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(BQ) Part 1 book “Davidson''s self-assessment in medicine” has contents: Clinical decision-making, clinical therapeutics and good prescribing, clinical genetics, clinical immunology, population health and epidemiology, principles of infectious disease,… and other contents.
e Davidson's Self-assessment in Medicine Edited by Deborah Wake MB ChB (Hans), BSc, PhD, Diploma Clin Ed, MRCPE Clinical Reader, University of Edinburgh; Honorary Consultant Physician, NHS Lothian, Edinburgh, UK Patricia Cantley MB ChB, FRCP, BSc Hans (Med Sci) CD Consultant Physician, Midlothian Enhanced Rapid Response and Intervention Team, Midlothian Health and Social Care Partnership and also Royal Infirmary of Edinburgh and Midlothian Community Hospital, Edinburgh, UK ::s CD ELSEVIER Edinburgh London New York Oxford St Louis Sydney 2018 Philadelphia II ELSEVIER © 2018, Elsevier Limited All rights reserved No part of this publication may be reproduced or transmitted in any form or by any means, electronic or mechanical, including photocopying, recording, or any information storage and retrieval system, without permission in writing from the publisher Details on how to seek permission, further information about the Publisher's permissions policies and our arrangements with organizations such as the Copyright Clearance Center and the Copyright Licensing Agency, can be found at our website: www.elsevier.com/ permissions This book and the individual contributions contained in it are protected under copyright by the Publisher (other than as may be noted herein) Notices Practitioners and researchers must always rely on their own experience and knowledge in evaluating and using any information, methods, compounds or experiments described herein Because of rapid advances in the medical sciences, in particular, independent verification of diagnoses and drug dosages should be made To the fullest extent of the law, no responsibility is assumed by Elsevier, authors, editors or contributors for any injury and/or damage to persons or property as a matter of products liability, negligence or otherwise, or from any use or operation of any methods, products, instructions, or ideas contained in the material herein ISBN: 978-0-7020-7151-5 International ISBN: 978-0-7020-7145-4 !J~ Book Aid International Working together to grow libraries in developing countries www.elsevter.com • www.bookaid.org Printed in Poland Last digit is the print number: Executive Content Strategist: Laurence Hunter Development Specialist: Carole McMurray Project Manager: Louisa Talbott Design: Miles Hitchen Illustration Manager: Nichole Beard Illustrator: MPS North America LLC Marketing Manager: Deborah Watkins Cont~nt I Contents Preface Introduction Contributors Abbreviations vii ix xi XV Clinical decision-making Clinical therapeutics and good prescribing Clinical genetics 14 Clinical immunology 22 Population health and epidemiology 28 Principles of infectious disease 32 Poisoning 37 Envenomation 46 Environmental medicine 51 10 Acute medicine and critical illness 54 11 Infectious disease 73 12 HIV infection and AIDS 96 13 Sexually transmitted infections 103 14 Clinical biochemistry and metabolic medicine 107 15 Nephrology and urology 115 16 Cardiology 132 17 Respiratory medicine 154 18 Endocrinology 185 19 Nutritional factors in disease 203 20 Diabetes mellit.us 212 21 Gastroenterology 225 / Preface This is the first edition of Davidson's Self-assessment in Medicine, designed as an accompanying volume to the internationally renowned textbook Davidson's Principles and Practice of Medicine Since the original Davidson's was first published in 1952, it has acquired a large following of medical students, doctors and health professionals Alongside the success of the main textbook, a demand has emerged for a complementary self-assessment book covering a broad range of general medicine topics Our new book uses typical clinical scenarios to test the reader Each chapter is written by a specialty expert and the contents follow the style and chapter layout of Davidson's This book can be used either independently or in conjunction with the main book This book has been built around modern educational principles and utilises a contemporary assessment style, in line with current undergraduate and postgraduate teaching It is designed to help and support students in their final undergraduate years and in the early years after qualification The style is compatible with that used in modern postgraduate examinations across the world The clinical scenarios have been chosen to be suitable for clinicians at any stage in their career, supporting ongoing professional development Clinical reasoning and judgement are encouraged, with questions mirroring the situations and presentations that clinicians will meet in their everyday practice The content is applicable to a global audience and is based on current evidence-based best practice The modern physician needs not only a sound knowledge base but also the ability to apply that understanding appropriately to individual patients The vision of the editors is to create a resource that stimulates readers to build and apply their clinical knowledge to real-life scenarios, resulting in excellent patient -centred care Deborah Wake and Patricia Cantley Edinburgh, 2018 Introduction This book offers a broad education through formative self-assessment in general internal medicine The majority of the questions have been designed around clinical scenarios, with a number of optional answers offered to the question posed In general, the 'best fit' answer is sought unless otherwise stated Full explanations are given as appropriate to assist the reader in their learning The questions aim to cover a wide range of topics, divided into specialist chapters in line with Davidson's Principles and Practice of Medicine The questions have in general been based on UK clinical practice and pharmacology, but where appropriate generic drug names are used and the underlying principles are applicable internationally Whilst the answers given are in line with best evidencebased clinical practice, patient choice and cultural factors should always be considered when applying the learning in individual patients and situations How to use this book This self-assessment book can be used either independently or in conjunction with Davidson's.! Readers may find it useful to read the relevant