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Deborah Wake
CD
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)
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
II
::s
Edinburgh London New York Oxford
CD
Philadelphia
ELSEVIER St Louis Sydney 2018
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~
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Printed in Poland
Last digit is the print number: 9 8 7 6 5 4 3 2 I
1. Clinical decision-making 1
2. Clinical therapeutics and good prescribing 6
3. Clinical genetics 14
4. Clinical immunology 22
5. Population health and epidemiology 28
6. Principles of infectious disease 32
7. Poisoning 37
8. Envenomation 46
9. Environmental medicine 51
1
Contributors
Anna Anderson MBChB, MRCP, PhD Harry Campbell MD, FRCPE, FFPH, FRSE
Specialist Registrar Diabetes and Endocrinology, Professor of Genetic Epidemiology and Public
Western General Hospital, Edinburgh, UK Health, Centre for Global Health Research, Usher
Institute of Population Health Sciences
Brian J Angus BSc (Hons), DTM&H, FRCP, and Informatics, University of Edinburgh,
MD, FFTM(Gias) Edinburgh, UK
Associate Professor, Nuffield Department of
Medicine, University of Oxford, UK C Fiona Clegg BSc (MedSci), MBChB,
MRCP (UK)
Quentin M Anstee BSc (Hons), MBBS, PhD, Clinical Lecturer in Gastroenterology, School of
MRCP, FRCP Medicine, Medical Sciences and Nutrition,
Professor of Experimental Hepatology, Institute University of Aberdeen, Aberdeen, UK
of Cellular Medicine, Newcastle University,
Newcastle upon Tyne, UK; Honorary Consultant Gavin Clunie BSc, MBBS, MD, FRCP
Hepatologist, Freeman Hospital, Newcastle upon Consultant Rheumatologist and Metabolic Bone I
1
Tyne NHS Hospitals Foundation Trust, Newcastle Physician, Cambridge University Hospitals NHS
upon Tyne, UK Foundation Trust, Addenbrooke's Hospital,
Cambridge, UK
Jennifer Bain MBChB, MRCP, FRCA, FFICM
Fellow in Vascular Anaesthesia, Scottish Lesley A Colvin MBChB, BSc, FRCA, PhD,
Thoraco-abdorninal & Aortic Aneurysm Service, FRCP (Edin), FFPMRCA
Royal Infirmary of Edinburgh, Edinburgh, UK ConsultanVHonorary Professor in Anaesthesia
and Pain Medicine, Department of Anaesthesia,
Leslie Burnett MBBS, PhD, FRCPA . Critical Care and Pain Medicine, University
Chief Medical Officer, Genome.One, of Edinburgh, Western General Hospital,
Garvan Institute of Medical Research, Edinburgh, UK
Darlinghurst, Sydney; Honorary Professor,
University of Sydney, Sydney Medical School, Bryan Conway MB, MRCP, PhD
Sydney; Conjoint Professor, UNSW, St Senior Lecturer, Centre for Cardiovascular
Vincent's Medical School, Darlinghurst, Science, University of Edinburgh; Honorary
Sydney, Australia Consultant Nephrologist, Royal Infirmary
Edinburgh, Edinburgh, UK
Mark Byers OBE, FRCGP, FFSEM, FIMC,
MRCEM Nicola Cooper MBChB, FAcadMEd, FRCPE,
Consultant in Pre-Hospital Emergeney Medicine, FRACP
Institute of Pre-Hospital Care, London, UK Consultant Physician, Derby Teaching Hospitals
NHS Foundation Trust; Honorary Clinical
Associate Professor, Nottingham University,
Division of Medical Sciences and Graduate Entry
Medicine, Nottingham, UK
Ruth Darbyshire MB BChir, MA(Cantab) Sara J Jenks Bsc (Hons), MRCP, FRCPath
Specialty Trainee in Ophthalmology, Yorkshire Consultant in Metabolic Medicine, Department of
and Humber Deanery, Yorkshire, UK Clinical Biochemistry, Royal Infirmary of
Edinburgh, UK
Graham Dark MBBS, FRCP, FHEA
Senior Lecturer in Medical Oncology and Cancer Sarah Louise Johnston MB ChB, FCRP,
Education, Newcastle University, Newcastle upon FRCPath
Tyne, UK Consultant in Immunology & HIV Medicine,
Department of Immunology and Immunogenetics,
Richard J Davenport DM, FRCP (Edin), North Bristol NHS Trust, Bristol, UK
BM BS, BMedSci
Consultant Neurologist and Honorary Senior David E J Jones MA, BM BCh, PhD, FRCP
Lecturer, University of Edinburgh, Edinburgh, UK Professor of Uver Immunology, Institute of Cellular
Medicine, Newcastle University; Consultant
David Dockrell MD, FRCPI, FRCP (Gias), Hepatologist, Freeman Hospital, Newcastle upon
FACP Tyne, UK
Professor of Infection Medicine, MAC/University of
Edinburgh Centre for Inflammation Research, Peter Langhorne MBChB, PhD, FRCP (Gias),
University of Edinburgh, Edinburgh, UK Hon FRCPI
Professor of Stroke Care, Institute of
Emad EI-Omar BSc (Hons), MBChB, Cardiovascular and Medical Sciences, University
MD (Hons), FRCP (Edin), FRSE of Glasgow, Glasgow, UK
Professor of Medicine, St George and Sutherland
Clinical School, University of New South Wales, Stephen Lawrie MD (Hons), FRCPsych,
Sydney, Australia Hon FRCP (Edin)
Professor of Psychiatry, University of Edinburgh,
Sarah Fadden BA, MB BChir, FRCA Edinburgh, UK
Senior Registrar in Anaesthesia, Royal Infirmary of
Edinburgh, Edinburgh, UK John Paul Leach MD, FRCP
Consultant Neurologist, Institute of Neurological
Catriona M Farrell MBChB, MRCP (UK) Sciences, Glasgow; Head of Undergraduate
Specialist Registrar Endocrinology and Diabetes, Medicine, University of Glasgow, Glasgow, UK
Ninewells Hospital, Dundee, UK
Andrew Leitch MBChB, BSc (Hons), PhD,
Amy Frost MA (Cantab), MBBS, MRCP MSc (Ciin Ed), FRCPE (Respiratory)
Clinical Genomics Educator, Affiliated to St Consultant Respiratory Physician, Western
George's University NHS Foundation Trust, General Hospital; Honorary Senior Lecturer,
London, UK University of Edinburgh, Edinburgh, UK
Michael MacMahon MBChB, FRCA, FICM, David E Newby BA, BSc (Hons), PhD, BM,
EDIC OM, DSc, FMedSci, FRSE, FESC, FACC
Consultant in Anaesthesia and Intensive Care, British Heart Foundation John Wheatley Chair of
Victoria Hospital, Kirkcaldy, Fife, UK Cardiology, British Heart Foundation Centre for
Cardiovascular Science, University of Edinburgh,
Rebecca Mann BMedSci, BMBS, MRCP, Edinburgh, UK
FRCPCh
Consultant Paediatrician, Taunton and Somerset John Olson MD, FRPCE, FRCOphth
NHS Foundation Trust, Taunton, UK Consultant Ophthalmic Physician, Aberdeen
Royal Infirmary; Honorary Reader, University of
Lynn Manson MBChB, MD, FRCP, FRCPath Aberdeen, UK
Consultant Haematologist, Scottish National
Blood Transfusion Service, Department of Paul J Phelan MBBCh, MD,
Transfusion Medicine, Royal Infirmary of FRCP (Edin)
Edinburgh, Edinburgh, UK Consultant Nephrologist and Renal Transplant
Physician, Honorary Senior Lecturer, University of
Amanda Mather MBBS, FRACP, PhD Edinburgh, Royal Infirmary of Edinburgh,
Consultant Nephrologist, Department of Renal Edinburgh, UK
Medicine, Royal North Shore Hospital; Conjoint
Senior Lecturer, Faculty of Medicine, University of Eric M Przybyszewski BS, MD
Sydney, Sydney, Australia Resident Physician, Department of Medicine,
Massachusetts General Hospital, Boston, USA
Simon R Maxwell BSc, MBChB, MD, PhD,
FRCP, FRCPE, FHEA Stuart H Ralston MBChB, MRCP, FMedSci,
Professor of Student Learning/Clinical FRSE
Pharmacology & Prescribing, Clinical Professor of Rheumatology, Rheumatic Diseases
Pharmacology Unit, University of Edinburgh, Unit, University of Edinburgh, Edinburgh, UK
Edinburgh, UK
Jonathan Sandoe MBChB, PhD, FRCPath
David McAllister MBChB, MD, MPH, MRCP, Associate Clinical Professor, University of Leeds,
MFPH UK
Wellcorne Trust Intermediate Clinical Fellow
and Beit Fellow, Senior Clinical Lecturer in Gordon Scott BSc, FRCP
Epidemiology and Honorary Consultant in Consultant in Genitourinary Medicine, Chalmers
Public Health Medicine, University of Glasgow, Sexual Health Centre, Edinburgh, UK
Glasgow, UK
Alan G Shand MD, FRCP (Ed)
Mairi H Mclean BSc (Hons), MBChB (Hons), Consultant Gastroenterologist, Gastrointestinal
PhD, MRCP Unit, Western General Hospital, Edinburgh, UK
Senior Clinical Lecturer in Gastroenterology,
School of Medicine, Medical Sciences and Robby Steel MA, MD, FRCPsych
Nutrition, University of Aberdeen; Honorary Department of Psychological Medicine, Royal
Consultant Gastroenterologist, Digestive Disorders Infirmary of Edinburgh; Honorary (Clinical) Senior
Department, Aberdeen Royal Infirmary, Aberdeen, Lecturer, Department of Psychiatry, University of
UK Edinburgh, Edinburgh, UK
~-
ABBREVIATIONS • xvii
N Cooper
Clinical decision-making
Multiple Choice Questions
1.1. In the specialty of internal medicine, 1.4. A test is performed to detect the presence
diagnostic error occurs in approximately what of a disease in a specific population. The
percentage of cases? results of the test can be summarised in the
A. 0-5% table below.
B. 6-10%
C.11-15% Disease No disease
D. 16-20% Positive test A B
E. 21-25% Negative test c D
1.2. A doctor is considering whether a patient Which of the following describes the positive
presenting with headache, fever and nuchal predictive value of the test?
rigidity may have meningitis. Regarding A. A/(A+B) X 100
likelihood ratios (LRs) for each clinical finding, B. A/(A+C) X 100
which of the following statements is true? c. A/(A+D) X 100
A. An LR greater than 1 decreases the D. D/(D+B) X 100
probability of disease E. D/(D+C) X 100
B. An LR greater than 1 increases the
probability of disease 1.5. An elderly woman fell and hurt her left hip.
C. An LR is the probability of the finding in On examination the left hip was extremely
patients with the disease painful to move and she was unable to stand.
D. An LR of 0 means the diagnosis is unlikely The pre-test probability of a hip fracture was
E. An LR of 1 means the diagnosis is certain deemed to be high. Plain X-rays of the pelvis
and left hip were requested.
1.3. A test is performed to detect the presence Which of the following statements best
of a disease. The results of the test can be describes 'post -test probability'?
summarised in the table below. A. The adjustment of probability after
Disease No disease I taking individual patient factors in
Positive test A B I to account
Negative test C D I B. The chance that a test will detect true
positives
Which of the following describes the C. The prevalence of disease in the population
sensitivity of the test? to which the patient belongs
A. A/(A+B) X 100 D. The probability of a disease after taking
B. A/(A+C) X 100 new information from a test result into
c. A/(A+D) X 100 account
D. D/(D+B) X 100 E. The proportion of patients with a test res,ult
E. D/(D+C) X 100 who have the disease
B. To rely too much on the first piece of following statements is true regarding the
information offered interpretation of a 0-dimer result?
C. To stop searching because we have found A. A negative 0-dimer result in a high clinical
something that fits probability patient excludes acute VIE
B. To subconsciously see what we expect to B. A positive 0-dimer result means that acute
see VIE is present
E. To want to confirm our diagnoses with C. 0-dimer is a useful screening test in patients
others before making a decision presenting with breathlessness
D. 0-dimer testing in suspected acute VIE
1.15. The D-dimer test has a sensitivity of at results in lots of false negatives
least 95% in detecting acute venous E. 0-dimer testing in suspected acute VIE
thromboembolism (VTE). However, it has a low results in lots of false positives
specificity of around 40%. Which of the
Answers
1.1. Answer: C. exclude those without it. Even a very good test,
It is estimated that diagnosis is wrong 11-15% with 95% sensitivity, will miss 1 in 20 people
of the time in the undifferentiated specialties with the disease. Every test therefore has 'false
of internal medicine, emergency medicine positives' and 'false negatives'.
and general practice. Diagnostic error is A very sensitive test will detect most
associated with greater morbidity than other disease but may generate abnormal findings in
types of medical error, and the majority of healthy people. A negative result will therefore
diagnostic errors are considered to be reliably exclude the disease, but a positive test
preventable. is likely to require further evaluation. On the
other hand, a very specific test may miss
1.2. Answer: B. significant pathology but is likely to establish
Likelihood ratios (LRs) are clinical diagnostic the diagnosis beyond doubt when the result is
weights. positive.
1.3. Answer: B.
1.5. Answer: D.
Sensitivity= A/(A +C) x 100 Post-test probability is the probability of a
disease after taking new information from a test
Sensitivity is the ability to detect true result into account. The.pre-test probability of
positives; specificity is the ability to detect true disease is decided by the doctor - it is an
negatives. There is no test that can 100% of opinion based on gathered evidence prior to
the time detect people with a disease and ordering the test. Bayes' Theorem can be used
to calculate post-test probability for a patient in overload and time pressure. Poor team
any population. It is a mathematical way to communication and poorly designed equipment
describe the post-test probability of a disease or clinical processes also increase the likelihood
by incorporating pre-test probability, sensitivity of error. Age, gender and working alone are not
and specificity. factors that affect cognition. Use of checklists
has been shown to improve decision-making in
1.6. Answer: D. clinical settings.
The treatment threshold combines factors such
as the risks of the test, and the risks versus 1.1 0. Answer: B.
benefits of treatment. The point at which the Suspected pulmonary embolism is a
factors are all evenly weighted is the threshold. common problem referred to UK ambulatory
If a test or treatment for a disease is effective emergency care centres. Unexplained pleuritic
and low risk, then one would have a lower chest pain and/or a history of breathlessness
threshold for going ahead. On the other hand, are the most common symptoms. Vital signs at
if a test or treatment is less effective or high rest and the physical examination may be
risk, one requires greater confidence in the normal. The only feature presented with a
clinical diagnosis and potential benefits of negative likelihood ratio in the diagnosis of
treatment first. In principle, if a diagnostic test pulmonary embolism is a heart rate of less than
will not change the management of the patient, 90beats/min. In other words, the other normal
then it should not be requested, unless there physical examination findings (including normal
are other compelling reasons to do so. oxygen saturations) carry little diagnostic
weight.
1.7. Answer: A.
Psychologists believe we spend 95% of our 1.11. Answer: A.
daily lives engaged in type 1 thinking - the 'Patient-centred evidence-based medicine'
intuitive, fast, subconscious mode of refers to the application of best available
decision-making. In everyday life we spend little research evidence while taking individual patient
time (5%) engaged in type 2 thinking. Imagine factors into account - these include clinical
driving a car; it would be impossible to function factors (e.g. bleeding risk when consideri?g
efficiently if every decision and movement was anticoagulation) and non-clinical factors (e.g.
as deliberate, conscious, slow and effortful as the patient's inability to attend for regular' blood
in our first driving lesson. With experience, tests if started on warfarin).
complex procedures become automatic, fa:st
and effortless. The same applies to medical 1.12. Answer: D.
practice. Many studies demonstrate a correlation
between effective clinician-patient
1.8. Answer: A. communication and improved health outcomes.
Cognitive biases are subconscious errors that If patients feel they have been listened to and
lead to inaccurate judgement and illogical understand the problem and proposed
interpretation of information. In evolutionary treatment plan, they are more likely to adhere
terms, it is thought that cognitive biases to their medication and less likely to re-attend.
developed because speed was often more Whenever possible, doctors should quote
important than accuracy. This property of numerical information using consistent
human thinking is highly relevant to clinical denominators (e.g. '90 out of 100 patients who
decision-making. Confirmation bias is the have this operation feel much better, 1 will die
tendency to look for confirming evidence to during the operation and 2 will suffer a stroke').
support a theory rather than looking for Visual aids can be used to present complex
contradictory evidence to refute it, even if the statistical information.
latter is clearly present. Confirmation bias is Relative risk exaggerates small effects that
common when a patient has been seen first by distort people's understanding of true
another doctor. probability. Longer consultations and the use
of visual aids are tools to facilitate good
1.9. Answer: B. communication but in themselves do not
Cognition is affected by things like fatigue, guarantee this is the case. Gender by itself is
illness, emotions, interruptions, cognitive not a factor.
2.23. A 56 year old man is being treated with 2.24. A 78 year old wornan is reviewed in the
intravenous gentamicin for Gram-negative emergency department of a hospital with i
~·I
septicaemia that is presumed to be of urinary
tract origin. He is well hydrated and his renal
bruising. She is taking warfarin 3 rng and 4 rng
orally on alternate days as prophylaxis against
~ll
function is normal. He has had two previous recurrent pulmonary emboli. Her last 3-rnonthly
doses of gentamicin 360 mg as a 30-minute INR rneasurernent was 2.7. She has been
intravenous infusion at 1000 hrs on Wednesday otherwise well with no other new syrnptorns
and Thursday. Both previous plasma and she has not been put on any new
gentamicin concentrations have been checked medicines. Her investigations reveal a normal
by the senior doctor in charge of the ward and full blood count but an INR of 6. 7.
the third dose of gentamicin has been What is the appropriate course of action?
prescribed and is now due (Friday morning at A. Stop warfarin and give phytornenadione
1000 hrs). (vitamin K1) 1-3 rng by slow intravenous
When should the next plasma gentamicin injection
concentration be taken? B. Stop warfarin and give phytornenadione
A. 0400 hrs (Saturday) (vitamin K1) 1-5 rng by rnouth
B. 1400 hrs (Friday) C. Stop warfarin and start apixaban
C. 1800 hrs (Friday) D. Stop warfarin alid start low-molecular-weight
D. lrnrnediately after the infusion is completed heparin injections
E. lrnrnediately before the third dose E. Stop warfarin for 2 days only
Answers
2.1. Answer: A. the same active site as the agonist but does so
Aspirin acts on the enzyrne cyclo-oxygenase irreversibly, or (iii) the antagonist interferes with
and is a non-selective and irreversible inhibitor. the signal transduction rnechanisrn preventing 1
Hydrocortisone is a corticosteroid and acts on receptor-agonist binding resulting in a
a DNA-linked receptor. Insulin acts on a pharmacological effect
kinase-linked receptor. Lidocaine blocks a
voltage-sensitive Na+ channel. Morphine acts 2.4. Answer: D.
on a G-protein-coupled receptor. Rifampicin is a very potent enzyme inducer. ·
All of the other options are well recognisec:j EJ.S
2.2. Answer: B. enzyme inhibitors.
The potency of a drug is related to its affinity
for a receptor. Less potent drugs are given in 2.5. Answer: D.
higher doses. The lower potency of a drug can The clearance rate of rnost drugs increases
be overcome by increasing the dose. Option D progressively as their plasma concentration
refers to the 'efficacy' of a drug. increases ('first -order metabolism'). For a
srnall number of common medicines, their
2.3. Answer: A. rnetabolisrn is 'saturable', meaning that the
The terrn 'non-competitive antagonist' is used rate of clearance cannot increase further
to describe two distinct situations where an ('zero-order kinetics'). For those drugs, further
antagonist binds to a receptor, or its associated dose increases can cause disproportionate
signal transduction rnechanisrn, to prevent the increases in exposure and the likelihood of
agonist activating the receptor. The cornrnon toxicity.
feature is that increasing the concentration of
agonist cannot outcornpete the antagonist. 2.6. Answer: A.
The receptor is rendered inactive and so the The apparent volume of distribution 0/d) is the
rnaxirnal response of which the cell or tissue is volume into which a drug appears to have
capable is reduced. This can occur in three distributed following intravenows injection. It is
ways: (i) the antagonist binds to an allosteric calculated frorn the equation Vd = D/C 0 , where
site of the receptor, (ii) the antagonist binds to D is the amount of drug given and C0 is th'e
initial plasma concentration. Drugs that are CYP206 ('poor metabolisers'), and are less
highly bound to plasma proteins may have a vd able to deliver sufficient morphine levels. Some
below 10 L (e.g. warfarin, aspirin), while those individuals carry more than two functional
that diffuse into the interstitial fluid but do not copies of the CYP206 gene ('ultra-rapid
enter cells because they have low lipid solubility metabolisers') and are able to metabolise
may have a Vd between 10 and 30 L codeine to morphine more rapidly and
(e.g. gentamicin, amoxicillin). It is an 'apparent' completely. They may develop symptoms
volume because those drugs that are lipid of morphine toxicity (e.g. drowsiness,
soluble and highly tissue-bound may have delirium and shallow breathing) even at
a Vd of greater than 100 L (e.g. digoxin, low doses.
amitriptyline). Drugs with a larger Vd have longer
half-lives, take longer to reach steady state on 2.9. Answer: A.
repeated administration and are eliminated Drug hypersensitivity is typically immune
more slowly from the body following mediated. Some drugs (especially large
discontinuation. Females have a greater . molecules) may themselves stimulate immune
proportionate content of fat in their bodies and reaction but many others (or their metabolites)
so the volume of distribution of lipid-soluble act as 'haptens' that bind covalently to serum
drugs is increased. or cell-bound proteins, including peptides
embedded ·in major histocompatibility complex
2.7. Answer: A. (MHC) molecules. This makes the protein
Drugs that enter the enterohepatic circulation immunogenic, stimulating antibody production
are reabsorbed into the body after excretion in targeted at the drug or T-cell responses against
the bile. This occurs because intestinal flora the drug. The reaction can produce a variety of
split the water-soluble conjugated drug, reactions ranging from mild rashes through to
allowing the free drug to be reabsorbed into life-threatening anaphylaxis. These reactions are
the body and thus increasing its bioavailability. often rare and discovered later in the drug
Gastroenteritis favours more rapid transit development process. The susceptibility to
through the small intestinal absorptive region of hypersensitivity reactions is, in many cases,
the bowel and reduces oral bioavailability. strongly related to genetics. Those who are /
Hypoalbuminaemia may alter the proportion of susceptible will often react immediately to 1
the drug retained in plasma after absorption but minimal exposure to the drug, making it
does not alter the overall bioavailability in the very difficult to identify a dose-response
body. Impaired renal function may influence relationship.
clearance of a drug but does not influence
bioavailability. Aqueous solutions, syrups, elixirs, 2.10. Answer: D.
and emulsions do not present a dissolution Voluntary reporting is a continuously ope~ating
problem and generally result in fast and often and effective early warning system for
complete absorption as compared to solid previously unrecognised rare ADRs. It is better
dosage forms. Due to their generally good suited than most other methods to early
systemic availability, solutions are frequently detection of previously unknown reactions,
used as bioavailability standards against which especially for medicines that are prescribed in
other dosage forms are compared. high volume. Although doctors were initially the
main source of reporting, most other healthcare
2.8. Answer: B. professional groups, and patients, are now able
Codeine is an opioid analgesic drug that is to report in the UK. Their reports have been
licensed for the treatment of mild to moderately shown to be of equivalent value to those
severe pain, and it belongs to the drug class of produced by the medical reporters. Its
opioid analgesics. Codeine is metabolised by weaknesses include low reporting rates (only
the hepatic cytochrome P450 206 (CYP2D6) 3% of all ADRs and 10% of serious ADRs are
enzyme, which also metabolises many other ever reported), an inability to quantify risk
prescribed drugs. CYP2D6 converts codeine to (because the ratio of ADRs to prescriptions is
its active metabolite, morphine, which is unknown) and the influence of·prescriber
responsible for the analgesic effect. The awareness on likelihood of reporting {reporting
analgesic effect of codeine is attenuated in rates rise rapidly following publicity about
individuals who carry two inactive copies of potential ADRs).
-·
target INR should be 2.5. She now presents for 2 days and then resume (at a lower dose)
with the INR out of control and this can be before re-measuring the INR. In the absence of
caused by several different factors (e.g. erratic bleeding or an INR greater than 8.0, there is no
tablet taking, altered liver function, dietary indication to give vitamin K, which will largely
change, interacting drug). The loss of control reverse the action of warfarin and put the I
puts her at increased risk of bleeding although patient at risk of thromboembolic events until it
there are no symptoms suggestive of a serious can be restarted or replaced with an alternative
bleeding episode. The appropriate course of anticoagulant.
action at this point is to withhold the warfarin
Clinical genetics
Multiple Choice Questions
3.1. Deoxyribonucleic acid (DNA) repair A. Acetylation of histone protein
mechanisms exist to repair damage that may B. Alternative splicing
arise spontaneously or as a result of C. Epigenetic modification
environmental exposures. Failure to repair DNA D. Gene silencing by microRNA species
damage prior to replication results in mutations. E. Post-translational glycosylation
Spontaneous deamination of a cytosine results
in its conversion to a uracil. If this were not 3.4. You receive a genetic test result for a 3
repaired prior to replication, what would be the year old boy with a history of Wilms' tumour
result? and microcephaly, confirming a diagnosis of
A. Conversion of a GA pair to a CT pair mosaic variegated aneuploidy (MVA), a rare
B. Conversion of a GC pair to an AT pair inherited predisposition to chromosomal
C. Conversion of a GT pair to an AC pair non-dysjunction. The genetic test has identified
D. Conversion of an AC pair to a GT pair a mutation in BUB1B, a key component of/.
E. Conversion of an AT pair to a GC pair the mitotic spindle checkpoint. You now need
to explain these results to his parents.
3.2. The central dogma of molecular biology Non-dysjunction occurs during cell division
describes the steps by which information when the sister chromatids attach to the mitotic
encoded by the DNA determines protein spindle and are pulled apart to separate poles
production. One of these steps is transcription. of the cell. What is this phase of the cell/ cycle
Which of the following elements are all essential called?
components in transcription? A. Anaphase
A. Promoter sequence, deoxynucleotides, DNA B. Interphase
polymerase C. Metaphase
B. Promoter sequence, DNA template, DNA D. Prophase
polymerase E. Telophase
C. Promoter sequence, DNA template,
ribonucleic acid (RNA) polymerase 3.5. You receive a referral to see a 32 year old
D. Ribosomes, DNA template, RNA polymerase woman who has recently been diagnosed with
E. Ribosomes, messenger RNA (mRNA) triple-negative breast cancer. Triple-negative
template, transfer RNAs (tRNAs) breast cancer is defined by the absence of
oestrogen receptors, wogesterone receptors
3.3. In thyroid C cells, the calcitonin gene and human epidermal growth factor receptor
encodes the osteoclast inhibitor calcitonin, 2 (HER2) expression, and this tumour type is
whereas in neurons, the same gene encodes particularly common in BRCA 1 mutation
calcitonin-gene-related peptide. Which of the carriers. Genetic testing of the BRCA 1 and
mechanisms of controlling gene expression BRCA2 genes reveals a heterozygous BRCA 1
listed below is responsible for this mutation (BRCA 1 c.37 48G>T). This mutation
multi-functionality? substitutes a G for a T, resulting in the creation
(C' }< ,, )) /)
1 2 3 4 5
type I collagen genes, resulting in the
production of an abnormal protein that
interferes with the normal functioning of the
)( It lI >I >I U I~
wild-type protein. What is the name for this
type of mutation?
10 12
A. Dominant negative mutation
fl () nu JJ
14 15 16 17 18
B.
C.
Gain-of-function mutation
Loss-of-function mutation
19
II
20 ••
21
u
22
J D.
E.
Protein-truncating mutation
Stop-gain mutation
A. Edward's syndrome 3.11. You are asked to review a 17 year old boy
B. Klinefelter's syndrome with a diagnosis of Becker muscular dystrophy.
C. Lynch's syndrome He has two siblings, an unaffected brother and
D. Patau's syndrome a sister whose status is unknown. His parents
E. Turner's syndrome are fit and well; however, his maternal
grandfather also had Becker muscular
3.8. You receive a referral to review an 18 dystrophy. You need to.construct an
month old girl with developmental delay. She is appropriate pedigree for your notes. What
the first child of unrelated parents and there is symbol would you conventionally use to
no significant family history. On examination represent his mother in this case?
