 Lyme disease is well known in the West. Other diseases include tick-borne relapsing fever (Borrelia spp.), Rocky mountain spotted fever (Ricketssia ricketsii), Mediterranean spotted fever (R. conorii), Ehrlichosis (Ehrlichia spp.), babesiosis (Babesia spp.), and tick-borne encephalitis (virus). Answer 28 22 SARS is due to a previously unknown coronavirus. The reservoir includes civet cats, racoons, ferrets, badgers and animals that are sold in 4 Infectious diseases, tropical medicine and STI some Chinese food markets. Strict control of this practice has brought the epidemic under control. Bats are the likely host species. Further reading Guan Y et al. (2004) Molecular epidemiology of the novel corona virus that causes severe actue respiratory syndrome. Lancet 363: 99–104. Answer 29 A chronic carrier is a patient who continues to carry the organism, usually in the gall bladder, for several months after clinical recovery. A ‘carrier’ implies no symptoms. A recurrence of disease occurs because of reinfection. Answer 30 Blood culture, which is positive in up to 80% of cases. Answer 31 Human-to-human transmission is rare at the moment and most cases have been from transmission from birds and animals. The concern is that efficient transmission between humans will become substantial with changes in viral antigenicity. The 2009 H1N1 virus is a triple-reassortant virus with genes from human, swine and avian influenza viruses. Human-to-human transmission occurs with this virus. Answer 32 Yes. Agglutination levels of 1/160 can persist for years. A four-fold rise in titre is needed to make a diagnosis of acute infection. Answer 33 These terms are defined in terms of the parasitaemia rate in adults or palpable spleen rates in children 2–9 years of age: hypoendemic is less than 10% mesoendemic 11–50% hyperendemic 51–75% holoendemic greater than 75%. Answer 34 Yes, you are correct. The main problem with malarone is its expense. Remember, no drug is 100% effective. Always use insect repellents and insecticide-treated nets at night. Always check on the likelihood of chloroquine resistance in the country you are going to visit. 23 4 Infectious diseases, tropical medicine and STI Answer 35 Yes. Injectible cholera vaccine provides unreliable protection and is not available in UK. Oral vaccine containing inactivated Inaba strains (including El-Tor) and Ogawa strains is much better. However, this does not mean that precautions with the local drinking water should not be undertaken. Answer 36 We can’t easily explain this; metronidazole is very effective in invasive amoebiasis. The most likely reason is that in this patient the diagnosis is wrong and you’re dealing with another cause of bloody diarrhoea (e.g. inflammatory bowel disease) and the E. histolytica is present in the stool of your patient who is a carrier (i.e. not cause and effect). It may be E. dispar which is non-pathogenic. Answer 37 The definitive diagnosis is made by demonstrating microfilariae in the blood but absence does not exclude the disease. Eosinophilia is usually present during the acute phase of inflammation, so in the correct clinical context this could be used as a guide to treatment. Answer 38 To get tapeworms you need to ingest cystercera (not eggs), usually from eating undercooked pork. If you eat tapeworm eggs, as a result of faecal contamination of food, human cysticercosis might occur. Answer 39 Fitz-Hugh–Curtis syndrome was originally described as a complication of gonorrhoea infection, which still occurs. Chlamydia infection is now a much more common cause. Answer 40 Placebo-controlled trials have shown that treatment of the male partner does not improve clinical outcome of treatment of BV or reduce recurrences. These trials included the use of metronidazole. The current guidelines do not recommend treatment of male partners. BV does seem to be acquired sexually so the reason for the lack of benefit of treatment is obscure. Answer 41 24 HIV is shed into the cervical/vaginal birth canal as well as being present in the blood, which is why caesarean sections were used. However, with the use of highly active antiretroviral therapy (HAART) during pregnancy, the viral count is low and there is now no advantage in doing a caesarean section. 4 Infectious diseases, tropical medicine and STI Answer 42 HIV is transmitted by blood and not usually by other fluids. There is very little contact between the baby and blood in a caesarean section. Answer 43 1. Breast-feeding doubles the risk of mother-to-child transmission of HIV infection. 2. No. Answer 44 Yes, it is true but only in a very few patients. One explanation is that mutations in the gene expressing the receptor for chemokine CCR5 (see K&C 7e, p. 185) might impair entry of HIV into cells and therefore confer some resistance to infection. Answer 45 Yes, but not while the baby is severely immunosuppressed. Answer 46 This sounds like meningococcal septicaemia, which can occur with meningococcal meningitis. It could be due to DIC, which certainly occurs, but the best clinical evidence of this is subcutaneous haemorrhages, gastric bleeding or bleeding from venepuncture sites. Answer 47 1. One of the most common causes is related to highly active antiretroviral therapy (HAART), e.g. megaloblastic anaemia, red call aplasia with zidovudine. Always remember to check drug therapy and side-effects. Other causes include anaemia of chronic disease and pancytopenia secondary to overwhelming opportunistic infection. 2. In 2000, an assay for HIV RNA was introduced into blood-donor screening. HIV RNA appears earlier than p24 viral protein or HIV antibody. The window period is now thought to be 6–38 days. Transfusion of ‘window-period’ blood probably accounts for all HIV transmitted by transfusion in developed countries. Answer 48 Ciprofloxacin IV 400 mg twice daily. Untreated, the mortality rate is 90% and even in cases treated with ciprofloxacin for 60 days (in the USA) the mortality rate was still 45%. Answer 49 A test for glucose-6-phosphate activity should be performed before using primaquine as this drug can cause haemolysis in G6PD-deficient patients. 25 4 Infectious diseases, tropical medicine and STI Answer 50 Sensitivity is 98% and specificity 94% for PCR. Both HSV-1 and HSV-2 are tested. Answer 51 This relates to the degree of immunosuppression. You are right; the diseases that you mention are not usually associated with herpes simplex. However, cases have been described where the patient has severe immunosuppression with decreased cellular immunity and tuberculosis and herpes simplex have occurred together. Answer 52 Yes; use a broken ‘orange stick’. Answer 53 Yes: the sting releases both catecholamines from the adrenal gland and acetylcholine from postganglionic parasympathetics. These have an effect on cerebral blood flow. 26 Nutrition 5 QUESTIONS Question 1 Please give examples of red meat, white meat and lean meat. Question 2 What is lean body weight and how does it differ from routine measurement? Question 3 Is the combination of drugs sibutramine and orlistat more effective in reducing obesity than using these on their own? Question 4 Why does vitamin B12 deficiency cause glossitis? Question 5 Is a dosage of 2.5 mg/day of methyltestosterone, as a component in some multivitamin formulae, safe in the long-term? Question 6 What is the effect of sodium/potassium imbalance on the microminerals? Question 7 What is the role of fluoride in healing? Question 8 In K&C 7e (Box 5.6, p. 239) it states ‘Do not drink [alcohol] during the daytime’. Please explain why this is not recommended. Question 9 Could you please tell me about the aetiology of ‘refeeding syndrome’? 