section of the main textbook in advance of tacklin~ the self-assessment; or they can use it subsequently to explore the topic in greater detail The questions, followed by their corresponding answers, have been arranged in the same chapter order as Davidson's The chapters are free-standing and can be read independently in any order Some of the questions are based on accompanying clinical images and radiology Where it is appropriate to see the image in colour, it has also been reproduced in a colour photographic SE;ction at the back of the book Normal Reference Ranges for tests have not been used within the questions or explanations, but can be found in the laboratory reference range chapter, at the end of the book Standard abbreviations are found within the text and are generally explained at first use A full list of abbreviations can be found at the front of the book r i Contributors Anna Anderson MBChB, MRCP, PhD Specialist Registrar Diabetes and Endocrinology, Western General Hospital, Edinburgh, UK Brian J Angus BSc (Hons), DTM&H, FRCP, MD, FFTM(Gias) Associate Professor, Nuffield Department of Medicine, University of Oxford, UK Quentin M Anstee BSc (Hons), MBBS, PhD, MRCP, FRCP Professor of Experimental Hepatology, Institute of Cellular Medicine, Newcastle University, Newcastle upon Tyne, UK; Honorary Consultant Hepatologist, Freeman Hospital, Newcastle upon Tyne NHS Hospitals Foundation Trust, Newcastle upon Tyne, UK Jennifer Bain MBChB, MRCP, FRCA, FFICM Fellow in Vascular Anaesthesia, Scottish Thoraco-abdorninal & Aortic Aneurysm Service, Royal Infirmary of Edinburgh, Edinburgh, UK Leslie Burnett MBBS, PhD, FRCPA Chief Medical Officer, Genome.One, Garvan Institute of Medical Research, Darlinghurst, Sydney; Honorary Professor, University of Sydney, Sydney Medical School, Sydney; Conjoint Professor, UNSW, St Vincent's Medical School, Darlinghurst, Sydney, Australia Mark Byers OBE, FRCGP, FFSEM, FIMC, MRCEM Consultant in Pre-Hospital Emergeney Medicine, Institute of Pre-Hospital Care, London, UK Harry Campbell MD, FRCPE, FFPH, FRSE Professor of Genetic Epidemiology and Public Health, Centre for Global Health Research, Usher Institute of Population Health Sciences and Informatics, University of Edinburgh, Edinburgh, UK C Fiona Clegg BSc (MedSci), MBChB, MRCP (UK) Clinical Lecturer in Gastroenterology, School of Medicine, Medical Sciences and Nutrition, University of Aberdeen, Aberdeen, UK Gavin Clunie BSc, MBBS, MD, FRCP Consultant Rheumatologist and Metabolic Bone I Physician, Cambridge University Hospitals NHS Foundation Trust, Addenbrooke's Hospital, Cambridge, UK Lesley A Colvin MBChB, BSc, FRCA, PhD, FRCP (Edin), FFPMRCA ConsultanVHonorary Professor in Anaesthesia and Pain Medicine, Department of Anaesthesia, Critical Care and Pain Medicine, University of Edinburgh, Western General Hospital, Edinburgh, UK Bryan Conway MB, MRCP, PhD Senior Lecturer, Centre for Cardiovascular Science, University of Edinburgh; Honorary Consultant Nephrologist, Royal Infirmary Edinburgh, Edinburgh, UK Nicola Cooper MBChB, FAcadMEd, FRCPE, FRACP Consultant Physician, Derby Teaching Hospitals NHS Foundation Trust; Honorary Clinical Associate Professor, Nottingham University, Division of Medical Sciences and Graduate Entry Medicine, Nottingham, UK -, Ii xii • CONTRIBUTORS i Dominic J Culligan BSc, MBBS, MD, FRCP, FRCPath Consultant Haematologist and Honorary Senior Lecturer, Aberdeen Royal Infirmary, Aberdeen, UK Sally H Ibbotson BSc (Hons), MBChB (Hons), MD, FRCP (Edin) Professor of Photodermatology, Photobiology Unit, Dermatology Department, University of Dundee, Dundee, UK Ruth Darbyshire MB BChir, MA(Cantab) Specialty Trainee in Ophthalmology, Yorkshire and Humber Deanery, Yorkshire, UK Sara J Jenks Bsc (Hons), MRCP, FRCPath Consultant in Metabolic Medicine, Department of Clinical Biochemistry, Royal Infirmary of Edinburgh, UK Graham Dark MBBS, FRCP, FHEA Senior Lecturer in Medical Oncology and Cancer Education, Newcastle University, Newcastle upon Tyne, UK Richard J Davenport DM, FRCP (Edin), BM BS, BMedSci Consultant Neurologist and Honorary Senior Lecturer, University of Edinburgh, Edinburgh, UK David Dockrell MD, FRCPI, FRCP (Gias), FACP Professor of Infection Medicine, MAC/University of Edinburgh Centre for Inflammation Research, University of Edinburgh, Edinburgh, UK Emad EI-Omar BSc (Hons), MBChB, MD (Hons), FRCP (Edin), FRSE Professor of Medicine, St George and Sutherland Clinical School, University of New South Wales, Sydney, Australia Sarah Fadden BA, MB BChir, FRCA Senior Registrar in Anaesthesia, Royal Infirmary of Edinburgh, Edinburgh, UK Catriona M Farrell MBChB, MRCP (UK) Specialist Registrar Endocrinology and Diabetes, Ninewells Hospital, Dundee, UK Amy Frost MA (Cantab), MBBS, MRCP Clinical Genomics Educator, Affiliated to St George's University NHS Foundation Trust, London, UK Neil Grubb MD, FRCP Cardiology Consultant, Royal Infirmary of Edinburgh; Honorary Senior Lecturer, Cardiovascular Sciences, University of Edinburgh, Edinburgh, UK Jyoti Hansi Department of Gastroenterology, Royal Infirmary of Edinburgh, Edinburgh, UK Sarah Louise Johnston MB ChB, FCRP, FRCPath Consultant in Immunology & HIV Medicine, Department of Immunology and Immunogenetics, North Bristol NHS Trust, Bristol, UK David E J Jones MA, BM BCh, PhD, FRCP Professor of Uver Immunology, Institute of Cellular Medicine, Newcastle University; Consultant Hepatologist, Freeman Hospital, Newcastle upon Tyne, UK Peter Langhorne MBChB, PhD, FRCP (Gias), Hon FRCPI Professor of Stroke Care, Institute of Cardiovascular and Medical Sciences, University of Glasgow, Glasgow, UK Stephen Lawrie MD (Hons), FRCPsych, Hon FRCP (Edin) Professor of Psychiatry, University of Edinburgh, Edinburgh, UK John Paul Leach MD, FRCP Consultant Neurologist, Institute of Neurological Sciences, Glasgow; Head of Undergraduate Medicine, University of Glasgow, Glasgow, UK Andrew Leitch MBChB, BSc (Hons), PhD, MSc (Ciin Ed), FRCPE (Respiratory) Consultant Respiratory Physician, Western General Hospital; Honorary Senior Lecturer, University of Edinburgh, Edinburgh, UK Gary Maartens MBChB, FCP(SA), MMed Professor of Medicine, University of Cape Town, Cape Town, South Africa Lucy Mackillop BM BCh, MA (Oxon), FRCP Consultant Obstetric Physician, Oxford University Hospitals NHS Found01tion Trust; Honorary Senior Clinical Lecturer, Nuffield Departmentof Obstetrics and Gynaecology, University of Oxford, Oxford, UK l T 00 • HIV INFECTION AND AIDS Acute HIV syndrome Wide dissemination of virus Seeding of lymphoid organs Opportunistic diseases Prima~ I ;nrefFlrl _ Clinical Constitutional la_t Je, n_cY_ _ _s_y_m.,ptoms 'f 1200 I · E 1100 < ]11 000 10 ~ ~ 900 )> +-' () c 800 ::J 10s.g u 700 gf Q) 600 -o > u 500 104 !!l c 400 Q_ r E 300 -o _;::, 1o3 PI 1- 200 + Ill '_5120 Antitreponemal immunoglobulin M Negative (lgM) EIA Which of the following is most compatible with these results? A B C D E Early latent syphilis Partially treated late syphilis Primary syphilis Secondary syphilis Untreated late syphilis 13.9 A 19 year old woman complains of moderate lower abdominal pain that has been present for weeks, and is particularly noticeable during sex Which of the following actively supports a diagnosis-of chlamydial salpingitis? A dipstick urine test showing haematuria +++ A positive pregnancy test A temperature of 36.3"C Diarrhoea E Right upper quadrant tenderness A B C D 13.10 A 22 year old MSM presents for an STI screen His only complaint is of pain on defecation Examination reveals an anal fissure Serological tests for syphilis are as follows: Test Antitreponemal lgG EIA APR TPPA Antitreponemal lgM EIA Result Negative Negative Positive - titre 160 Positive - optical density 3.4 Which of the following is the most likely explanation of the serology? A Early latent syphilis B False-positive syphilis serology C Primary syphilis D Secondary syphilis E Treated syphilis 13.11 A 38 year old married man tells you that he had unprotected sex exactly week ago with a woman who he thinks may be an intravenous drug user (IOU) Which of the following statements is true? A He can safely have sex with his wife B C D E if all tests for STis taken today are negative He can safely have sex with his wife if/ given treatment with a single dose of ; azithromycin g ,,· He is at significant risk of acquiring h,~patitis C (HCV) ' He should be offered post-exposur~ prophylaxis (PEP) against HIV / He should be offered vaccination against hepatitis B (HBV) 13.12 A symptomless 29 year old MSM presents for an STI screen Serological tests for syphilis are as follows: Test Antitreponemal lgG EIA APR TPPA Antitreponemal lgM EIA Result Positive - optical density 33 Negative Positive - titre > 5120 Positive - optical density 11.4 Which of the foii9I!Ving is the most likely explanation of the serology? A Early latent syphilis B False-positive syphilis serology C Fully treated late latent syphilis D Partially treated late latent syphilis E Untreated late latent syphilis SEXUALLY TRANSMITTED INFECTIONS • I 05 13.13 The following infections are not thought of as being STis, but which is the only one that cannot be sexually transmitted? A B G D Cytomegalovirus (CMV) Hepatitis A (HAV) Plasmodium vivax Shigella sonnei E Zika virus the last year Which of the following statements is most appropriate? A As her partner has been symptom-free for a B G 13.14 A 27 year old woman is 24 weeks pregnant She mentions to you that her current male partner has a previous history of genital herpes caused by herpes simplex virus type I (HSV-1) Although he has had few recurrences in the past, he has had no symptoms at all in D E year, she can be reassured that there is no risk of transmission to her Primary genital herpes is more likely to lead to disseminated infection if it is caused by HSV-2 She should avoid unprotected sex for the duration of the pregnancy She should be commenced on valaciclovir 500 mg once daily to prevent transmission Her baby should be delivered by caesarean section Answers 13.1 Answer: E Chlamydia can cause a cervicitis, and the resulting friability may present as unexpected bleeding, especially after sexual intercourse Urethritis resulting in dysuria is less common, but may be mistaken for eubacterial cystitis Deep dyspareunia and lower abdominal pain are symptoms of ascending infection (salpingitis/pelvic inflammatory disease), which occurs less frequently than was believed previously Increased vaginal discharge is possible, but in most cases is probably due to an unrelated condition like bacterial vaginosis or candidiasis 13.2 Answer: B Early studies using aciclovir to suppress recurrences found that 200 mg four times daily was more effective than 400 mg twice daily, but the difference is small enough to recommend the less frequent dosing regime, which is going to make adherence easier Valaciclovir and famciclovir are more expensive and so reserved for cases where aciclovir is ineffective The recommended dose of valaciclovir is 500 mg once daily as per option E, but the correct starting dose of famciclovir is 250 mg twice daily 13.3 Answer: D Lymphogranuloma venereum is the likeliest cause of severe proctitis and is most often diagnosed in HIV-positive MSM in the UK Gonococcal proctitis is usually less severe than in this case, as are the rare cases of syphilitic proctitis Campylobacter infection is seen in MSM but diarrhoea would be a more prominent symptom Cytomegalovirus (CMV) colitis is only seen in end-stage HIV infection, which is clearly not the case here 13.4 Answer: E Typical manifestations of DGI include monoarthropathy, vasculitic rash and tenosynovitis Endocarditis is seen rarely The sexually transmitted infection {STI) associated with uveitis is secondary syphilis 13.5 Answer: A Coronal papillae are a normal anatomical feature, which become more prominent in adolescence, and young men can mistake these normal skin appendages for an infection, especially genital warts Warts would not be limited to the corona, and are usually either more papular or keratotic Molluscum lesions are umbilicated Lichen planus typically presents as violaceous flat-topped papules Sebaceous glands, also known as Fordyce spots, are seen on the shaft and base of the penis 13.6 Answer: B Erythromycin and oxytetracycline were used before the advent of azithr9mycin and doxycycline, respectively/Ofloxacin is a quinolone with antichlarnydial efficacy, but this is not the case for ciprofloxacin Somewhat surprisingly, amoxicillin w.,as found to be effective in the treatment of Chlamydia in pregnancy, although azithromycin is much preferred now , 06 • SEXUALLY TRANSMITTED INFECTIONS 13.7 Answer: E The percentage of infected patients who develop visible warts is unknown, but is definitely a small minority Although homosexual men (MSM) are relatively more likely to get perianal warts, the majority of cases present in heterosexual men The