Fig. 3.14
A. Affected father and affected son 3.18. A 27 year old woman is referred to your
B. Affected members in each generation clinic by her family physician for advice. She
C. Affected son and affected maternal uncle was worried about her family history of breast
D. The presence of an affected fernale cancer and decided to undergo genetic testing
E. Variable expressivity through a private company offering a
next -generation sequencing (NGS) breast
cancer susceptibility gene panel test. They sent
3.15. You review a 39 year old wornan with
her the report but she is having trouble
advanced breast cancer. She has been referred
understanding some of the terminology used
to you for genetic testing because of her young
and needs some clarification. In NGS, what
age at diagnosis. You undertake diagnostic
does the term 'capture' refer to?
genetic testing but are unable to identify a
pathogenic mutation in either BRCA 1 or A. Binding of the library fragments as they are
BRCA2. Which of the following mechanisms washed over the flow cell
could be a contributing mechanism in her B. Downloading the relevant read data into the
tumour formation? analysis software
C. Identifying the differences between the reads
A. Apoptosis
and the reference genome
B. Autocrine stimulation
D. Pulling out the part of the genome to be
C. Gain-of-function mutation in a turnour
sequenced
suppressor gene
E. Successfully identifying a disease-causing
D. Loss-of-function mutation in an oncogene
variant
E. Passenger mutation
3.19. You review a family, several members of
3.16. You receive an array comparative genomic whorn have the same, rare condition, for which
hybridisation (array CGH) report for a patient no genetic cause has yet been identified. You
with developmental delay and autism. The are considering a clinical research project with
report is normal and has not identified a cause the aim of identifying the disease-causing
for the patient's difficulties. Which of the mutation in this family. You are trying to decide
following statements is true about what array whether whole-exome sequencing or
CGH is able to reliably detect? whole-genome sequencing would be a better
A. It will reliably detect aneuploidy approach. Which of the following is an
B. It will reliably detect balanced translocations advantage of whole-genome sequencing ovef
C. It will reliably detect intragenic deletions whole-exome sequencing? '
D. It will reliably detect mosaicism at the A. Increased detection of gene dosage
1% level abnormalities
E. It will reliably detect triploidy B. Increased detection of mosaicism
C. Increased likelihood that a variant detected
3.17. A 2 year old boy with global will be pathogenic
developmental delay and facial dysmorphism D. Less expensive
attends with his parents for the results of his E. Lower risk of identifying incidental findings
array CGH testing. His parents are healthy and
there is no family history of note. The test has 3.20. You are asked to review a 39 year old
identified a 446-kB deletion at 18p23, which woman who has had a positive result for
has been reported as a copy number variant trisomy 21 during non-invasive prenatal testing
(CNV) of uncertain significance. What would be for aneuploidy screening. She is very upset and
your next step in his management? is asking you if there is any chance that the
A. Exome sequencing of the boy and his test could be wrong. Which of the following is a
parents possible cause of a false-positive result in this
B. Intellectual disability gene panel testing circumstance?
C. Parental array CGH testing A. Confined placental mosaicism
D. Repeat the array using more closely spaced B. High maternal body IJlass index (BMI)
probes to give a higher resolution C. Maternal smoking
E. Request a karyotype to exclude a balanced D. Previous miscarriage of aneuploid fetus
translocation E. Test done too early in gestation
3.21. You are reviewing a 35 year old woman 3.22. You review a 42 year old woman who
with triple-negative breast cancer, in whom you developed breast cancer at the age of 27 that
have identified an underlying BRCA 1 mutation. was successfully treated, and has now
Her oncologisthas recommended that she developed an osteosarcoma in her right femur.
enters a trial of treatment with a poly ADP On discussion of her family history she tells you
ribose polymerase (PARP) inhibitor. She wants that her mother died when she was very young
to know more about how they work. Which of of brain cancer (glioblastoma) and that her
the following statements about the mechanism brother is currently receiving treatment for a
of PARP inhibitors is true? rhabdomyosarcoma. Apart from evidence of a
A. They block the double-stranded DNA previous mastectomy, there are no additional
break-repair pathway phenotypic features on physical examination.
B. They block the double-stranded DNA You suspect a familial cancer predisposition
break-repair pathway and up-regulate the syndrome. Which of the following cancer
single-stranded DNA break-repair pathway predisposition syndromes would be the best fit
C. They block the single-stranded DNA for this tumour spectrum?
break-repair pathway A. Birt-Hogg-Dube syndrome
D. They repair the double-stranded DNA B. Cowden's syndrome
break-repair pathway C. Gorlin's syndrome
E. They repair the single-stranded DNA D. Li-Fraumeni syndrome
break-repair pathway E. Lynch's syndrome
Answers
3.1. Answer: B. be joined together (alternative splicing) to
In DNA, bases are paired as follows: adenine produce more than one form of mRNA,
(A) with thymine (T) and guanine (G) with which may be tissue specific, as in this
cytosine (C). In RNA, the pairing is the same example.
except that adenine (A) pairs with uracil (U). If
unrepaired prior to replication, deamination of a 3.4. Answer: A.
cytosine (C) to a uracil (U) will result in pairing Whilst the other answers are all stages of the
with adenine (A), ultimately replacing the original cell cycle, it is during anaphase that the ~pindle
GC pair with an AT pair. fibres attach to the sister chromatids a~d pull
them apart.
3.2. Answer: C.
Transcription describes the production of RNA 3.5. Answer: D.
from the DNA template. RNA polymerase binds A stop-gain (or nonsense) mutation introduces
to the promoter sequence on the DNA a premature stop codon, resulting in a
template strand, then moves along the strand truncated protein. A synonymous mutation
producing a complementary mRNA molecule. is a base substitution that does not result in
DNA polymerase is not required for a change in the amino acid (because more
transcription but is an essential component of than one codon may encode a particular amino
DNA replication. Translation (production of the acid). A missense (or non-synonymous)
protein encoded by the mRNA) occurs on the mutation is a base substitution that results in a
ribosome, and requires an mRNA template and change in the encoded amino acid. A deletion
tRNAs. is the loss of one or more nucleotides. If the
number of nucleotides deleted from within a
3.3. Answer: B. coding region is not a multiple.of three, this
Transcription produces a nascent transcript, results in a frameshift mutation, with a typically
which then undergoes splicing to generate the severe effect.
shorter 'mature' mRNA molecule that provides
the template for protein production. Splicing 3.6. Answer: A.
removes the intronic regions and joins together Myotonic dystrophy type 1 (DM1) is a triplet-
the exons. Different combinations of exons may repeat disorder, caused by pathological
expansion of a run of CTG repeats within the produces a shorter, non-functional protein and
OMPK gene, located on chromosome 19. It is therefore an example of a loss-of-function
-'
shows autosomal dominant inheritance so mutation. A gain-of-function mutation results in
there is a 50% chance that the patient's baby activation or alteration of a protein's normal
will be affected, regardless of gender. function.
Expanded repeats are unstable and may
expand further during meiosis, so that offspring 3.11. Answer: E.
inheriting the condition are often more severely Becker muscular dystrophy is an X-linked ·
affected than the affected parent - a disorder. Since his grandfather was also
phenomenon known as anticipation. affected, the condition cannot have
Anticipation most commonly occurs during the arisen in your patient de novo and his mother is
transmission of the condition from mother to an obligate carrier. In genetic pedigrees,
child. The vast majority of individuals with females are represented by circles, and
DM1 have inherited their expanded CTG allele unaffected female carriers of X-linked
from a parent; new expansions of a normal conditions are represented by an open circle
allele are rare. with a central dot. Female carriers of autosomal
recessive conditions are represented by a
3.7. Answer: E. half-shaded circle. Fully shaded symbols
Turner's syndrome is a sex chromosome represent affected family members.
aneuploidy where there is rnonosomy of the X Diamonds are used to represent ongoing
chromosome (note the single X chromosome pregnancies.
and absence of Y chromosome in the
karyotype). Girls with Turner's syndrome are 3.12. ·Answer: E.
typically shorter than average and have Autosomal dominant conditions typically show
underdeveloped ovaries, resulting in delayed or variable penetrance - not all people who inherit
arrested development of secondary sexual a mutation will develop the disease. Affected
characteristics, delayed or absent menstruation individuals typically occur in each generation
and commonly infertility. (unless the mutation has arisen de novo in an
affected individual). Males and females are
3.8. Answer: A. equally affected. /
The initial management step here is to exclude The recurrence risk for a couple with an
a chromosomal cause for her difficulties. Array affected child will depend on whether the
CGH would be the most appropriate first-line mutation has arisen de novo in the affected
investigation as it provides a genome-wide child (in which case it is low, typically < 1%), or
screen for chromosomal abnormalities. It has has been inherited from a parent, in which,'c,ase
superseded the use of karyotyping in this it is 50%.
context as it provides a much higher-resolution
screen. Fragile X is a recognised cause of 3.13. Answer: A.
developmental delay but is unlikely here in the In mitochondrial inheritance, the mutation is in
context of the microcephaly. If the array CGH is the mitochondrial DNA and, since mitochondria
normal, then you may wish to proceed to are contributed by the oocyte and not by the
exorne sequencing, or a developmental delay sperm, inheritance is exclusively via the
gene panel. maternal line. Males and females are equally
affected. Variable penetrance and expressivity
3.9. Answer: E. is common in mitochondrial disorders due to
Translocation is the result of joiniog of two the degree of mitochondrial heteroplasmy (not
segments of DNA from different chromosomes. due to X-inactivation, as in X-linked disorders).
All the other answers describe structural Whilst it is possible that th,e condition has
rearrangements that may be founct within a arisen in the proband de •novo, it is more likely
single chromosome. that it was inherited from her mother. If her
mother is indeed a carrier, she will have
3.10. Answer: A. transmitted the conditio[l to all her offspring.
A dominant negative mutation interferes with Both the mother and siblings should therefore
the function of the wild-type protein. A be offered genetic testing, regardless of clinical
protein-truncating (or stop-gain) mutation symptoms.
3.22. Answer: D.
Mutations in the TP53 gene cause Li-Fraumeni
syndrome, a hereditary predisposition to
Clinical immunology
Multiple Choice Questions
4.1. Which of the following statements best A. Each component is able to function
describes a key feature of innate immunity? independently
A. It improves with repeated exposure to a B. It is ready to act immediately on pathogen
given antigen exposure
B. It includes interaction between pattern C. Primary lymphoid tissues include the spleen
recognition receptors on phagocytes and and mucosa-associated lymphoid tissue
pathogen-associated molecular patterns D. T- and B-cell receptors are antigen specific
C. It is not associated with primary immune E. Vaccination efficacy does not require
deficiency functional adaptive immunity
D. It requires antigen processing for activation
E. Memory and specificity are characteristic 4.5. Which of the following statements is cor1ect
features regarding primary immune deficiency? /
A. A number of X-linked conditions are ;'
4.2. Which of the following statements best recognised
describes a key feature of phagocytes? B. Bone marrow transplantation is required for
A. They are derived from thymic progenitors B-cell immune deficiency
B. They are involved in intra- and extracellular C. Gene therapy has not yet been applied to
killing of microorganisms primary immune deficiencies '
C. They do not damage host tissue D. Primary immune deficiency is invariably fatal
D. They have a long half-life without treatment
E. They include monocytes, macrophages, E. Primary immune deficiency only presents in
neutrophils and natural killer (NK) cells childhood
4.3. Which of the following statements 4.6. Which of the following statements is correct
describes a key function of cytokines? in relation to immunoglobulins?
A. They are routinely measured in clinical A. They are constructed of two identical heavy
practice chains and two identical light chains
B. They are small molecules that act as B. They are derived from thymic precursors
intercellular messengers C. They are limited to the intravascular
C. They do not require receptor interaction compartment
D. They have distinct and non-olierlapping D. They include six isotypes
biological functions E. They protect predominantly against
E. They have not been shown to have a role in intracellular infection
disease pathogenesis
4.7. Which of the following statements is
4.4. Which of the following statements is correct most consistent with immunoglobulin
with regard to adaptive immunity? deficiency?
4.11. Which of the following statements is 4.16. Which one of the following statements is
correct regarding hypersensitivity reactions? true regarding disease-modifying therapy in
A. The predominant cell type involved in type IV autoimmune disease?
hypersensitivity is the basophil A. Anti-tumour necrosis factor (TNF) therapy
B. Type I hypersensitivity is lgG mediated has been shown to alter the course of
C. Type II hypersensitivity results in circulating disease progression i11. rheumatoid arthritis
immune complexes B. Biological agents are generally now
D. Type Ill hypersensitivity" results in considered first -line therapy for inflammatory
complement activation bowel disease
C. Inhibition of integrins has no proven efficacy diagnostic tests. Which of the following
D. Mononclonal antibodies used in autoimmune statements best fits the clinical scenario?
disease have not been associated with A. A defect in T-cell immunity is most likely
serious side-effects B. A periodic fever syndrome is most likely
E. Small-molecule inhibitors targeting C. An X-linked immune deficiency is most likely
intracellular signalling pathways have yet to D. Primary immune deficiency is ruled out by
be developed the patient's age
E. The diagnostic test would be lymphocyte
4.17. Which of the following statements is true immunophenotyping
regarding organ transplantation?
A. Acute rejection typically occurs within the 4.20. A 70 year old man presents to his family
first week post-transplant physician with recurrent lower respiratory tract
B. Chronic rejection is immune mediated infection. Sputum culture has confirmed
C. Co-stimulatory blockade has not been Streptococcus pneumoniae and Moraxel/a
shown to improve outcomes catarrhalis on multiple occasions. Which of the
D. Hyperacute rejection occurs as a result of following tests would have the lowest yield (i.e.
recipient pre-formed antibody would be LEAST helpful) in this context?
E. Post-transplant immunosuppression is only A. Full blood count with white cell differential
required for the first 6 months B. Lymphocyte immunophenotyping
C. Neutrophil function tests
4.18. A 57 year old woman with a 20-year D. Serum immunoglobulins and electrophoresis
history of rheumatoid arthritis presents to the E, Thoracic computed tomography (CT) imaging
emergency department with a right basal
pneumonia. She has received a number of 4.21. A 35 year old woman presents to the
disease-modifying drugs for the arthritis, allergy clinic for investigation of venom
including methotrexate, and has most recently hypersensitivity. She reports rapid onset of
been on rituximab, an anti-CD20 monoclonal localised swelling at the site of a wasp sting on
antibody targeting B cells. Which of the her forearm, with subsequent dyspnoea and;
following statements is correct? altered vision prior to collapsing. She was /
A. Immunoglobulin measurement is unlikely to treated at the scene by the paramedics pribr to
be informative transfer to her local hospital. She lives in q, rural
B. Immunoglobulin measurement should include area, is a keen cyclist and often cycles in·
paraprotein assessment for appropriate remote areas. Which of the following
interpretation statements is correct?
C. Methotrexate is not a risk factor for A. Component-resolved diagnostics sh~t1ld be
secondary immune deficiency the first -line test
D. Opportunistic infection does not need to be B. From the clinical history given, an adrenaline
considered (epinephrine) auto-injector is not indicated
E. The patient is at low risk of secondary C. The clinical history is not suggestive of
immune deficiency anaphylaxis
D. The patient's regular drug history is not
4.19. A 5 year old boy presents to the relevant
paediatric team with right upper quadrant pain E. Venom immunotherapy should be
and fever. He has a temperature of 38.5°C, considered for this patient
tenderness over a mildly enlarged liver and is
noted to have gingivitis. At the age of 3 years 4.22. Which of the following clinical scenarios is
he developed a cutaneous abscess following correctly paired with the underlying immune
minor trauma. His younger brother died at 2 deficiency?
years of age of sepsis; further details are not A. A 26 year old man presenting with
known. On imaging he is found to have a oesophageal candidiasis = primary antibody
5x6 em hepatic abscess, aspiration confirming deficiency
Staphylococcus aureus infection. On the B. A 40 year old woman presenting with
post-take ward round you are asked to increasing delirium; cerebral imaging ,and
consider the differential diagnosis and biopsy confirm central nervous system (CNS)
Answers
4.1. Answer: B. cytokines have a role in disease pathogenesis'.
Pathogen-associated molecular patterns, found They are not currently routinely measured in
on invading pathogens, are recognised by clinical practice.
pattern recognition receptors on phagocytic
cells, allowing phagocytosis and subsequent 4.4. Answer: D.
pathogen destruction. Memory, specificity and T and B lymphocytes carry unique
the need for antigen processing are features antigen-specific receptors, conferring specificity
of adaptive immunity. Primary immune of the adaptive immune response. Antigen
deficiencies affecting innate immunity are well processing is required by T cells, such that the
recognised. adaptive response requires time to develop.
Components of the adaptive immune response
4.2. Answer: B. work in concert rather than functioning
Phagocytic cells are derived from bone marrow independently. Primary lymphoid tissues are the
precursors. They include rnonocytes, bone marrow and thymus.
macrophages and neutrophils, and are involved
in intra- and extracellular killing of 4.5. Answer: A.
microorganisms. They may cause damage to Primary immune deficiency often presents in
host tissue and have a short half-lim. childhood but can present later. A number of
X-linked conditions are recognised.
4.3. Answer: B. Immunoglobulin replacement therapy is
Cytokines are small molecules that act as standard treatment for primary B-cell immune
intercellular messengers via interaction with deficiency. Gene therapy has been applied
specific cytokine receptors. They have to a number of specific primary immune
overlapping biological functions. Many deficiencies. There is a spectrum of immune
5.7. In a clinical trial where participants are B. The NNT is one minus the absolute risk
randomly allocated to a treatment or control reduction
group, which one of the following statements C. The NNT is the number of patients who will
is true? benefit from a treatment if 100 typical
A. In randomisation, the doctor generally knows patients are treated
which treatment the patient will be allocated D. The NNT is the reciprocal (inverse) of the
to before they are enrolled in the trial difference in risk between different treatment
B. In randomisation, the patient generally knows groups
which treatment they will be allocated to E. The NNT is the reciprocal (inverse) of the risk
before they are enrolled in the trial ratio
c. Randomisation is performed so that the
number of patients in the treatment and 5.11. In a clinical trial, 2000 patients were
control groups are the same randomly allocated on a 1-to-1 basis to either a
D. Randomisation is primarily used to reduce placebo or 'Novotreat', a new drug. After
1-year of follow-up, 130 patients in the placebo
bias
E. Randomisation is primarily used to reduce group and 100 in the treatment group had
confounding died. What was the absolute risk reduction?
A.3%
B. 23%
5.8. In a case-control study examining the
effect of coffee consumption on lung cancer,
c. 0.77
D. 1.30
which one of the following might lead to
E. 33.33
confounding?
A. People with lung cancer are more likely to 5.12. A city has a population of 100000. Each
over-report smoking year 10 000 people are diagnosed with heart
B. People with lung cancer are more likely to disease for the first time after presenting to
under-report coffee consumption their doctor and 5000 people die of heart
C. Smokers with lung cancer drink more coffee disease. Of the latter, 1000 are not found to
than smokers without lung cancer have heart disease until after they died. /
D. Smoking is commoner in coffee drinkers Assuming that there are no other ways that /
E. There is a lot of variation in the amount of new cases are identified, which of the following
caffeine in different coffees is true of heart disease in this city?
A. The case fatality is 20%
5.9. Which of the following is a true description B. The incidence is 10 per 100 person-yea~s .
of a cohort study, as used in epidemiological C. The incidence is 11 per 100 person-yeafs,/
research? D. The incidence is 5 per 100 person-years
A. Cohort studies generally enrol people without E. The prevalence is 10%
disease
B. Odds ratios cannot be calculated 5.13. Which of the following is true of national
C. Participants are randomly assigned to health information systems?
different exposures A. Definitions of non-psychiatric illnesses are
D. People with the disease of interest are agreed nationally
selected along with similar people without B. Few countries produce national mortality
the disease of interest statistics
E. Risk ratios cannot be calculated C. Incidence rates can generally be easily
compared across countries
5.10. Which of the following is true of the D. Most countries record attendances at
number needed to treat (NNT), calc;:ulated from primary care facilities by cause
a randomised controlled trial? E. Most countries use an international standard
A. The more effective a treatment, the larger classification system for recording cause of
the NNT death
Answers
5.1. Answer: D. a disease to be important globally, e.g. malaria
Congenital anomalies were ranked 10 in 2013 or primary liver cancer, but not important in a
in the GBD Exercise initiated by the World specific country. The test should be whether it
Bank. Asthma is a major cause of burden of is an important public health problem in the
disease but not of premature deaths. Protein specific country or region.
energy malnutrition has been declining as an
important cause of death due to economic 5.7. Answer: E.
development globally. Alzheimer's disease and Randomisation is performed primarily to ensure
colorectal cancer are both important causes of that, on average, different treatment (or
premature death but are both outside the top intervention) groups are similar, apart from the
20 (rank 29 and 27, respectively). intervention being studied. It is only true to say
that the groups are the same on average,
5.2. Answer: A. however, as differences can arise by chance.
HIV/AIDS rose from rank 27 in 1990 to rank 6 Randomisation only works if the treatment
in 2013 due to the global epidemic. Most other allocation is masked until after the decision is
infections, including meningitis, measles and taken to enrol a participant. In some trials, the
maternal infections, fell due to increased treatment allocation continues to be concealed
implementation of successful control measures. after enrolment, but this is done for a separate
Iron deficiency anaemia ranking fell from 35 . reason, to reduce bias.
to 45.
5.8. Answer: D.
5.3. Answer: E. Confounding is where a cause of the disease
Schizophrenia was ranked 11 as a cause of (or a marker of such a cause) is commoner in
YLD in 2013. Epilepsy is an important cause of the exposure group of interest, and is not itself
YLD but outside the top 20 (rank 23). Cataract, a consequence of that exposure. If coffee per
neural tube defects and alcohol use disorders se, caused smoking, it would not be j
are causes of disability but are all well below confounding but a causal chain. !'
the top 15 ranked causes.
5.9. Answer: A.
5.4. Answer: A. Cohort studies are observational studies where
Alcohol use was ranked 6 as a cause of GBD participants are selected to reflect sorrie
in 2013. Suboptimal breastfeeding is ranked 19 population, characterised according ti:Jitheir
in 2013, down from rank 11 in 1990, and baseline characteristics and followed dp over
vitamin A deficiency is ranked 23, down from time to observe occurrences of one or more
rank 36. Low-fibre diet (25) and low physical diseases of interest. The relationship between
activity (17) are also of lower rank. an exposure and outcome of interest can then
be studied. Risk ratios, odds ratios and rate
5.5. Answer: E. ratios can all be calculated in cohort studies.
Self-selection bias, lead-time bias and length Studies that enrol people with disease and then
bias are all classic sources of bias in evaluation follow up these people over time are better
of screening trials. Incomplete follow-up is also called case series with follow-up.
an important problem in all trials. Screening
evaluations normally are based on recorded 5.10. Answer: D.
events for their primary evaluations and do Developed by David Sackett, the number
not depend on recall of past events, so needed to treat (NNT) aims to provide doctors
recall bias is not one of the most important and patients with a more intuitive statistic for
problems. quantifying treatment effects than the standard
ratios and differences. It is calculated as the
5.6. Answer: B. inverse of the abwlute risk reduction (or risk
The important question is how common is the difference) between treatment groups. Like
condition in the specific population in whom the absolute risk reductions, NNTs are only
screening will be implemented. It is possible for comparable if the risks being reported are the
same, including the time over which the risk know the proportion of the people with heart
applied, e.g. 1-year absolute risk reductions disease who die from any cause. Additional
and 5-year absolute risk reductions are not assumptions would also be needed to estimate
comparable. the prevalence of heart disease.
group, (3) the risk ratio of the treatment versus defined. In most countries (the most notable
the placebo group and the (4) relative risk exception being the USA where the Diagnostic I
reduction. and Statistical Manual of Mental Disorders is
used), lCD criteria are also used to define
5.12. Answer: C. psychiatric illnesses. For non-psychiatric
The incidence rate is the number of new events illnesses, definitions are not included as part of
per unit of person-time. As 1000 of the people the lCD system, although there are some
who died with heart disease were not separate definitions of certain conditions such
previously diagnosed, these also represent new as diabetes which have been adopted widely
events. You do not have sufficient information {http://www.who.int/diabetes/publications/
to estimate the case-fatality as you do not diagnosis_diabetes2006/en/).
I
/
//
Principles of
infectious disease
Multiple Choice Questions
6.1. A 53 year old lawyer from South Africa who She complains of severe headaches, slurred
is human immunodeficiency virus (HIV)- speech and right arm weakness, and a
seropositive has a medical review, which computed tomography (CT) head scan
reveals a positive interferon-gamma release shows multiple space-occupying lesions in
assay (IGRA), showing T cells reactive to her brain. What are her symptoms most likely
Mycobacterium tuberculosis antigens. He is due to?
asymptomatic and a chest X-ray is reported as A. Antiretroviral drug-related side-effect
negative. Which of these most accurately B. HIV-related damage to brain
describes his mycobacterial status? C. Immune reconstitution inflammatory
A. Active pulmonary disease syndrome (IRIS)
B. Commensal flora D. Metastatic carcinoma
C. Extrapulmonary infection E. Syphilitic gumma
D. Latent infection
E. Opportunistic infection 6.4. A 59 year old woman presents with a
pelvic tumour and is found to have cer\.tical
6.2. A 9 month old infant has a temperature of carcinoma. The use of which vaccine lfl'
39.5oC and is not feeding. The parents attend childhood would have reduced the chance of
the local clinic where the doctor can find no this cancer developing?
abnormalities on physical examination other A. Hepatitis B virus vaccine
than erythema of the right tympanic membrane. B. Human papilloma virus (HPV) vaccine
Treatment with which of the following is C. Measles vaccine
appropriate as a simple and safe intervention D. Pneumococcal conjugate vaccine
that may decrease the body temperature? E. Rubella vaccine
A. Anti-tumour necrosis factor (TNF) antibody
B. Aspirin 6.5. A 33 year old Nigerian man who has had a
C. Erythromycin haematopoeitic stem cell transplant for aplastic
D. Paracetamol anaemia six months previously returns to visit
E. Penicillin his family in Nigeria once a year. He attends
your vaccine clinic. which of the following
6.3. A 44 year old woman is diagnosed with vaccines should be avoided?
HIV infection and a low CD4 T-cell count. She A. Hepatitis B virus vaccine
starts antiretroviral therapy to treat her infection B. Influenza inactivated vaccine
and is seen at clinic 3 months later when she C. Pneumococcal protein conjugate vaccine
has an undetectable HIV viral load and a D. Tetanus toxoid
significant increase in her CD4 T-cell counts. E. Yellow fever virus vaccine
6.6. A 45 year old man is admitted to the there is purulent drainage from a wound in the
intensive care unit with a short history of right hip and aCT scan reveals a collection,
respiratory symptoms and shortness of breath. which is aspirated. The microbiologists identify
He arrived in the country 2 days ago. Initial Gram-positive cocci in clusters that they identify
polymerase chain reaction (PCR) for routine as Staphylococcus aureus. The presence of
respiratory viruses is negative but a sample which genetic element will influence therapy
sent to the national laboratory detects a decisions for this patient?
-
specific geographically restricted coronavirus. A. ampC extended-spectrum P-lactarnase ·
Travel to which of the following countries is B. mecA penicillin-binding protein
most likely to be associated with this virus? C. NDM-1 carbapenemase
A. Brazil D. TEM-12 P-lactamase
I
B. China E. vanA gene cluster
C. Saudi Arabia
D. United States of America 6.1 D. A 73 year old patient develops
E. Zambia Staphylococcus aureus bacteraernia with a
meticillin-sensitive strain that remains persistent
6.7. A 63 year old retired international aid despite flucloxacillin therapy. All prosthetic
worker who last worked abroad 15 months ago material and collections of infection have been
presents with fever and fatigue. He had worked removed or drained. Which intervention may
in many African countries but particularly in enhance the success of the therapy?
Sudan and West Africa. On examination he is A. Administering therapy as an infusion
found to have splenomegaly and his full blood B. High-dose once-a-day therapy
count reveals anaemia and thrombocytopenia. C. Increasing the dose frequency
Which of the following tropical infections is D. Prolonging treatment duration
most consistent with the clinical scenario? E. Switching to glycopeptide therapy
A. Dengue
B. Leishmaniasis 6.11. A 60 year old man with acute myeloid
C. Plasmodium falciparum leukaemia develops pulmonary aspergillosis. He l
D. Trypanosoma brucei gambiense is placed on treatment with voriconazole. Whic~'
E. Typhoid fever of the following is a recognised adverse effect )
of voriconazole therapy that the patient shoulq
6.8. Your hospital has had three cases of be counselled about?
severe community-acquired pneumonia in the A. Aplastic anaemia
last 3 weeks that have had positive tests for B. Dermatitis
urinary Legionel/a antigen. You typically have C. Oesophageal ulcer
one to two cases per year. The cases were D. Proximal renal tubular injury
cared for in different units and there was no E. Tendon rupture
direct contact between the cases while
hospitalised. All three cases have the same 6.12. A 33 year old man develops chicken pox
postal code. You contact the public health with pulmonary involvement. He is previously fit
doctors to discuss these cases. How would and well and has had no prior therapy for viral
you best describe the clustering of these infections. He is hypoxic and has tachypnoea.
cases? His chest X-ray reveals widespread nodules. In
A. Common source outbreak addition to oxygen, which antiviral agent should
B. Epidemic he receive?
C. Nosocomial linked cluster A. Aciclovir
D. Pandemic B. Amantadine
E. Person-to-person community spmad C. Cidofovir
D. Foscarnet
6.9. A 56 year old patient has had multiple E. Valaciclovir
orthopaedic operations to deal with
complications of a road traffic accident. These 6.13. A 35 year old wildlife photographer plans
have involved plates and screws for several a trip to Kenya and asks for advice about
fractures. Three weeks after the last operation antimalarial treatment. She has a long history of
Answers
,,l
6.1. Answer: D. suspicion of a drug-related side-effect, 'but the
The test result with a positive IGRA nature of the lesions on brain scan are not
but no symptoms or signs on chest X-ray consistent. They have occurred at a time when
suggesting infection and no evidence of active the immunodeficiency associated with HIV has
disease point to latent infection. Active been reversed, which raises suspicibri of IRIS.
pulmonary and extrapulmonary disease HIV itself can cause chronic loss of brain
would have signs and/or symptoms and volume but not space-occupying lesions, and
M. tuberculosis would not be found as syphilitic gumma or metastatic carcinoma
commensal flora. (although differential diagnoses) are not
associated with therapy and immune
6.2. Answer: D. reconstitution.
Temperature elevation involves generation of
cytokines and prostaglandins. Paracetamol is a 6.4. Answer: B.
simple intervention that can inhibit generation of The HPV vaccine is now part of the vaccine
prostaglandins and act as antipyretic. Although schedule for girls in many countries and
aspirin would do the same, it is not decreases the risk of cervical carcinoma. The
recommended routinely for children due to the hepatitis B vaccine also reduces the incidence
risk of Reye's syndrome. Anti-TNF therapy has of a cancer, in this case hepatocellular
other medical indications arid antimicrobials carcinoma, but the other vaccines do not have
would not be appropriate for what appears to an obvious link to reduction of cancer
be a viral illness. incidence.