27 5 Nutrition Question 10 What is the Atkin’s diet? Question 11 What is meant by bariatric surgical procedures? Question 12 In a patient with marked obesity, is bariatric surgery better than a balloon inserted into the stomach? Question 13 Does intravenous nutrition always have to be given via a central vein? Question 14 Why has there been an explosion of obesity in the young? Question 15 Are proteins mostly absorbed from the intestinal lumen into the blood as amino acids? Question 16 What are ‘congeners’ in alcohol? Question 17 Cholesterol is synthesized in the body. What is the comparative role of diet and endogenous production in the level of serum cholesterol? Question 18 We frequently read of the severe but ‘rare’ side-effect of myositis with statins. Do these drugs have more ‘common’ side-effects? Question 19 Is there a relationship between brain disease and alcohol intake? Does alcohol have a proven toxic effect on the brain? Question 20 What is the difference between malabsorption and malnutrition and how can these be differentiated clinically? Question 21 What are the health hazards of eating smoked foods such as meat or fish? Question 22 28 What are the benefits of royal jelly (from bees)? 5 Nutrition ANSWERS Answer 1 Red meat: beef, lamb. White meat: chicken, turkey. Lean meat: ostrich, venison. Answer 2 Lean body mass approximates fat-free mass; it is not used in routine clinical nutrition. There is a formula for its calculation – if you really want it! Answer 3 No; there is no additive effect and there is no interaction between the drugs. The use of sibutramine is suspended in Europe. Answer 4 Vitamin B12 plays a major role in the formation of DNA (see K&C 7e, Fig. 8.12, p. 398). Many epithelial cells show evidence of atrophy, including the tongue – hence the glossitis. Small bowel and stomach are also affected. Answer 5 Yes, as far as anyone knows (see Chapter 19, Question 32). Answer 6 We know of no evidence of sodium/potassium imbalance affecting microminerals. Answer 7 Fluoride might stimulate new bone formation but this is of no clinical value. Fluoride is added to water to prevent dental caries. Answer 8 ‘Do not drink during the daytime’ is good advice in that it shortens the time available to drink and helps drinkers keep their consumption low. It is particularly useful advice to those who work in the wine and spirit trade. Answer 9 The ‘refeeding syndrome’ occurs after feeding has restarted in severely malnourished patients. The features are: Fluid overload leading to heart failure sometimes producing acute pulmonary oedema. Sodium and water reabsorption in the kidney is increased by insulin, and the low serum albumin also contributes to the fluid overload. 29 5 Nutrition Hypokalaemia, hypomagnesaemia and hypophosphataemia occur as insulin stimulates cellular uptake of these ions. Cardiac arrhythmias are also prominent. Answer 10 The Atkins’ diet is a low-carbohydrate diet used to promote weight loss. The principle is that the body will switch from burning glucose to burning fat. Atkins did (in addition to the diet) recommend exercise and nutritional supplements. However, like all diets, although there might be short-term gains, permanent weight loss is rare and patients should be encouraged to maintain the recommended healthy intake of food (Table 5.1). In the long-term, the diet may increase the development of atherosclerosis. Answer 11 The term ‘bariatric’ is derived from a Greek word meaning ‘weight’. Procedures are designed to reduce weight by restricting the size of the stomach or by-passing the stomach. Stomach operations include: Gastric banding: a band is placed laparoscopically around the upper part of the stomach (lap-banding), creating a small pouch and a narrow passage into the stomach. Table 5.1 Recommended healthy dietary intake 30 Dietary component Approximate amounts (% of total energy unless otherwise stated)* General hints Total carbohydrate 55 (55–75) Free sugar Protein 10 (⬍10) 15 (10–15) Total fat Saturated fat Unsaturated fat 30 (15–30) 10 (⬍10) 20 Cholesterol Salt ⬍300 (⬍300) mg/day ⬍6 (⬍5) g/day Total dietary fibre 30 (⬎25) g/day Increase fruit, vegetables, beans, pasta, bread Decrease sugary drinks Decrease red meat (see fat below) Increase vegetable (including olive oil) and fish oil and decrease animal fat Decrease meat and eggs Decrease prepared meats and do not add extra salt to food Increase fruit and vegetables and wholegrain foods *Values in parentheses are goals for the intake of populations, as given by the World Health Organization (including populations who are already on low-fat diets). Some of the extreme ranges are not realistic short-term goals for developed countries, e.g. 75% of total energy from carbohydrate and 15% fat. (From Kumar and Clark Clinical Medicine 7e.) 5 Nutrition Roux-en-Y gastric bypass. These are effective long-term treatments but have complications and side-effects. Answer 12 There are no comparative data as they are two different treatments. Balloon insertion into the stomach is used for 6 months only to help obese patients lose weight. Bariatric surgery is used on morbid obese patients when all medical therapy has failed. Answer 13 It is usual to give parenteral nutrition via a central catheter but there are specially formulated mixtures for use via a peripheral line. Peripheral parenteral nutrition is useful initially, as the catheter only lasts 5 days. Answer 14 There is no single lifestyle factor. There appear to be number of causes, including taking less exercise, watching television and playing computer games, as well as an increase in food intake, particularly of fatty, sugary foods that are very rich in calories. The different degrees of overweight are shown in Table 5.2. Answer 15 No, unlike carbohydrates, which are hydrolysed to monosaccharides and then absorbed, proteins are broken down to small peptides and only some amino acids prior to absorption. Answer 16 During the distillation process of spirits, in addition to ethyl alcohol, other alcohols (e.g. isoamyl alcohol) are produced. It is thought that these ‘congeners’ play a big role in ‘hangovers’! Port and bourbon have a higher congener content than gin and vodka. Obviously, the quantity drunk also plays a role! Table 5.2 Ranges of body mass index (BMI) used to classify degrees of overweight and associated risk of comorbidities WHO classification BMI (kg/m2) Risk of comorbidities Overweight Obese Class I Class II Class III 25–30 ⬎30 30–35 35–40 ⬎ 40 Mildly increased Moderate Severe Very severe 31 5 Nutrition Answer 17 Cholesterol is synthesized in the body, mainly in the liver. The higher the amount of cholesterol in the diet, the lower the amount of cholesterol synthesized, and vice versa. Thus, it is difficult to significantly lower your serum cholesterol by diet alone unless the diet is very restrictive. Familial hypercholesterolaemia is related to a reduction in the number of low-density lipoprotein (LDL) receptors. Answer 18 Gastrointestinal side-effects, including abdominal pain, flatulence, constipation, diarrhoea, nausea and vomiting, occur frequently but are often tolerated without complaint. Answer 19 Yes, alcohol has a toxic effect on the brain; try mental arithmetic after a few drinks. Alcohol causes blackouts and memory lapses, even in small amounts. Wernicke–Korsakoff syndrome due to thiamine deficiency is seen in chronic abusers, as are epilepsy and dementia. Answer 20 Malabsorption is the term used to describe a failure of absorption of nutrients. Malnutrition is weight loss which, when severe, has a high mortality. It is usually due to poor dietary intake (e.g. in sub-Saharan Africa) or secondary to malignant disease in the West. Malabsorption, if severe, can lead to malnutrition but this is now relatively rare. In a patient with malnutrition, malabsorption must be excluded, usually on the patient’s history. Answer 21 Smoked fish as used by most probably has no health risk. The high incidence of gastrointestinal cancers in some countries, e.g. Japan, has been attributed to an excess consumption of smoked fish. Answer 22 There are no randomized controlled trials for royal jelly! It is recommended for virtually everything! We suspect the benefits are marginal. 