mode of inoculation is unclear Liquid nitrogen destroys infected tissue but does not clear HPV infection HPV types 6/11 are not associated with genital cancer - HPV types 16/18 are the most common oncogenic types Cervarix vaccine only protects against HPV types 16/18; Gardasil also protects against types 6/11 13.8 Answer: B A diagnosis of primary or secondary syphilis is based on typical clinical findings so cannot be applied to a symptomless individual The negative lgM makes early latent syphilis unlikely, and the RPR titre in untreated early or late latent syphilis would be expected to be much higher - at the very least 32 The titre here of is more likely to represent accidental treatment - in this case, antibiotics for a dental infection It would still be prudent to offer definitive treatment, e.g with a course of three injections of benzathine penicillin at weekly intervals 13.9 Answer: E Right upper quadrant tenderness is a feature of perihepatitis, a rare complication of ascending chlamydia! infection Diarrhoea is not a symptom suggestive of salpingitis Haematuria would be more suggestive of a urinary tract infection A normal temperature neither supports nor refutes the diagnosis A positive pregnancy test would raise concerns about a possible ectopic pregnancy 13.10 Answer: C The positive lgM is suggestive of early infection False-positive lgM tests are possible, but a second positive test, in this case the TPPA, makes that unlikely The low TPPA titre is compatible with very early infection Although the chancre of primary syphilis is usually painless, this is not necessarily so for an anal chancre, so primary infection is most likely The RPR would be strongly positive in secondary or early latent syphilis In treated infection, the lgG EIA would remain positive, but the lgM would become negative 13.11 Answer: E A rapid course of vaccination against hepatitis B - with inoculations today, and in and weeks' time - would give good protection against this infection that is more common in IDUs PEP for HIV is only effective if given up to 72 hours following risk Female to male sexual transmission of HCV is extremely rare One week after exposure is too soon to rely upon negative tests for any STI Negative tests for Chlamydia and gonorrhoea become reliable at weeks, negative fourth-generation HIV tests· become reliable at weeks, and negative tests for HBV and HCV are reliable at months Azithromycin is only reliably curative for chlamydia! infection, less so for syphilis and gonorrhoea, and would have no effect upon viruses such as HIV or HBV 13.12 Answer: A Three of the four tests are positive, so this is not a false-positive scenario The negative RPR is almost certainly false and represents a prozone phenomenon where the very high antibody titre prevents formation of the antibody-antigen lattice necessary to observe flocculation in the test Diluting the serum will allow this to be observed The strongly positive lgM test makeslate infection extremely uflkely 13.13 Answer: C / Male to female transmission of Zika viruJ is !r described Outbreaks of shigellosis and 'HAV are seen in MSM CMV is shed in genital secretions Plasmodium vivax (malaria;}' is not known to be sexually transmitted 13.14 Answer: C Both HSV-1 and HSV-2 have a greater risk of causing disseminated disease in pregnancy, so it is important that she is counselled effectively to prevent acquisition Symptomless shedding of virus can continue in the absence of clinical episodes, so there is a risk of transmission in this scenario Valaciclovir has been shown to reduce HSV transmission in sera-discordant couples, is probably safe to take in pregnancy, but would be a suboptimal strategy Caesarean considered if she section would only developed primar/infection around the time of delivery Avoidance of sex or consistent condom use repre(lents the safest strategy in this case ,tie A Mather, D Burnett, DR Sullivan Clinical biochemistry and metabolic medicine Multiple Choice Questions 14.1 What is a particular advantage of obtaining a test analysis and result using a point-of-care test (POCT) system rather than using a traditional central laboratory? A POCT analysers often have a wider menu of available tests than central laboratories B POCTs avoid the need to use the laboratory programmes What is the most common form of inheritance of these LSDs? A Autosomal dominant B Autosomal recessive G Multifactorial D X-linked dominant E X-linked recessive or the medical records C POCTs provide test results at the time of seeing the patient D POCTs are generally cheaper than traditional testing E POCTs use newer technology and are generally more accurate and precise 14.2 Which of the following is an autosomal recessive inherited disorder, often diagnosed through newborn screening programmes and treated with dietary modification, which can present with wide-ranging clinical manifestations, including vascular disorders, skin hypopigmentation, ectopia lentis, and disorders of the central nervous or skeletal systems? A B C D Cystathionuria Cystinosis Cystinuria Homocystinosis E Homocystinuria 14.3 There have been many different lysosomal storage diseases (LSDs) discovered, and some of these have been included in successful population-wide community genetic screening 14.4 In the investigation of glycogen storage / diseases (glycogeneses), which of the following is a commonly used non-invasive test or finding that may be useful in diagnosing this condition? A Cataract in the lens of the eye B 'Cherry-red spot' in the fundus of the ey,k G Dislocated lens (ectopia lentis) in the eye D Exercise-induced fatigue or pain in muscles E Hypopigmentation of the skin 14.5 A 59 year old man presents for cardiovascular risk assessment, but he has not fasted for the blood collection that was to be performed during his appointment Which of the following plasma lipid or lipoprotein levels is most likely to be affected by his recent consumption of food? A Calculated low-density lipoprotein (LDL) cholesterol B High-density lipoprotein (HDL) cholesterol G Lipoprotein (a) D Non-HDL cholesterol E Total cholesterol 14.6 The same 59 year old man returns with a set of fasting results that include: total l 08 • CLINICAL BIOCHEMISTRY AND METABOLIC MEDICINE cholesterol mmoi/L (259 mg/dL), fasting triglyceride 3.3 mmoi/L (292 mg/dL), HDL cholesterol 0.9 mmoi/L (35 mg/dL), calculated LDL cholesterol 4.3 mmoi/L (166 mg/dL), non-HDL cholesterol 5.8 mmoi/L (224 mg/dL) and fasting serum glucose 6.9 mmoi/L (124 mg/ dL) What is the best indicator of the metabolic component of his cardiovascular risk? A Calculated LDL cholesterol B Fasting plasma glucose C HDL cholesterol D Non-HDL cholesterol E Total cholesterol 14.7 The same 59 year old man fails to improve his lipid profile following diet and exercise advice, and pharmacological treatment is deemed necessary Which of the following medications may have a detrimental effect on the triglyceride component of his lipid profile? A An anti-PCSK9 monoclonal antibody B Cholestyramine C Ezetimibe D Niacin E Rosuvastatin 14.8 The same 59 year old man commences atorvastatin 20mg every evening His follow-up lipid profile and glucose reveals: total cholesterol mmoi/L (143 mg/dL), fasting triglyceride 1.1 mmoi/L (97 mg/dL), HDL cholesterol 1 mmoi/L (42 mg/dL), calculated LDL cholesterol 2.1 mmoi/L (81 mg/dL), non-HDL cholesterol 2.6 mmoi/L (1 00 mg/dL) and fasting serum glucose 8.9 mmoi/L (160 mg/ dL) A subsequent glucose tolerance test is diagnostic of new-onset type diabetes What best describes the relationship between the onset of diabetes and the use of statins? A Diabetes development is more likely in those with pre-existing impaired fasting glucose B The development of diabetes is inconsistent with the fact that fasting triglyceride has improved C The development of diabetes is unrelated to the dose or potency of the statin D The development of diabetes means that statins are now contraindicated in that individual E The onset of diabetes and the use of statins are completely unrelated 14.9 A 57 year old man is having a blood test and the resident doctor finds it difficult to take blood When she receives the results she is worried that the test is inaccurate due to haemolysis of the cells whilst performing venepuncture What is the dominant intracellular cation that may be inaccurately reported in this situation? A Bicarbonate B Calcium C Magnesium D Potassium E Sodium 14.10 One litre of normal saline is given to a patient in the emergency department How is this fluid likely to be distributed between the fluid compartments? A Intracellular fluid mL, extracellular fluid 1000 mL, plasma volume 1000 mL B Intracellular fluid mL, extracellular fluid 1000 mL, plasma volume 200 mL C Intracellular fluid 1000 mL, extracellular fluid mL, plasma volume mL D Intracellular fluid 500 mL, extracellular fluid 500 mL, plasma volume 500 mL E Intracellular fluid 666 mL, extracellular fluid 334 mL, plasma volume 68 mL 14.11 In comparison to the ultrafiltrate foLf.ld in Bowman's capsule, which of these term~ best describes the filtrate that leaves the pro~(mal tubule? p A B C D E Hyperosmolar Hypertonic Hypo-osmolar Hypotonic Isotonic ( I 14.12 Amino acids are almost entirely reabsorbed from the glomerular filtrate via active transport in which section of the nephron? A Collecting duct B Early distal tubule C Late distal tubule D Loop of Henle E Proximal tubule I 14.13 A 35 year o)d man has been hiking in hot weather He collapses and is brought into the emergency department He is found to have a blood pressure of 95/62 mmHg with a postural drop of 15 mmHg His1 pulse rate is 112 beats/ min, his jugular venous pressure is npt visible and he has a dry tongue Which statement CLINICAL BIOCHEMISTRY AND METABOLIC MEDICINE • 109 describes an element of his physiological response to this clinical scenario? A Increased atrial natiuretic peptide release B Increased catecholamine release C Increased glomerular filtration rate D Reduced renin release E Vasoconstriction of renal efferent arterioles 14.14 Which statement best explains why loop diuretics are the most effective at promoting salt and water excretion? A Vasopressin (antidiuretic hormone, ADH) acts on the ascending limb of the loop of Henle to increase water permeability B Loop diuretics block the triple co-transporter that prevent the reabsorption of potassium C The ascending limb of the loop of Henle is permeable to both water and sodium D The ascending limb of the loop of Henle is the last segment to reabsorb sodium E The sodium reabsorptive capacity of the segments distal to the ascending limb of the loop of Henle is limited 14.15 An 83 year old woman presents to the emergency department delirious and disorientated She has a history of hypertension, treated with a thiazide diuretic Her blood tests reveal the following: serum sodium 116 mmoi!L; serum osmolality 239 mmol/kg; urinary osmolality 385 mmol/kg Which of the following abnormalities is responsible for her inability to maximally dilute her urine? A Abnormal function of the early distal tubule B Inadequate vasopressin in the circulation C Inadequate response of the collecting duct to vasopressin D Inadequate solute delivery to the early distal tubule E Inadequate solute delivery to the loop of Henle 14.16 A 67 year old man with hypertension and diabetes has chronic kidney disease with a stable serum creatinine of 2671J-moi!L (3.02 mg/ dL) Amongst other symp}oms, he complains of nocturia Which of the following abnormalities is responsible for his inabilit¥ to maximally concentrate his urine? A Abnormal function of the early distal tubule B Excess vasopressin release into the circulation C Excess aldosterone release into the circulation D Inadequate solute delivery to the early distal tubule E Inadequate solute delivery to the loop of Henle 14.17 A 17 year old male presents to the emergency department with poorly controlled type I diabetes He is found to be hyponatraemic with the following results: sodium 123 mmoi/L and plasma glucose 35 mmoi/L (630 mg/dL) Which one of the following is the most likely cause of the abnormal sodium reading? A Autoimmune hypothyroid disease B Hyperosmotic hyponatraemia secondary to hyperglycaemia C Hypoglycaemic agent-induced hyponatraemia D Loss of water in excess of sodium E Osmotic diuresis-induced hypovolaemic hyponatraemia 14.18 A 32 year old man who has been diagnosed with chronic schizophrenia lives with his mother and has been managing well in the community on stable medications for some time An ambulance was called to the house when he started having seizures and his blood~ on presentation to the emergency department/ are as follows: sodium 116 mmoi!L; potassiu\f\ I 4.0mmoi/L; chloride 88mmoi/L; bicarbonate'' 20mmoi/L; urea 9mmoi/L (54mg/dL); creatinine 661J-moi/L (0 75 mg/dL} His mot~er cannot recall any changes to his medications or in his