--
and presence of a geographically restricted theory, improved by continuous infusion.
coronavirus raise the possibility of Middle East Increasing the dose would be appropriate only
respiratory syndrome (MERS) coronavirus. for antimicrobials that kill by dose-dependent
Travel-related cases have been seen in many killing (e.g. aminoglycosides).
1
countries but the majority of cases have initially
been associated with travel to countries in the 6.11. Answer: B.
Middle East. Voriconazole can cause photosensitive
dermatitis and patients should be advised to
6.7. Answer: B. avoid sun exposure or to use a high-level
The clinical scenario with fever, splenomegaly sunblock on light-exposed areas. The other
and abnormalities on the full blood count could side-effects are associated with other
be seen with most of these travel-associated antimicrobials.
infections, although at this late stage
Trypanosoma brucei would generally present 6.12. Answer: A.
with encephalopathy. The key feature here is All the listed choices except amantadine are
the incubation period. Of these infections, only active against herpes virus infections but for
leishmaniasis and sleeping sickness would someone with an end-organ complication such
present with such a long incubation period. The as pneumonia, high-dose intravenous therapy
clinical scenario suggests visceral leishmaniasis aciclovir would be indicated. Valaciclovir would
not sleeping sickness. be appropriate for milder disease and foscarnet
for someone who has an infection with
6.8. Answer: A. resistance to aciclovir as may occur in an
The cases are most consistent with a common immunocompromised patient with frequent
source outbreak that is linked to some exposure.
common environmental source. Since the
patients were cared for in different units, there 6.13. Answer: A.
is no evidence of hospital transmission. Atovaquone when combined with proguanil is
Person-to-person transmission in the active against Plasmodium falciparum. This is a
community would be a less likely scenario for good choice as it is well tolerated. Mefloquine
this organism. The numbers are not consistent is associated with neurocognitive side-effects
with a pandemic or epidemic. and can worsen symptoms of pre-existing
psychiatric conditions. Doxycycline is another
6.9. Answer: B. option but can cause photosensitive dermatitis
The mecA gene encodes a penicillin-binding and may not be a good choice for someone
protein with low affinity for penicillins, including who will be working out of doors. Resistance
antistaphylococcal penicillins, and is the means chloroquine is no longer a suitable
usual basis of resistance in meticillin-resistant option in most malaria-endemic areas.
Staph. aureus (MRSA). Presence of this lvermectin is used against helminths not
genetic element, which is often screened malaria.
for in Staph. aureus strains, necessitates
use of an antimicrobial other than an 6.14. Answer: A.
antistaphylococcal penicillin (e.g. fl1:1cloxacillin). Tetracyclines absorption is limitedby cations
vanA encodes a penicillin-binding protein that such as calcium, iron and antacids that contain
has low affinity for glycopeptides and is found aluminium or magnesium. The other
in enterococci. The other options are medications will not alter absorption.
~-lactamase or carbapenemase enzymes Tetracyclines should be taken at a different
that mediate resistance in Gram-negative time, several hours separate from the
bacteria. cation-containing medicine.
Poisoning
Multiple Choice Questions
7.1. Which one of the following is most likely to D. lsosorbide mononitrate
produce significant toxicity if ingested E. Paracetamol
accidentally by a child?
A. A 1 em length of pencil lead 7.4. A family of four people living in Jamaica
B. One combined oral contraceptive tablet develop vomiting, diarrhoea and abdominal
C. One liquid laundry detergent capsule pain a few hours after eating a well-cooked
D. One mouthful of emulsion paint meal of snapper fish in a seafood restaurant.
E. One prednisolone 5 mg tablet This subsequently progresses to unsteadiness
of gait, blurred vision and tingling in the hands
7.2. A patient develops prolonged and recurrent and feet. Which of the following is the most
episodes of torsades de pointes associated likely diagnosis?
with no palpable cardiac output after an A. Aconite poisoning
overdose of sotalol. All of these interventions B. Ciguatera poisoning
may be useful except one. Which one is NOT C. Paralytic shellfish poisoning
likely to be helpful in the management of this D. Salmonella poisoning
situation? E. Scombrotoxic fish poisoning
A. Cardiac pacing
B. Correction of hypokalaemia 7.5. Which of the following is the most likely
C. Intravenous bolus dose of magnesium explanation for the following clinical features
sulphate in an adult patient after drug overdose:
D. Intravenous infusion of isoproterenol tachycardia, delirium, hallucinations, fever,
E. Intravenous bolus dose of procainamide diarrhoea, shivering, inducible prolonged
clonus, seizures, raised creatine kinase?
7.3. A 33 year old male attends the emergency A. Anticholinergic toxidrome
department with breathlessness and chest pain B. Intercurrent infection
after using a recreational substance/street drug. C. Recent use of gamma hydroxybutyrate
On examination he looks cyanosed and has a D. Serotonin syndrome
tachycardia (120 beats/min). On supplemental E. Stimulant toxidrome
oxygen, his arterial blood gases show W
52.5 nmoi/L (pH 7.28), PaC0 2 2.7 kPa 7.6. A 54 year old man presents unconscious.
(20.3 mmHg), Pa0 2 17.3 kPa (129.8 mmHg) His pulse is 88 and blood pressure 142/78.
and 35% methaemoglobinaemia. Which Initial investigations reveal normal urea and
of the following is the most likely causative electrolytes, creatinine of 101 11moi/L (1.14 mg/
agent? dl) and glucose 7.3 m111oi/L (131.4 mg/dl).
A. Cocaine Arterial blood gases results include W
B. Gamma hydroxybutyn'ite 81.3 nmoi/L (pH 7.09), PaC02 1.8 kPa
C. Isopropyl nitrite (13.5 mmHg), base excess of -13 mmoi/L,
Answers
7.1. Answer: C.
These are all substances of low toxicity (Box
7.1 Substances of very low toxicity
7.1) with the exception of liquid laundry
detergent capsules, which can cause CNS Writing/educational materials, e.g. pencil lead, crayons,
chalk
depression in children and are also corrosive,
Decorating products, e.g. emulsion paint, wallpaper paste
sometimes causing stridor, pulmonary Cleaning/bathroom products (except dishwasher tablets
aspiration and airway burns, as well as ocular and liquid laundry detergent capsules, which can be
damage if the liquid gets into the eyes. corrosive)
Pharmaceuticals: oral contraceptives, most antibiotics (but
not tetracyclines or antituberculous drugs), vitamins B, C
7.2. Answer: E. and E, prednisolone, emolliWlts and other skin creams,
These are all useful interventions for torsades baby lotion .
de pointes except procaihamide. Magnesium Miscellaneous: plasticine, silica gel, most household
plants, plant food, pet food, soil
sulphate reduces the risk of torsades without
-
• Naphthalene may occur in severe cases need treatment at lower
• Copper sulphate concentrations
Fig. 7.3
7.6. Answer: B.
7.5A Anticholinergic and serotonergic
feature clusters This patient has marked metabolic acidosis
with greatly elevated lactic acid. While all of
Anticholinergic Serotonin syndrome
these diagnoses may cause metabolic acidosis,
Common Benzodiazepines SSRis
causes Anti psychotics MAOIs only cyanide and carbon monoxide are
TCAs TCAs associated with elevated lactic acid in the
Antihistamines Amphetamines absence of cardiovascular shock. Carbon
Scopolamine Tryptamines monoxide poisoning has probably been
Benzatropine Buspirone
Belladonna Bupropion excluded by the normal carboxyhaemoglobin
Some plants and (especially in result, unless exposure was many hours earlier.
mushrooms (see combination) Diabetic ketoacidosis and salicylate poisoning
Box 7.16B) are also excluded by the normal blood glucose
Clinical features and salicylate concentration, respectively.
Cardiovascular Tachycardia, Tachycardia,
hypertension hyper- or
hypotension 7.7. Answer: D.
Central Delirium, Delirium, Lead poisoning can be treated with oral DMSA
nervous hallucinations, hallucinations, (also called succimer) or parenteral sodium
system sedation sedation, coma
calcium edetate (Box 7.7). Indications for the
Muscle Myoclonus Shivering, tremor,
other listed chelating agents include poisoning
myoclonus, raised
creatine kinase with cyanide {hydroxocobalamin, dicobalt
Temperature Fever Fever edetate) or iron (desferrioxamine). Dimercaprol
Eyes Diplopia, mydriasis Normal pupil size has been used for heavy metal poisoning,
Abdomen Ileus, palpable Diarrhoea, vomiting including mercury, but has now been largely
bladder superseded by other chelating agents, because
Mouth Dry these are better tolerated.
Skin Flushing, hot, dry Flushing, sweating
Complications 'seizures Seizures
Rhabdomyolysis 7.8. Answer: E.
Renal failure The anion gap measures the difference
Metabolic acidosis between measured catiQns (sodium and
Coagulopathies potassium) and anions {chloride and
(MAO!= monoamine oxidase inhibitor,· SSRI = selective bicarbonate) and is usually calculated as [Na+ +
serotonin re-uptake inhibitor; TCA = tricyclic antidepressanV K+]- [cl- + HC03-]. The 'gap' reflects the
Rhabdomyolysis '
Renal failure
Metabolic acidosis
Coagulopathies
(MAO/= monoamine oxidase inhibitor; SSRI = selective serotonin re-uptake inhibitor; TCA = tricyclic antidepressan~
hypotension and cardiogenic shock poisoning but are uncommon and likely to
(Box 7.16B). be associated with severe cardiovascular
effects.
7.17. Answer: D.
Mefenamic acid is a non-steroidal 7.18. Answer: A.
anti-inflammatory drug (NSAID) with a very high These are typical features of cyanide poisoning.
propensity to cause seizures. Other common Sarin can also cause vomiting, breathlessness
causes of seizures in the context of drug (associated with bronchospasm and
overdose include tricyclic antidepressants, bronchorrhoea) and convulsions, but small
antipsychotic drugs, antiepileptic drugs, other pupils, abnormalities on respiratory examination
NSAIDs (although much less commonly than and reduced plasma. or red cell
with mefenamic acid), anticonvulsants and acetylcholinesterase activity would be expected.
theophylline (Box 7.17). Paracetamol, diazepam Sulphur mustard, lewisite and phosgene can
and digoxin do not cause seizures. Seizures cause respiratory effects but convulsions and
have been reported with severe amlodipine coma would not be expected.
Envenomation
8.6. A patient presents at a small rural hospital data is considered, by experts, to be a reliable
you are working in, with a history of snakebite figure indicating the impact of snakebite?
and on investigation she has local bruising and A. Snakebite causes about 3000 deaths per
swelling around the bite site with oozing of year in India
blood, a coagulopathy, renal failure and B. Snakebite causes about 45 000 deaths per
developing flaccid neurotoxic paralysis. In which year in India
country is this hospital likely to be? C. Snakebite causes more than 200 000 deaths
A. Bangladesh per year worldwide
B. Burma D. Snakebite causes only about 20 000 deaths
C. India per year worldwide
D. South Africa E. Snakebite is less important than
E. Sri Lanka land mines in causing injuries requiring
an amputation
8.7. You are working in a hospital in Brazil and
you are asked to assess a young man with a 8.11. You are working in a hospital in northern
history of snakebite, occurring at around dusk. England, near areas of national parks, when a
He did not see the snake properly, so cannot 10 year old boy is presented with a history of
provide a description. The bite site is not stepping on and being bitten by a snake while
showing much swelling or local pain, but there playing in his garden, near natural parkland.
are obvious fang marks and he has bilateral The boy's father, who was not present when
ptosis and a positive 20WBCT. Which snake is the bite occurred, describes the snake as grey
the most likely cause? in colour, with indistinct darker markings along
A. Coral snake (Micrurus frontalis) the sides of the body and a pale narrow band,
B. Green racer (Philodryas o/fersit) like a collar, behind the head. What type of
C. Jararaca (Bothrops jararaca) snake might this be?
D. Neotropical rattlesnake or cascabel (Crotalus A. A European adder (Vipera berus)
durissus terrificus) B. A form of legless lizard ('slow worm', Anguis
E. Tiger snake (Notechis scutatus) tragi/is)
C. A grass snake (Natrix natrix) I
I·
I
8.8. You are working in a hospital in rural D. A smooth snake (Carone/la austri<;J.ca)
Nigeria. A patient presents with a snakebite E. An escaped exotic snake, most likely a small
and already has local swelling and bruising mamba
around the bite site. A 20WBCT is positive
(blood not clotted at 20 minutes). Which of the 8.12. With regard to the patient in Question 1 ,
following snakes is most likely involved? 8.11 , this boy has now developed significant
A. Black-necked spitting cobra (Naja nigricollis) local swelling and bruising around the bite site,
B. Forest cobra (Naja melanoleuca) which is painful and swelling extends to much
C. Green mamba (Dendroaspis jamesom) of the bitten limb. He appears shocked, has
D. Puff adder (Bitis arietans) poor urine output and the preliminary report
E. Saw-scaled (carpet) viper (Echis ace/latus) from the laboratory indicates he may have a
coagulation abnormality. Questioning also
8.9. For a forest cobra bite (Naja melanoleuca), reveals that the father's description of the
which of the following is likely to be the most snake may not be accurate. What do you now
useful and effective first aid, if applied think is most likely to have bitten this boy?
correctly? A. A European adder (Vipera berus)
A. Electric shock B. A form of legless lizard ('slow worm', Anguis
B. Pressure bandage and immobilisation (PBI) tragi/is)
1
C. None of these listed C. A grass snake (Natrix 9atrix)
D. Scarification of the bite site D. A smooth snake (Carone/la austriaca)
E. Tourniquet E. An escaped exotic snake, most likely a small
mamba
8.1 0. Snakebite is variously claimed to be either
an important or quite unimportant medical 8.13. A young man presents to the emergency
problem. Which of the following epidemiological department of the London hospital you are
working in, claiming he has been bitten spider it is. What sort of spider would you be
by a large spider that he was keeping concerned about?
as a pet. The bite occurred 6 hours ago, has A. Australian funnel web spider
been very painful locally and his attempts to B. Black widow spider
control the pain with oral analgesia have failed. C. Brazilian wandering spider
He was given the spider by a friend who D. Brown recluse spider
worked for an importer of fruit such as E. Mexican orange-kneed tarantula
bananas. He does not know what type of
Answers
8.1. Answer: A. for envenoming. Serum electrolytes may be
Options C, D and E are all necessary urgent useful, but not critical to initial assessment, and
requirements in managing a patient with may be hard to obtain in a rural hospital
suspected envenoming, but ensuring there is setting, as may extended coagulation studies.
no problem with the classic 'ABC' of airway, The latter will take far more time to provide an
breathing and circulation, and treating any answer than will the 20WBCT. Arterial blood
problems found, is the most urgent action. gas is not a critical test in initial assessment of
Snakebite patients, particularly in Asia, still die snakebite and if there is a coagulopathy,
unnecessarily because bystanders and health insertion of the needle or a line may pose
professionals forget about the ABC and fail to significant risks for the patient.
provide airway protection and external
respiratory support, when required, following 8.3. Answer: D.
envenoming by neurotoxic snakes such as The history tells us he was bitten in a paddy
kraits and some cobras. field, so likely a wetlands agricultural area, a
Option B might seem like an obvious answer, classic setting for a Russell's viper (Daboia
but not every patient bitten/stung by a russelii and Daboia siamensis) and this snal)e
venomous animal will develop medically causes coagulopathy, plus other effects. In I'
r!
significant envenoming, therefore not every some areas, such as Myanmar, Russell's 1ipers
patient needs antivenom. The other issue is also commonly cause acute renal failure. , ·
choosing which antivenom to use, and what Saw-scaled vipers (Echis spp.) also caJse
dose to administer, particularly in countries with coagulopathy, but tend to inhabit dry areas
several different antivenoms. In countries such rather than paddy fields. However, there are
as India, where only a polyvalent antivenom is sometimes exceptions, so knowing preci~ely
available, there is no requirement to delay while where the bite occurred and matching that to
choosing the right antivenom, but that does not the known local venomous fauna might assist
imply every patient should be given antivenom, in deciding if a saw-scaled viper might be the
so CPR, if indicated, takes precedence. cause. Cobras (Naja spp.) do not cause
coagulopathy, neither do kraits (Bungarus spp.)
8.2. Answer: A. nor Indian red scorpions (Hottentotta tamu/us).
A number of snakes may cause rapid
envenoming with development of a 8.4. Answer: A.
coagulopathy that can present as prolonged The greatest risk when giving antivenom is an
bleeding from the bite site, any other recent anaphylactic reaction, which, if not correctly
wound, or the gums. The 20WBCT is a rapid managed, may prove fatal. Managing
and simple test that can provide a useful guide anaphylaxis requires a multifaceted approach,
to the presence of snakebite coagulopathy. but the key drug is adr~naline (epinephrine), in
That, in turn, can help in determining what type most instances administered intramuscularly.
of snake may be involved and, if there are Adrenaline should always be immediately
several different antivenoms available, which available, in an appropriate dose, prior to giving
one to consider using. any antivenom.
Blood pressure is certainly an important test, Adrenaline, as a dilute subcutaneous
but an abnormal result is not a specific marker injection, has also been suggested as a
Environmental· medicine
Multiple Choice Questions
9.1. Research on individuals exposed to 9.3. A 67 year old patient is brought to the
radiation from the atomic bombs in Hiroshima emergency department having been found
and Nagasaki has shown an increased relative unwell in an unheated apartment during the
risk of developing malignancy (leukaemia, oral winter in Northern Europe. Severe reversible
cavity, oesophagus, stomach, colon, lung, hypothermia is best characterised by which of
breast, ovary, urinary bladder, thyroid, liver, the following?
non-melanoma skin and nervous system) A. A core temperature below 32°C
as a result of radiation exposure. Which of B. Bradycardia, a J wave on the
these statements best describes this electrocardiogram and loss of consciousness
observation? C. Chest and abdomen rigidity with a core
A. The Japanese have higher rates of cancer temperature below 13°C and serum I
than the world average potassium > 12 rnrnoi/L. ("
B. This is a deterministic effect of radiation D. Shivering, white peripheries and irritability
C. This is a stochastic (random) effect of E. Tachycardia, tachypnoea and slight delirium
!,'
radiation
D. This is an observational effect unrelated to 9.4. A family consult their family physician for.
the atomic bomb advice regarding a forthcoming holiday in thE:l
E. This is because of background radiation in tropics. Heat illness is a spectrum of disease
Japan affecting both the young and old. Which of
these statements is most correct?
9.2. Radiation can be divided into ionising and A. Complications of heat stroke include
non-ionising forms. Ionising radiation carries hypovolaemic shock, lactic acidosis,
enough energy to free electrons from atoms or rhabdomyolysis, hepatic failure and
molecules, thereby ionising them, and this can pulmonary oedema
damage tissues and cells. Which of these B. Exertional heat illness is more common in
forms of therapy is most likely to cause the elderly than in younger people
long-term radiation injury through high levels of C. Heat acclimatisation is characterised by
ionising radiation exposure to patients? decreased sweat volume, reduced sweat
A. Chest X-ray to diagnose a spontaneous sodium content and secondary
pneumothorax hyperaldosteronism to n;aintain body sodium
B. Radiofrequency ablation for cardiac balance
arrhythmias D. Heat stroke commonly occurs above 39°C
C. Serial whole-body computed tomography E. Heat syncope is another term for heat stroke
(CT) for cancer screening
D. Transurethral microwave therapy for prostatic 9.5. Acclimatisation is the proc(lss of the body
hypertrophy adjusting to the decreased availability of oxygen
E. Ultraviolet therapy for psoriasis at high altitudes. This becomes noticeable
above 2500m. Which of these changes occurs B. In about 10% of cases, no water enters the
in healthy individuals? lungs and death follows intense
A. A shift in the oxygen dissociation curve to laryngospasm ('dry' drowning)
the left after 2-3 days C. Long-term outcome depends on the severity
B. Deep prolonged sleep with vivid dreams of the cerebral hypoxic injury and is
C. Deep, slow breathing to maximise oxygen predicted by the duration of immersion and
uptake delay in resuscitation, but is independent of
D. Erythropoiesis and haemoconcentration the presence of cardiac arrest
mediated through the endocrine system D. Salt water is hypertonic and inhalation
E. Fluid retention to counteract the raised provokes alveolar oedema, producing a
haematocrit due to hypoxia distinct clinical picture from freshwater
drowning
E. Those rescued alive (near-drowning) are
9.6. A 36 year old mountaineer ascends to
often unconscious and not breathing.
3800m. He complains of feeling tired and
Hypoxaemia and metabolic alkalosis are
unwell. His companions notice that he is
common features during resuscitation
staggering and delirious. Which of the following
statements is true regarding illness at altitude?
9.8. A 48 year old woman is planning to do
A. Acetazolamide is the treatment of choice for some diving on her forthcoming holiday to the
high-altitude cerebral oedema (HACE) Caribbean. She is reading about the possible
B. Altitude sickness usually occurs between risks involved. Which of the following
1500 m and 2500 m, is characterised by statements is true?
vomiting and resolves spontaneously after a
A. Ambient pressure under water increases by
few days
101 kPa (1 atmosphere, 1 ata) for every 10m
C. High-altitude pulmonary oedema (HAPE) is a
of seawater depth, with the nitrogen in air
life-threatening condition that initially presents
causing narcosis below 30m of seawater
with symptoms of dry cough, exertional
and oxygen becoming toxic at inspired
dyspnoea and extreme fatigue
pressures above 40kPa (0.4ata) .·
D. Monge's disease (chronic mountain sickness)
B. As divers descend, the partial pressurfs of
is characterised by polycythemia and
the gases they are breathing decreas13 and
hypoxia that does not improve if the patient
the blood and tissue concentrations .bf
moves to lower altitudes to live
dissolved gases change accordinglyt
E. The cardinal signs of HACE are headache,
C. She can be confident that she will be able to
unilateral pupillary dilatation and dizziness
undertake a final dive on the morning of her
return flight home provided she h~s taken
1
9.7. A 5 year old boy is brought to the enough time on her final ascent '
emergency department following a drowning D. She should hold her breath on ascent to
incident. Which of the following statements is avoid arterial embolisation through a patent
true with regard to a drowned patient? foramen ovale
A. Fresh water is hypotonic and impairs E. The bends are caused by bubbles of carbon
surfactant function, causing alveolar collapse dioxide being released into the body tissues
and left-to-right shunting of unoxygenated whilst a diver ascends; this can be treated
blood with recompression therapy
Answers
I
9.1. Answer: C. interval of around ,2-5 years and solid tumours
Stochastic (chance) effects occur with after an interval of about 10-20 years.
increasing probability as the dose of radiation
increases. Carcinogenesis represents a 9.2. Answer: C.
stochastic effect, with not all exposed CT scans result in relatively high-radiation
individuals being affected. With acute exposure and whole-body CT screening has
exposures, leukaemias may arise after an not been demonstrated to meet generally
accepted criteria for screening. The risks The cardinal signs of HACE are ataxia and
associated are outweighed by the benefits of altered consciousness. It is rare, life-threatening
diagnostic CT and there is a small increase in and usually preceded by AMS. In addition to
lifetime risk of developing cancer. Options B, D features of AMS, the patient suffers confusion,
and E are non-ionising radiations and the disorientation, visual disturbance, lethargy and
radiation dose from one chest X-ray is ultimately loss of consciousness. Monge's
negligible. disease improves if the patient moves to lower
altitudes to live.
9.3. Answer: B.
Hypothermia occurs when the core 9.7. Answer: B.
temperature drops below 35°C. Severe Drowning remains a common cause of
hypothermia is characterised by a temperature accidental death throughout the world and is
below 28°C, bradycardia, bradypnoea, relatively common in young children. Fresh
arrhythmias and loss of consciousness. A rigid water causes alveolar collapse and right-to-left
chest and abdomen with a core temperature shunting of unoxygenated blood. Saltwater and
below 13°C and serum potassium > 12 mmoi/L freshwater drowning produce a similar clinical
is probably incompatible with life. picture. In near-drowning, metabolic acidosis is
Body temperature is controlled in the almost universal and cardiac
hypothalamus, which is directly sensitive to arrest is a poor prognostic indicator in recovery
changes in core temperature and indirectly from drowning. It is true that in about 10%
responds to temperature-sensitive neurons in of cases, no water enters the lungs and
the skin. The normal 'set-point' of core death follows intense laryngospasm ('dry'
temperature is tightly regulated within drowning).
37±0.5°C.
9.8. Answer: A.
9.4. Answer: A. The underwater environment is extremely
Exertional heat illness is more common in hostile. Other than drowning, most diving illness
athletes and sweat volumes increase with is related to changes in barometric pressure
acclimatisation. Heat stroke is rare below 40oC and its effect on gas behaviour. Partial
and heat syncope is a distinct condition and far pressures of gases increase with descent and
less serious than heat stroke. the bends are caused by the nitrogen bubbles
on ascending again. Arterial embolisation may
9.5. Answer: D. occur if the gas load in the venous system '!
Hyperventilation is caused by hypoxia sensed exceeds the lungs' abilities to excrete nitrogen,
through the carotid bodies and a diuresis or when bubbles pass through a patent ;
occurs secondary to haemoconcentration. After foramen ovale. A patent foramen ovale occ~rs
2-3 days the oxygen dissociation curve moves in 25-30% of asymptomatic individuals. A diver
to the right, making it easier for haemoglobin to must ascend slowly and breathe regularly
release oxygen to the tissues. Sleep and during ascent to avoid barotrauma.
nocturnal breathing patterns are frequently Recompression is the definitive therapy for
disturbed at altitude. decompression illness. Recompression reduces
the volume of gas within tissues (Boyle's law),
9.6. Answer: C. forces gas back into solution and is followed by
Above 2500m, high-altitude illnesses may slow decompression that allows the gas load to
occur in previously healthy people, and above be excreted.
3500m these become common. Acute Decompression illness can be provoked by
mountain sickness (AMS) symptoms develop a flying. Diving tables should be consulted to
few hours after ascent and include dizziness, p
leave a safe gap between final dive and a
fatigue and headache. subsequent plane journE:)Y·
(120 mmHg). There is respiratory effort but no C. Positive end-expiratory pressure (PEEP)
audible air entry on auscultation. He is should be weaned to zero before extubation
unconscious and preparations are being is considered
made to intubate and ventilate him. Other than D. The fraction of inspired oxygen (Fi0 2) should
severe asthma, he has no other past medical be weaned to achieve a Pa02 of 15 kPa
history. (113 mmHg) and above
Which of the following statements is E. Tracheostomy should be immediately
CORRECT? performed if the patient fails a spontaneous
A. Large cannulae should be inserted bilaterally breathing trial
into the second intercostal space at the
mid-clavicular line 10.7. Which of the following findings suggests
B. Once intubated, a high respiratory rate and that ongoing intensive care treatment still has
large tidal volumes should be used initially to a realistic chance of a good neurological
--
clear the carbon dioxide outcome following cardiac arrest?
C. Once intubated, a respiratory rate of A. A computed tomography (CT) brain showing
12 breaths/min, a tidal volume of 6 mUkg preserved grey-white differentiation
and a prolonged expiratory time should be B. Absent corneal reflexes at 72 hours after
1
used initially return of spontaneous circulation (ROSC)
D. The blood gas is likely to be erroneous as C. Absent motor response to painful stimulus
his Pa02 is too high 72 hours after ROSC
E. The C0 2 will return to normal if the oxygen D. Bilaterally absent N20 spike on
mask is removed somatosensory evoked potentials
E. Myoclonic jerking within the first 24 hours
10.5. Which of the following statements best after ROSC
describes good practice when using sedation
and analgesia in intensive care? 10.8. A 37 year old previously healthy man is
A. A Richmond Agitation and Sedation Score brought into the emergency department by
(RASS) score of 0 suggests sedation is ambulance having stopped the car he was /
optimal driving. When the paramedics arrived he was .'
B. Etomidate is the most cardia-stable sedative conscious but appeared confused. This •/
and should be used as an infusion in progressed over the following 30 minutes to !,'
patients who are very unstable aphasia and the development of bilateral upp~r
C. Muscle relaxants can be used to reduce the and lower limb weakness with bilateral cranip.l
need for sedation nerve palsies. CT head scan on arrival is
D. Patients should be deeply sedated to reduce reported as normal.
the risk of delirium Which investigation is most likely to reveal
E. Sedation should not be stoppecj abruptly as the underlying pathology?
there is an unacceptable risk of A. CT angiogram of the circle of Willis
self-extubation B. CT scan of the cervical spine
C. Electrocardiogram (EGG)
10.6. A 45 year old man is being ventilated for D. Erythrocyte sedimentation rate (ESR)
acute respiratory distress syndrome (ARDS) E. Lumbar puncture
following a lobar pneumonia. The bedside
nurse has a number of questions regarding the 10.9. A 63 year old man is weaning from
strategy for ventilating this man as his lung mechanical ventilation. He has been ventilated
function improves. in the ICU for 3 months with Guillain-Barre
Which of the following points is correct? syndrome and profound ~eakness. A
A. During weaning, patients should"not be percutaneous tracheost9r'ny was placed 2
allowed to go for long periods with no months ago. He has suddenly developed
mechanical ventilator support if they are respiratory distress after a bout of coughing.
showing signs of respiratory distress He is now extremely tachypnoeic, sweating
B. If the patient is febrile, minute volumes will and in respiratory distress. He. has no
be lower and it is a good opportunity to previous history of any laryngeal or tracheal
wean the ventilatory support problems.