32 Gastrointestinal disease 6 QUESTIONS Question 1 Please explain the role of the sympathetic nervous system in the gastrointestinal tract. Question 2 What is the difference between a submandibular salivary gland swelling and swelling of a salivary lymph node? Question 3 How does Barrett’s oesophagus develop? Question 4 Is it recommended to treat asymptomatic endoscopically diagnosed reflux oesophagitis with acid suppression and/or antireflux measures? Question 5 Is it recommended to give a young patient, diagnosed endoscopically to have mild reflux oesophagitis, life-long proton pump inhibitors (PPIs) to prevent the development of Barrett’s oesophagitis? Question 6 Is it safe to give a patient with reflux oesophagitis who is on proton pump inhibitors (PPIs) for treatment of acid suppression, aspirin in antiplatelet doses (75–325 mg per day)? Question 7 Does a combination of magnesium and aluminium hydroxide salts, taken as antacid for reflux oesophagitis, have serious long-term adverse effects? 33 6 Gastrointestinal disease Question 8 In the treatment of reflux oesophagitis with a proton pump inhibitor (PPI), should the PPI be life long or given for 4–8 weeks, as mentioned by the drug manufacturers? Question 9 Would a patient who suffers with reflux oesophagitis as a result of a hiatus hernia, and who is not responsive to proton pump inhibitors (PPIs), benefit from a highly selective vagotomy? Question 10 1. What are the causes of belching and what appropriate drug can be used? 2. What are the effects of smoking on the gastrointestinal tract and what is its role in peptic ulcer disease? Question 11 Dear authors, why are gastric ulcers more common along the lesser curve, near the pylorus of the stomach? Question 12 What is the best time of day to administer omeprazole, and why? Question 13 Is it safe to use the drugs omeprazole and ranitidine during pregnancy? Question 14 Are non-steroidal anti-inflammatory drugs harmful to the stomach when taken parenterally, for example by intravenous or intramuscular routes? Question 15 Is it safe to give a patient with a past history of bleeding peptic ulcer aspirin in an antiplatelet dose of 75–325 mg? Question 16 Is sulpiride effective in the treatment of a peptic ulcer or gastrooesophageal reflux disease (GORD)? Question 17 Is clopidogrel gentle on the stomach? Question 18 34 Is there a drug interaction between non-steroidal anti-inflammatory drugs (NSAIDs) and proton pump inhibitors (PPIs)? 6 Gastrointestinal disease Question 19 Do antacids enhance mucosal resistance in the gastric mucosa? If so, please indicate the mechanism. Question 20 Is there a drug interaction between antacids and H2-receptor blockers? Question 21 Does the combination of aluminium and magnesium hydroxide, given as an antacid, decrease the absorption of omeprazole if these are co-administered to help relieve heartburn quickly? Question 22 Should proton pump inhibitors be used with caution in patients with renal impairment? Question 23 Has cisapride been withdrawn from the market because of the danger of ventricular fibrillation? Question 24 In peptic ulcer disease: 1. What are the indications for an upper gastrointestinal endoscopy? 2. As this is an invasive procedure, is an oesophagogastroduodenoscopy (OGD) or barium meal X-ray preferable? Question 25 Is telithromycin as, or more, effective than clarithromycin in the treatment of Helicobacter pylori? If so, what is the recommended dosage and how long should treatment be continued? Question 26 Currently favoured regimens for eradication of Helicobacter pylori are triple therapy with a proton pump inhibitor along with two antibiotics for 1 week. For example: Omeprazole 20 mg ⫹ metronidazole 400 mg and clarithromycin 500 mg (all twice daily). Omeprazole 20 mg ⫹ clarithromycin 500 mg and amoxicillin 1 g (all twice daily). Resistance to amoxicillin has not yet been demonstrated. Previously, regimens such as omeprazole, metronidazole, amoxicillin and clarithromycin were recommended; are these regimens no longer used? The reason behind this question is the ‘sky-high’ cost of clarithromycin in Pakistan, which is inversely proportional to patient compliance (that is, low-cost regimens tend to have a higher rate of compliance). 35 6 Gastrointestinal disease Question 27 What is the difference between the management of a gastric and of a duodenal ulcer? Question 28 How does omeprazole suppress Helicobacter pylori? Question 29 Does omeprazole cause rebound hyperacidity? Does this also apply to H2-blockers? Question 30 On (K&C 7e, p. 249), you state that the postsynaptic neurotransmitter that inhibits the relaxation of lower oesophageal sphincter (LOS) is nitric oxide (NO). I have understood NO to promote relaxation of LOS by acting on the non-adrenergic, non-cholinergic (NANC) inhibitory neurones, which inhibits the action of cholinergic excitatory neurones. Could you please explain this paradox? Question 31 It is stated that nitric oxide (NO) inhibits the relaxation of the lower oesophageal sphincter (LOS) and that sildenafil is given for treating achalasia. As far as I know, sildenafil acts to increase the guanine monophosphate (GMP), just as NO uses the same mechanism to relax the LOS. Could you explain this paradox? Question 32 In Kumar and Clark Clinical Medicine you mention that auscultation is not important in cases of gastrointestinal disorders, but Harrison’s Principles of Internal Medicine gives this as being of equal importance because succussion splash and bowel sounds can help in presumptive diagnosis. Succussion splash indicates gastric obstruction (e.g. gastroparesis) and likewise bowel sounds can help determine the status of developing ileus. Would you agree that this is therefore a diagnostic tool? Question 33 Is it hazardous to give aspirin in the antiplatelet doses (75–325 mg/day) to a patient with a past history of haematemesis proved to be from a peptic ulcer? Question 34 36 How can upper gastrointestinal (GI) bleeding be distinguished from lower GI bleeding by using faecal analysis? 6 Gastrointestinal disease Question 35 In upper gastrointestinal bleeding, without knowing the cause or source of bleeding, why do we give proton pump inhibitors (PPIs, e.g. omeprazole)? What is the role of these, if the source of bleeding is not peptic or duodenal ulcer? Question 36 Why is the incidence of coeliac disease increasing in many countries? Question 37 Are small amounts of gluten harmful to a patient with coeliac disease? Question 38 I refer to the treatment of complications related to diverticular disease. Under ‘bleeding’ you mention that ‘Persistent bleeding can often be arrested by undertaking an “instant” barium enema, which acts to plug the offending diverticulum’. When I mentioned this to my consultant he said he had never heard of this. Could you clarify how this would work and where I could obtain more information? Question 39 In children with abdominal pain and fever, does a white cell count help establish a diagnosis of appendicitis? Question 40 I have always been taught that ulcerative colitis only affects the large bowel with some associated proctitis. I read in your chapter on gastrointestinal disease that it can cause mouth ulcers and am now confused. Question 41 In pseudomembranous colitis, what is the first treatment of choice, metronidazole or vancomycin? Question 42 Is Crohn’s disease considered as an autoimmune disease. If it is, are there other predisposing factors to it other than genetics? If it is not, what is its nature? Question 43 Why does carcinoma of the ascending colon cause more anaemia than obstruction, and carcinoma of the descending colon more obstruction features and less anaemia? 