behaviour but does comment that he has been drinking up to L of water per day Which of the following results are most likely to be found on further investigation? A Serum osmolality 235mmol/kg; urine osmolality 74mmol/kg; urine sodium 24mmoi!L B Serum osmolality 262mmol/kg; urine osmolality 112 mmol/kg; urine sodium 5mmoi/L C Serum osmolality 270mmol/kg; urine osmolality 135mmol/kgj urine sodium 42mmoi/L / D Serum osmolality 290 mmol/kg; urine osmolality 84mmol/kg; urine sodium 34mmoi/L E Serum osmolality 280mmol/kg; urine osmolality 64mmol!kg; urine sodium 44mmoi/L - I 110 • CLINICAL BIOCHEMISTRY AND METABOLIC MEDICINE 14.19 In which one of the following clinical scenarios is urine sodium excretion likely to be less than 20 mmol/24 hrs? A Acute diarrhoea B Adrenal insufficiency C Hypothyroidism D Renal disease E Syndrome of inappropriate antidiuretic hormone (vasopressin) secretion (SIADH) 14.20 A 57 year old man with hypertension is found to have a tumour arising in the zona glomerulosa of the adrenal gland that leads to uncontrolled secretion of a hormone that is responsible for his hypertension Which of the following would you expect to decrease in this scenario? A Extracellular fluid volume B Plasma concentration of bicarbonate C Plasma concentration of potassium D Thyroid-stimulating hormone E Tubular reabsorption of sodium 14.21 A 12 year old boy is being investigated for fatigue A physical examination, including blood pressure, is normal Blood results show: sodium 135 mmoi/L, potassium 3.1 mmoi/L, bicarbonate 35 mmoi/L; 24-hour urine results: potassium 245 mmol/24 hrs, calcium 12mmol/24hrs (N < 7.5) What is the most likely diagnosis? A B C D E Bartter's syndrome Gitelman's syndrome Laxative abuse Primary hyperaldosteronism Type renal tubular acidosis (RTA) 14.24 The amount of potassium excreted by the kidneys will decrease in which of the following situations? A When dietary intake of potassium increases B When distal tubule sodium delivery increases C When plasma aldosterone concentration increases D When the patient has acute metabolic acidosis E When the patient has respiratory alkalosis 14.25 A 42 year old patient has the following bloods Arterial blood gases: W 57.5nmoi/L (pH 7.24); Pa0 11.1 kPa (83 mmHg); PaC02 4.3 kPa (32 mmHg); bicarbonate 15 mmoi!L Serum biochemistry: sodium 134 mmoi/L; potassium 2.4mmoi/L; chloride 109mmoi/L Urine pH 5.2; following administration of intravenous sodium bicarbonate, urine pH is 5.8 What is the likely underlying cause of these abnormalities? A B C D E Loop diuretic abuse Thiazide diuretic abuse Type (distal) renal tubular acidosis Type (proximal) renal tubular acidosis Type renal tubular acidosis 14.26 A 38 year old man presents with a; 1-week history of arthralgia, rash, haem9,turia and mild peripheral oedema Blood test~ taken in the emergency department show thdt his serum creatinine is 6201-!moi/L (7.01 m~/dL) What pattern of acid-base disorder is most likely to occur in this clinical scenario'? I A Metabolic acidosis with no respiratory compensation B Metabolic acidosis with respiratory 14.22 Metabolic acidosis is seen in conjunction with which cause of hypokalaemia? A B C D E Diarrhoea Gitelman's syndrome Loop diuretics Primary hyperaldosteronism Vomiting compensation C Metabolic alkalosis with respiratory compensation D Respiratory acidosis with metabolic compensation E Respiratory alkalosis with metabolic compensation 14.27 A 42-year-old homeless man is brought 14.23 Hypokalaemia may be seen in association with normal blood pressure in which of the following conditions? A B C D E Bartter's syndrome Cushing's syndrome Gordon's syndrome Liddle's syndrome Primary hyperaldosteronism into the emergency pepartment He is known to have a history 9f' alcohol abuse and presents on this occasion with delirium, shortness of breath and blurred vision Initial investigations show the following Arterial blood gases (ABG): H+ 58.9nmoi/L (pH 7.23); PaC0 3.6kPa (27 mmHg); bicarbonate 12 mmoi/L Blood results: sodium 130 rnrnoi/L; potassl~m I CLINICAL BIOCHEMISTRY AND METABOLIC MEDICINE • 111 4.3mmoi/L; urea 7.2mmoi/L (43mg/dL); creatinine 113!lmoi/L (1 28 mg/dL); chloride 97 mmoi/L; glucose 4.2 mmoi/L (76 mg/dL) What is the most likely diagnosis? C Haemoglobin D Hydrogen phosphate E Proteins A Acute kidney injury B Diabetic ketoacidosis 14.29 A high school student is nervous about an upcoming exam and breathes rapidly with anxiety before fainting If you were to take an ABG at this point, what would you most likely find? c Ethylene glycol ingestion D Methanol ingestion E Severe ethanol intoxication 14.28 Which of the following is the most important buffer in the blood? A Ammonia B Bicarbonate A High pH; high HC03-, high PC0 B C D E High pH; High pH; Low pH; Low pH; normal HC03-, low PC02 low HCQ3-, low PC0 high HC0 3-, high PC02 low HC03-, high PC02 Answers 14.1 Answer: C The key advantage of POCT testing over central laboratory testing is that rapid availability of the result enables immediate medical decisions and actions POCTs are generally more expensive than the equivalent test performed in a central laboratory While POCT instruments often use new technology, the requirement for portability or miniaturisation may involve design or engineering compromises that result in less accuracy or precision than the equivalent standard laboratory test Most POCT instruments are designed for a specific environment or group of tests, and so their menu is usually more restrictive than standard laboratory analysers All laboratory and pathology results, including POCT, should always be recorded in the medical records 14.2 Answer: E Homocystinuria is inherited in an autosomal recessive manner It is most commonly caused by loss of function of the cystathionine ~-synthase (CBS) gene This affects the metabolism of the amino acid methionine and causes accumulation of the related amino acids homocysteine and methionine It is often diagnosed through newborn screening programs Dietary treatment is avaiiEJble, designed to correct the imbalance in the amino acids caused by the missing enzyme function There is no condition called homocystinosis This should not be confused with hornocystinuria (see option E) Cystinuria is an aminoaciduria, inherited in an autosomal recessive pattern It is characterised by high concentrations of cysteine in the urine, leading to cysteine stone formation in the urinary tract Cystinosis is a lysosomal storage