All of the actions below would be Which management plan is most likely to be
appropriate, except for one. Which of the successful?
following actions would NOT be considered A. Commencement of an adrenaline infusion.
best practice .in this situation? B. Immediate percutaneous coronary
A. Applying a facial high-flow oxygen mask intervention (PCI)
B. Applying a self-inflating bag to the C. Insertion of an intra-aortic balloon pump
tracheostomy and giving the patient several D. Intubation and ventilation with high levels of
large breaths PEEP
C. Calling for help E. Venous-arterial extracorporeal membrane
D. Passing a suction catheter through the oxygenation (ECMO)
tracheostomy to check patency
E. Removing the inner tube of the tracheostomy 10.12. Which of the following statements is
TRUE regarding gas carriage in the blood?
10.10. Which one of the following ventilated A. For a given PaC0 2, more carbon dioxide can
patients has ARDS according to the Berlin be carried by blood with haemoglobin that is
definition? 80% saturated with oxygen in comparison to
A. A man with a severe influenza pneumonia. 1 00% saturated
He has bilateral infiltrates on chest X-ray B. In capillaries with a high carbon dioxide
and a Pa02 of 10 kPa (75 mmHg) on an Fi0 2 content, e.g. exercising muscle, oxygen is
of 0.4 bound more tightly to haemoglobin, i.e. the
B. A man with left lower lobe pneumonia, a haemoglobin-oxygen dissociation curve is
normal echocardiogram and a Pa02 of shifted to the left
10 kPa (75 mmHg) on an Fi0 2 of 0.6 C. The majority of carbon dioxide is transported
C. A man with long-standing, progressive in the blood bound to haemoglobin
idiopathic pulmonary fibrosis. He has bilateral D. There is a greater oxygen than carbon
chest X-ray infiltrates, a normal dioxide content in arterial blood
echocardiogram and a Pa0 2 of 10 kPa E. When core temperature drops, for a given
(75 mmHg) on an Fi0 2 of 0.5 blood content of carbon dioxide, the P~C0 2
D. A woman with acute pancreatitis. She has will increase l
bilateral chest infiltrates, pleural effusions, a /
normal echocardiogram and a Pa02 of 10.13. A 45 year old man is admitted to 1the ICU
14 kPa (1 05 mmHg) on an Fi0 2 of 0.3 following coronary artery bypass surgery. He is
E. A woman with endocarditis and severe tachycardic, hypotensive and has a high
mitral regurgitation from a leaflet perforation. lactate. Clinical examination is unremarkable
She has bilateral chest X-ray infiltrates and and there is no bleeding apparent. Ah
,ECG
a Pa0 2 of 10 kPa (75 mmHg) on an Fi0 2 shows a sinus tachycardia with no other
of 0.6 abnormalities. His haemodynamic data (from
his pulmonary artery catheter) are as follows
(reference ranges are also given):
10.11. A 60 year old man becomes acutely
unwell on the medical ward. He was admitted
4 days prior with non-specific symptoms
(malaise, fever, coryza). On admission, his ECG Patient data Reference range
Cardiac output 10.2 Umin 4-8 Umin
showed sinus rhythm with no acute ST
Cardiac index 5.42 Umin/m' 2.5-4 Uminlm'
changes, but his serum troponin level taken
Pulmonary artery 15/9 mmHg 15-30/5-15 mmHg
24 hours post-admission was markedly raised.
pressures
A viral throat swab was positive for adenovirus. Pulmonary artery 7 mmHg 2-10 mmHg
He is tachycardic (180 beats/min), capillary wedge
hypotensive (65/30 mmHg), pale and clammy. pressure
On examination his chest is clear but he looks Central venous 6 mmHg 6-12 mmHg in
pressure ventilated patients
very unwell and a blood gas shows a lactate of
1 0 mmoi/L (90 mg/dl) with a haemoglobin of
120 g/L. His ECG now shows left bundle Which of the following statements is true?
branch block and a bedside echocardiogram A. An infusion of an inotrope such as.
confirms global left ventricular dysfunction. dobutamine is indicated
10.15. A 75 year old man who had been 10.17. A 65 year old woman is brought to /
/,'
previously fit and well was admitted to hospital intensive care after an acute deterioration on ,1
with shortness of breath. His chest X-ray the stroke ward. She had been recovering after
showed a left lower lobe pneumonia and he a left partial anterior circulation infarct when she
was commenced on intravenous antibiotics. His was noted to be acutely agitated and then
admission ECG showed a sinus tachycardia became drowsy. This progressed quickly t¢' 1
with left ventricular hypertrophy (by voltage unconsciousness and she was intubated t6;
criteria). Approximately 12 hours after facilitate a CT scan.
admission he acutely deteriorated with The CT head scan confirmed a large
tachypnoea, tachycardia, hypotension haemorrhagic transformation of the infarcted
(70/40 mmHg) and reduced oxygen area with 10 mm of midline shift, effacement of
saturations. On examination he is agitated, the ventricles and downward herniation of the
managing only incomprehensible sounds, with cerebellar tonsils. Twelve hours after arrival in
increased work of breathing and bilateral intensive care she is unresponsive (Glasgow
coarse crepitations. His ECG confirms atrial Coma Scale (GCS) score 3 despite no sedation
fibrillation with a ventricular rate of 120 beats/ for 4 hours), normothermic, and her pupils are
min. Which one of the following statements is fixed and dilated.
most accurate? Which of the following statements is true?
A. Antibiotics should be switched to a A. As she is not waking u8, a neurosurgeon
carbopenem should be asked to drain the haematoma
B. DC cardioversion is likely to resolve the B. Brain-death testing should be undertaken
clinical situation C. She has a good prognosis, provided she can
C. Intubation and ventilation is contraindicated survive the acute bleEl_d
due to advanced age D. She requires an electroencephalogram (EEG)
D. It is likely that this man is too unstable for and magnetic resonance imaging brain scan
anaesthetic agents to be used: if intubation to confirm brain death (under UK law)
patient sustained a few grazes and bruises to 64% when he was being moved into the
the right side of her body, including her head. ambulance, and symptoms improved slightly
The carer reports that the patient has also after administration of oxygen and morphine.
become increasingly unsteady on her feet and Clinical examination reveals respiratory rate of
has been complaining of having a headache 28 breaths/min, Sp0 2 90% on 8 L oxygen and
and blurred vision. She has been more sleepy reduced chest expansion on the right side,
than usual, but only intermittently. The patient's temperature 37.2°C, troponin and an ECG
cardiorespiratory observations are are unremarkable. A venous blood gas shows
unremarkable. From the options below, W is 51 nmoi/L (pH 7.29), PC0 2 7.0 kPa
what is the most likely cause of her current (52.5 mmHg), P02 3.1 kPa (23.3 mmHg),
symptoms? HC03- 25.5 mmoi/L, base excess -2.0 rnmoi/L
A. Chronic subdural haematoma and pulmonary vascular markings are absent
B. Dementia on the right on the chest X-ray. Which of the
C. Encephalopathy following is the most likely diagnosis?
D. Intracerebral haemorrhage A. Acute myocardial infarction
E. Subarachnoid haemorrhage B. Musculoskeletal chest pain
C. Pneumonia
10.25. A 24 year old woman with a body mass D. Primary spontaneous pneumothorax
index (BMI) of 38 kg/m 2 presents to the E. Secondary spontaneous pneumothorax
emergency department with a swollen and
tender right calf (3.5 em larger than the left). 10.28. A 20 year old man is brought to the
She has recently returned from a European emergency department after self-extricating
holiday resort and has sunburn, but is from a burning block of flats. He was trapped
otherwise well. She suffers from well-controlled inside the building for 15 minutes, in a flat on
asthma, for which uses inhalers, and is also the floor above the source of the fire. He has
taking the combined oral contraceptive pill. sustained no obvious injuries, but has a
Which of the following is the most likely persistent cough and feels 'dizzy'. Paramedics
diagnosis? have applied oxygen via a face mask, and the
A. Calf muscle tear patient's Sp0 2 is 99% on 2 L oxygen. An
B. Cellulitis secondary to an insect bite arterial blood gas sample is taken from the
C. Deep vein thrombosis patient. What additional test, not routinely
D. Dependent oedema requested on an arterial blood gas sample,
E. First -degree burn (sunburn) should be done?
A. Carboxyhaemoglobin
i''
10.26. Which of the following causes a leftward B. Fetal haemoglobin
shift of the haemoglobin-oxygen dissociation C. Haemoglobin A
curve? D. Nitrous oxide
A. Acidosis E. Superoxide
B. Decreased temperature
C. Increased 2,3-diphosphoglycerate (2,3-DPG) 10.29. Which of the following is a 'red flag'
D. Increased PC0 2 symptom in a person presenting with a
E. Increased temperature headache?
A. Associated with taking codeine tablets for a
10.27. Paramedics arrive in the emergency week
department resuscitation room with a 70 year B. Gradual onset (over an hour or more)
old man who has multiple comorbidities, C. Improved by lying down
including pulmonary fibrosis and chronic D. Right arm weakness
obstructive pulmonary disease (COPD; on E. Visual aura
home oxygen, with oxygen saturations normally
of 88-92% on air). He suddenly developed 10.30. A 60 year old woman with a previous
right-sided sharp chest pain and dypsnoea. head injury is admitted with collapse. Taken
The paramedics report that the patient initially from the history alone, which one feature may
had a respiratory rate of 34 breaths/min and point to a diagnosis of syncope rather than
Sp0 2 of 88% on 2 Umin oxygen, which fell to seizure?
10.31. Which one of the following does not 10.35. A 52 year old office worker is brought in
score points on routinely used early warning by ambulance to the emergency department.
systems in the context of medical observation She was found collapsed in the toilets at work,
monitoring? having earlier complained of a 4-day history of
A. Capillary blood glucose mild headache. She has a past medical history
B. Glasgow Coma Scale score of well-controlled hypertension, diet-controlled
C. Heart rate type 2 diabetes mellitus and she smokes 40
D. Sp0 2 cigarettes a day. Her partner reports that she
E. Temperature drinks three glasses of wine a week and has
never previously been admitted to hospital.
10.32. A 38 year old man is admitted for The paramedics have been supporting her
observation after falling over the handlebars of ventilation using an oropharyngeal airway and
his pushbike. He was wearing a helmet and bag-valve-mask. Examination reveals heart rate
had no loss of consciousness, although he of 50 beats/min, respiratory rate of 6breaths/
feels nauseated and 'faint' when standing up. min (without support), BP 190/105 mmHg,
You are asked to see him, as his heart rate has Sp02 90% on 15 L oxygen, temperature
increased from 95 to 150 beats/min over the 37.1°C, blood glucose 4.8 mmol/L (86.4 mg/
first hour of his admission. He is complaining of dl), GCS score 6 (E1, V2, M3) with no
upper abdominal pain and mild shortness of lateralising signs. There is no visible rash or
breath. Non-invasive BP is 100/60 mmHg and external evidence of injury.
he feels cool peripherally. His chest is clear, Which one of the following conditions is the
with no clinical evidence of pneumothorax or rib most likely cause of this patient's presentation?
fracture. His respiratory rate is 25 breaths/min, A. Alcohol withdrawal /
Sp0 2 99% on 4 Umin oxygen. His GCS score B. Bacterial meningitis ,/
is 15 with normal limb movements. You have C. First presentation of epilepsy 1
/
rate of 25 breaths/min, heart rate of 120 beats/ clammy, but alert and has no chest pain. ECG
min, BP 130/80 mmHg. He finds talking demonstrates a sinus tachycardia with
difficult. He is otherwise fit and well. He does low-voltage QRS complexes. Which of the .
not yet have IV access. following is the most likely underlying
Which of the following is your first treatment diagnosis?
priority? A. Cardiac tamponade
A. IV access and crystalloid bolus B. Cardiogenic pulmonary oedema
B. I 0 11g adrenaline (epinephrine) IV C. Extension of the original infarction
C. 50 11g adrenaline intramuscularly (IM) D. Neurogenic pulmonary oedema
D. 0.5 ml I :I 000 adrenaline IM E. Pulmonary embolism
E. 5 ml I :10000 adrenaline sublingually
10.48. A 67 year old woman is admitted to the
10.46. A 75 year old man presents to the ICU after cardiac arrest. She received
hospital with a 4-day history of diarrhoea and immediate bystander CPR, and was found to
vomiting. He has a history of moderate left be in ventricular fibrillation when the ambulance
ventricular failure, prostate cancer and chronic crew arrived. She received 3x DC shocks
kidney disease stage 4. His regular medication before return of spontaneous circulation, and
includes aspirin 75 mg once daily, bisoprolol
5 mg once daily and ramipril 5 mg once daily.
had a total 'downtime' of 32 minutes. She was
intubated and ventilated on arrival in the I
On admission his observations are as follows:
heart rate of 60beats/min, BP 90/45 mmHg,
emergency department. Her best GCS prior to
that was El, VI, M2. Which of the following
I
respiratory rate of 16 breaths/min, Sp02 94% would suggest the potential for a good
on air. He is lethargic and slow to respond to neurological outcome?
questions. He is oliguric after catheterisation. A. A neuron-specific enolase >33 11g/L
ECG demonstrates peaked T waves. Blood B. Burst suppression on EEG
results include haemoglobin I 01 g/L, white cell C. CT head with poor grey-white matter
count 16 x 109/L, platelets 190 x 109/L, urea differentiation
20.2 mmoi/L (121 mg/dl), creatinine
367 11moi/L (4.15 mg/dl), sodium 134 mmoi/L,
potassium 8.3 mmoi/L. He receives two
D. Extensor motor response
E. Immediate bystander CPR I
/
1/
boluses of calcium gluconate and two infusions
of insulin/dextrose to manage his potassium. 10.49. Using checklists for interventionf in the
After this, a venous blood gas demonstrates W ICU is a key component of good patient care.
Which of the following forms part of the 'FAST
84 nmoi/L (pH 7.08) and potassium 1
HUG' checklist? ·
8.2 mmoi/L.
What would be your next step in managing A. Foot care
this man? B. Gowning and gloving
A. 40 mg IV furosemide bolus C. Spinal problems
B. Critical care referral for monitoring and D. Teeth
consideration of renal replacement therapy E. Ulcer prophylaxis
C. Further bolus calcium gluconate
D. Further fluid resuscitation 10.50. A 56 year old man sustains a significant
E. Further insulin/dextrose infusion lower limb injury after becoming trapped
between a wall and a car. He is admitted to an
10.47. A 63 year old man has been admitted to orthopaedic ward for observation and operative
the coronary care unit after percutaneous planning. You are asked to see him 12 hours
coronary intervention for ST elevation later with a swollen, painful calf and suspected
myocardial infarction (MI). Fdur hours after compartment syndrome. Which of the following
admission he develops acute respiratory is true regarding this condition?
distress. Observations are as follows: heart rate A. A serum D-dimer is both sensitive and
of 120 beats/min, BP I 00/75 mmHg, specific for compartment syndrome
respiratory rate of 28 breaths/min, Sp02 96% B. Absent peripheral pulses are an early sign
on 15 Umin oxygen. His jugular venous suggestive of developing compartment
pressure (JVP) is elevated. He is pale and syndrome
c. His leg should be reviewed by a consultant 10.54. A 68 year old woman, who has
surgeon on the morning ward round the previously been fit and well, required intubation
next day and ventilation in the ICU with severe
D. Pain is worse with passive stretching pneumonia. After 10 days, tracheostomy to aid
E. Sensation in the leg is likely to be normal ventilatory weaning proves difficult, secondary
to respiratory muscle weakness, and she
10.51. A 62 year old man is sedated and requires a further 19 days of ventilation before
ventilated in the ICU after a severe being weaned off her tracheostomy. On
subarachnoid haemorrhage. He has an neurological examination she has global
intracranial pressure (ICP) monitor in situ, which proximal muscle. weakness with no lateral ising
has been reading 15 mmHg consistently. He is signs. Sensory examination is normal. Reflexes
being sedated and analgesed with propofol and are generally decreased. Nerve conduction
alfentanil infusions. On a sedation break his ICP studies demonstrate reduced amplitude of
--
increases to 45 mmHg and his pupils increase transmitted voltage action potential with
in size bilaterally. His mean arterial pressure is preserved velocity. Muscle biopsy is normal
90 mmHg. Which would be your first action to and creatine kinase is unremarkable. What
manage his ICP? condition is most likely responsible for this
A. Administer mannitol bolus woman's difficulty in weaning from ventilation? II
B. Administer neuromuscular blockade A. Brainstem stroke
I
C. Increase propofol and alfentanil infusion rates B. Critical illness myopathy
D. Refer to neurosurgery for decompressive C. Critical illness polyneuropathy
craniectomy D. Guillain-Barre syndrome
E. Remove the intracranial pressure monitor E. Multiple sclerosis
10.52. A 45 year old man is admitted to the ICU 10.55. A 24 year old man is admitted to the ICU
after banding of oesophageal varices and after sustaining a severe head injury after a fall
significant upper gastrointestinal (GI) from a height at work. CT head on admission
haemorrhage. He has alcoholic liver disease demonstrates massive intracranial haemorrhage .
and continues to drink 1 L of vodka per day. with midline shift, andthe clinical opinion is thatj
He is haemodynamically stable with good gas of brain death. His family say that he previously1;
exchange and is extubated 12 hours expressed a wish to donate his organs if this /'
post-procedure. He is moved to a medical situation ever arose. Which of the following /'
ward for ongoing management. Seventy-two would prevent testing for brain death?
hours later he becomes confused and agitated, A. Administration of 10 mg morphine IV 2 hours
with evidence of tremor and paranoid ideation. previously ,' '
What is the best treatment for his current B. Administration of a bolus of atracurium 72
condition? hours previously
A. Benzodiazepines C. Core temperature of 36"C
B. IV haloperidol 2.5 mg D. Normal thyroid function tests
C. Oramorph E. Serum sodium of 133 mmoi!L
D. Quetiapine
E. Thiamine 10.56. Which of these is an early complication
of percutaneous tracheostomy carried out in
10.53. Which of these statements is true the ICU?
regarding the use of intra-aortic balloon A. Haemorrhage
pump (IABP)? B. Laryngeal stenosis
A. Carbon dioxide is used to inflate the balloon C. Tracheal stenosis
B. It is associated with improved sui'Vival in D. Tracheomalacia
cardiogenic shock E. Wound site infection
C. It is commonly inserted via the brachial artery
D. It is designed to improve diastolic pressure 10.57. A 67 year old man.presents to the
proximal to the balloon, emergency department with a 3-day history of
E. There is no risk of mesenteric ischaemia haematemesis and melaena. He has a past
when inserted correctly medical history of alcoholic liver disease and
mild asthma (well controlled). His observations count 5. 7 x 109/L, platelets 41 x 109/L, sodium
are: heart rate of 100beats/min, respiratory rate 132 mmoi/L, potassium 5.6 mmoi/L, urea
of 16 breaths/min, BP 85/40 mmHg 16 mmoi/L (96 mg/dl), creatinine 75 Jlmoi!L
(70/35 mmHg on standing), Sa0 2 95% on 6 L (0.85 mg/dl), lactate 4.5 mmoi/L (40.5 mg/dl).
oxygen, temperature 36.5°C, blood glucose Which of the following would be your
4.2 mmoi/L (75.7 mg/dl), GCS score 15. On immediate next step in managing this man?
examination, he is pale, cool peripherally, A. Arrange urgent upper Gl endoscopy
talking in full sentences, and his chest is clear. B. Critical care referral for monitoring ·
His abdomen is soft and non-tender but fresh C. Insertion of a Sengstaken-Biakemore tube
melaena is found on rectal examination. He is D. Large-bore IV access and red cell transfusion
not actively vomiting currently. Initial laboratory E. Terlipressin 2 mg IV
results show haemoglobin 42 g/L, white cell
Answers
10.1. Answer: E. framework of the country and the ethical values
This man has developed multi-organ of the patient, usually expressed through the
dysfunction following arthroplasty. The family. This woman has severe underlying
pathology is not well understood but may disease and a poor prognosis from the trauma,
involve an inflammatory response to the 'so although there is a theoretical chance of
cement. As the glomerular filtration rate (GFR) surviving the injuries, it may be ethically
falls, there may also be an accumulation of justifiable to withdraw active treatment
antihypertensive drugs, causing a cycle of (although a consensus must be reached with
organ dysfunction. If normal physiology is not the family). The decision regarding withdrawal
restored with 30 mUkg of fluid in a short of treatment should not be made by the family
period of time, it is unlikely that ongoing in isolation - the clinical team must guide t~e
intravenous fluid will be beneficial. Furosemide process. An advance directive provides u~eful,;
and dopamine may improve the urine output, information about the values of the patie~t.
but have no effect on the GFR in this context. Once a decision has been made to withctlraw
Renal replacement therapy is not required at treatment, it is an ethical obligation to pfovide
this stage and will not improve the renal palliative care (sedatives and analgesia)· and
outcome. A noradrenaline (norepinephrine) extubation is a reasonable course of ~ction. If
infusion is the best option as it will improve the the other injuries are deemed unsurvivable, it is
mean arterial pressure (MAP) and may improve not strictly necessary to stop all sedation/
the GFR by vasoconstriction of the efferent analgesia as this may cause a great deal of
arteriole (which is dilated by ACE inhibition). pain and suffering.
this can cause cardiovascular collapse. Whilst infarction or bilateral cerebral infarcts are the
pneumothorax is a consideration, inserting most likely causes. ACT angiogram of the
cannulae without evidence of pneumothorax is circle of Willis has the highest diagnostic yield
likely to be harmful. in the acute setting. It is possible that this man
has locked-in syndrome.
10.5. Answer: A.
Patients should ideally be calm, able to follow 10.9. Answer: B.
commands and tolerate endotracheal intubation This scenario is likely to be an obstructed or
(a RASS score of 0). This is not always possible displaced tracheostomy tube. The most likely
as the tracheal tube is very stimulating and problem is that the inner tube has become
patients may need sedation to synchronise their blocked with secretions; this is easily remedied
breathing with the ventilator. Deep sedation by removing the inner tube and exchanging it
does not reduce the incidence of delirium or for a fresh one. A tracheostomy can become
post-traumatic stress disorder following displaced whereby it passes into a false tract
intensive care discharge: it probably increases alongside the trachea. Initial management
the risk of both complications. Daily sedation should focus on supplementing oxygen via the
breaks are used safely in many intensive care upper airway and establishing if the
units. There are many sedative agents that tracheostomy is patent (by attempting to pass
are used safely; however, etomidate is not a suction catheter). If it is not possible to pass
used by infusion as it causes adrenocortical a suction catheter, then the tracheostomy
suppression. should be removed and the patient re-intubated
via the oral route. It is dangerous to apply
10.6. Answer: A. positi~e pressure to a potentially dislodged
Weaning should occur when the primary tracheostomy. It can cause a large amount of
pathology has resolved. During a febrile surgical emphysema, which can prevent oral
episode, C0 2 production is increased and a intubation.
higher minute volume is required to maintain
normocapnia: not a good time to wean. During 10.10. Answer: A.
I
the weaning process, the PEEP is usually ARDS is a syndrome characterised by
maintained to keep the lung bases open, while infiltration of the lungs by an inflammatory
the pressure support and Fi0 2 are weaned exudate. This causes the features of
(although a Pa0 2 of > 10 kPa (75 mmHg) would hypoxaemia and reduced lung compliance. T~e
be a more usual target). A spontaneous Berlin definition of ARDS stipulates that the
breathing trial with minimal or no ventilator following must be present:
support is frequently used to assess if a patient (,
• The time of onset must be within 1 week ?f
is ready for extubation - if it is unsuccessful,
a known clinical insult, or new or worsening
the support should be reinstituted before any
respiratory symptoms, i.e. not long-standing
lung injury is incurred and further options
pulmonary disease
considered to optimise respiratory function. A
• Bilateral opacities present on chest X-ray,
tracheostomy is usually only considered when
not fully explained by effusions, lobar/lung
there is repeated failure to wean.
collapse or nodules, i.e. not lobar pneumonia
in isolation
10.7. Answer: A.
The loss of grey-white differentiation on a CT • Respiratory failure not fully explained by
scan is suggestive of a diffuse ischaemic injury cardiac failure or fluid overload. Objective
to the brain. All the other signs are strongly assessment (e.g. by echocardiography) must
predictive of a poor neurological outcome. exclude hydrostatic oedema if no risk factors
are present. (Therefore mitral regurgitation
10.8. Answer: A. causing pulmonary oecje"ma is this scenario
The differential diagnosis here is a cerebral would not classify) ·
vascular event, a rapidly progressive • Impaired oxygenation: Pa0,!Fi0 2 ratio of
encephalomyelitis or a form of seizure disorder. <40 kPa (300 mmHg)_
Given the speed of onset and the bilateral In this question ARDS in association with
neurological deficits, it is likely that there has influenza pneumonia is the only case that
been a vascular event. A vertebrobasilar meets these criteria
100
93
87
6"' 75
~
c
0
~
~ 50
<f)
c '----+Normal
:.a0 P50 = 3.5 kPa
=26 mmHg
OJ
0
~ 25
"'
I
0~~~~~.-.-.-+-.-.-r-r-r-r
kPa 0 1 2 3 4 5 6 7 8 9 10 1112 13 14
mmHg 0 25 50 75 100
P0 2 (kPa or mmHg)
Fig. 10.26
10.42. Answer: A.
10.39. Answer: A. This woman has sepsis, the initial treatment of
Severity of hypoxaemia is calculated using a which includes early antibiotics and IV fluid. The
Pa/Fi0 2 ratio. This is a number calculated by other options may ~II be used to manage
the Pa0 2 from an arterial blood gas divided by sepsis; however, Jhey are not first line and
the fraction of inspired oxygen (Fi0 2 , expressed should only be used with critical care
as a fraction). For example, a patient with a oversight.
Pa0 2 of 10 kPa (75 mmHg) on 50% oxygen,
i.e. Fi0 2 of 0.5, would have a Pa/Fi0 2 ratio of 10.43. Answer: E.
20 kPa (150 mmHg). This would be defined as Non-invasive ventilation is the first -lif!e therapy
moderately severe ARDS, if the other Berlin in patients with type II respiratory failure usually
I
/
Infectious disease
Multiple Choice Questions
11.1. A 29 year old woman returns from a trip C. Hepatitis A serology
to Vietnam. She ignored pre-travel advice and D. Hepatitis B serology
vaccinations. She ate local foods, including E. Leptospirosis serology
several freshwater fish dishes. One month after
her return she starts to note migratory nodules 11.4. A 12 month old child presents to casualty
over her abdomen, which are itchy. Her with his father. He has been eating poorly and
eosinophil count is mildly elevated. What is the running a fever for the last 36 hours, after which
most likely cause of this clinical picture? he developed a widespread maculopapular rash
A. Ascaris lumbricoides on the trunk. There are no localising findings on
B. Clonorchis sinensis physical examination. The father tells you that
C. Fasciola hepatica his son has had all his vaccinations, including
D. Gnathostoma spinigerum measles, mumps and rubella (MMR). What is
E. Wuchereria bancrofti the potential cause of this infection?
A. Coxsackie virus
11.2. A 34 year old man who works as an army B. Enterovirus 71
reservist presents with bilateral facial nerve C. Human herpesvirus 6
palsy coming on over a period of a few days. D. Parvovirus B19
Otherwise, neurological examination of cranial E. Rubella
nerves is normal. He has been on regular army
exercises in rural Wales. He does not 11.5. A 26 year old pregnant woman, in the
remember any tick bites or a typical rash for seventh month of pregnancy, presents
Lyme disease. What is the likeliest diagnosis? concerned that she was visited 5 days ago by
A. Botulism her niece who the next day developed an itchy
B. Cerebovascular infarction vesicular rash. The niece stayed in her house
C. Complex migraine for 3 days. The niece saw her family physician
D. Neuroborreliosis on her return home and has been diagnosed
E. Tetanus with chickenpox. The woman is concerned
because she does not remember ever having
11.3. A 42 year old businessman presents chickenpox as a child, a fact confirmed by her
with fever and back pain. He had visited family mother. You arrange to check a varicella zoster
in Pakistan 8 months previously. He has a serology, which is negative. Which of the
temperature of 38.6°C. Urine dipstick'is negative following should you offer to prescribe?
as is his chest X-ray. Blood tests show a mild A. Aciclovir orally for 7 days
hepatitis and mild thrombocytopenia. What test B. Intravenous immunoglobulin
will be most likely to establish the diagnosis? C. Vaccination against varicella zoster virus
A. Blood film D. Valaciclovir orally ·
B. Dengue serology E. Varicella zoster immunoglobulin
11.6. A 54 year old man receives a cadaveric referred to an outpatient clinic and initial history
renal transplant. Before transplantation he is and physical examination have revealed no
found to be cytomegalovirus (CMV) obvious abnormalities. The travel history is
immunoglobulin G (lgG) negative and he unremarkable and she has never lived in
receives a transplant from a person who is countries with risk of tropical infections or
CMV lgG positive. Administration of which drug tuberculosis. Routine bloods show normal full
lessens his chance of developing CMV and its blood count but C-reactive protein (CRP) and
associated complications post-transplantation? erythrocyte sedimentation rate (ESR) that are
A. Brincidofovir elevated. Liver function tests show minor
B. Cidofovir abnormalities and the urinalysis shows some
C. Foscarnet protein and red blood cells. Human
D. Valganciclovir immunodeficiency virus (HIV) serology is
E. Zanamivir negative. Routine blood cultures are negative
and a chest X-ray, computed tomography (CT)
11.7. A 28 year old man returns from a holiday abdomen and echocardiogram are all reported
to Brazil. After a short febrile illness he is as normal. What would be an appropriate next
diagnosed with Zika virus. What practical step in investigation?
advice should he be given? A. Bone marrow aspirate for culture
A. Avoid alcohol for 2 months B. Cerebrospinal fluid examination
B. Avoid sharing towels for 1 week C. Liver biopsy
C. Avoid strenuous exercise for 2 weeks D. Mammogram
D. Condom usage for 6 months .E. Positron emission tomography (PET) scan
E. Sexual abstinence for 2 weeks
11.11. A 29 year old man is referred to clinic
11.8. A survivor from the West African Ebola virus because of 4 weeks' symptoms of fevers,
disease outbreak presents for routine medical arthralgia and sore throat. On examination he
check-up. Which of the following is a late has enlarged cervical lymph nodes but the
complication, frequently described in survivors, pharynx shows no erythema or purulence ..
which it may be appropriate to assess for? There is hepatosplenomegaly and you no~ a
pale pink macular rash over the abdornery.