37 6 Gastrointestinal disease Question 44 Can you explain why a patient with colorectal carcinoma might present with diarrhoea and abdominal pain? Question 45 What causes the blood to be altered in the presentation of melaena: is it intestinal juice? Question 46 What is the differential diagnosis of multiple rectal ulcers in an 18-yearold female? Question 47 What is the best surgical technique in a chronic (2–3 years) painful anal fissure that is located sagittally posteriorly? Question 48 Can I make a diagnosis of irritable bowel syndrome (IBS) in a 40-year-old female patient without doing gastrointestinal investigations? Question 49 What is the cause of abdominal bloating, which is often a symptom in patients with irritable bowel syndrome (IBS)? Question 50 1. Where is the Traub’s area situated anatomically? 2. What does it mean if it is dull on percussion? 3. What is the proper way to percuss this area? Question 51 In general, it is claimed that only water and some salts are absorbed in the large gut, whereas the small gut is practically free of bacteria (which are present only in the large gut). In a patient on broad-spectrum antibiotics, bleeding can occur as a result of vitamin K deficiency. If the flora synthesizing vitamin K is disturbed, how can vitamin deficiency occur when the large gut is not supposed to absorb? How can this be due to a change in bacterial flora? Question 52 Why does colonic cancer more commonly occur on the left rather than the right side of the colon? 38 6 Gastrointestinal disease Question 53 How much more likely are patients with reflux oesophagitis to develop cancer of the oesophagus than normal people and does aggressive treatment with H2-blockers or proton pump inhibitors nullify this increased risk? Question 54 In Crohn’s disease localized to the ileum there are long-term side effects and pros and cons of drug therapy. Is ileal resection a better option (if Crohn’s disease is localized to the ileum) than long-term medicine therapy which risks complicating lymphoma of the ileum? 39 6 Gastrointestinal disease ANSWERS Answer 1 Sympathetic fibres are distributed along the entire length of the gut; the stimulation or inhibition of these plays a role in many aspects of gut motility. Increased sympathetic stimulation produces the well-known anxiety symptoms, for example before exams when increased stimulation produces diarrhoea. Answer 2 The salivary lymph glands are part of the superficial lymphatic drainage of the neck; enlargement occurs in infection and in malignant disease. The submandibular gland is swollen if there is blockage of the duct or if a tumour is present. It can also be affected by the mumps virus, although parotid involvement is more common. Answer 3 Barrett’s oesophagus is defined as areas of columnar epithelium with intestinal metaplasia extending upwards in the lower oesophagus replacing the normal squamous epithelium. It is due to chronic gastrooesophageal reflux. Answer 4 No, it is not recommended to treat asymptomatic reflux oesophagitis. However, many gastroenterologists do treat it in the hope that long-term complications (e.g. stricture, Barrett’s and cancer) can be averted. Answer 5 No, there is no indication to give long-term PPIs in patients with mild reflux oesophagitis; there is no evidence that this prevents the development of Barrett’s. Answer 6 Yes, it is safe to give aspirin to a patient already on a PPI, which is – of course – cytoprotective. Answer 7 No, there are no serious long-term adverse effects. Usually, however, in patients who require long-term treatment, an H2-receptor antagonist or a proton pump inhibitor is used. Answer 8 40 Patients with reflux oesophagitis usually have a low lower oesophageal sphincter pressure, so that reflux is a permanent event. After stopping 6 Gastrointestinal disease PPIs, the symptoms return and life-long therapy may be necessary. Some would regard this as an indication for surgery. Answer 9 No. A highly selective vagotomy will only do the same as the PPIs, that is, reduce the acid output. Try increasing the dose of the PPI to twice daily. Answer 10 1. Belching is due to swallowing air. It is often picked up as a habit and it is not usually associated with pathology. Occasionally, patients who have upper gastrointestinal symptoms, such as heartburn or abdominal discomfort, swallow air in an attempt to ease their symptoms, and end up belching. Treatment can be difficult; no drugs are effective. 2. Smoking impairs the healing of peptic ulcer disease and also makes gastro-oesophageal reflux worse. It is also associated with relapse in patients with Crohn’s disease (but not in ulcerative colitis) therefore all patients with Crohn’s should be encouraged to stop smoking. Answer 11 There is no definitive reason why gastric ulcers are more common on the lesser curve. They are usually just distal to the transitional zone between the body (acid-secreting mucosa) and antrum (non-acid-secreting mucosa). Reflux of bile and other duodenal contents into the stomach is thought to play a role. Answer 12 Either morning or evening. It has a prolonged action so that the effect lasts over 24 hours. Answer 13 Neither drug is recommended in pregnancy, but ranitidine is probably safe. No drug should be used in pregnancy unless absolutely essential. Answer 14 Yes; the inhibition of gastric mucosal cyclo-oxygenase (COX) activity is a systemic effect. Answer 15 A patient with a bleeding peptic ulcer, which is usually due to Helicobacter pylori, should have eradication therapy. In the case of a bleeding ulcer, eradication must be checked with a 13C urea breath test or a stool antigen test. When eradication has been shown to be successful, it 41 6 Gastrointestinal disease is safe to use low-dose aspirin. (Note: patients with and without a history of ulcers can bleed even with low-dose aspirin.) Answer 16 Sulpiride is not used. It does have an antimuscarinic action, which would reduce acid production, but in GORD this is offset by a reduction in lower oesophageal sphincter tone. It is therefore not useful in peptic ulcer or GORD. Answer 17 Clopidogrel does cause dyspepsia and abdominal pain, and it can lead to gastrointestinal bleeding. So, is it ‘gentle’? The answer must be ‘No’. Answer 18 There is no drug interaction. Indeed, PPIs are used as mucosal cytoprotective agents in patients on NSAIDs. Answer 19 If, by antacids, you mean aluminium hydroxide or magnesium trisilicate the answer is ‘Yes’, but only in very large doses. They work by neutralizing acid, which in turn makes the mucosa more resistant to damage. A proton pump inhibitor is more practical. Answer 20 No, but there is little point in using both except for immediate symptom relief, e.g. with an alginate containing antacid in gastro-oesophageal reflux disease (GORD). Answer 21 Omeprazole is formulated as enteric-coated granules and is absorbed in the small intestine. Antacids therefore have no effect on its absorption. Answer 22 No. Answer 23 Yes, it increases the Q-Tc interval. Answer 24 42 1. Endoscopy is used in: Gastric ulcer: for diagnosis and to take biopsies to exclude malignancy; it is also used for follow-up of gastric ulcers. Duodenal ulcer: for diagnosis, although in young patients with Helicobacter pylori antibodies and typical history endoscopy is not necessary. 