disease and is also inherited in an autosomal recessive manner There is accumulation of cystine within tissues It is one of the causes of Fanconi's syndrome, in which there is abnormal renal tubular function Cystathionuria (also called cystathionase deficiency) is also an autosomal · recessive disorder, in which there is abnormal { accumulation of plasma cystathionine, leading,# to increased urinary excretion It is often ~c considered to be a benign biochemical ;' anomaly I I 14.3 Answer: B Most lysosomal storage diseases exhibit an autosomal recessive pattern of inheritance, although a few can be X-linked recessive (e.g Fabry's disease) 14.4 Answer: D Exercise-induced fatigue or pain in muscles is associated with several of the glycogenoses An ischaernic lactate forearm test can be used as a clinical diagnostic test for some forms of glycogen storage disease The cherry-red spot in the fundus is typically ays'ociated with Tay-Sachs disease, one/of the inherited GM2 gangliosidoses Hypopigrnentation, ectopia lentis and cataracts can be associated with many conditions, some of which are inherited, but the glycogenoses are not typically part of this group 112 • CLINICAL BIOCHEMISTRY AND METABOLIC MEDICINE 14.5 Answer: A Calculated LDL cholesterol is correct because the calculation includes the triglyceride level, which increases following food consumption The effect of food consumption on the other measurements is small by comparison, especially in relative terms 14.6 Answer: D Non-HDL cholesterol is correct because it allows for the presence of small dense LDL and other atherogenic lipoproteins This is particularly relevant in hypertriglyceridaemia, with or without accompanying elevation of fasting plasma glucose It is more strongly associated with cardiovascular disease (CVD) in studies where comparison has been made with the other alternatives 14.7 Answer: B Cholestyramine reduces recirculation of bile acids, down-regulates the farnesoid X receptor (FXR) and stimulates the replacement of the bile acids by conversion of cholesterol via alpha-hydroxylase The response to the down-regulation of FXR includes increased synthesis and secretion of triglyceride and very low-density lipoproteins (VLDLs) The other agents have neutral or favourable effects on triglyceride levels 14.8 Answer: A Type diabetes following statin therapy is likely in those with pre-existing impaired fasting glucose It is proportional to the dose and potency of the statin, but the CVD benefit of the response clearly outweighs the CVD risk of the diabetes Statins modestly improve triglyceride, even in the presence of diabetes 14.9 Answer: D The dominant intracellular cation is potassium If cells haemolyse during venepuncture, increased potassium will be released from the cells and a patient may be erroneously diagnosed with hyperkalaemia 14.10 Answer: B Total body water is about one-third extracellular fluid (ECF) and two-thirds intracellular fluid ECF is about one-fifth plasma and four-fifths interstitial fluid Fluids that contain neither sodium nor protein (such as 5% dextrose) will distribute in all the body fluid compartments in proportion to the normal distribution of total body water, as in option E Fluids that are rich in proteins (such as concentrated albumin) will remain in the plasma volume, as in option A Normal saline distributes within only the extracellular compartment as in option B 14.11 Answer: E In the proximal tubule, water reabsorption closely matches sodium reabsorption, meaning that the fluid that enters the loop of Henle is isotonic with the fluid that leaves the Bowman's capsule 14.12 Answer: E The proximal tubule reabsorbs filtered sodium by coupling re-entry of sodium into the proximal tubular cell with amino acids as well as glucose, phosphate and other organic molecules 14.13 Answer: B This man has hypovolaemia and sodium depletion as evidenced by his symptoms and signs on presentation The kidneys respond to this scenario by activating mechanisms that will increase sodium reabsorption, thereby restoring sodium and fluid balance Mechanisms that will increase sodium reabsorption include increased catecholamine release and increased renin/ release In order to restrict fluid loses the / kidneys will reduce glomerular filtration ra,fe in part by vasoconstriction of renal afferen~/ arterioles /' 14.14 Answer: E I Loop diuretics inhibit the Na,K,2CI triple co-transporter in the ascending limb of the loop of Henle and are the most effective diuretics as this transporter reabsorbs about 25% of the sodium load More distal reabsorption by the sodium-chloride transporter in the distal tubule only accounts for about 5% of sodium reabsorption and increased delivery to this segment when using a loop diuretic overwhelms the reabsorptive capacity of that transporter Option C is incorrect as the ascending limb is permeable only to sodium; the triple co-transpor)er does transport potassium as in opJi6n B, but this is not relevant to the diuretic effect; in option D, the ascending limi;J of the loop of Henle is not the last segment to reabsorb sodium, as outlined above; and in option A, vasopressin acts on the collecting ducts to increase wate~ permeability T i CLINICAL BIOCHEMISTRY AND METABOLIC MEDICINE • 113 14.15 Answer: A In order to maximally dilute urine, there needs to be normal function of both the loop of Henle and the early distal tubule Thiazide diuretics inhibit the normal function of the early distal tubule by blocking the sodium-chloride co-transporter An inability to maximally dilute urine can also result from options D and E but this is not the mechanism of thiazide diuretics Absence of vasopressin is required for maximal dilution of the urine 14.16 Answer: E Chronic kidney disease results in poor solute delivery to the loop of Henle causing a failure to generate the medullary concentration gradient Adequate solute delivery to and function of the early distal tubule is required for maximal dilution of urine but not concentration Failure of vasopressin effect, either through inadequate release or blunted action at the level of the collecting duct (rather than excess vasopressin), contributes to poor urinary concentration 14.17 Answer: B Hyperglycaemia causes osmotic shifts of water from the intracellular to the extracellular space, causing a relative dilutional hyponatraemia The serum sodium corrects to 131 mmoi/L when using the correction factor of 1.6mmoi/L for every 