A. Anterior uveitis
Initial blood tests show an increase in ,,
B. Diabetes mellitus
polymorphonuclear leucocytes and a m#rkedly
C. Hypothyroidism
elevated ferritin. Routine cultures and
D. Immune thrombocytopenic purpura
autoantibodies are negative and an HIV test is
E. Ulcerative colitis I,
pending. What would be an initial empiric
treatment? ·
11.9. A 23 year old nurse, previously fit and
well, presents with fever, persistent sore throat A. Antiretroviral therapy
and stridor. He is unable to eat or drink. B. Erythromycin
On examination he has tonsillar enlargement C. Non-steroidal anti-inflammatory drugs
and anterior and posterior cervical D. Penicillin
lymphadenopathy. A spleen tip is palpable E. Prednisolone
in the abdomen. Blood tests reveal a
lymphocytosis and borderline elevation of the 11.12. A 50 year old man is being treated for
transarninases. A blood film shows frequent acute myelogenous leukaemia with
atypical lymphocytes. Which of the following chemotherapy. He develops neutropenic fever.
should be used to treat his condition? Physical examination is unremarkable and the
central venous catheter '(CVC) tunnel site
A. Aciclovir
B. Cytotoxic T lymphocytes demonstrates no erythema or pus. Which of
C. Prednisolone the following would/be most helpful in
D. Rituximab establishing a diagnosis of a eve line
E. Valaciclovir infection?
A. Differential time to positivity of CVC versus
11.10. A 61 year old woman presents with 3 peripheral blood culture
weeks' unexplained fever. She has been B. Negative peripheral blood cultures
D. Mumps
E. Parvovirus Bl 9
treated with penicillin and his symptoms has a long history of consuming unpasteurised
recover. One week later his mother presents milk and the initial work-up includes testing
with a similar history and is also treated with with a serum agglutination test, which comes
penicillin. Six weeks later the child is bought back positive at high titre. What would be an
back by his mother with acute pharyngitis and appropriate initial antimicrobial regimen?
a throat swab confirms group A streptococcal A. Doxycycline, rifampicin and gentamicin
infection. His medical history is otherwise B. Flucloxacillin with rifampicin
unremarkable. In addition to prescribing C. Fluconazole with flucytosine
penicillin what additional steps would be D. lmipenem followed by doxycycline and
appropriate? co-trimoxazole
A. Aspirin prescription for 6 months E. Streptomycin with chloramphenicol
B. Blood tests for immunodeficiency
C. Clindamycin 11.23. A 40 year old with HIV presents with a
D. Erythromycin treatment 3-week history of headache. He is an
E. Throat swabs on all the family and treatment intravenous drug user and has not engaged
of all carriers of group A streptococci . with care or antiretroviral therapy. His last
recorded CD4 T-cell count was 48cells/mm 3
11.20. A 32 year old teacher presents with 18 months ago. His neurological examination
severe pain in her left leg, specifically and a CT scan of his head are all normal. A
excruciating pain in the calf. On examination lumbar puncture is performed. Which essential
there is an area of purplish discoloration but diagnostic test would help establish the
otherwise little to see. Temperature is 39.5°C, diagnosis? .
pulse rate 122 beats/min and blood pressure
(BP) 90/60 mmHg. Which of the following is the
A. ~-o-glucan
assay in serum
B. Cryptococcal antibody measurement )n
I
most appropriate initial investigation to promptly ~rum v
!/
establish a diagnosis? C. Cryptococcal antigen test on cerebrospinal
A. CT scan leg fluid (CSF)
B. Doppler leg D. Cryptococcal PCR on CSF I
C. Inspection of muscles in theatre by a E. Galactomannan enzyme-linked
surgeon immunosorbent assay (ELISA) on CSF
D. MRIIeg
E. Ultrasound leg 11.24. An 84 year old nursing home resident is
re-admitted with Clostridium difficile infection.
11.21. A 25 year old man from Somalia She has been on a prolonged course of
presents to the hepatologist because of antimicrobials to treat an intra-abdominal
derangements in his liver function tests. Blood infection that arose as a complication of a
tests reveal an elevated alkaline phosphatase ruptured diverticular abscess but these have
and bilirubin as well as a blood eosinophilia. now stopped. Her first bout of C. difficile
Abdominal ultrasound shows a mass in the left infection was severe and treated with
lobe of the liver and some lymph node vancomycin. She then relapsed and was
enlargement around the porta hepatis. He has treated in a clinical trial with fidaxomicin. This is
been previously well and takes no regular her second relapse over a 3~month period.
medications and drinks no alcohol but does Prior to her diverticular abscess she had
chew khat leaves. Serology for which parasite been well and was only on treatment for
may be positive in this case? hypertension. WhC!,_t is a potential therapeutic
A. Enterobius vermicularis option to manage her/elapsing infection?
B. Fasciola hepatica A. Ciprofloxacin
C. Gnathostoma spinigerum B. Glucocorticoids
tip but no other abnormalities. The full blood and meningism. He recently returned back to
count identifies a relative lymphocytosis and his horne in a rural area of Vietnam for a
mild elevation of transaminases. HIV tests and 3-week visit. A lumbar puncture is performed,
malaria films are negative. What would be the which shows a marked increase in white cells
best test, if available, to establish a diagnosis? and protein, and he commences treatment with
A. Blood film ceftriaxone. Later that evening the laboratory
B. Bone marrow aspirate contact you to say they have reviewed the
c. Liver biopsy white blood cells and performed sorne
D. Lymph node aspirate additional stains, which confirm there are
E. Splenic aspirate significant numbers of eosinophils, in this case
reported as 20% of the total white blood cells.
11.37. A 26 year old woman receiving total Which of the following is a potential cause of
parenteral nutrition for management of short this man's eosinophilic meningitis?
bowel syndrome, caused as a complication of A. Angiostrongylus cantonensis
Crohn's disease, is admitted because of fever B. Japanese encephalitis virus
and fatigue. Blood cultures grow Candida C. Non-prescription analgesics
tropicalis both from her peripheral blood
cultures and from the lumen of her tunnelled
central venous catheter, with the line cultures
D. Schistosoma japonicum
E. Taenia solium a.
turning positive 4 hours before the peripheral I
11.40. A 32 year old female anthropologist was
cultures. The central venous catheter is
living in remote regions of the Brazilian
removed, temporary venous access is
rainfqrest, studying the indigenous population.
established and treatment with anidulafungin is
While there, she lived in local dwellings.
commenced. In addition, which of the following
Approximately 3 months frorn the end of her
should be performed?
trip she developed an illness with an indistinct
A. CT abdomen rash and noted some enlarged lymph nodes.
B. Lumbar puncture Before returning home she went to a large
C. MRI head clinic in Brazil where she was noted to have
D. Oesophagogastroduodenoscopy lymphadenopathy and splenomegaly. They I·
E. Ophthalmological review performed sorne additional tests, including .1
xenodiagnostics with a triatomine bug, which 1;'
11.38. A 47 year old man with acute resulted in a diagnosis. She was advised she(1
myelogenous leukaemia is admitted with
needed treatment but she preferred to defer '
neutropenic fever. There are no localising signs
treatment until she was back home. Which i
or symptoms. Cultures through the central
medication is most likely to treat this / '
venous catheter and the peripheral cultures are
condition?
negative. A CT chest scan is negative, as is a
galactomannan assay. Despite treatment with A. Nelfinavir
piperacillin-tazobactam, and subsequent B. Niclosamide
addition of caspofungin and teicoplanin, he C. Nifurtimox
remains febrile but there are still no localising D. Nitazoxanide
signs. His other medications include allopurinol, E. Nystatin
omeprazole and alendronic acid. Increasing
lymphadenopathy is noted and there are 11.41. A 23 year old woman attends her family
abnormal liver function tests but no other physician having noticed a 'bull's eye' rash on
abnormalities. Which of the following is a likely her thigh and developing flu-like symptoms.
cause of this syndrome? She walks her dog regularly through local
woodland in southern England. What action
A. Allopurinol hypersensitivity reaction
should be taken? ,/
B. Cytomegalovirus infection
C. Epstein-Barr virus infection A. Ensure tetanus vaccination is up to date
D. Invasive fungal infection B. No action required
E. Penicillin allergy C. Prescribe intravenous. ceftriaxone for
2 weeks
11.39. A 25 year old man from South-east Asia D. Prescribe oral doxycycline for 2 weeks
presents with severe headache, photophobia E. Test for antinuclear antibodies
11.42. A 55 year old man returns from Medina 11.45. A 42 year old businessman presents with
in the Kingdom of Saudi Arabia. He developed a history of seizures over the last 3 weeks. He
a coryzal illness, which progressed rapidly to has been previously fit and well. He lives in a
severe dyspnoea 4 days ago and he was large house with domestic servants. A CT scan
hospitalised for 3 days in Medina before he of his head shows a number of small cystic
took his own discharge and flew home. On space-occupying lesions with a characteristic
reaching horne his family were concerned he appearance, some of which demonstrate an
was increasingly short of breath and took him opacified area protruding into the cyst. What is
to hospital. He is known to have diabetes the likely organism causing this presentation?
mellitus and chronic lymphocytic leukaemia. A. Angiostrongyloides cantonensis
On examination he is febrile; his pulse rate is B. Taenia solium
106 beats/min, respiratory rate is 20 breaths/ C. Gnathostoma spinigerum
min and oxygen saturation is 90% on air. His D. Toxocara spp.
BP is 116/78 mmHg. The examination shows E. Trichinella spiralis
bilateral crackles through both lung fields and
the chest X-ray shows bilateral infiltrates. Which 11.46. A 34 year old native Australian man is
of the following illnesses should first be admitted to a hospital in Darwin, Australia, with
excluded in this case? a widespread itchy rash with crusting lesions all
A. Acute respiratory distress syndrome (ARDS) over his body. Some have secondary infection
complicating pneumonia and he has a heart murmur. What is the
B. Avian influenza likeliest diagnosis?
C. Meningococcal sepsis . A. Impetigo
D. Middle East respiratory syndrome B. Melioidosis
coronavirus (MERS-CoV) C. Pustular psoriasis
E. Severe acute respiratory syndrome (SARS) D. Scabies
E. Varicella zoster
11.43. A 44 year old intravenous drug user is
admitted with fever, tachycardia and low blood 11.47. A 68 year old man is admitted to h9spital
pressure. Chest X-ray shows multiple nodules complaining ofabdorninal pain radiating t6 his
in the lungs. After initial blood cultures are back, following a bout of food poisoning/ Blood
performed, which intravenous antimicrobial cultures are recurrently positive with twc/ out of
should be included in initial empirical therapy? two bottles growing Salmonella Enteritidis.
(Local antimicrobial-resistance patterns suggest What is the investigation most likely to. reveal
good activity can be expected.) the diagnosis? /' ,
A. Flucloxacillin A. CT scan abdomen
B. Meropenem B. HIV serology
C. Moxifloxacin C. Serum electrophoresis
D. Piperacillin-tazobactam D. Transoesophageal echocardiograrn
E. Tigecycline E. Transthoracic echocardiogram
11.44. A 42 year old woman presents with fever. 11.48. A 24 year old female student returned
She returned from a holiday in India 2 months from a trekking holiday in Nepal 25 days ago
previously having spent 8 months travelling in with fever and diffuse abdominal pain. She has
rural areas. She has a temperature of 38.2°C. not had diarrhoea. On examination, pulse is
Urine dipstick is negative. Blood tests show 56 beats/min, BP 97/54 mmHg and
a mild hepatitis and thrombocytopenia. A temperature 39.4°C. She has a tender right
diagnosis of vivax malaria is made on blood iliac fossa and small faint spots on her
film. What test will help with f\]rther treatment? abdomen but no other skin lesions. What is the
A. Antiplatelet antibodies likeliest diagnosis?
B. Haemoglobin electrophoresis A. Appendicitis
C. Hepatitis B serology B. Cyclosporiasis •
D. Test for glucose-6-phosphate C. Dengue
dehydrogenase (G6PD) deficiency D. Scrub typhus
E. Ultrasound of spleen E. Typhoid
11.49. A 21 year old man presents to an with pain and tenderness on the left side of his
emergency department in the UK with a 3-day neck. On examination he is fevered and
history of bloody diarrhoea and right iliac fossa shocked with low oxygen saturations on room
abdominal pain. He had eaten takeaway food 2 air. Chest X-ray shows a blood-borne
days previously but other members of his family pneumonia and ultrasound shows left internal
had also eaten the meal and were well. He has jugular vein thrombosis. What is the diagnosis?
a family history of ulcerative colitis. What is the A. Adult Still's disease
likeliest diagnosis? B. Haemophagocytic lymphohistiocytosis (HLH)
A. Amoebiasis C. Kikuchi's disease
B. Bacillus cereus toxin food poisoning D. Lemierre's syndrome
C. Campylobacter infection E. Streptococcal toxic shock syndrome
D. Crohn's disease
E. Ulcerative colitis 11.54. A 44 year old truck driver was involved in
a road traffic collision; this resulted in a
11.50. A 21 year old student returns from a trip traumatic injury to his pelvis, which was
to Belize in Central America with a non-healing contaminated with soil from a ditch. He
ulcer on his face. A biopsy and PCR confirm develops a brain abscess, which is drained,
a clinical diagnosis of leishmaniasis. The and on microscopy shows long, filamentous,
organism is identified a L. braziliensis. What is branching Gram-positive rods that are weakly
the most appropriate treatment? acid-fast. What is the likeliest organism
A. Cryotherapy involved?
B. lntralesional stibogluconate A. Actinomyces israelii
C. Liposomal amphotericin B. Clostridium perfringens
D. No treatment indicated C. Mycobacterium chelonae
E. Paromomycin D. Nocardia asteroides
E. Sporothrix schenckii
11.51. A 34 year old man is admitted to
intensive care with a diagnosis of Pneumocystis 11.55. A 35 year old anthropology researcher ,.
pneumonia. He is noted to have widespread returned from a trip to Sarawak studying ·
violaceous papules on his skin and hard palate. primate behaviour 7 days previously. He had Qb
1
On biopsy these are Warthin-Starry silver stain history of monkey bites but had been workind
positive. What is the likeliest diagnosis? close to primates. He complains of fever, 1
A. Bacillary angiomatosis headache and diarrhoea. Examination reveals
B. Kaposi's sarcoma hepatosplenomegaly and his full blood cou.nt
C. Malignant melanoma shows mild anaemia, a mildly elevated white
D. Sporotrichosis cell count and a platelet count of 76x109/L.
E. Stevens-Johnson syndrome Malaria rapid diagnostic test is negative. What
is the likeliest diagnosis?
11.52. A 4 7 year old man is admitted to A. Chesson variant Plasmodium vivax infection
intensive care with a diagnosis of Pneumocystis B. Herpes B infection
pneumonia and HIV. He is noted to have C. Monkeypox
widespread purple papules on his skin and D. Plasmodium knowlesi infection
hard palate. On biopsy these are human E. Rabies
herpesvirus 8 (HHV-8) DNA positive. What is
the likeliest diagnosis? 11.56. An 18 year old female presents unwell
A. Bacillary angiomatosis with sudden onset of bloody diarrhoea with
B. Kaposi's sarcoma fever and abdominal pain. Temperature is
C. Malignant melanoma 38.9°C, pulse 110 beats/min and BP
D. Sporotrichosis 93/56 mmHg. She looks jaundiced and pale
E. Stevens-Johnson syndrome with diffuse abdominal pain. Blood tests show
a haemoglobin of 67 g/L, white cell count
11.53. A 19 year old man develops a sore 18.6x109/L, platelets 110x10~/L; bilirubin
throat and fever; 2 days after the onset, he 98 f.Lmoi/L (5.73 mg/dl), aspartate
develops left-sided chest pain and haemoptysis aminotransferase (AST) 21 U/L, creatinine
I
On examination he has a area of ulceration on D. Necator americanus j
his right hand with axillary lymphadenopathy.
What is the likeliest infecting organism?
E. Taenia solium
I
I
I•
Answers
11.1. Answer: D. 11.5. Answer: E.
The presentation suggests exposure to a The patient is non-immune to varicella zoster
zoonotic parasite. The clinical scenario with virus 0/ZV) and has had a significant exposure
itchy migratory nodules emerging after eating during pregnancy within the last 7 days so
local freshwater fish dishes suggests
gnathostomiasis. Ascariasis and filariasis, the
should receive passive immunisation with
varicella zoster immunoglobulin.
0.
latter caused by Wuchereria bancrofti, are not Immunoglobulin would not have as high levels I
caused by zoonotic parasites while both of antibodies. Vaccination would take too long
fascioliasis and Clonorchis sinensis infections to generate immunity. Treatment with aciclovir
primarily involve the hepatobiliary system. or valaciclovir is not indicated (Box 11.5).
arthritis. The other conditions listed have not monoclonal antibody) or cytotoxic
been reported as common late sequelae. T lymphocytes, but these do not have a role in
treatment for immunocompetent individuals.
11.9. Answer: C.
Glucocorticoids are sometimes used to treat 11.1 0. Answer: E.
complications of Epstein-Barr virus (EBV) The patient has features of pyrexia of unknown
infection. Potential indications include massive origin and evidence of raised inflammatory
tonsillar enlargement causing airway markers with some a9normalities in the liver
compromise, haemolytic anaemia or tests and urinalysis:1 Potential concerns, in
thrombocytopenia, and sometimes neurological addition to infection, include connective tissue
complications. Antivirals such as aciclovir and disorders and malignancy. A PET scan may aid
valaciclovir have no role. Patients who are identification of sites of inflammation and
immunosuppressed may develop selection of potential sites for biopsy to
lymphoproliferative disorders with EBV infection, establish a diagnosis. Investigation for
which may be treated with rituximab (anti-CD20 malignancy rnay be undertaken, but its yield is
low if there are no clues to a potential source. test should combine detection of antigen with
Bone marrow aspirate for culture, lumbar antibody since the patient may not yet have
puncture and liver biopsy may be part of the developed an antibody to HIV. Although there
work-up but the diagnostic yield is low if there are several considerations in the diagnosis, the
are no signs localising to these sites, as in this clinical features and laboratory features are
case. compatible with acute retroviral syndrome
(primary infection) from recently acquired HIV
11.11. Answer: E. infection. All of the other diagnoses mentioned
The patient has presented with features of may be considered, but Behget's is a
pyrexia of unknown origin (PUO). Although comparatively rare cause of oral and genital
there is a history of sore throat there is no sign ulceration, syphilis is not diagnosed by bacterial
of pharyngitis and cultures are negative. The culture on cerebrospinal fluid but rather by
rash and markedly elevated ferritin, along with serology, and detection of a sexually
the other clinical features, make adult-onset transmitted infection such as lymphogranuloma
Still's disease a consideration, which is a venereum would not explain all the features in
clinical diagnosis that requires treatment with this case but would indicate the need for
prednisolone or alternative anti-inflammatory further tests to exclude sexually acquired HIV
therapy. There is no indication that this is infection.
streptococcal pharyngitis, so antibiotics are
not indicated. HIV-induced acute retroviral 11.14. Answer: B.
syndrome should always be considered There are multiple potential causes of diarrhoea
with presentation with PUO and rash but in travellers. In this case there is a relatively
should only be treated after diagnostic long history but an absence of acute
confirmation. inflammatory markers or evidence of dysentery.
This would fit best with a parasitic cause such
11.12. Answer: A. as cyclosporiasis, cryptosporidiosis or with
Central venous catheter infections are giardiasis. Shigella spp. and Entamoeba
suggested by detecting positive cultures in the histolytica cause a dysenteric illness and
sample from the eve at least 2 hours prior to Yersinia enterocolitica often presents with /
the peripheral blood sample, detecting 5- to abdominal pain mimicking an acute abdomen./
10-fold greater colony counts in the eve In chronic diarrhoea - usually defined as /
sample versus the peripheral blood sample or diarrhoea lasting at least 2-4 weeks - when jt
detecting at least 15 colony-forming units in infective causes have been excluded, other '
culture of the CVC tip. Peripheral blood cultures causes such as coeliac disease, inflammatoly
are frequently positive with eve line infections bowel disease and malignancy should alwdys
and a short time to culture positivity would be be considered.
suggestive of endovascular infection but not
specifically eve line infection. Although 11.15. Answer: C.
right-sided endocarditis may complicate eve Hookworm infection can cause iron deficiency
line infection, there is usually no reason for anaemia, which would be indicated by a low
left -sided endocarditis as evidenced by mean corpuscular volume. Haemolysis,
vegetations on the aortic valve. A positive urine indicated by raised reticulocytes, and
culture for P. aeruginosa would be more thrombocytopenia are associated with other
suggestive of a urinary catheter-related parasitic infections, notably malaria. Atypical
infection. lymphocytes are typically associated with viral
infections but occasionally are seen with
11.13. Answer: B. malaria and trypanosomiasis.
Any traveller with an unexplained illness should
have HIV infection excluded. In this case the 11.16. Answer: A.
presence of an anal lesion suggests the The scenario is suggestive of
possibility of unprotected anal intercourse. In neurocysticercosis for which albendazole is
addition to performing a genitourinary medicine most often prescribed. P.raziquantel is the
screen to establish the source of the lesion, an preferred alternative and the other anti-parasitic
HIV test should be performed. In this case, agents are not recommended treatment
since recent acquisition is a consideration, the options for this infection.
sometimes used in the treatment of bladder films may be positive, they are less likely to be
carcinoma and Salmonella Typhi carriage is positive than in T. brucei rhodesiense infection,
associated with Schistosoma mansoni infection except early on in the infection. Since this
in particular but not bladder carcinoma. infection has likely been present for some time,
Enterohaemorrhagic E. coli is associated with aspiration of the lymph nodes is more likely to
haemolytic uraemic syndrome but not bladder make a diagnosis. In addition, nothing has
carcinoma, and syphilis, caused by Treponema been noted on blood films sent for malaria
pallidum, is not associated with bladder testing, which should also reveal trypanosomes.
carcinoma. Serologic responses against T. brucei and a
lumbar puncture should also be performed. A
11 .33. Answer: A. bone marrow aspirate and splenic aspiration
The story is most suggestive of lymphatic are tests employed in the diagnosis of
filariasis, which would best be diagnosed by leishmaniasis and a liver biopsy would not be
looking for microfilaria on a blood film or by helpful in this case to determine the cause of
serology. An elevation of lgE is often seen in the liver function test abnormalities. In addition,
lymphatic filariasis but is not of itself diagnostic. these tests need specialist facilities, particularly
A slit-lamp examination or skin snip is used to splenic aspiration.
diagnose onchocerciasis, while a protruding
worm would be more suggestive of 11.37. Answer: E.
dracunculiasis. Candidaemia has a propensity to lead to
intraocular infection. This has resulted in the
11 .34. Answer: C. recommendation that all patients with
The occupation as a veterinarian and, in candidaemia should be assessed by an
particular, the recent contact with animals that ophthalmologist with dilated fundoscopy.
have been giving birth, puts this veterinarian at Oesophagogastroduodenoscopy is used to
risk of Coxiella burnetii infection. Although the assess Candida oesophagitis and the other
other microorganisms listed can all cause investigations are indicated if signs or
pneumonic illness they have distinct symptoms suggest infection at these sites.
epidemiological settings. Chlarnydophila psittaci
is associated with exposure to sick birds such 11 .38. Answer: A. (
as parrots and Legionella pneurnophlia with Drug fever is an important consideration in
11
contaminated water-cooling towers and other patients with pyrexia of unknown origin,/;
water systems. Bacillus anthracis has been· particularly in those who are on multipl~1
associated with bioterrorism and Yersinia medications. Allopurinol is a potential cause of
pestis, the causative agent of plague, with drug-related hypersensitivity and is aq~ociated
hunters and others exposed to endemic plaque with abnormal liver function tests and
in rural settings. lymphadenopathy. Penicillins and other
antimicrobials can cause fever but in this case
11.35. Answer: D. the fever predated use of piperacillin-
Despite the precautions this patient took, tick tazobactam. The failure to respond to
bites can be hard to avoid. The appearance of broad-spectrum antimicrobial therapy and the
eschars with no findings on blood film are absence of any localising features or positive
suggestive of African tick bite fever, and the microbiological tests mean that a
features of multiple eschars without rash are microbiological cause remains unproven and
more suggestive of Rickettsia africae than of other possibilities need to be excluded. Herpes
Rickettsia conorii. Borrelia duttonii is also virus aetiologies are important, particularly in
transmitted by ticks but results in relapsing solid organ transpl9-nt recipients or those who
fever. The other infections are less likely in this have received a haematopoietic stem cell
scenario as they do not link to the history of transplant, but these are not found in this case
tick bites, explain the eschars and would be and a patient with acute leukaemia on
expected to provide other laboratory findings. chemotherapy is not at particular risk of these
infections. lnvasive.fungal infection remains a
11 .36. Answer: D. diagnostic considera\ion, particularly for
The patient is likely to have Trypanosoma patients with acute myelogenous leukaemia,
brucei garnbiense infection. Although blood but the fever has remained despite addition of
caspofungin, and the galactomannan and chest the possibility of haematogenous spread of
CT scan has been negative. septic emboli from infected thrombophlebitis or
right-sided endocarditis. In an area with low
11.39. Answer: A. rates of MRSA, flucloxacillin is a good choice
Eosinophilic meningitis is seen with for empiric coverage of a potential
Angiostrongy/us spp. infections and also with endovascular Staph. aureus infection.
gnathostomiasis or coccidioidomycosis. The Meropenem and piperacillin-tazobactam might
other infections listed may be found in be considered in cases of sepsis but would
South-east Asia but cause alternative clinical not be first choice where Staph. aureus needs
neurological syndromes. to be treated. Tigecycline might be used
against MRSA in certain settings, such as skin
11.40. Answer: C. and soft tissue infection, but would not be first
The epidemiological setting, clinical scenario choice when potential bloodstream infection
and use of xenodiagnoses are consistent with a needs to be treated. Moxifloxacin is not usually
diagnosis of Chagas' disease (American used in Staph. aureus infection.
--
trypanosomiasis), which is treated with
nifurtimox. Niclosamide and nitazoxanide are 11.44. Answer: D.
used to treat other parasites. Radical cure of vivax malaria requires the use of
the 8-aminoquinoline drug primaquine. This
1
11.41. Answer: D. causes oxidative stress, which can result in
The likeliest diagnosis is acute Lyme borreliosis. massive haemolysis in patients who have low
This is increasing in frequency in the UK. The G6PD activity due to various inherited traits.
commonest organism responsible in Europe The other tests will not impact on the
is Borrelia burgdorferi. The recommendation treatment.
is for family physicians to treat with oral
doxycycline or amoxicillin for uncomplicated 11.45. Answer: B.
acute disease. Cysticercosis is caused by the pork tapeworm
Taenia solium and results when humans ingest
11.42. Answer: D. tapeworm ova, often from an infected
Any patient who has a history of recent travel household contact. The disease leads to cysts
to the Middle East along with fever and severe that can involve the subcutaneous tissue,
respiratory symptoms should have infection muscle and brain. The lesions are visible on CT
with MERS-CoV excluded before infection or MRI scan of the head and can have a
control measures can be relaxed. SARS is characteristic appearance. They can result in a
another coronavirus infection that leads to variety of neurological features, including ,
severe respiratory symptoms but circulated in new-onset seizures. Treatment is most often
2003. There are no risk factors for avian with albendazole.
influenza, which would require a history of
contact with chickens. ARDS complicating 11.46. Answer: D.
pneumonia would be in the differential but does Scabies with increasing drug resistance is a
not have the same influence on infection huge problem in indigenous populations in
control policy and therefore is not the first Australia. This is associated with
diagnosis to be excluded. Meningococcal post -streptococcal rheumatic fever with
sepsis has been reported after pilgrimages to rheumatic heart disease as a sequela.
the Middle East and sepsis can present with lverrnectin is used for large infestations. The
respiratory symptoms but would be expected other answers would not explain both the skin
to present with additional signs of sepsis. lesions and the heart murmur.
I
11.43. Answer: A. 11.47. Answer: A. /
The empiric therapy of fever in an intravenous Salmonellosis can invade and colonise aortic
drug user should include coverage of Staph. arteriosclerotic plaques and result in a mycotic
aureus. The specific agents will be influenced aortic aneurysm in older.patients. Endocarditis
by local antimicrobial resistance patterns and is uncommon with salmonellae.. Persistently
rates of meticillin-resistant Staph. aureus positive blood cultures raise the possibility of
(MRSA). In this scenario the chest X-ray raises endovascular infection and while this is most
1
would not prevent dissemination. 11.55. Answer: D. /'
1
Plasmodium knowlesi is the sixth human(
11.51. Answer: A. malaria now that Plasmodium ovate has 'been
Bacillary angiomatosis is caused by infection classified as two subspecies on the basis of
with Bartonella species, a slow-growing genetic homology. P. know/esi is asso~iated
Gram-negative bacillus that causes problems in with close contact with non-human primates
immunocompromised hosts. These include and is usually a mild infection, which does not
endocarditis, trench fever and bacillary peliosis relapse. Its life cycle is 24 hours (as opposed to
(widespread blood-filled cavities in major 48 hours for fa/ciparum), giving rapid changes
organs). Treatment is with doxycycline. in fever. Chesson strain vivax is relatively
Kaposi's sarcoma also can cause violaceous resistant to primaquine and is found in
papules but histology should show Indonesia.
characteristic spindle cell formations and would
not be positive with Warthin-Starry silver stain, 11.56. Answer: A.
which detects the Bartonella species. Similarly, Haemolytic uraemic syndrome is usually
the histology does not show features of associated with infection with E. coli 0157.
melanoma and this also would not have a Treatment is supportive. The other options
positive Warthin-Starry stain; nor would the would not give this combination of anaemia,
other conditions listed, which also would have jaundice and renal failure.
alternative dermatological appearances.