6 Gastrointestinal disease 2. Good double-contrast barium meals are comparable to endoscopy but as biopsies cannot be taken (e.g. for H. pylori and malignancy), their use is becoming less frequent. Answer 25 Telithromycin is a newly introduced macrolide and should be effective in H. pylori eradication regimens, 800 mg ⫻ 2 daily. However, you are always better to stick to the tried and tested – in this case the macrolide clarithromycin – until the evidence changes. Answer 26 The problem is metronidazole resistance, which runs at 50% at least and is probably higher in some areas. The other problem is the cost, as you say. It might be reasonable in your country to try omeprazole, metronidazole, amoxicillin and use clarithromycin instead of metronidazole for treatment failures. Tetracycline has been used in combination regimens it is also cheap and is a possible alternative to clarithromycin. Answer 27 Most duodenal ulcers and 80% of gastric ulcers are due to Helicobacter pylori infection. Eradication therapy of the organism is the same. It is usual to check that a gastric ulcer has healed (thereby excluding a malignant ulcer) by doing repeat gastroscopy; this is not necessary for duodenal ulcers. Answer 28 In vitro, omeprazole inhibits the growth of H. pylori below pH 7. Clinically, it is thought that omeprazole enhances the local immune response by increasing intragastric pH. It also reduces the washout of antibiotics from the mucosa and lowers the inhibitory concentrations of pH-sensitive antibiotics. Answer 29 Rebound increased acid secretion lasting about 2 months occurs after 40 mg a day of omeprazole for 2 days. Yes, rebound hyperacidity also occurs after withdrawing histamine H2-receptor antagonists. Answer 30 The LOS is tonically closed at rest. This resting tone is maintained by both myogenic properties and active tonic neural excitation. The reduction in tone and reduction of the LOS that occurs with swallowing is under the control of cholinergic and NANC neurones. As you say, NO acts on the NANC inhibitory neurones, which inhibit the excitatory cholinergic neurones, thus reducing acetylcholine release. 43 6 Gastrointestinal disease Answer 31 In achalasia there is a selective loss of the inhibitory neurones in the myenteric plexus. This leads to excitation of the smooth muscle at the LOS by mediators such as acetylcholine. Sildenafil increases NO production. It is the NO-containing neurones that are particularly affected in achalasia so that relaxation of the sphincter is impaired. Answer 32 In practice, outside the emergency room or postoperatively (looking for ileus), bowel sounds are not helpful. A succussion splash can indicate gastric obstruction but is seldom helpful in practice. Answer 33 Any patient who has bled from a peptic ulcer – and who is therefore presumably Helicobacter pylori (HP) positive – should have eradication therapy. Successful eradication of HP following a bleed must be checked with either an HP breath test or a stool test. After eradication, the same risks of aspirin therapy apply as to the normal population. Answer 34 There are no reliable ways of distinguishing lower from upper gastrointestinal bleeding by faecal analysis. Obviously bright red blood suggests lower GI bleeding – except when blood loss is huge, when blood loss from higher up can be bright red blood. Altered blood, e.g. a melaena stool, is from lesions proximal to the caecum. Answer 35 Approximately 50% of cases of GI bleeding are from peptic ulcer disease, and a PPI (e.g. omeprazole) reduces the rate of recurrent bleeding and the need for surgery. In many patients it is initially unclear where the bleeding is coming from, so PPIs tend to be given to everybody even though they have never been shown to be of value in, for example, variceal bleeding. Answer 36 The answer is that we have better serological screening tests, e.g. tissue transglutaminase and endomysial antibodies, which are now being used extensively. The general awareness of coeliac disease has also increased. Answer 37 44 Theoretically, yes! However, even a gluten-free diet has very tiny amounts of gluten and probably these small amounts are not overtly harmful in most patients. A few patients might be very sensitive. 6 Gastrointestinal disease Answer 38 This is anecdotal data and is probably incorrect; often the bleeding stops spontaneously. We have decided to remove this anecdotal piece of advice from future editions. Answer 39 Between 70 and 90% of patients with appendicitis have a raised white cell count ⬎15000. This has a sensitivity of 20–60%, with a specificity of 85–100% in children with appendicitis. Imaging (e.g. ultrasound and computed tomography) should now be used to make a diagnosis of appendicitis. Answer 40 You have been correctly taught. Ulcerative colitis (UC) only affects the large bowel, i.e. the colon and rectum, with a small number of patients having some inflammation of the very distal part of the ileum (called backwash ileitis). This distinguishes UC from Crohn’s disease, which affects anywhere from the mouth to the anus, most commonly the small and large bowel. Both diseases are, however, associated with ‘nonspecific’ mouth ulcers, which also occur in a number of gastrointestinal diseases (e.g. coeliac disease) and other conditions (e.g. Behçet’s disease). Answer 41 Metronidazole is the first choice, largely due to the cost of oral vancomycin. Answer 42 Crohn’s disease is not usually considered to be an autoimmune disease, although the immune system is very involved in the pathological process. We do not know the exact cause of Crohn’s disease but it is felt by most that some aetiological agent (perhaps a bacterium?) stimulates the immune system to over-respond in a genetically susceptible person. CARD 15 gene mutations contribute to disease susceptibility. Further reading Podolsky D (2002) Inflammatory bowel disease. New England Journal of Medicine 347: 417–429. Answer 43 Carcinoma of the caecum and ascending colon tend to bleed and cause anaemia but not obstruction because of the large size and ‘give’ in the right side of the colon. The reverse is true of the descending colon; a carcinoma is more likely to obstruct the smaller, more rigid left colon. Answer 44 Very often, the symptoms are not related and the colorectal cancer is found incidentally when a patient is investigated for pain or diarrhoea. 45 6 Gastrointestinal disease Right-sided colonic lesions do not usually produce gut symptoms. Lesions in the sigmoid do, probably by partial obstruction. Answer 45 No; it is bacteria. Answer 46 Multiple rectal ulcers are common in inflammatory bowel disease. They also occur in infective proctitis (e.g. due to amoebae) or in sexually transmitted infections (e.g. herpes viral infections). Rectal spread occurs in gonococcal infection and can produce ulcers. The answer is to take samples for cultures and biopsies for histological diagnosis. Answer 47 A lateral internal sphincterotomy is the best surgical procedure. This is the advice of the American Gastroenterological Association (AGA) in its Medical Position Statement 2002. Answer 48 You must first make sure that there are no ‘alarm’ symptoms (Box 6.1). Take a very careful history because most patients of this age with IBS will have a preceding history of IBS. Simple blood tests and a follow-up of the patient are also very helpful in the diagnosis. Answer 49 This is difficult to answer! We agree this is a very common symptom. It is not due to air/wind, which most patients think. Answer 50 Traub’s space is an area of resonance overlying the gas bubble in the left lateral hemithorax. Its size and localization depend on the contents and position of the stomach. Percuss with the patient on his or her right side. Answer 51 Small amounts of menaquinones (a form of vitamin K), which are synthesized by bacteria, are absorbed in the colon. Box 6.1 Alarm symptoms: indications for upper gastrointestinal endoscopy 46 Dysphagia Weight loss Protracted vomiting Anorexia Haematemesis or malaena 6 Gastrointestinal disease Answer 52 It is true that 55–60% of colonic tumours occur on the left side; this figure includes rectal cancers (20%). There is no convincing reason for this; suggestions include faecal stasis on the left side and mucosal deficiencies at a cellular level. Answer 53 Patients with weekly reflux symptoms are nearly eight times more likely to develop adenocarcinoma compared with those without symptoms. The greater the frequency, severity and duration of reflux symptoms, the greater the risk (Lagergren et al. 1999). The risk is unaffected by drug therapy as far as we know, but proton pump inhibitors (PPIs) are usually given. Reference Lagergren J et al. (1999) Symptomatic gastroesophageal reflux as a risk factor for esophageal adenocarcinoma. New England Journal of Medicine 340: 825–831. Answer 54 Not necessarily better as, of course, Crohn’s disease often recurs after surgery. It is, however, a useful treatment particularly if localized pain in the right iliac fossa (due to partial obstruction) is a prominent symptom. 