5.5mmoi/L increase in serum glucose The other causes of hyponatraemia are possible but would result in a genuine reduction in sodium concentration and option D would cause hypernatraemia 14.18 Answer: A These results are consistent with primary polydipsia which is the likely diagnosis here The serum osmolality is low, confirming hypotonic hyponatraemia and the urinary osmolality is also low suggesting relative excess water intake Option B, which demonstrates low urinary sodium, is seen in patients with low effective ar:terial volume due to either extrarenal losses or hypervolaemic states The high urinary sodium and osmolality seen in option C is consistent with SIADH or renal sodium loss Option D is consistent with hyperosmotic hyponatraemia, as seen in hyperglycaemia, and option E suggests isosmotic hyponatraemia such as with hyperlipidaemia 14.19 Answer: A Acute diarrhoea would result in extrarenal sodium and water loss and the normal renal response of sodium conservation In the other scenarios urine sodium would be high or normal due to effects of limited sodium reabsorption in the nephron secondary to vasopressin, or lack of cortisol/thyroxine response 14.20 Answer: C Aldosterone is produced in the zona glomerulosa of the adrenal gland and acts on the mineralocorticoid receptors in the distal tubules and collecting ducts of the nephron It acts to reabsorb sodium and excrete potassium In excessive quantities, such as in Conn's syndrome as described here, it causes hypertension and hypokalaemia 14.21 Answer: A Metabolic alkalosis associated with hypokalaemia and urinary potassium wasting is typical of diuretic use, or in this case Bartter's syndrome, which mimics loop diuretic use Gitelman's or thiazide diuretics would also present like this, but are associated with low, not high, urinary calcium Laxative abuse would be associated with renal conservation of / potassium and therefore low urinary potassium,' level Primary hyperaldosteronism is associated with hypertension and RTA with acidosis /1 ' 14.22 Answer: A Loop and thiazide diuretics, Bartter's syndr,bme and Gitelman's syndrome, and primary hyperaldosteronism are all associated with metabolic alkalosis As outlined in Fig 14.22, vomiting is also associated with metabolic alkalosis while diarrhoea causes loss of bicarbonate thereby resulting in a normal anion gap acidosis 14.23 Answer: A Answers B-E are associated with hypertension while Bartter's syndrome is associated with low or normal blood pressure readings I 14.24 Answer: D / A number of factors alter potassium secretion in the distal nephron segments Increased distal sodium delivery and increased plasma aldosterone concentration will result in greater luminal sodium entry through epithelial sodium channels, thereby increasing potassium 114 • CLINICAL BIOCHEMISTRY AND METABOLIC MEDICINE bicarbonate reabsorption, which makes type (proximal) RTA the most likely diagnosis Vomiting 14.26 Answer: B Acute kidney injury as seen in this patient with nephritic syndrome is associated with metabolic acidosis with respiratory compensation Gastric loss of Hypovolaemia I t Proximal Na+Hcoareabsorption Hypokalaemia I t Distal W secretion Metabolic alkalosis t H+ excretion I Fig 14.22 Generation and maintenance of metabolic alkalosis during prolonged vomiting Loss of HCI- generates metabolic alkalosis, which is maintained by renal changes secretion Acid-base disturbances have complex effects on renal potassium excretion Alkalosis is generally associated with increased potassium secretion while acute metabolic acidosis is associated with reduced renal potassium excretion However, over time, acidosis will cause an increase in distal sodium delivery and an increase in aldosterone production that will result in an increase in potassium secretion 14.25 Answer: D The patient has a metabolic acidosis with a low pH, low bicarbonate and compensatory low PaC0 • Acidosis with a low potassium, makes type I or renal tubular acidosis (RTA) the only possible answers Type renal tubular acidosis would be associated with hyperkalaemia and diuretic abuse is associated with metabolic alkalosis The urine pH is initially normal, but becomes alkalotic when bicarbonate is administered This is consistent with poor 14.27 Answer: D Looking first at the ABG, there is a low pH suggesting an acidosis Bicarbonate and carbon dioxide are both low, consistent with a· metabolic acidosis with respiratory compensation The anion gap = (Na+ + K+) - (CI HC03-) is 23, which is high This indicates the presence of unmeasured anions A high anion gap acidosis is commonly caused by an endogenous acid load as seen in diabetic ketoacidosis or kidney injury, but in this patient the absence of hyperglycaemia or significant renal impairment make these diagnoses unlikely Other causes of an increased anion gap acidosis are related to exogenous acid loads from poisoning Methanol poisoning typically presents with visual impairment and in severe cases results in permanent blindness L 14.28 Answer: B As outlined in the above questions, the m9;st important buffer system in blood and tissues involves the reaction of hydrogen ions (Hif with bicarbonate (HC03 -) to form carbonic acib (H 2C03) and ultimately C0 and H20 Hydrogen phosphate (HP04) and ammonia are in;/portant urinary buffers that associate with W ions secreted into the luminal space, thereby reducing luminal W concentration and allowing for continued acid secretion 14.29 Answer: C The student would have a respiratory alkalosis, best represented by option C Given the acute nature of the respiratory alkalosis, a small change in bicarbonate concentration occurs, but if respiratory alkalosis persists over days to weeks, the kidneys would have time to make adjustments to acid secretion and produce further compensation and reduction in HC0 3- concentration ... 54 11 Infectious disease 73 12 HIV infection and AIDS 96 13 Sexually transmitted infections 10 3 14 Clinical biochemistry and metabolic medicine 10 7 15 Nephrology and urology 11 5 16 Cardiology 13 2... A/(A+D) X D D/(D+B) E D/(D+C) X X 10 0 10 0 10 0 10 0 10 0 10 0 10 0 10 0 10 0 10 0 A The adjustment of probability after I I I C X D On examination the left hip was extremely painful to move and she was unable... below the top 15 ranked causes 5.4 Answer: A Alcohol use was ranked as a cause of GBD in 2 013 Suboptimal breastfeeding is ranked 19 in 2 013 , down from rank 11 in 19 90, and vitamin A deficiency