11.57. Answer: E.
11.52. Answer: B. Yersinia enteroco/itica is commonly found in
Kaposi's sarcoma is an angioproliferative pork, causes mild to moderate gastroenteritis
tumour related to HHV-8 infection in and can produce significant mesenteric adenitis
irnrnunocompromised hosts. The finding of after an incubation period of 3-7 days. It
--
are non-infectious and while all enter the would be more associated with injection into
differential, the scenario means one should the vein than skin popping. The other
consider hantavirus. conditions may cause ocular signs but are not
particularly associated with drug use.
1
11.59. Answer: D.
Bat bites have been associated with 11.63. Answer: A.
transmission of rabies and individuals who are Anthrax amongst drug users is related to heroin
bitten or likely to be exposed to bats should contaminated with anthrax spores. Urgent
have a rabies vaccine. The other infections are surgical debridement (to remove dead or
not associated with bats. devitalised tissue and drain any abscess/
collection) is most important. This should be
11.60. Answer: C. performed alongside empiric antibiotic
Monkeypox is a relatively harmless infection treatment to cover Bacillus anthracis as well as
with a poxvirus. Although similar in appearance other more common causes of soft tissue
to smallpox, it is a mild infection. The most infe.ction. Antibiotic treatment may involve
recent outbreak in the USA was related to ciprofloxacin and clindamycin intravenously in
importation of pet rats from The Gambia in combination with penicillin, flucloxacillin and
Africa. metronidazole (i.e. a five-drug combination).
Gas gangrene is not particularly associated \('iith
11.61. Answer: C. an eschar and is more associated with dusii'Y'
The cardinal feature of necrotising fasciitis is skin discoloration and crepitus. Neither Lyme
pain out of keeping with clinical signs. The disease not staphylococcal bacteraemia are
diagnosis is by surgical exploration with associated with an eschar, and necrotising
necrotic deep tissue being seen. It is usually fasciitis would typically be associated with more
due to a polymicrobial infection and treatment pain at the site and other skin features.
is with broad-spectrum antibiotics including a
macrolide to reduce toxin production plus 11.64. Answer: D.
surgical debridement. Gas gangrene is Some adults may not have been immunised
associated with wounds, and crepitus may be with MMR. The combination of neck swelling
detected in the skin. Splenic rupture would be due to parotitis and orchitis is highly suggestive
associated with trauma and there is no history of mumps. The other causes listed might
of this. Lemierre's syndrome presents as explain cervical swelling or the combination of
a pain in the neck, which results from a cervical and testicular prob~ms but are less
thrombophlebitis, typically of. the internal jugular consistent from the relatiyely healthy nature of
vein, complicating a sore throat. A colonic this patient and the short history of symptoms.
perforation would be considered with the
location of the abdomen pain but would not be 11.65. Answer: B.
expected to cause the skin lesion visible over Gas gangrene is due to infectiw with C.
the hip, which is a key feature that raises the perfringens. Treatment involves surgical
possibility of necrotising fasciitis. debridement and penicillin with clindamycin.
Tetanus would present with an eschar, and the presents with ulcerated skin lesions followed
other species are either not associated with skin by bone and joint deformity caused by
lesions or have alternative skin presentations. Treponema pal/idum pertenue. Treponema!
serology cross-reacts and so is unreliable.
11.66. Answer: D. Pinta is found mainly in South America and
Scornbroid fish can produce histamines, which bejel is mainly in the Middle East and West
increase when bacteria rnetabolise histidine. Africa.
This rapidly causes symptoms. Uncooked tuna
steaks are a common cause. Ciguatera 11.71. Answer: B.
poisoning presents with prominent abdominal Listeria should be considered in
symptoms and a range of neurological immunocompromised hosts as well as in
symptoms, and the neurological symptoms pregnancy and in people over 55 years of age.
may be prolonged. The dietary history, CSF is usually lymphocytic. Treatment is with
exposure history and lack of paralysis make the ampicillin as it is inherently resistant to
various other options unlikely. cephalosporins. TB is also a consideration,
especially if the patient has had anti-tumour
11.67. Answer: D. necrosis factor (TNF) therapy, but the short
Granulomatous cerebral angiitis is a rare history is against this. Cryptococcal disease is
complication of shingles, especially when in the often associated with lower cell numbers and
ophthalmic branch of the trigeminal nerve. It is would be associated with detection of
often fatal and only diagnosed post-mortem. cryptococcal antigen or identification of yeast
Aciclovir-induced encephalopathy is unusual on Indian ink testing. The other causes are also
with modern formulations and in the absence of possible but less likely in this scenario and
renal impairment. The combination of confusion would more usually produce neutrophils in
with more focal neurology makes the other the CSF.
possibilities unlikely.
11.72. Answer: B.
11.68. Answer: D. Francisella tularensis is a zoonotic infection
HTLV-1 is found in Japan, the Caribbean and associated with contact with wild rodents(
Central and South America and can cause including rabbits. It is spread by ticks in Jhe
T-cell lymphoproliferation. It may be wild and treatment is with aminoglycosi~es or
smouldering or aggressive but should be ciprofloxacin or doxycycline. The other ,~ptions
suspected in patients with T-cell are not associated with wild rodent contact
lymphoproliferation, particularly when from an leading to skin ulceration. I'
I
area where the virus is found. It is also I
I
!'
A. Cytomegalovirus polyradiculopathy
B. Human T-cell lymphotropic virus type 1
(HTLV-1) myelopathy
C. Multiple sclerosis
D. Tuberculosis of the spine
E. Vacuolar myelopathy
12.14. A 37 year old man with a CD4 count of prescribe a course of fluconazole for possible
24cells/mm 3 presents with painless, Candida oesophagitis. Two weeks later she
progressive visual loss. On fundoscopy the returns with no improvement. What is the most
vitreous is clear, and haemorrhages and likely cause of her dysphagia?
exudates are seen on the retina. What is the A. Cytomegalovirus oesophageal ulceration
most likely diagnosis? B. Herpes simplex virus oesophageal ulceration
A. Cytomegalovirus retinitis C. Kaposi's sarcoma of the oesophagus
B. HIV retinopathy D. Major aphthous ulceration of the ·oesophagus
C. Ocular syphilis E. Oesophagitis to azole-resistant Candida
D. Ocular toxoplasmosis species (e.g. C. kruse!)
E. Progressive outer retinal necrosis due to
varicella zoster virus 12.19. A 39 year old man presents with
asymmetric cervical lymphadenitis for 2
12.15. What is the mechanism of action of the months. His CD4 count is 234cells/mm 3 .
antiretroviral drugs raltegravir, dolutegravir and The largest node is 4x3 em and is fluctuant.
elvitegravir? Several nodes are matted together. What is the
A. Chemokine receptor CCR5 antagonist most likely diagnosis?
B. Fusion inhibitor A. HIV lymphadenopathy
C. lntegrase inhibitor B. Kaposi's sarcoma
D. Protease inhibitor C. Non-Hodgkin lymphoma
E. Reverse transcriptase inhibitor D. Pyogenic lymphadenitis
E. Tuberculosis
12.16. A 44 year old woman with a CD4 count
of 73cells/mm3 presents with a progressive left 12.20. Which of the following statements is
hemiplegia and headache over a week. Her correct about AIDS-associated Kaposi's
magnetic resonance imaging scan shows sarcoma?
multiple ring-enhancing mass lesions with A. It is a spindle-cell tumour of
surrounding cerebral oedema. What is the most lymphoendothelial origin /
likely diagnosis? B. It is associated with infection by hum:tn
A. Brain abscess herpesvirus 6 /
B. Cerebral toxoplasmosis C. Multiple skin lesions indicate a poor;/
C. Cryptococcoma prognosis
D. Primary central nervous system (CNS) D. The commonest site of visceral spread is the
lymphoma brain /'
I
E. Tuberculoma E. Women are more likely than men to develop
Kaposi's sarcoma
12.17. What is the correct statement regarding
the immune reconstitution inflammatory 12.21. Which of the following statements on viral
syndrome (IRIS)? load in HIV infection is correct?
A. Antiretroviral therapy (ART) should be A. A viral load change of 15 848 to
stopped if IRIS is suspected 10 000 copies/ml (difference of 0.21og 10) is
B. It is more common in patients responding regarded as a significant reduction 4 weeks
poorly to ART after starting antiretroviral therapy
C. It is more common when ART is initiated B. The viral load should be suppressed after 6
with higher baseline CD4 counts months of effective antiretroviral therapy
(> 200 cells/mm 3) C. Vaccination transiently decreases the viral
D. It usually presents within the first 3 months load
of initiating ART D. Viral load meas)Jres intracellular viruses
E. The mortality is high (approximately 25%) E. Viral load reaches a relatively stable plateau
2 weeks after seroconversion
12.18. A 26 year old woman with newly
diagnosed HIV infection and a CD4+ 12.22. A 42 year old man presents with severe
lymphocyte count of 34cells/mm 3 presents with headache and vomiting of 3 weeks' duration.
dysphagia. There is no oral candidiasis. You His CD4 count is 62cells/mm 3 . Computed
tomography (CT) scan of the brain is normal. 12.23. Which of the following features is
Lumbar puncture shows mild pleocytosis with characteristic of HIV-associated nephropathy
positive cryptococcal antigen test and elevated (HIVAN)?
opening pressure of 34cmH 2 0. You commence A. Heavy proteinuria (> 1 .5 g/24 hrs) is a usual
therapy with intravenous amphotericin B and finding
flucytosine for the cryptococcal meningitis. B. People of European descent are more likely
What is the most appropriate management for to develop HIVAN
the raised intracranial pressure? C. Severe hypertension is a characteristic
A. Acetazolamide feature
B. Dexamethasone D. Small kidneys on ultrasound are typically
C. Insert a ventriculo-peritoneal shunt seen when the creatinine clearance
D. Mannitol decreases to 30 mUmin or less
E. Therapeutic lumbar puncture, removing E. The course of the disease is relatively benign
enough cerebrospinal fluid to reduce with few progressing to end-stage renal
pressure to < 20 cmH 20 failure
Answers
12.1. Answer: B. Budding occurs after cleavage of proteins by
This is the main function of protease protease.
(Fig. 12.1 ). Fusion is mediated after binding to
CD4 and the chemokine receptor, reverse 12.2. Answer: C.
transcriptase mediates reverse transcription, Several factors increase this risk: sexually
and integrase mediates integration of viral DNA. transmitted infection (especially genital ulcers),
Attachment
to CD4 receptor
Fusion
•
inhibitors
Reverse
transcription
of viral RNA
genome
r
......0
. - ~'" 1\1\
Genom1c J\J v v -
Reverse
transcriptase
inhibitors
Dou. ble-stranded
DNA
Chemokine M.:<~r~ntm
(CCR5 or
t
Chemokine
receptor
antagonist
Protease
inhibitors
RNA ~-·~JM~Ji\. 1 Viral mRNA
Reverse
transcription
I
Cell nucleus
=-><#
~4-$,~
____
Transcription
Proviral DNA --"~~~Sffi
Fig. 12.1 Life cycle of HIV. Arrows indicate sites of action of antiretroviral drugs.
Prima~ I
;nrefFlrl _____ Clinical
la_t..Je,...
Constitutional
n_cY_ _ _s_y_m.,ptoms
'f 1200
I
· E 1100
]11 000 <
10 6 ~
~ 900 )>
+-'
c 800 ()
::J
10s.g
u 700
0
Q)
600
gf
>. -o
u 500 104 !!l
0
..c 400 3
Q_
r
E 300 -o
_;::,
1o3 PI
1- 200
+ 3
'<t 100 Ill
0
0 0 L-~~~~~~7~~~~~~~~=-~~~~~10 2
Weeks Years
Fig. 12.3 Virological and immunological progression of untreated HIV infection.
cervical ectopy, uncircumcised male partner papilloma virus infection; the other cancers
and menstruation. listed are not caused by viruses.
12.12. Answer: C.
OILS is a benign polyclonal CDS infiltration of
tissues, especially the parotids, and is
associated with human leucocyte antigen
(HLA)-DRB1. A number of autoimmune
disorders are seen in OILS, including
polymyositis.
12.13. Answer: C.
Several factors increase this risk: high viral load
in source patient, hollow-bore needle that was
in source patient's vessel, visible blood on the
needle.
12.14. Answer: A.
CMV retinitis is the commonest cause of visual Fig. 12.16 Cerebral toxoplasmosis. Multiple ring-enhancing
loss in AIDS. Toxoplasmosis often causes a lesions with surrounding oedema are characteristic.
concomitant vitritis and HIV retinopathy does
not cause visual loss. 12.16. Answer: B.
This is the commonest cause of
12.15. Answer: C. space-occupying lesions in patients with
The standard combination antiretroviral HIV infection- CD4 counts are usually
regimens are two nucleoside reverse < 100 cells/mm 3 and multiple lesions are typical
transcriptase inhibitors (NRTis) together with a (Fig. 12.16).
non-nucleoside reverse transcriptase inhibitor
(NNRTI), protease inhibitor (PI) or integrase 12.17. Answer: D.
inhibitor (Box 12.15). Dual NRTI cor-nbinations IRIS is an exaggerated intl£mmatory response
are usually emtricitabine or lamivudine (they seen in the first 3 months after starting ART. It
have the same mechanism of action and so are is most common in patients starting ART with
never combined) together with one of abacavir, low CD4 counts. It is us~jal to continue ART
tenofovir or zidovudine. See Fig. 12.1, above, and provide symptomatic relief for IRIS
for mechanisms of action •of the different manifestations; steroids may be useful with
antiretroviral drugs. life-threatening manifestations.
12.18. Answer: D.
Candida oesophagitis is the commonest cause,
12.21. Answer: B.
The level of viraemia is measured by
T
but failure to respond in this case virtually rules quantitative PCR of HIV RNA, known as the
this out (azole-resistant Candida species are viral load. Determining the viral load is crucial
usually only seen in patients with prolonged for monitoring responses to antiretroviral
azole use). The next commonest cause is major therapy. People with high viral loads (e.g.
aphthous ulceration, which responds well to > I 00 000 copies/ml) experience more rapid
steroids and ART. declines in CD4 count, while those with low
viral loads(< IOOOcopies/mL) usually have slow
12.19. Answer: E. or even no decline in CD4 counts. Viraemia
Tuberculosis nodes are often matted and may peaks during primary infection and then drops
fluctuate. Malignant nodes rarely fluctuate, as the immune response develops, to reach a
unless there is central necrosis. Persistent plateau about 3 months later (see Fig. 12.3,
generalised lymphadenopathy of HIV is typically above).
symmetrical and does not fluctuate. Transient increases in viral load occur with
intercurrent infections and immunisations, so
12.20. Answer: A. the test should be done at least 2 weeks
Kaposi's sarcoma (KS) is a spindle-cell tumour afterwards. Viral loads are variable; only
of lymphoendothelial origin. All forms of KS are changes in viral load of more than
due to sexually transmitted human herpesvirus 0.51og 10 copies/ml are considered clinically
8, also known as KS-associated herpesvirus. significant.
In Africa, the male: female ratio of
AIDS-associated KS is much lower than is seen 12.22. Answer: E.
with endemic KS, but men are still more The raised intracranial pressure is best
affected than women, despite the fact that the managed by therapeutic lumbar puncture as
seroprevalence of human herpesvirus 8 is the this is a communicating hydrocephalus.
same in both sexes. Steroids and acetazolamide have been shown
AIDS-associated KS is always a multicentric to be harmful. Shunting is seldom necessary.
disease. Early mucocutaneous lesions are Mannitol is irrational, as the primary proble/r.h is
macular and may be difficult to diagnose. As not cerebral oedema. ,"
'!
the disease progresses, the skin lesions
l
become more numerous and larger. 12.23. Answer: A. 11
Sexually transmitted
infections
Multiple Choice Questions
13.1. Most women with genital Chlamydia C. Gonorrhoea
trachomatis are symptomless. In women who D. Lymphogranuloma venereum
do develop symptoms, which of the following is E. Secondary syphilis
the most common?
A. Deep dyspareunia 13.4. Most of the following are complications of
B. Dysuria disseminated gonococcal infection (DGI). Which
C. Increased vaginal discharge would you be UNLIKELY to see as a
D. Lower abdominal pain recognised complication of DGI?
E. Unexpected vaginal bleeding A. Arthritis
B. Endocarditis
13.2. A patient with confirmed infection with C. Pustular rash
herpes simplex virus type 2 (HSV-2) has had D. Tenosynovitis
symptomatic recurrences approximately every E. Uveitis
/'
month for the last year. What is the standard /
first-line antiviral regime to be prescribed in this 13.5. What is the most likely diagnosis in this 17
case? year old young man who has become aware of
these painless "lumps"?
A. Aciclovir 200 mg four times daily
B. Aciclovir 400 mg twice daily
C. Famciclovir 250 mg once daily
D. Famciclovir 750mg once daily
E. Valaciclovir 500 mg once daily
13.6. Which of the following antimicrobial drugs 13.10. A 22 year old MSM presents for an
is unlikely to be effective against genital STI screen. His only complaint is of pain on
Chlamydia trachomatis infection? defecation. Examination reveals an anal
A. Amoxicillin fissure. Serological tests for syphilis are as
B. Ciprofloxacin follows:
C. Erythromycin
Test Result
D. Ofloxacin
Antitreponemal lgG EIA Negative
E. Oxytetracycline Negative
APR
TPPA Positive - titre 160
13.7. Which of the following statements is true Antitreponemal lgM EIA Positive - optical density 3.4
of infection with human papilloma virus (HPV)
types 6/11? Which of the following is the most likely
A. More cases of perianal warts are seen in explanation of the serology?
homosexual men than in heterosexual men A. Early latent syphilis
B. This is associated with penile cancer B. False-positive syphilis serology
C. This is cleared by treatment with topical C. Primary syphilis
liquid nitrogen D. Secondary syphilis
D. This is prevented by vaccination with Cervarix E. Treated syphilis
E. This will result in visible genital warts in less
than 50% of cases 13.11. A 38 year old married man tells you that
he had unprotected sex exactly 1 week ago
13.8. A symptomless 43 year old MSM with a woman who he thinks may be an
undergoes a routine STI screen for the first time intravenous drug user (IOU). Which of the
in 3 years. All tests for STis were previously following statements is true?
negative. His serological tests for syphilis are
A. He can safely have sex with his wife
now as follows:
if all tests for STis taken today are
negative
f---0-Te::.:sc=-t_ _ _ _ _ _ _ _ ____cR:..:.:esult
Antitreponemal immunoglobulin G Positive - optical B. He can safely have sex with his wife if/
f---0-(lg"-G-'--),---en-:-z'-ym_e_i_m_m-:-un_o_as_s_,ay---'(~EI--'A)_ _--cd_ensity 20.3 given treatment with a single dose of .;
f---'-'R2ap:c:id'-'p:c:lac:.smc=a"'re.:"ag""inc__('-'R'-'PR:!._)------'P-'ositive - titre 4 azithromycin 1 g ,,·
Treponema pal/idum particle Positive - titre C. He is at significant risk of acquiring h,~patitis
1--ag,_,g'---lu_tin_a_tio_n_a_ss_a-'--y-'--[T_PP_A-'--)_ _ _ _>_5120 C (HCV) '
Antitreponemal immunoglobulin M Negative D. He should be offered post-exposur~
(lgM) EIA
prophylaxis (PEP) against HIV /
E. He should be offered vaccination against
Which of the following is most compatible
hepatitis B (HBV)
with these results?
A. Early latent syphilis 13.12. A symptomless 29 year old MSM
B. Partially treated late syphilis presents for an STI screen. Serological tests for
C. Primary syphilis syphilis are as follows:
D. Secondary syphilis
E. Untreated late syphilis Test Result
Antitreponemal lgG EIA Positive - optical density 33
13.9. A 19 year old woman complains of APR Negative
moderate lower abdominal pain that has been TPPA Positive - titre > 5120
present for 2 weeks, and is particularly Antitreponemal lgM EIA Positive - optical density 11.4
noticeable during sex. Which of the following
actively supports a diagnosis-of chlamydial Which of the foii9I!Ving is the most likely
1
salpingitis? explanation of the serology?
A. A dipstick urine test showing haematuria +++ A. Early latent syphilis
B. A positive pregnancy test B. False-positive syphilis serology
C. A temperature of 36.3"C C. Fully treated late latent syphilis
D. Diarrhoea D. Partially treated late latent syphilis
E. Right upper quadrant tenderness E. Untreated late latent syphilis
13.13. The following infections are not thought the last year. Which of the following statements
of as being STis, but which is the only one that is most appropriate?
cannot be sexually transmitted? A. As her partner has been symptom-free for a
A. Cytomegalovirus (CMV) year, she can be reassured that there is no
B. Hepatitis A (HAV) risk of transmission to her
G. Plasmodium vivax B. Primary genital herpes is more likely to lead
D. Shigella sonnei to disseminated infection if it is caused by
E. Zika virus HSV-2
G. She should avoid unprotected sex for the
13.14. A 27 year old woman is 24 weeks duration of the pregnancy
pregnant. She mentions to you that her current D. She should be commenced on
male partner has a previous history of genital valaciclovir 500 mg once daily to prevent
herpes caused by herpes simplex virus type I transmission
(HSV-1). Although he has had few recurrences E. Her baby should be delivered by caesarean
in the past, he has had no symptoms at all in section
Answers
13.1. Answer: E. MSM but diarrhoea would be a more prominent
Chlamydia can cause a cervicitis, and the symptom. Cytomegalovirus (CMV) colitis is only
resulting friability may present as unexpected seen in end-stage HIV infection, which is clearly
bleeding, especially after sexual intercourse. not the case here.
Urethritis resulting in dysuria is less common,
but may be mistaken for eubacterial cystitis. 13.4. Answer: E.
Deep dyspareunia and lower abdominal pain Typical manifestations of DGI include
are symptoms of ascending infection monoarthropathy, vasculitic rash and
(salpingitis/pelvic inflammatory disease), which tenosynovitis. Endocarditis is seen rarely. The
occurs less frequently than was believed sexually transmitted infection {STI) associated
previously. Increased vaginal discharge is with uveitis is secondary syphilis.
possible, but in most cases is probably due to
an unrelated condition like bacterial vaginosis or 13.5. Answer: A.
candidiasis. Coronal papillae are a normal anatomical
feature, which become more prominent in
13.2. Answer: B. adolescence, and young men can mistake
Early studies using aciclovir to suppress these normal skin appendages for an infection,
recurrences found that 200 mg four times daily especially genital warts. Warts would not be
was more effective than 400 mg twice daily, but limited to the corona, and are usually either
the difference is small enough to recommend more papular or keratotic. Molluscum lesions
the less frequent dosing regime, which is going are umbilicated. Lichen planus typically presents
to make adherence easier. Valaciclovir and as violaceous flat-topped papules. Sebaceous
famciclovir are more expensive and so reserved glands, also known as Fordyce spots, are seen
for cases where aciclovir is ineffective. The on the shaft and base of the penis.
recommended dose of valaciclovir is 500 mg
once daily as per option E, but the correct 13.6. Answer: B.
starting dose of famciclovir is 250 mg twice daily. Erythromycin and oxytetracycline were used
before the advent of azithr9mycin and
13.3. Answer: D. doxycycline, respectively/Ofloxacin is a
Lymphogranuloma venereum is the likeliest quinolone with antichlarnydial efficacy, but this
cause of severe proctitis and is most often is not the case for ciprofloxacin. Somewhat
diagnosed in HIV-positive MSM in the UK. surprisingly, amoxicillin w.,as found to be
Gonococcal proctitis is usually less severe than effective in the treatment of Chlamydia in
in this case, as are the rare cases of syphilitic pregnancy, although azithromycin is much
proctitis. Campylobacter infection is seen in preferred now.
-
the last segment to reabsorb sodium D. Loss of water in excess of sodium
E. The sodium reabsorptive capacity of the E. Osmotic diuresis-induced hypovolaemic
segments distal to the ascending limb of the hyponatraemia
loop of Henle is limited
14.19. In which one of the following clinical 14.24. The amount of potassium excreted by
scenarios is urine sodium excretion likely to be the kidneys will decrease in which of the
less than 20 mmol/24 hrs? following situations?
A. Acute diarrhoea A. When dietary intake of potassium increases
B. Adrenal insufficiency B. When distal tubule sodium delivery increases
C. Hypothyroidism C. When plasma aldosterone concentration
D. Renal disease increases
E. Syndrome of inappropriate antidiuretic D. When the patient has acute metabolic
hormone (vasopressin) secretion (SIADH) acidosis
E. When the patient has respiratory alkalosis
14.20. A 57 year old man with hypertension is
found to have a tumour arising in the zona 14.25. A 42 year old patient has the following
glomerulosa of the adrenal gland that leads to bloods. Arterial blood gases: W 57.5nmoi/L (pH
uncontrolled secretion of a hormone that is 7.24); Pa0 2 11.1 kPa (83 mmHg); PaC02 4.3 kPa
responsible for his hypertension. (32 mmHg); bicarbonate 15 mmoi!L. Serum
Which of the following would you expect to biochemistry: sodium 134 mmoi/L; potassium
decrease in this scenario? 2.4mmoi/L; chloride 109mmoi/L. Urine pH 5.2;
following administration of intravenous sodium
A. Extracellular fluid volume
bicarbonate, urine pH is 5.8.
B. Plasma concentration of bicarbonate
What is the likely underlying cause of these
C. Plasma concentration of potassium
abnormalities?
D. Thyroid-stimulating hormone
E. Tubular reabsorption of sodium A. Loop diuretic abuse
B. Thiazide diuretic abuse
14.21. A 12 year old boy is being investigated C. Type 1 (distal) renal tubular acidosis
for fatigue. A physical examination, including D. Type 2 (proximal) renal tubular acidosis
blood pressure, is normal. Blood results show: E. Type 4 renal tubular acidosis
sodium 135 mmoi/L, potassium 3.1 mmoi/L,
bicarbonate 35 mmoi/L; 24-hour urine results: 14.26. A 38 year old man presents with a;
potassium 245 mmol/24 hrs, calcium 1-week history of arthralgia, rash, haem9,turia
12mmol/24hrs (N < 7.5). and mild peripheral oedema. Blood test~ taken
What is the most likely diagnosis? in the emergency department show thdt his
serum creatinine is 6201-!moi/L (7.01 m~/dL).
A. Bartter's syndrome
What pattern of acid-base disorder is most
B. Gitelman's syndrome
likely to occur in this clinical scenario'?
C. Laxative abuse I
Answers
14.1. Answer: C. recessive pattern. It is characterised by high
The key advantage of POCT testing over concentrations of cysteine in the urine, leading
central laboratory testing is that rapid availability to cysteine stone formation in the urinary tract.
of the result enables immediate medical Cystinosis is a lysosomal storage disease and
decisions and actions. POCTs are generally is also inherited in an autosomal recessive
more expensive than the equivalent test manner. There is accumulation of cystine within
performed in a central laboratory. While POCT tissues. It is one of the causes of Fanconi's
instruments often use new technology, the
requirement for portability or miniaturisation
may involve design or engineering compromises
syndrome, in which there is abnormal renal
tubular function. Cystathionuria (also called
cystathionase deficiency) is also an autosomal .·
I
that result in less accuracy or precision than recessive disorder, in which there is abnormal {
the equivalent standard laboratory test. Most accumulation of plasma cystathionine, leading,#
POCT instruments are designed for a specific to increased urinary excretion. It is often ~c
environment or group of tests, and so their considered to be a benign biochemical
menu is usually more restrictive than standard anomaly. ;'
I
laboratory analysers. All laboratory and
pathology results, including POCT, should 14.3. Answer: B.
always be recorded in the medical records. Most lysosomal storage diseases exhibit an
autosomal recessive pattern of inheritance,
14.2. Answer: E. although a few can be X-linked recessive (e.g.
Homocystinuria is inherited in an autosomal Fabry's disease).
recessive manner. It is most commonly caused
by loss of function of the cystathionine 14.4. Answer: D.
~-synthase (CBS) gene. This affects the Exercise-induced fatigue or pain in muscles is
metabolism of the amino acid methionine and associated with several of the glycogenoses.
causes accumulation of the related amino acids An ischaernic lactate forearm test can be used
homocysteine and methionine. It is often as a clinical diagnostic test for some forms of
diagnosed through newborn screening glycogen storage disease. The cherry-red spot
programs. Dietary treatment is avaiiEJble, in the fundus is typically ays'ociated with
designed to correct the imbalance in the amino Tay-Sachs disease, one/of the inherited GM2
acids caused by the missing enzyme function. gangliosidoses. Hypopigrnentation, ectopia
There is no condition called homocystinosis. lentis and cataracts can be associated with
This should not be confused with many conditions, some of which are inherited,
hornocystinuria (see option E). Cystinuria is an but the glycogenoses are not typically part of
aminoaciduria, inherited in an autosomal this group.
14.5. Answer: A.
Calculated LDL cholesterol is correct because
body water, as in option E. Fluids that are rich
in proteins (such as concentrated albumin) will
T
i
the calculation includes the triglyceride level, remain in the plasma volume, as in option A.
which increases following food consumption. Normal saline distributes within only the
The effect of food consumption on the other extracellular compartment as in option B.
measurements is small by comparison,
especially in relative terms. 14.11. Answer: E.