47 7 Liver, biliary tract and pancreatic disease QUESTIONS Question 1 Please could you tell me the normal range of values for the liver function test serum alkaline phosphatase. The only mention of the parameters is that a reading of ⬎1000 ⫽ serious liver condition. Question 2 What is the best single test of liver function to exclude liver cell failure in the routine work-up of a patient with early dementia? Question 3 How valuable is the measurement of the liver span in a physical examination? Question 4 Why has the term ‘chronic liver disease’ replaced terms such as ‘chronic hepatitis’? What exactly does this new term mean and what conditions does it cover? Question 5 Can jaundice occur early in schistosomal hepatic fibrosis and, if so, how? Question 6 My patient has been found to have a serum bilirubin of 34 μmol/L (2 mg/dL) on three occasions. The other liver tests are normal. He tells me he has Gilbert’s disease; how can I prove this? Question 7 48 Why is urinary urobilinogen increased in haemolytic jaundice? If the bilirubin in this condition is unconjugated, how does it reach the terminal ileum to be converted into urobilinogen? 7 Liver, biliary tract and pancreatic disease Question 8 How does cholestatic jaundice affect the kidney? Question 9 What is the mechanism by which cholestatic jaundice causes bradycardia? Question 10 Are ‘jaundice’ and ‘icterus’ one and the same? I was taught that icterus is yellowing of the sclera, while jaundice is yellowing of the skin and the mucous membranes. As a result, carotenaemia can produce jaundice but not icterus: is this so? I would be grateful if you would clarify this for me. Question 11 I am a third-year student nurse and am currently researching a case study based on the biopsychosocial history of a patient who suffers from chronic hepatitis C, which initially occurred as a result of injecting drugs. I am confused about the biological effect of hepatitis: how exactly does it affect the liver? Question 12 What are the admission criteria for a case of acute viral hepatitis? Question 13 I would like to know where I can find details on hepatitis B virus (HBV) infection: chronic carrier, asymptomatic [normal liver function tests, HBV DNA/real-time polymerase chain reaction (PCR) ⫽ 240 copies/mL, core less than 0.1]. Does a patient with such a profile need therapy or fine needle aspiration (FNA) biopsy? What is the possibility of hepatocellular carcinoma (HCC) in such a patient? Question 14 In chronic hepatitis B virus (HBV) infection, when anti-hepatitis B e antibody (anti-HBe) develops (seroconversion), the antigen disappears and there is a rise in alanine transferase (ALT). However, the graph in your book (K&C 7e, p. 337, Fig. 7.16) seems to show a fall in ALT at this point. Which is correct? Question 15 Interferon can be used in prophylaxis from hepatitis C after exposure. Could you explain how this can be used, and what degree of success can be expected as a result? Question 16 What is the latest recommended drug treatment for hepatitis C? 49 7 Liver, biliary tract and pancreatic disease Question 17 Can hepatitis C disease be treated in a carrier state completely by giving interferon? Question 18 I am a carrier of hepatitis C (HCV) and am going to have antiviral treatment soon. Are the side-effects of antiviral treatment for HCV bound to occur? I am very worried. Question 19 Besides needle-pricks, how else is it possible to contract hepatitis C from a hepatitis C (HCV)-positive patient? Are the patient’s skin/sweat (or other bodily secretions) infectious? Question 20 What is the risk of infection with hepatitis C from blood splashed into the eyes? Question 21 Hepatitis C (HCV): if results from the polymerase chain reaction (PCR) examination are inconclusive, what does this mean? Should further investigations be undertaken and, if so, will there be a risk of chronicity? Question 22 In a patient with hepatitis C and autoimmune hepatitis, can corticosteroids be prescribed for the autoimmune hepatitis? Question 23 We were told that the more vascular a structure is, the more antigen (HLA/blood groups) matching is needed for transplantation, e.g. cornea transplant needs no matching. However, the liver is a very vascular organ; I don’t know why liver transplantation needs blood group matching only but renal transplantation needs much more HLA matching. Question 24 About steatohepatitis: please give me more information about the occurrence of cirrhosis in such patients (non-alcoholic) and is there any role and indication for lipotropic agents and hypocholesterolaemic drugs? Question 25 50 I am working on non-alcoholic fatty liver disease (NAFLD) but I did not find anything regarding it. Can you tell me about its relationship with lipids? 7 Liver, biliary tract and pancreatic disease Question 26 Is NASH a valid term or not and what manifestation has it? Question 27 Is terlipressin better in controlling variceal bleeding than somatostatin? Question 28 Why is there a hyperdynamic circulation in cirrhosis? Question 29 Why is there an increased level of immunoglobulin G (IgG) in patients with cirrhosis? Question 30 Cirrhosis of liver is reversible according to your book. What is the progress and when will we be able to counteract the ‘tissue inhibitors of metalloproteinases’ (TIMPs) and thus save the lives of our patients? Question 31 What are the criteria for knowing the prognosis of cirrhosis (Child’s criteria)? Question 32 What is the recommended treatment for cirrhosis of the liver? Question 33 Is there any role for liver dialysis in hepatic encephalopathy? Question 34 I have been asked to write an essay on ‘caring’ for a client who has been an alcohol abuser for more than 10 years and is in the ‘recovery’ stage. I am aware there are many different factors, such as length of abuse, amount consumed, age, gender etc.... My question is: how long will it take the liver to ‘recover’ or to return to normal after stopping drinking? I am especially interested in blood tests, fatty deposits and gammaglutamyl transpeptidases (γ-GTs). Question 35 Can patients with liver cell failure suffer from myocardial infarction? Question 36 What is the definition of liver cell failure (decompensated liver disease)? 51 7 Liver, biliary tract and pancreatic disease Question 37 Flapping tremors: why do we get flapping tremors and no other types of tremor in liver failure? What is their mechanism and in which other conditions do they occur? Question 38 In a patient with liver cell failure, can there be resting and action tremors or parkinsonian features if it is confirmed that the patient does not have Wilson’s disease? Question 39 Does the absence of any cirrhosis of the liver, together with normal liver enzymes, in a 9-year-old boy complaining of chorea of a 5-year duration, exclude Wilson’s disease? Question 40 Can Wilson’s disease be excluded in a patient complaining of movement disorder for over 2 years, when there is an absence of cirrhotic liver change? Question 41 What drugs cause Budd–Chiari syndrome? Question 42 I recently saw a patient with pyrexia of unknown origin (PUO). He was not particularly unwell and not jaundiced. But 1 week later he was found to have a liver abscess on ultrasound. How can one make the diagnosis earlier? Question 43 What is the most recent management of HCC (hepatocellular carcinoma)? What is radiofrequency ablation? What is its role in the management of HCC and its prognosis? Question 44 