In the proximal tubule, water reabsorption
14.6. Answer: D. closely matches sodium reabsorption, meaning
Non-HDL cholesterol is correct because it that the fluid that enters the loop of Henle is
allows for the presence of small dense LDL and isotonic with the fluid that leaves the Bowman's
other atherogenic lipoproteins. This is capsule.
particularly relevant in hypertriglyceridaemia,
with or without accompanying elevation of 14.12. Answer: E.
fasting plasma glucose. It is more strongly The proximal tubule reabsorbs filtered sodium
associated with cardiovascular disease (CVD) in by coupling re-entry of sodium into the
studies where comparison has been made with proximal tubular cell with amino acids as well
the other alternatives. as glucose, phosphate and other organic
molecules.
14.7. Answer: B.
Cholestyramine reduces recirculation of bile 14.13. Answer: B.
acids, down-regulates the farnesoid X receptor This man has hypovolaemia and sodium
(FXR) and stimulates the replacement of the bile depletion as evidenced by his symptoms and
acids by conversion of cholesterol via 7 signs on presentation. The kidneys respond to
alpha-hydroxylase. The response to the this scenario by activating mechanisms that will
down-regulation of FXR includes increased increase sodium reabsorption, thereby restoring
synthesis and secretion of triglyceride and very sodium and fluid balance. Mechanisms that will
low-density lipoproteins (VLDLs). The other increase sodium reabsorption include increased
agents have neutral or favourable effects on catecholamine release and increased renin/
triglyceride levels. release. In order to restrict fluid loses the /
kidneys will reduce glomerular filtration ra,fe in
14.8. Answer: A. part by vasoconstriction of renal afferen~/
Type 2 diabetes following statin therapy is likely arterioles.
in those with pre-existing impaired fasting
glucose. It is proportional to the dose and 14.14. Answer: E. I
/'
potency of the statin, but the CVD benefit of Loop diuretics inhibit the Na,K,2CI triple
the response clearly outweighs the CVD risk of co-transporter in the ascending limb of the loop
the diabetes. Statins modestly improve of Henle and are the most effective diuretics as
triglyceride, even in the presence of diabetes. this transporter reabsorbs about 25% of the
sodium load. More distal reabsorption by the
14.9. Answer: D. sodium-chloride transporter in the distal tubule
The dominant intracellular cation is potassium. only accounts for about 5% of sodium
If cells haemolyse during venepuncture, reabsorption and increased delivery to this
increased potassium will be released from the segment when using a loop diuretic
cells and a patient may be erroneously overwhelms the reabsorptive capacity of that
diagnosed with hyperkalaemia. transporter. Option C is incorrect as the
ascending limb is permeable only to sodium;
14.10. Answer: B. the triple co-transpor)er does transport
Total body water is about one-third extracellular potassium as in opJi6n B, but this is not
fluid (ECF) and two-thirds intracellular fluid. ECF relevant to the diuretic effect; in option D, the
is about one-fifth plasma and four-fifths ascending limi;J of the loop of Henle is not the
interstitial fluid. Fluids that contain neither last segment to reabsorb sodium, as outlined
sodium nor protein (such as 5% dextrose) will above; and in option A, vasopressin acts on
distribute in all the body fluid compartments in the collecting ducts to increase wate~
proportion to the normal distribution of total permeability.
71.----------------------------------------------------.
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16.05.1991 11.05.1995 06.05.1999 01.05.2003 26.04.2007 21.04.2011
A. Adult polycystic kidney disease dl), increased from 126 iJ.mOI/L (1.43 mg/dl) 3
T
B. Microscopic polyangiitis months previously). Urinalysis: blood 1+, protein
C. Multiple myeloma 2+, no leucocytes; ultrasound scan of graft
D. Post -infectious glomerulonephritis revealed no hydronephrosis. What is the most
E. Renovascular disease likely explanation for the deterioration in renal
function?
15.17. A 42 year old woman with lgA A. Acute pyelonephritis
nephropathy and stage 3 CKD (eGFR 45 mU B. Acute rejection due to non-adheren'ce with
min/ I. 73 m 2 ) is developing proteinuria immunosuppression
(protein: creatinine ratio is I 20 mg/mmol). BP is C. Anti-glomerular basement membrane disease
I 58/86 mmHg and she is commenced on an D. Chronic allograft injury
ACE inhibitor (lisinopril I 0 mg daily). Two weeks E. Thrombosis in the artery to the graft
later her eGFR has fallen to 37 mUmin/1 .73 m2
and her potassium has risen from 5.2 to 15.21. A previously fit 17 year old male presents
5.9 mmoi/L, although BP and protein: creatinine with a 2- to 3-week history of arthralgia and
ratio have fallen to 146/82 mmHg and 30 mg/ more recently has developed a skin rash on the
mmol, respectively. She is already on a lower legs. Just prior to admission to hospital
low-potassium diet. What is the most he developed abdominal discomfort with
appropriate management? blood-stained stool. On examination, he has a
A. Add a thiazide diuretic widespread non-blanching rash over his limbs.
B. Add a ~-adrenoceptor antagonist (~-blocker) Initial investigations reveal: urinalysis: blood 3+;
C. Commence calcium resonium protein 3+; eGFR 46 mUmin/1 ,73 m 2 ;
D. Increase the lisinopril dose protein: creatinine ratio 220 mg/mmol;
E. Stop the lisinopril haemoglobin 120 g/L, white cell count
12.9x 109 /L; platelet count 259x 109 /L;
15.18. Which of the following is true regarding C-reactive protein 62 mg/L. What is the most
peritoneal dialysis? likely diagnosis?
A. Fluid removal is achieved by increasing the A. Anti-glomerular basement membrane di sease
concentration of sodium in the dialysate
B. Hyperkalaemia is less common than for
B.
C.
Haemolytic uraemic syndrome
Henoch-Schonlein purpura
7
;!
haemodialysis D. Post -streptococcal glomerulonephritis f
C. It is associated with improved patient survival E. Systemic lupus erythematosus ;,
compared with haemodialysis
D. It is unsuitable for elderly patients 15.22. A 62 year old man presents witlil' sudden
E. Peritonitis is usually caused by gut bacteria anuria on a background history of sev~ral
traversing the bowel wall weeks of 'not passing much urine'. He denies
dysuria or haernaturia but admits to having
15.19. Which of the following is typical of the a poor stream for many years. He is
development of pre-eclampsia? normotensive and otherwise looks well and has
A. Low serum urate level no systemic symptoms. What is the best initial
B. Maternal history of cigarette smoking diagnostic investigation?
C. Occurrence in the mother's first pregnancy A. Blood test for electrolytes and renal function
D. Onset of hypertension in the second B. CT of kidneys and urinary tract with contrast
trimester C. Renal biopsy
E. Prolonged prothrombin time D. Renal ultrasound scan
E. Urinalysis for red cell casts
15.20. A 14 year old boy with end-stage renal
disease due to reflux nephropathy received a 15.23. An 18 year old male presents with
renal transplant from his mother. Aged 17 he haematuria and proteinuria. He undergoes renal
transferred to the adult renal service and he left biopsy which shows a mesangiocapillary
home to go to university the following year. Six glomerulonephritis !Olattern of injury.
months later he attends the transplant clinic. Immunofluorescence shows complement C3
He is asymptomatic, but his graft function has staining with no immunoglobulin depqsition.
deteriorated (creatinine 297 llmoi!L (3.36 mg/ Electron microscopy, demonstrates
electron-dense deposits in a ribbon-like pattern dL), potassium 6.8 mmoi/L, corrected calcium
in the glomerular basement membrane (so 1.97 mmoi/L (7.90 mg/dL), international
called 'dense deposits'). What is the most likely normalised ratio (INR) 2.0. Urine dipstick shows
underlying cause of his mesangiocapillary haematuria but no proteinuria. Direct urinalysis
glomerulonephritis? revealed no cells or casts. What is the likely
A. Autoimmune disease cause of his kidney injury?
B. Genetic defect of alternative complement A. Acute interstitial nephritis
pathway B. ATN due to viral infection
C. Hepatitis B infection C. Haemorrhage into the kidneys
D. Hepatitis C infection D. Pre-renal injury due to dehydration from
E. Monoclonal gammopathy alcohol
E. Rhabdomyolysis
15.24. A 49 year old woman presents with
acute kidney injury after an acute illness 15.27. A patient with acute kidney injury has
manifested by myalgia, diarrhoea and vomiting. been anuric for 12 hours despite fluid
Her BP is 84/50 mmHg and she has dry challenges. Potassium is 5.2 mmoi/L, urea is
mucous membranes. She was taking ibuprofen, very high and a pericardia! rub is audible. The
paracetamol and domperidone during the patient appears euvolaemic. A decision is made
illness. Her renal function improves rapidly with to commence haemodialysis due to concerns
intravenous (IV) fluids. Which one of the regarding uraemia and specifically uraemic
following findings are likely to be present? pericarditis. What will the first dialysis session
A. Dense granular ('muddy brown') casts on involve?
urinalysis A. A large surface area dialyser
B. Hypercalcaemia B. A short 2-hour session initially
C. Hyponatraemia C. Heparin anticoagulation
D. Low (< 1 %) fractional excretion of sodium D. High blood flow rate of 400 mUmin
E. Low urine specific gravity E. Ultrafiltration of 2 L (fluid removal)
15.25. A 68 year woman develops malaise and 15.28. In a patient presenting with renal
a low-grade fever. She has no rash and impairment, which of the following is most
appears euvolaemic. She takes atorvastatin, helpful in discriminating between AKI and a lat.e
omeprazole, amlodipine and digoxin regularly presentation of CKD? )
and takes ibuprofen intermittently. Urinalysis A. Anaemia
shows some leucocytes but no casts, B. Hyperphosphataemia ;'
I
haematuria or proteinuria. She has a creatinine C. Hyponatraemia
of 320 11moi/L (3.62 mg/dL), which has been D. Renal biopsy showing interstitial fibrosis and
68 11moi/L (0.77 mg/dL) 1 year previously. tubular atrophy
What is the likely cause of renal injury? E. Small echogenic kidneys on ultrasound
A. Acute interstitial nephritis
B. ATN due to rhabdomyolysis 15.29. A 32 year old man with lgA nephropathy
C. Glomerulonephritis since the age of 18 received a well human
D. Pre-renal injury due to NSAIDs leucocyte antigen (HLA)-matched kidney
E. Urinary obstruction transplant from his older brother. He had no
pre-formed anti-HLA antibodies and the kidney
15.26. A 55 year old man with significant functioned immediately. One week later his
cardiovascular disease and diabetes has acute urine output is noted to be lower than the
kidney injury in the context of a viral illness. He previous days and his. creatinine is increased,
was at a social gathering where he consumed having previously droppetto normal in the
alcohol and woke the next morning unwell. He first few days post-transplant. His BP is
had fever, aches and pains, headache and felt 180/90 mmHg, he has dipstick-positive blood
thirsty. He takes atorvastatin, lansoprazole, on urinalysis and he look§ euvolaemic. What is
amlodipine, bisoprolol, warfarin, digoxin the likely diagnosis?
regularly. He passed a small amount of dark A. Acute cellular rejection
urine. His creatinine is 190 11moi/L (2.15 mg/ B. BK polyomavirus nephropathy
G. Hyperacute rejection
D. Recurrent lgA nephropathy
A. A granulomatous interstitial nephritis
B. Calcium deposition in the tubules
T
E. Renal artery stenosis G. Focal segmental glomerulosclerosis (FSGS)
D. Necrotising cresentic glomerulonephritis
15.30. A 56 year old woman with polycystic E. Widespread interstitial fibrosis and tubular
kidney disease received her second kidney atrophy
transplant. She had pre-formed anti-HLA
antibodies (from the first transplant) but the 15.33. Patients with advanced liver disease are
cross-match was negative so she proceeded at risk of developing AKI, termed hepatorenal
to transplant using induction therapy syndrome. Which of the following is true of this
(anti-thymocyte globulin; ATG). She had syndrome?
immediate function of the transplant but A. Aggressive dialysis may prevent hepatic
suffered an acute rejection after 2 months, encephalopathy
which was successfully treated with IV B. lgA deposition is a common cause
glucocorticoids. She developed a urinary tract G. Kidney biopsy should be performed for an
infection (UTI) in the week after the steroids accurate diagnosis
were administered, which cleared with D. Outcomes are good with haemodialysis
oral antibiotics. Her renal function has E. The aetiology is haernodynamically mediated,
deteriorated again at 4 months and her so urine sodium will be reduced
serum shows BK polyomavirus on polymerase
chain reaction testing. A biopsy reveals 15.34. Which of the following is true in diabetic
BK polyomavirus nephropathy. Risk factors nephropathy?
for BK polyomavirus include which of the A. ACE inhibitors generally cause resolution of
following? proteinuria and stabilisation of renal function
A. Augmented immunosuppression (ATG and B. Biopsy is generally needed to confirm the
high-dose steroids) diagnosis
B. Polycystic kidney disease G. It is an uncommon cause of end-stage renal
G. Presence of anti-HLA antibodies disease (ESRD) outside of North America
D. Previous UTI D. Sodium-glucose co-transporter-2 (SGLTi)
E. Second transplant inhibitors, such as ernpagliflozin, may bEll
associated with improved cardiovasculcit /,
and
15.31. What is the pathogenesis of 'myeloma renal outcomes and work by improving'·
kidney' (cast nephropathy)? insulin sensitivity
A. Glomerular light chain deposition due to light E. The natural history is of slow development of
chains, and rarely heavy chains, often giving rnicroalbuminuria over years, with ov~rt
a nodular pattern of injury proteinuria and renal impairment at a late
B. Light chain misfolding, creating glomerular stage
deposits that are Congo red positive
G. Light chains precipitating with Tamm-Horsfall 15.35. A 23 year woman presents with a facial
protein in the tubular lumen rash and arthralgia soon after getting married.
D. Proximal tubular injury and dysfunction due She is found to have an eGFR of 106 mU
to light chain deposition in tubular epithelial min/1.73 m 2 , red cell casts in her urine and
cells 5.5 g/24 hrs of proteinuria. Renal biopsy
E. Tubular damage due to hypercalcaemia confirms lupus nephritis. Which of the following
is true in this patient?
15.32. A patient with known sarcoidosis has A. Best treatment for this patient is with
developed renal impairment over the past 2 cyclophosphamide gnd glucocorticoids
months. Corrected serum calciom is slightly B. Mycophenolate mofetil would be the
high (2.7 rnrnoi/L; 10.82 mg/dl). A renal biopsy induction agent of choice, along with
is performed and glucocorticoids are glucocorticoids
commenced. Renal function gradually G. She probably has.mild lupus nephritis that
normalised over a period of several weeks. can be managed with an ACE inhibitor alone
What would the likely initial renal biopsy findings D. She should be referred immediately to the
show? transplant team
15.45. A 25 year old woman from Uganda who 15.50. A 49 year old woman presents with
has recently delivered a baby presents with visible haematuria. A cystoscopy is normal, but
new continuous incontinence. What is she likely a contract-enhanced CT scan of chest,
to be suffering with? abdomen, pelvis reveals a 17 -em left renal
A. Duplex kidney with insertion of upper pole mass, consistent with a renal cell cancer. What
moiety into the vagina is the best treatment option for this woman?
B. Overflow incontinence A. Cryotherapy
C. Stress urinary incontinence B. External beam radiotherapy
D. Urge incontinence C. Open radical nephrectomy
E. Vesicovaginal fistula D. Robotic partial nephrectomy
E. Tyrosine kinase in~ibitor (TKI)
15.46. What is the most likely Gause of painless,
visible haematuria in a 60 year old man?
/
15.51. A 72 year old fit ex-smoking man is
A. Ureteric stone identified on flexible cystoscopy to have a 4-cm
B. Bladder cancer bladder tumour. C)'Stoscopy and transurethral
C. lgA nephropathy resection of bladder tumour provides tissue
D. Systemic lupus erythematosus that on pathological examination shovys a
E. Upper urinary tract urothelial cancer G3pT2 urothelial cell cancer. What is the
I
optimal management for this muscle-invasive 15.55. In a 67 year old man with benign
cancer? prostatic hypertrophy (BPH) who has a large
prostate (70 cc) and is already treated with an
A. Brachytherapy
B. Chemotherapy (gemcitabine and cisplatin) a-blocker but with ongoing bothersome
c. Observation with regular flexible cystoscopy symptoms of hesitancy and poor flow, which of
D. Partial cystectomy the following options is most appropriate?
E. Radical cystectomy A. 5a-reductase inhibitor such as finasteride
B. High-intensity focused ultrasound therapy
15.52. A healthy 81 year old man presents C. Open prostatectomy
with back pain to his family physician. A PSA D. Robot-assisted laparoscopic radical
is undertaken, which measures 2350 ng/ml. prostatectomy
The patient is referred to a urologist who E. Transurethral resection of the prostate
identifies a craggy, hard prostate gland and
undertakes a bone scan, which shows multiple 15.56. A 81 year old man attends as an
bone metastases. What is the best treatment emergency having passed nothing more than
option for this man? 50 ml of urine for 2 days. He has nocturnal
A. Active surveillance enuresis, a palpable bladder and a creatinine of
B. External beam radiotherapy to pelvis 378 [!moi/L (4.28 mg/dl). What is the most
C. Gonadotrophin-releasing hormone (GnRH) appropriate initial management?
agonist therapy A. Bilateral ureteric stent insertion
D. High-frequency focused ultrasound B. Haemodialysis
E. Radical prostatectomy C. Start an a-blocker, i.e. tamsulosin
D. Transurethral resection of the prostate
15.53. What is the most appropriate set of E. Urethral catheterisation
investigations for a 71 year old male smoker who
presents with dysuria and the family physician 15.57. A 54 year old female has stress
identifies persistent non-visible haematuria? incontinence proven by urodynamics. What is
A. DMSA static scan, mid-stream urine (MSU) the most appropriate initial management?
for microbiology culture, renal tract A. Anticholinergic medication
ultrasound B. Botulinum neurotoxin type A
B. MRI pelvis and MSU C. Pelvic floor exercises
C. MSU, flexible cystoscopy, renal tract D. Sacral nerve stimulation
ultrasound E. Tension-free vaginal tape
D. Nil, only investigate when visible haematuria {
E. Non-contrast CTKUB, transrectal ultrasound 15.58. Which of the following statements is 'true
scan and biopsy regarding erectile dysfunction (ED)?
A. lntracavernosal alprostadil should be
15.54. An 18 year old male presents with considered as a first-line treatment option
long-standing mild left testicular pain, with a B. Perineal trauma is the most common cause
hard 1-cm lump in the testicle. What is the C. PSA should be checked in all men
most appropriate course of action? D. Pudendal artery angiography is useful in early
A. Analgesia and observation assessment
B. CT scan E. Risk factors for cardiac disease should be
C. Intravenous antibiotics and observation assessed
D. Nuclear medicine scan
E. Scrotal ultrasound
Answers
15.1. Answer: D. heart sound) or chronic liver disease and there
He has no clinical evidence of heart failure (JVP is no history of obstructive urinary symptoms;
not elevated, no basal crepitations, no third therefore there is no indication to perform
--
Alport's disease is a possibility, although the The combination of low haemoglobin, low
absence of deafness and a family history of platelets and schistocytes on blood film
renal disease renders this less likely. suggest microangiopathic haemolytic anaemia,
Membranous nephropathy presents with which may be due to a number of conditions,
nephrotic syndrome and vesica-ureteric reflux including haemolytic uraemic syndrome or l
would rarely cause isolated haematuria with no thrombotic thrombocytopenic purpura. The
evidence of proteinuria or CKD. Ultrasound antecedent bloody diarrhoea and predominant
scan and cystoscopy to exclude uroepithelial renal versus neurological complications are I
tumour would need to be considered if he were
over 40 years old.
consistent with HUS rather than TIP. The
negative E. coli 0157 stool cultures do not rul~''
I
out HUS as they have been taken after the [
15.11. Answer: B. diarrhoeal phase of the illness. Malignant
The Study of Heart and Renal Protection hypertension may also cause microangiopathic
(SHARP) provides evidence for reduced haemolytic anaemia; however, the blood /
cardiovascular events with statins in patients pressure is typically much higher than observed
with CKD with or without renal artery here. Scleroderma renal crisis, but not lupus,
disease. The patient's renal function is stable may cause microangiopathic haemolytic
and blood pressure is well controlled and anaemia and AKI. While vomiting and diarrhoea
she has proteinuria, and therefore her lisinopril predispose to pre-renal failure, his high blood
should be continued; however, she should pressure and leg swelling would indicate that
be informed to discontinue lisinopril he is hypervolaemic, not hypovolaemic.
transiently should she develop vomiting,
diarrhoea or fever. The Angioplasty and 15.14. Answer: E.
Stenting for Renal Artery Lesions (ASTRAL) High serum calcium due to excess calcium or
and Cardiovascular Outcomes in Renal vitamin 0 consumption should suppress the
Atherosclerotic Lesions (CORAL) trials have PTH level. The PTH level here is inappropriately
not found any benefit from renal artery elevated, indicating hyperp9rathyroidism. Serum
revascularisation in this context and·similarly phosphate should be low.in primary
there is no evidence for the use of warfarin. hyperparathyroidism. In patients with CKD,
Plasma renin activity does not help discriminate calcium is initially maintained in the normal
those who might benefit from angioplasty range by elevated PTH (q_econdary
and will be difficult to interpret in the hyperparathyroidism); however,. as here,
context of angiotensin-converting enzyme (ACE) eventually the gland may become autonomous
inhibition. and the PTH level will be very high, resulting in
gout, hypomagnesaemia and abnormal liver glomerular perfusion. ACE inhibitors cause
function tests. COL4A5 mutations cause efferent arteriolar vasodilatation, further
X-linked Alpert's syndrome, which would not fit dropping intra-glomerular pressure and hence
here (male-to-male transmission, cystic disease, GFR. The diuretic may cause volume depletion,
other features). He likely has an autosomal adding to the insult. Rhabdomyolysis is not the
dominant condition but he does not have cause, as the atorvastatin is not a recent
polycystic kidney disease as no cysts are medicine, and urine myoglobin causes a
evident on scanning. UMOD mutations may false-positive dipstick for blood.
cause a chronic interstitial nephritis and gout,
but would not explain the other features 15.42. Answer: D.
(diabetes, pancreatic atrophy). This patient has developed the nephrotic
syndrome after taking NSAIDs so the
15.38. Answer: A. possibilities are minimal change disease,
Anti-GBM antibodies may develop due to characterised by normal light microscopy, or
normal type IV collagen subunits expressed on membranous nephropathy. Option D refers to
the donor kidney. Female carriers of X-linked minimal change disease and none of the
disease may be symptomatic, although milder answers describe membranous nephropathy.
than males, due to random inactivation of the X Option A refers to thrombotic microangiopathy,
chromosome. Deafness may occur due to the which NSAIDs do not cause. Options B and E
presence of abnormal cochlear type IV collagen. refer to acute interstitial nephritis and acute
Some patients with type IV collagen mutations tubular necrosis. Both may be caused by
develop subtle abnormalities manifested NSAIDs, but do not cause the nephrotic
clinically by haematuria only (thin basement syndrome. Option C refers to rapidly
membrane disease). Alport's syndrome is
usually X-linked (COL4A5 mutations) but
progressive glomerulonephritis such as ANCA
vasculitis.
~
autosomal recessive and dominant disease
may occur (COL4A3 and COL4A4 mutations).
15.39. Answer: D.
15.43. Answer: E.
The micturition cycle has a storage (filling)
phase and a voiding (micturition) phase. During
I
Patients with APKD are at risk of liver cysts, the filling phase, the high compliance of the
cerebral berry aneurysms and mitral valve detrusor muscle allows the bladder to fill
prolapse. A ruptured liver cyst would not cause steadily without a rise in intravesical pressure.
sudden death but a berry aneurysm certainly As bladder volume increases, stretch receptors
would. Mitral valve prolapse is usually in its wall cause reflex bladder relaxation and
asymptomatic but may lead to mitral increased sphincter tone. At approximately
regurgitation; however, it would be a rare cause 75% bladder capacity, there is a desire to void ..
of sudden death. Voluntary control is now exerted over the desire
to void, which disappears temporarily.
15.40. Answer: A. Compliance of the detrusor allows further
The patient has APKD. It is an autosomal increase in capacity until the next desire to
dominant condition, so offspring have a 50% void. Just how often this desire needs to be
chance of inheriting it. Given his preserved inhibited depends on many factors, not the
renal function and good prognosis in affected least of which is finding a suitable place in
family members, the mutation is likely located in which to void.
the PKD2 gene. While liver cysts are common, The act of micturition is initiated first by
liver failure is very rare in APKD, particularly in voluntary and then by reflex relaxation of the
men. Tolvaptan is indicated for patients pelvic floor and distal sphincter mechanism,
deemed to be high risk for progression, which followed by reflex detrusor ;;ontraction. These
this man is not, given his preserved·renal actions are coordinated lj¥' the pontine
function well into his 60s and good prognosis micturition centre. ·
in affected family members.
15.44. Answer: E.
15.41. Answer: A. Although MRI and CT scanning may identify
NSAIDs cause prostaglandin-induced afferent some large bone metastases in the area
arteriolar vasoconstriction, which drops scanned, they will not identify smaller deposits
DE Newby, NR Grubb
Cardiology
Multiple Choice Questions
16.1. A 55 year old man with a history of poorly elevated jugular venous pressure (JVP). Which
controlled hypertension presents with a history of the following conditions is most likely to
of sudden-onset central chest pain. There are explain this physical finding?
no diagnostic electrocardiogram (EGG) A. Aortic stenosis
abnormalities, and an interval troponin B. Dehydration
concentration is not diagnostic of myocardial C. Exacerbation of asthma
infarction. What diagnosis should be confirmed D. Increased left atrial pressure
or excluded next? E. Recurrent pulmonary embolism
A. Anxiety
B. Aortic dissection 16.5. A 56 year old man presents with a history
C. Myocarditis of headache. He is noted to have a loud
D. Pericarditis second heart sound on auscultation. Whic~ of
E. Pneumothorax the following pathologies could explain thi~
. d'1ng.?
f1n /I
16.2. The term 'orthopnoea' refers to A. Aortic incompetence
breathlessness (dyspnoea) in a particular B. Essential hypertension
situation. Which answer below describes that C. Mechanical mitral valve replacement
situation? D. Mitral incompetence
A. After several hours of sleep E. Postural hypotension
B. Due to asthma
C. Immediately on lying flat 16.6. Which of the following pathologies can be
D. On exertion associated with an early diastolic murmur?
E. On sitting upright A. Long QT syndrome type 1
B. Marfan's syndrome
16.3. A 75 year old woman presents to her C. Mitral valve prolapse
family physician with a 24-hour history of rapid, D. Myotonic dystrophy
irregular palpitations accompanied by fatigue. In E. Wolff-Parkinson-White syndrome
an elderly patient, what is the most likely cause
of palpitations? 16.7. An 80 year old woman with a history of
A. Atrial ectopic (premature) beats palpitation presents with a painful left leg. On
B. Atrial fibrillation examination, pulse rate is 80 beats/min and
C. Supraventricular tachycardia irregular, blood pressure (BP) 170/96 mmHg.
D. Ventricular ectopic (premature) beats The left leg is pale, cold, and sensation is
E. Ventricular tachycardia reduced. The popliteal, dorsalis pedis and
posterior tibial pulses cannot be felt. Her only
16.4. A 74 year old woman presents with regular medications are aspirin and digoxin.
breathlessness. She is found to have an What is the most likely diagnosis?
A. Acute arterial plaque rupture with lower limb A. A normal baseline troponin and elevated
ischaemia 6-hour troponin level is suspicious of
B. Deep venous thrombosis with secondary myocardial infarction
reduction of arterial blood flow B. A normal EGG excludes myocardial infarction
G. Dissection of the femoral artery due to G. A normal initial troponin level excludes
uncontrolled hypertension myocardial infarction
D. Peripheral embolism with lower limb ischaemia D. Failure of chest pain to resolve with nitrates
E. Reduced lower limb perfusion due to cardiac confirms myocardial infarction
failure E. T-wave inversion on the EGG confirms
myocardial infarction
16.8. A 50 year old man is assessed because
of 3 weeks of fever and influenza-like 16.12. A 72 year old hypertensive woman
symptoms. Examination findings are presents with a history of sudden-onset, rapid,
tachycardia (heart rate 105 beats/min), and a irregular palpitation. She has had several
large pulse pressure, BP 140/45 mmHg. Initially episodes over the previous 3 months, which
it was thought a murmur was present but have resolved within 1 hour. She feels tired and
repeat examination reveals no murmur. slightly lightheaded during episodes. From this
Investigations reveal no evidence of chest or history, which of the following most likely
urinary infection. What are these findings most explains her symptoms?
compatible with? A. Atrial fibrillation
A. Acute myocarditis B. Sinus arrhythmia
B. Acute viral pericarditis G. Supraventricular tachycardia
G. Infective endocarditis affecting the aortic valve D. Ventricular ectopic beats (extrasystoles)
D. Infective endocarditis affecting the tricuspid E. Ventricular tachycardia
~.
valve
E. Influenza 16.13. In the management of cardiac arrest, ~
which of the following most accurately
16.9. You assess a 62 year old woman 2 days describes basic life support (BLS)?
after treatment for anterior myocardial
infarction. On examination she is tachycardic
A. Administration of intravenous drugs and j
external defibrillation (the two 'D's)
and tachypnoeic, and has a harsh systolic B. External cardiac massage only
murmur radiating to the right side of the chest. G. Support of airway, breathing and circulation
There are fine inspiratory crepitations audible at (ABC)
the lung bases. What is the most likely D. Support of airway, breathing and circulation,
explanation for these findings? and assessment of disability and exposure
A. Acute aortic incompetence (ABC DE)
B. Left ventricular free wall rupture E. Support of airway, breathing and circulation,
G. Papillary muscle rupture and mitral and assessment of disability and exposure,
incompetence treatment of fibrillation (ABCDEF)
D. Post -infarction pericarditis with pericardia! rub
E. Rupture of the interventricular septum 16.14. Which of the following statements is true
of a pulseless electrical activity (PEA) cardiac
16.10. Which of the following physical signs is arrest?
associated with left ventricular failure?