How do you differentiate haemorrhagic ascitic fluid due to malignancy and accidental rupture of blood vessel while withdrawing the fluid? Question 45 Is there any place for the medical treatment of gallstones with ursodeoxycholic acid? Question 46 52 In a case of common bile duct stones, where it is acknowledged that spontaneous passage within 24 hours is observed in approximately 50% of patients provided the stone is small, and that in these cases there is no need for a sphincterotomy, is the use of antispasmodics, e.g. Buscopan (active ingredient hyoscine-N-butylbromide), recommended? Surely 7 Liver, biliary tract and pancreatic disease these will reduce the pain and improve the chance of a spontaneous release of obstruction without surgical procedure? Question 47 What is sphincter of Oddi dysfunction? Question 48 I would like to know: what is the role of lysosomal hydrolases (cathepsin B) in the pathogenesis of acute pancreatitis? Question 49 What is the role of octreotide in management of acute pancreatitis? Question 50 Why does paralytic ileus occur in pancreatitis? Question 51 How sensitive is the increase in serum lipase levels in the case of acute pancreatitis? Question 52 What is the association between chronic pancreatitis and peripheral vascular disease (PVD)? Question 53 Please, can you explain to us the mechanism of pancreatitis in hypertriglyceridaemias? Question 54 Is there any role for chemotherapy in carcinoma of the pancreas? Question 55 1. How should portal hypertension be managed in patients with bronchial asthma, where beta-blockers are contraindicated? 2. How should diuretics for these patients with hypertension be added? Question 56 Is cirrhosis a prerequisite for the development of hepatocellular carcinoma (HCC) in hepatitis B (HBV)? Question 57 Should therapy with interferons in the treatment of hepatitis C (HCV) and hepatitis B (HBV) commence when the polymerase chain reaction (PCR) is positive, irrespective of serum glutamyl pyruvate transaminase (SGPT) levels? 53 7 Liver, biliary tract and pancreatic disease Question 58 What is the degree of sensitivity of the CA19-9 as a marker of cancer in the head of the pancreas? Question 59 What are the benefits and drawbacks of silymarin in the treatment of liver cell failure? (This treatment is widely used in my country.) Question 60 If using zinc in the treatment of Wilson’s disease, should the salt used to treat the disease be zinc acetate, or is any zinc-containing salt such as zinc sulphate sufficient? Question 61 Is alkaline phosphatase of value in the differential diagnosis of jaundice? If so, in what type is this raised? 54 7 Liver, biliary tract and pancreatic disease ANSWERS Answer 1 The normal serum alkaline phosphatase is 40–100 IU/L. Levels of 400⫹ are common in cholestatic liver disease. Levels of 1000 and over are seen in primary biliary cirrhosis and liver metastases. (Note: remember alkaline phosphatase is also found in bone so that bone disease, e.g. Paget’s, is also associated with a raised serum alkaline phosphatase.) Answer 2 Liver function is assessed with the serum albumin as the well as the prothrombin time. The other routine liver tests, e.g. transferases and alkaline phosphatase reflect liver damage not function. You can therefore measure either the prothrombin time or the albumin. Answer 3 Quite useful but less valuable since the widespread use of ultrasound scans. Answer 4 Chronic liver disease is a general term for all types of liver disease that are chronic (by definition greater than 6 months’ duration). It has not replaced terms such as chronic hepatitis, which is used for a hepatitis that is chronic. Answer 5 No. Hepatocellular function remains good. Answer 6 In Gilbert’s, hepatic glucuronidation of bilirubin is 30% of normal so that there is excess of unconjugated bilirubin. To prove the diagnosis you should measure the total and unconjugated bilirubin in the serum, the unconjugated will be high. A normal reticulocyte count will exclude haemolysis and you have the diagnosis. Genetic studies are not necessary. Answer 7 This is because increased unconjugated bilirubin also leads to some increase in conjugated bilirubin, which can then be secreted into the gut and converted to urobilinogen. Answer 8 Cholestatic jaundice does produce tubular necrosis, albeit rarely. This can occur following surgery. It can be prevented by intravenous infusion of mannitol. 55 7 Liver, biliary tract and pancreatic disease Answer 9 It used to be said that this was due to the effect of the high level of bile salts on the sinoatrial node. However, recent evidence suggests that bradycardia in adults is rare in cholestatic jaundice. Answer 10 ‘Jaundice’ and ‘icterus’ are the same. In the main, people use the word ‘jaundice’ most of the time. ‘Anicteric’ is sometimes used to describe a person who is not jaundiced. Answer 11 Hepatitis means inflammation of the liver. It can occur from many causes but in your patient the hepatitis C virus seems to have been the cause of the inflammation. 60–80% of patients who develop hepatitis C go on to chronic liver disease; 20–30% of these will develop cirrhosis of the liver over a period of 20–30 years. The damage to the liver in the chronic situation is due to the immunological response to the hepatitis C virus. Answer 12 Most patients with acute viral hepatitis do not need to be admitted to hospital. Patients who appear to be developing hepatic failure do need admission. Clinical features are then of a severely jaundiced patient with some degree of drowsiness. Answer 13 The patient described is sometimes referred to as a ‘healthy carrier’. These patients seem tolerant of the virus and the prognosis is very good. Liver histology in such patients shows no significant damage and biopsies or therapy are not recommended. 90% of patients who are HBV carriers who develop HCC have cirrhosis, which is rare in a healthy carrier as described above. Further reading Lok AS, Heathcote EJ, Hoofnagle JH (2001) Management of hepatitis B. Gastroenterology 120: 1828–1853. Online. Available: http://www.hepb.org/ Answer 14 When seroconversion occurs there may be a ‘flare’, i.e. a short rise in ALT, but then the ALT falls usually to normal. This is reflected in the graph. Answer 15 56 Monotherapy with 5 M units daily for 4 weeks then 5 M units three times a week for 20 weeks of alpha-interferon was used in one trial with a high 7 Liver, biliary tract and pancreatic disease success rate, (i.e. no RNA detected). Pegylated interferon is now used instead because of its better side effect profile. Answer 16 Pegylated interferon combined with ribavirin. The dosage and length of treatment depends on the genotype. Further reading Hoofnagle JH, Seoff LB (2006) Peg interferon and ribavirin for chronic hepatitis C. New England Journal of Medicine 355: 2444–2451. Answer 17 There is strictly no carrier state for hepatitis C because there is always some degree of liver damage in patients who have persistence of the virus. At the present time, the treatment of hepatitis C is pegylated interferon and ribavirin. Treatment should be given to those patients with chronic hepatitis on liver histology, HCV RNA in their serum and who have had raised serum aminotransferases for more than 6 months. Patients who have persistently normal aminotransferases and abnormal histology can also be treated with the same combination. Answer 18 Some side-effects are almost universal with interferon, although pegylated interferon produces fewer side-effects. You must discuss the treatment with your specialist. Answer 19 Only blood spread is implicated in HCV hepatitis. Sexual spread is rare. Answer 20 It is rare. There is only one reported case. Answer 21 PCR testing for HCV RNA is very variable, depending on the laboratory used and on the technique. In addition, the HCV RNA may only be present in small amounts and viraemia may be intermittent. Repeat tests at 6 months. Answer 22 Yes, under careful supervision. Treatment of the hepatitis C should also be undertaken if treatment criteria are met. Answer 23 The liver is a vascular organ that often behaves as a ‘privileged tissue’ in that little immune reaction occurs. The liver appears to induce a state of 57 7 Liver, biliary tract and pancreatic disease suppression by the secretion of large amounts of donor-soluble major histocompatibility (MHC) class 1 antigen with the migration of large numbers of donor dendritic cells from the donor liver into the host. This was first shown by Sir Roy Calne in pigs. Answer 24 Non-alcoholic steatohepatitis (NASH) is now thought to be a subgroup of patients with non-alcoholic fatty liver disease (NAFLD). With NASH, not only is there fat in the liver but there is inflammation on liver histology obtained at biopsy. Cirrhosis does occur in patients with NASH, so that liver biopsies are probably indicated in patients with NAFLD and raised transferases (over 100 IU). Weight reduction, drugs to lower cholesterol and triglycerides are used but there is no good evidence of their efficacy. Further reading Maher J (2001) Antidiabetic treatment for NASH. Hepatology 33: 1338–1339. Teli MR, James OF, Burt AD et al. (1995) The natural history of nonalcoholic fatty liver: a follow-up study. Hepatology 22: 1714–1719. Answer 25 It has been recognized for many years that a fatty liver is sometimes found in patients who do not drink alcohol. The term ‘non-alcoholic steatohepatitis’ (NASH) was introduced in the 1990s. Subsequently, it has been recognized that some patients have a fatty liver on biopsy with no accompanying inflammation; this group is called non-alcoholic fatty liver disease (NAFLD). It seems that only patients with evidence of NASH on biopsy progress to chronic liver disease with fibrosis and cirrhosis. Some of these patients do have high lipid levels (both cholesterol and triglycerides) but this is by no means invariable. NAFLD is associated with the metabolic syndrome (Box 7.1). Box 7.1 Metabolic syndrome (NCEP APT III*) Three or more of the following: High blood pressure (⬎130/85 mmHg) Elevated serum triglycerides (⬎150 mg/dL or 1.695 mmol/L) Decreased HDL cholesterol (⬍40 mg/dL or ⬍0.9 mmol/L in men and ⬍50 mg/dL or ⬍1 mmol/L in women Increased abdominal circumference [⬎102 cm (40 inches) men or ⬎88 cm (35 inches) women] Impaired fasting glucose (⬎110 mg/dL or ⬎6.1 mmol/L) 58 * National Cholesterol Education Programme Adult Treatment Panel III 7 Liver, biliary tract and pancreatic disease Further reading Malnick SD et al (2003) Nonalcoholic fatty liver disease. Quarterly Journal of Medicine 96: 699–709. National Cholesterol Education Adult Treatment Programme III (2001) Journal of the American Medical Association 285: 2486–2497. Answer 26 NASH, non-alcoholic steatohepatitis, was introduced a few years ago for patients with fatty liver not due to alcohol. The meaning has now been changed slightly in that the term ‘NASH’ is used only for a small group of patients with non-alcoholic fatty liver disease (NAFLD) who have inflammation as well as fat on liver histology. Further reading Malnick SD et al (2003) Nonalcoholic fatty liver disease. Quarterly Journal of Medicine 96: 699–709. Answer 27 Terlipressin has been shown to reduce mortality but has more side-effects than somatostatin. Answer 28 The hyperdynamic circulation that occurs is partly due to the opening of portosystemic collaterals. In addition, there are increased levels of circulatory vasodilators, e.g. glucagon and vasoactive intestinal polypeptide (VIP). There is also an increased production of nitric oxide, which is a potent vasodilator. Answer 29 Antigen absorbed from the gut bypasses the liver in cirrhosis and also there is decreased function of the Kupffer cells in cirrhosis. Both of these allow antigen to stimulate the reticuloendothelial system in the spleen and lymph nodes to produce immunoglobulins. Answer 30 There is some evidence that fibrosis following liver damage is reversible. There are no drugs currently available to act on TIMPS. Further reading Benyon RC, Iredale JP (2000) Is liver fibrosis reversible? Gut 46: 443–446. Answer 31 Nowadays the model for end-stage liver disease (MELD) is used as a predictor for liver transplantation in decompensated as well as compensated liver disease. It is based on serum creatinine, serum total protein and the international normalized ratio. The Child criteria are given in Table 7.1. 59 7 Liver, biliary tract and pancreatic disease Table 7.1 The Child criteria for end-stage liver disease Child’s grade Serum bilirubin (mg/dL) Serum albumin (g/L) Ascites Encephalopathy 1-year survival A B C ⬍2 35 None None 85% 2–3 33 Easily manageable None 30% ⬎3 ⬍30 Poorly controlled Coma Approximately 5% Answer 32 There is no treatment for cirrhosis per se. Antifibrotic drugs might be used in the future. At the present time: 1. Treat the cause, e.g. stop alcohol, remove iron in hereditary haemochromatosis. 2. Treat the complications: portal hypertension and bleeding ascites portosystemic encephalopathy. 3. Refer for liver transplantation Answer 33 There is no role for liver dialysis in hepatic encephalopathy. We do not know the toxic products that cause encephalopathy but they are too small to be removed by dialysis. Answer 34 It is difficult to answer these questions because it depends on how abnormal the tests are when the patient stops drinking. Small elevations in liver enzymes, e.g. alanine transferase (ALT) 80 units, will take weeks, whereas an ALT of 200 units will take months. Indeed, the liver might be permanently damaged. The γ-GT rises in response to alcohol ingestion as well as liver disease. Moderate fat in the liver disappears within 3–4 months. Answer 35 Yes. Many patients with alcoholic liver disease also smoke, which is a risk factor for coronary artery disease. Answer 36 60 Decompensated liver disease is the term used to describe a patient with chronic liver disease (cirrhosis) who develops complications, e.g. bleeding, ascites or encephalopathy. In such a patient, the serum albumin is usually low and the patient might be jaundiced. The term ‘liver cell failure’ is sometimes used to describe acute hepatocellular failure or fulminant hepatic failure. 7 Liver, biliary tract and pancreatic disease Answer 37 Flapping tremors occur in hepatic encephalopathy and in chronic obstructive pulmonary disease with carbon dioxide retention. The mechanisms are unclear but ammonia seems to be involved in the tremor seen in hepatic encephalopathy. Answer 38 Yes; patients with hepatic encephalopathy can have basal ganglia signs without having Wilson’s disease. Answer 39 In this age group, it is usual for the liver disease to present first. The liver disease is variable, from mild hepatitis to acute fulminant hepatitis and also cirrhosis. If there is any doubt, Wilson’s disease should be further excluded by examination of the child and investigation of copper levels in the blood (low) or in the liver (high). Answer 40 No; the liver disease is variable. Wilson’s disease should be excluded by appropriate investigations of copper metabolism. Answer 41 Oral contraceptives have been implicated as a cause of Budd–Chiari syndrome but, in general, drugs are not a cause of the pathology of this condition. Answer 42 A liver abscess can present as a very indolent condition and it can take a long time to diagnose. The best clues are a slightly raised alkaline phosphatase and a raised serum vitamin B12. You must have a high degree of suspicion. Answer 43 Hepatocellular carcinoma can be treated with surgical treatments: Resection Cryo-ablation Liver transplantation. Non-surgical therapies are: Chemotherapy Radiation Chemoembolization Percutaneous ethanol injection Radiofrequency ablation. Radiofrequency ablation involves passing a high-frequency alternating current to th