A. Cardiopulmonary resuscitation (CPR) should
A. A gallop rhythm with a fourth heart sound be carried out for 1 minute before the rhythm
B. A gallop rhythm with a third heart sound is reassessed
G. A loud second heart sound B. Intravenous amiodarone will restore cardiac
I
D. A quiet first heart sound output /
E. Fixed splitting of the second heart sound G. It is initially managed with immediate
defibrillation
16.11. A 55 year old man with type 2 diabetes D. Reversible causes incLude hyperthyroidism
presents with a 1-hour history of severe central and hypercalcaemia
chest pain. Which of the following statements E. Reversible causes include hypothermiaand
is true? hypoxia
16.23. A 75 year old woman has a history of A. A 26 year old man with polymorphic
hypertension and diabetes. She presents with ventricular tachycardia (torsades de pointes)
atrial fibrillation. What is her CHA2 DS 2 -VASc occurring after cocaine use
score? B. A 48 year old man who presents with acute
inferior myocardial infarction complicated
A. 2 within the first 6 hours by ventricular
B.3
fibrillation
c. 4 C. A 55 year old woman with syncope; EGG
D.5
monitoring shows sinus rhythm with
E. 6
third-degree atrioventricular block
D. A 75 year old man with syncope; ambulatory
16.24. Which of the following drugs is known to
EGG shows sinus bradycardia and daytime
be effective in preventing stroke in patients with
sinus pauses of up to 5 seconds
atrial fibrillation?
E. An 80 year old man with a history of anterior
A. Amiodarone myocardial infarction 6 months previously; he
B. Apixaban is fit, has never experienced arrhythmia, and
C. Aspirin a cardiac magnetic resonance scan shows
D. ~-blocker poor left ventricular function (left ventricular
E. Clopidogrel ejection fraction 28%)
worried about the risk of sudden death. Which 16.43. A 75 year old male smoker presents
of the following treatments is known to reduce with a 6-week history of progressive exertional
her risk of sudden death? breathlessness and fatigue. Latterly he has
A. Aspirin noticed his ankles swelling in the afternoon.
B. ~-blocker (e.g. metoprolol) On examination, pulse is I 00 beats/min and
c. Calcium channel blocker (e.g. verapamil) regular; BP 92/60 mmHg. The JVP is elevated
D. Loop diuretic (e.g. furosemide) and rises on inspiration. Heart sounds are quiet
E. Percutaneous coronary intervention (PCI) and there are no added sounds. There is
bilateral pitting oedema to the knees. A chest
16.39. A 55 year old woman presents with a X-ray is requested, which shows apparent
history of acute, severe, constricting central cardiomegaly with a globular cardiac
chest pain associated with anterior ST segment silhouette. You suspect a possible pericardia!
elevation on the 12-lead EGG. She immediately effusion. Which of the following statements
undergoes coronary angiography, which shows is true?
no evidence of coronary artery disease and no A. A large effusion can be a sign of
coronary occlusion. An echocardiogram shows malignancy
left ventricular apical dilatation, with normal left B. A pericardia! rub is always heard if the
ventricular basal contraction. Which of the effusion is large
following factors is most likely to have C. An EGG is the best investigation to confirm
precipitated this illness? the diagnosis
A. Acute emotional stress D. High-dose diuretic therapy will resolve the
B. Cigarette smoking pericardia! effusion
C. Excessive alcohol consumption E. In symptomatic patients, cardiac surgery is
D. Genetic factors required to remove the pericardia! fluid
E. Viral infection
16.44. An 18 year old man presents with
16.40. Which of the following is associated with sudden onset of sharp chest pain.
excessive alcohol consumption? The pain is made worse by deep inspiration
A. Atrial fibrillation or lying down flat. It is relieved by sitting
B. Diverticulitis forward and taking shallow breaths. He
C. Hypertrophic cardiomyopathy presents to the emergency department and
D. Hypotension an EGG is recorded because the attending
E. Supraventricular tachycardia doctor suspects acute pericarditis. What
is the most specific EGG change in
16.41. Atrial myxoma is the most common pericarditis?
primary cardiac tumour. Which of the following A. PR interval prolongation
is true of atrial myxoma? B. PR segment depression
A. Atrial myxomas are usually malignant C. ST depression
B. It occurs more commonly in the right atrium D. ST elevation
than in the left atrium E. T-wave inversion
C. Surgery is not indicated because atrial
myxomas are benign 16.45. A 46 year old man has recently fractured
D. Surgery is usually indicated to prevent his leg, which is in a plaster cast. He suddenly
embolic complications such as stroke becomes very breathless, unwell and collapses.
E. The tumour commonly obstructs the aortic The attending doctor suspects a pulmonary
valve embolus from a deep vein thrombosis. The
doctor performs an EGG. What is the most
16.42. Which of the following conditions may common EGG change in patients with
result in chronic pericardia! constriction? pulmonary embolism? /
A. Acute myocardial infarction A. Anterior T-wave inversion
B. Dilated cardiomyopathy B. Atrial fibrillation
C. Excessive alcohol consumption C. 'SIQ3T3'
D. Osteoarthritis D. Sinus tachycardia
E. Tuberculosis E. ST elevation
Answers
16.1. Answer: B. hypertension), the second heart sound may
In a patient with poorly controlled hypertension, be loud. Postural hypotension will have little
aortic dissection should be considered as a effect on the intensity of heart sounds at rest.
potential cause of acute chest pain. While Aortic incompetence is often associated
interscapular pain is a common feature of acute with a quiet second heart sound, and mitral
aortic dissection, the presentation is highly incompetence with a quiet or absent first heart
variable and central chest pain commonly sound. A mechanical mitral valve replacement
occurs. If antiplatelet or antithrombotic drugs will produce a loud mechanical first heart
are given before excluding this diagnosis, fatal sound.
bleeding may occur.
16.6. Answer: B.
16.2. Answer: C. Marfan's syndrome is a connective tissue
Orthopnoea refers to breathlessness occurring disorder that is associated with abnormal
immediately on lying flat, whereas the term production of elastic tissues. This can affect the
'paroxysmal nocturnal dyspnoea' refers to aorta, aortic root and aortic valve. Aortic root
sudden episodes of breathlessness occurring dilatation can lead to aortic regurgitation and is
at night -time. It can occur with respiratory also associated with increased risk of aortic
pathologies such as chronic obstructive dissection. Aortic regurgitation occurs with
pulmonary disease but is most often associated onset at the beginning of diastole, as soon as
with heart failure. It is caused by the aortic valve closes, and produces an early
gravity-dependent changes in pulmonary diastolic murmur. Myotonic dystrophy is
capillary hydraulic pressure leading to alveolar associated with dilated cardiomyopathy and
oedema. conducting system problems, which can lead
to atrioventricular block and ventricular
arrhythmias. Long OT syndrome is an inherited
16.3. Answer: B.
arrhythmia syndrome that is not usually
The most common cause of a rapid, irregular
associated with any structural cardiac
rhythm in the elderly is atrial fibrillation. In
abnormality. Mitral valve prolapse produces a
patients with very frequent atrial or ventricular
late systolic murmur. Wolff-Parkinson-White
ectopic beats, the pulse is also very irregular
syndrome is rarely associated with structural
but a regular pattern can usually be perceived
cardiac abnormalities (which are Ebstein's
within it.
anomaly and rarely hypertrophic
cardiomyopathy) and is not associated with
16.4. Answer: E. aortic incompetence.
The internal jugular vein is in direct continuity
with the right atrium, and there is no venous 16.7. Answer: D.
valve between the two. The JVP therefore is a Clinical features of acute limb ischaemia include
reflection of right atrial pressure, which pallor, pain, pulselessness, paraesthesia and
becomes elevated in conditions where either 'perishing-with-cold' -the five 'P's. Deep
there is increased resistance to right ventricular venous thrombosis would cause limb swelling,
ejection (e.g. pulmonary hypertension due to venous engorgement, and a dusky blue
chronic lung disease, or recurrent pulmonary discoloration, and this does not affect arterial
embolism) or mechanical dysfunction of the flow. In cardiac failure, peripheral blood flow is
right heart (e.g. right ventricular infarction, not sufficiently reduced to cause limb ischaemia
right-sided valve disease). except in cardiogenic shock. In a patient with a
history of atrial fibrillation.(ernbolisation from
16.5. Answer: B. the left atrial appendage is the most likely
The second heart sound, which occurs at the cause of limb ischaemia. Aspirin does not
beginning of ventricular diastole, occurs when provide effective prophylaxis against this and
the aortic and pulmonary valves close. When current guidelines recommend the use of
either aortic or pulmonary artery diastolic warfarin or a direct oral anticoagulant such as
pressure is high (e.g. in essential or pulmonary apixaban.
--
vasodilator medication can reduce this and preceding increase in the P-R interval before
improve cardiac function. the blocked P wave. This reflects block in the
His-Purkinje system where conduction is
16.17. Answer: A. 'ali-or-nothing'. In contrast, Mobitz type I
Cardiac failure is associated with activation of second-degree AV block is characterised by 1
the sympathetic nervous system and RAAS. progressive lengthening of the P-R interval
The resulting production of noradrenaline block. This reflects block in the AV node itself, .
(norepinephrine) and angiotensin II cause where conduction is 'decremental', i.e. the AV1
peripheral vasoconstriction. BNP production node exhibits signs of 'fatigue' with each /
increases in cardiac failure in response to successive beat.
ventricular stretch.
16.22. Answer: E.
16.18. Answer: B. Sinoatrial disease is characterised by
Loop diuretics interfere with the countercurrent abnormalities of sinus rate, and atrial
sodium exchanger in the loop of the nephron. arrhythmias such as atrial flutter, atrial
This prevents water reabsorption and results in tachycardia and atrial fibrillation. Ventricular
loss of sodium and water (natriuresis). arrhythmias are not commonly associated with
this condition.
16.19. Answer: D.
~-Blockers have several beneficial effects in 16.23. Answer: D.
chronic cardiac failure - improvement of The CHA2 DS 2 -VASc score is used to assess
diastolic filling, reduction of myocardial stroke risk in patients with atrial fibrillation (and
ischaemia, and prevention of ventricular atrial flutter). The mnemonic takes account of
arrhythmias and atrial fibrillation, ~-Blockers clinical risk factors for stroke (C, congestive
reduce heart rate so should not be heart failure = 1 point; H, hypertension = 1
used if the patient is already bradycardic. In point; A2 , age 2 75 years/2 points; D,
acute cardiac failure (e.g. acute left ventricular diabetes mellitus = 1 po1nt; S2 , previous
failure or cardiogenic shock),. in which left stroke or transient ischaemic attack = 2 points;
ventricular systolic function i(l acutely V, vascular disease= 1 point; A, age 65-74
compromised, ~-blockers should not be used years = 1 point; Sc, sex category female = 1
as they may further impair systolic point). In this case, the score is 5 points (2
function. points for age 275 years, 1 point each for
activation and all of the agents listed except by diastolic dysfunction - the inability of the left
dipyridamole act via this receptor. Dipyridamole ventricle to fill properly in diastole.
is a phosphodiesterase inhibitor, which blocks
the response to ADP by inhibiting breakdown 16.52. Answer: D.
of cyclic adenosine monophosphate (cAMP) Both the sympathetic nervous system and the
and inhibits the re-uptake of adenosine into RAAS systems are activated in heart failure.
platelets. Vasopressin may also be released from the
posterior pituitary in response to reduced ·
16.49. Answer: E. cardiac output. Thyroid hormone levels are
smoking is by far the strongest. modifiable risk generally unaffected in cardiac failure but
factor for coronary artery disease. Obesity is profound hypo- or hyperthyroidism can cause
associated with hypertension, type 2 diabetes heart failure.
and unfavourable lipid profile, and is thus
associated with risk of myocardial infarction. 16.53. Answer: E.
High levels of dietary saturated fat (e.g. from Troponin I is a structural myocardial protein
red meat and processed meat products) are subunit, and not an enzyme. Along with the
also known to be associated with increased other markers listed, it is released into the
cardiovascular risk. blood stream after acute myocardial infarction
from injured myocardial tissue.
16.50. Answer: E.
Both percutaneous coronary intervention and 16.54. Answer: C.
fibrinolytic drug therapy are treatment If the patient has occluded his stent, then
modalities for acute ST elevation myocardial the EGG will show an acute inferior ST
infarction. Both treatments aim to re-open the segment elevation myocardial infarction.
culprit coronary vessel to restore perfusion to Electrocardiographic features of acute inferior
the infarct territory. In randomised studies, myocardial infarction include ST segment
administration of tPA or other fibronolytic drugs elevation in the inferior leads (II, Ill and aVF) and
had a strongly time-dependent beneficial effect. sometimes atrioventricular block.
If administered more than 8-10 hours after the
onset of symptoms, risk of treatment begins to 16.55. Answer: A.
outweigh benefit. As fibrinolytic drugs take Sudden, severe pulmonary oedema after
time to work, and may not completely restore myocardial infarction may be a sign of a
flow in the culprit vessel, they are best mechanical complication. Acute papillary
administered early. Percutaneous coronary muscle rupture causes sudden and very severe
intervention and the other therapies described mitral regurgitation, which, in turn, is
do not have such a time-dependent effect on complicated by pulmonary oedema. Acute
outcome. When primary percutaneous coronary pericarditis causes sharp chest pain but does
intervention cannot be provided within 2 hours, not cause pulmonary oedema. Free wall rupture
fibrinolytic therapy should be administered usually causes pulseless electrical activity (PEA)
immediately. cardiac arrest and is almost always fatal. Atrial
septal defect is not a complication of
16.51. Answer: E. myocardial infarction. Left ventricular mural
Dilated cardiomyopathy, myocarditis and thrombus is usually asymptomatic, and is
myocardial infarction all reduce left ventricular detected on echocardiography. It can lead to
systolic function and are associated with low stroke and peripheral embolism.
left ventricular ejection fraction (LVEF), a
measure of the percentage of left ventricular 16.56. Answer: E.
blood ejected in systole. Aortic stenosis is Ventricular fibrillation is an, early complication
associated with either normal LVEF, or if of acute myocardial info/6tion and is the
severe, sometimes low LVEF. Restrictive leading preventable cause of death. Early
cardiomyopathy is associated with myocardial recognition of myocardial infarction is therefore
infiltration and sometimes reduction in left important. Sudden death rates rnay be reduced
ventricular cavity size, but normal systolic by education of the public about symptoms
function. LVEF is high but stmke volume low of myocardial infarction and the need to
due to small cavity size. Heart failure is caused seek immediate medical help, and by the
Patients with left ventricular impairment are at abnormalities develop are likely to have a high
increased risk of acute cardiac failure and ischaemic threshold and are not at high risk of
haemodynamic problems in the perioperative major cardiovascular events. Conversely,
phase. Insulin-treated diabetic patients and patients with new-onset, rapidly progressive, or
those with renal failure may have occult limiting symptoms may have critical coronary
coronary artery disease and are at increased artery disease. Patients with poor left ventricular
risk of perioperative myocardial infarction. Aortic function have poor cardiac reserve and carry
stenosis with a relatively small peak pressure higher than average risk because they tolerate
gradient is not likely to cause haemodynamic myocardial ischaemia poorly.
problems during or after surgery.
16.86. Answer: D.
16.85. Answer: E. Smoking is the strongest risk factor for the
Exercise tolerance testing can be used to development of coronary artery disease.
identify patients with coronary artery disease More than any other lifestyle modification, or
who have a low threshold for myocardial any other preventative therapy, smoking
ischaemia. Patients who can exercise into cessation makes the largest difference to
stage 3 of the Bruce Protocol before ECG cardiovascular risk.
I'
Respiratory medicine
Multiple Choice Questions
17.1. A 46 year old woman has a recent diagnosis small vessel disease. Arterial blood gas: W
of adenocarcinoma of the lung made at 60 nmoi/L (pH 7.22), Pa0 2 8.7 kPa
bronchoscopy 1 week ago. She presents to the (65 mmHg), PaC02 10 kPa (75 mmHg),
emergency department acutely short of breath HC0 3- 26 mmoi/L. What is the most likely
with a non-productive cough. She has an ache in .cause of her deteriorating conscious level?
the centre of her chest that is made worse by A. Cholesterol embolism - ventilation/perfusion
breathing in. She is apyrexial. Oxygen saturations (i/16.) mismatch
are 91% on 40% oxygen. Respiratory rate is B. Chronic obstructive pulmonary disease
30 breaths/min. Blood pressure (BP) is (COPD) with oxygen toxicity - loss of hypoxic
100/65 mmHg and pulse is 110 beats/min. drive
Examination reveals decreased expansion of C. Flail segment due to rib fracture - loss of
I
the right side with dullness to percussion elastic recoil j
throughout the right side. Her trachea is D. Opi~te toxicity - suppression of the
1
deviated to the right and the apex beat is not respiratory centre j
palpable. Breath sounds are reduced on the E. Undetected fracture of C3 - diaphragmatic
right. What is the most likely diagnosis? failure
A. Collapse of the right lung
B. Pericardia! effusion 17.3. A 55 year old man has smoked 30
C. Right-sided pleural effusion cigarettes per day since he was 15 years old.
D. Right-sided pneumonia He is a taxi driver. He finds he is increasingly
E. Right-sided pneumothorax breathless on exertion. Oxygen saturations are
98% on room air. Examination reveals tracheal
17.2. An 83 year old woman was passenger in tug, reduced cricostemal distance and a barrel
a car that collided with a lamppost in the city chest. He has reduced cardiac dullness
centre. She was initially complaining of pain in and symmetrically reduced air entry. CXR
her right hip and ribs but has become reveals hyperinflation and spirometry reveals
increasingly drowsy since the paramedics moderate airways obstruction. The patient
administered 2 mg of morphine. She is brought walks 300 m on an incremental walk test
to the emergency department by ambulance. before becoming breathless; oxygen saturations
Urgent X-rays reveal a pelvic fracture, and a are maintained.
single right -sided rib fracture. · What pathologic~;~hange best explains why
Having, initially been drowsy but responsive he is breathless on exertion?
she is now unresponsive. Oxygen saturations A. Activation of central chemoreceptors
are 87% on 2 Umin oxygen via nasal cannulae. B. Exercise-induced bronchospasm
She is apyrexial. BP is 110/66 mmHg, pulse is C. Loss of elastic recoil
65 beats/min. There are no new findings on D. Paradoxical diaphragm movement
examination. An urgent CT brain reveals only E. Pulmonary hypertension
A. Bronchoscopy
B. CT chest, abdomen, pelvis
C. D-dimer
D. Echocardiogram
E. Positron emission tomography
(PET) scan
-
past medical history of alcohol dependency,
alcoholic liver disease and chronic pancreatitis.
He has smoked 10 cigarettes per day for 30
A. Bronchial carcinoma years and still drinks 28 units a week. He
B. Granulomatous polyangiitis worked as a casual labourer on building sites
C. Lung abscess where asbestos was removed when he was in
D. Pulmonary and pleural tuberculosis (fB) his 20s.
E. Pulmonary infarct What is most likely to be causing the CXR
shown below?
17.5. A 26 year old woman presents with 24
hours of central chest pain and progressive
shortness of breath over a month. Examination
reveals pulse 105 beats/min, BP
105/65 mmHg, oxygen saturations 96% on
room air, apyrexial, respiratory rate 16 breaths/
min. Chest clear; heart sounds dual, no
murmurs. Electrocardiogram, (ECG): sinus
tachycardia; no other abnormalities.
Blood tests: haemoglobin 11 0 g/L, white cell
count 0NCC) 9 x 109/L, platelets 340 x 109/L,
urea and electrolytes normal range, C-reactive
protein (CRP) 67 mg/L.
Given the CXR below, what should the next
test be?
A. Bronchial carcinoma·
B. Empyema
C. Hepatic hydrothorax
D. Mesothelioma
E. Pleural effusion secondary to pancreatitis
11.16. A 73 year old woman has struggled Blood tests reveal: haemoglobin 143 g/L,
with increasing shortness of breath on WCC 12 x 109 /L {neutrophilia), platelets
exertion over the last year. In addition, she 435 x I 09/L, urea 9 mmoi/L (54 mg/dL),
has a dry cough. She worked in an office until creatinine I 02 J.l.moi!L (1.15 mg/dL), sodium
she retired. She has a pet dog. She has 128 mmoi/L, bilirubin 12 J.l.rnoi/L (0. 70 mg/dL),
osteoarthritis, osteoporosis and hypothyroidism. alanine transaminase (ALT) 243 U/L, y-glutamyl
She takes regular paracetamol, a transferase (GGT) 354 U/L, alkaline
bisphosphonate and calcium/vitamin D phosphatase 250 U/L, CRP 334 mg/L. His ·
supplementation. Her sister was treated CXR is below.
for TB when they were children and
she had X-ray screening that she thinks
was clear. Examination reveals finger
clubbing and bi-basal crackles. Her CT scan is
shown below.
17.20. A 38 year old man presents with cough 17.22. A 75 year old man with no past medical
l I
productive of blood-streaked sputum, fever and history presents with increasing shortness of
left-sided pleuritic chest pain. In addition he has breath over 6 months. He previously worked at
developed troublesome cold sores. His past a shipyard where he had significant exposure
medical history includes appendicectomy. He to asbestos. He has a large right-sided pleural
works in a bank. His CXR is below. effusion. Pleural aspiration is performed and
reveals an exudate but cytopathological
examination identifies no malignant cells. CT
scanning reveals circumferential pleural
thickening but no other abnormalities.
Which test is most likely to give a diagnosis?
A. Abrams needle biopsy
B. Bronchoscopy
C. Echocardiogram
D. Repeat pleural aspiration
E. Thoracoscopy
17.29. A 75 year old woman has been referred She has never been an active person but now
with a daily, chronic non-productive cough struggles with breathlessness on exertion,
that has been present for at least I 0 years. especially walking uphill or when carrying
She has no nocturnal and no nasal symptoms. shopping bags. She stopped smoking
Her only other symptom is of back pain 15 years ago when her husband had a heart
following a further vertebral fracture in the last attack. She had smoked 20 cigarettes per day
month. before that.
Her past medical history includes: Her spirometry is within normal limits but her
osteoporosis (multiple vertebral fractures and CXR suggests a hilar abnormality. A
kyphosis), previous duodenal ulcer, TB subsequent CT scan demonstrates that this
meningitis as a child. She is a life-long was a projectional anomaly and excludes a
non-smoke~. Her medication includes: sinister cause. The image below is from the CT
orneprazole 20 rng once daily, alendronic acid scan performed 2 months previously.
once a week, calcium and vitamin D, and cod
liver oil capsules. CXR reveals a large hiatus
hernia and significant kyphosis.
What is the most likely cause of her cough?
A. Asthma
B. Gastro-oesophageal reflux
C. Hypercalcaemia
D. Lung cancer
E. Tuberculosis
17.34. A 45 year old man attends his family 17.37. A 67 year old man has a CT
physician with a sprained wrist following a colonogram as a screening test for /
mistimed punch at his karate class. The doctor iron-deficiency anaemia. No colonic abnormalj{y
notices that he has clubbed fingers. The patient is identified but a 6-mm nodule is identified in
has no past medical history of note, is a the right lower lobe of the lung. The radiologist
non-smoker and, apart from his painful wrist, is suggests referral to the respiratory team for/
asymptomatic. He says people have always ongoing follow-up.
commented on his fingers and that his father's With regard to pulmonary nodules, the risk of
fingers are similar in appearance. On checking malignancy increases with which of the
the patient's record the doctor notes finger following?
clubbing was first recorded in his teenage A. A smooth margin
years. B. Central deposition of calcification
What is the next step the family physician C. Lack of smoking history
should take? D. Size< 4 mm
A. Check bloods (including ~FTs, thyroid E. Upper lobe distribution
function tests and erythrocyte sedimentation
rate) 17.38. A 65 year old woman with rheumatoid
B. CXR to exclude cancer arthritis has a CT scan to determine whether
C. Reassurance I she has an associated int(:lrstitial lung disease.
D. Referral to respiratory clinic She has mild basal interlobular septal
E. Sweat test to exclude c~stic fibrosis thickening in keeping with early interstitial lung
disease (ILD}. The radiologist also identifies a
17.35. A patient presents acutely having speculated, 1 .5 cm-diarn"eter right upper lobe
coughed up 50 ml of fresh red blood suddenly nodule that he suggests may require further
that morning. He is well known to the investigation.
although she is very worried about taking any 17.46. A 57 year old woman has been coughing
medications whilst pregnant. for 3 years. She always carries tissues with her
What should be the next step in her to collect the phlegm she coughs up
management? throughout the day. Sometimes her phlegm
A. Low-molecular-weight heparin (LMWH) can be green and she feels run-down and
unwell. Antibiotics seem to help but she only
B. Oral amoxicillin
feels better for 2-3 weeks.
C. Oral prednisolone
D. Reduce high-dose leS/LABA The patient is a non-smoker who works ·in an
office. She finds her cough embarrassing and
E. Stop montelukast
work colleagues have been giving her a hard
time. What would be the best investigation for
17.44. A 48 year old asthmatic is referred to
this patient?
clinic because of increased frequency of
asthma exacerbations. He has been waking at A. a,-Antitrypsin levels
night with cough and breathlessness that B. Bronchoscopy
require extra doses of inhaled salbutamol. C.eXR
Spirometry reveals an obstructive defect and D. High-resolution eT chest
blood tests reveal an eosinophilia of E. Immunoglobulin levels
0.67 x 109/L. eXR is clear. The patient's
current therapy includes Flixotide 500 11g/ 17.47. A patient who attends the asthma clinic
salmeterol 25 11g 1 puff twice a day; salbutamol has been experiencing significant deterioration
2 puffs, as required. The patient has started in control. The main problem is a cough
prednisolone 40 mg for 5 days as prescribed productive of green sputum that is difficult to
by his family physician today. expectorate and a right -sided pleuritic chest
In line with British Thoracic Society pain that has developed in the last 48 hours.
guidelines, what should be suggested in order Since then breathing has been more difficult.
to step-up therapy? Blood tests reveal: haemoglobin 136 g/L, wee
A.
B.
C.
Add amoxicillin
Add montelukast
Double prednisolone dose
14 x 109/L (neutrophils 7 x 109/L, lymphocytes
1.46 x 109/L, monocytes 0.8 x 109/L, eosinophils
4.7 x 109/L), platelets 340 x 109/L, eRP
~I
D. Provide home nebuliser 120 mg/L. eXR is shown below. I
E. Start omalizumab
17.48. A 24 year old man with cystic 17.51. A 32 year old man presents with a 5-day
fibrosis has recently moved into the history of left -sided pleuritic chest pain, fever
area. He keeps relatively well and and cough productive of rusty sputum.
missed some appointments at his previous Observations include: BP 100/60 mmHg, pulse
service. He has had two exacerbations of 105 beats/min, temperature 38.2°C, respiratory
bronchiectasis in the last year and is rate 21 breaths/min, oxygen saturations 87%
disappointed with his most recent lung on room air. Examination reveals dullness to
function measures. He has heard about a new percussion and bronchial breathing on the left.
medicine called ivacaftor that is only beneficial Nasolabial cold sores are noted.
to some patients with cystic fibrosis and Which organism is likely to be responsible for
wonders if he qualifies. this presentation?
lvacaftor is a small-molecule drug that A. Aspergillus fumigatus
corrects the function of which of the following B. Herpes simplex virus (HSV)
cystic fibrosis transmembrane regulator (CFTR) C. Mycobacterium tuberculosis
gene defects? D. Pneumocystis jirovecii
A.l1F508 E. Streptococcus pneumoniae
B. G542X
C. G551D 17.52. A 53 year old businessman presents with
D.R117H fever, chills, cough and shortness of breath. He
E. W1282X has recently returned from a trip to the Middle
East where he visited a number of countries
17.49. A 24 year old cystic fibrosis patient has .and spent time in the city as well as visiting
failed to recover from a recent exacerbation of more rural areas.
her bronchiectasis. Previously Haemophilus Examination reveals temperature of 40°C,
influenzae and Staphylococcus aureus have pulse 115 beats/min, BP 100/50 mmHg,
been isolated from her sputum. A 2-week oxygen saturations 80% on room air. CXR
course of co-amoxiclav followed by 2 weeks of shows diffuse infiltrates.
doxycycline have failed to improve spirometry Which of the following statements is most
or reduce sputum load. CXR is unchanged and accurate? -
blood tests are unrevealing, apart from CRP of A. Burkholderia pseudomallei needs to bf
134 mg/L. covered /
The microbiology team have isolated B. He should be isolated and tested for
Pseudomonas aeruginosa in the most recent carbapenemase-producing
sample provided. Which one of the following Enterobacteriaceae (CPE) 1
statements is true of P. aeruginosa in cystic C. He should be isolated and tested for Middle
fibrosis? East respiratory syndrome (MERS)
A. Intravenous antibiotic therapy is rarely D. He should be isolated and tested for severe
required acute respiratory syndrome (SARS)
B. It is a benign coloniser of the bronchiectatic E. Local antibiotic protocol for
airways community-acquired pneumonia (CAP)
C. It is one of the earliest bacteria isolated in should be followed ·
sputum from CF patients
D. Nebulised azithromycin 3 times a week 17.53. A 73 year old man has been in hospital
suppresses infection for 3 days having undergone elective hip
E. Nebulised tobramycin is an effective surgery. He is acutely c;onfused in the middle of
treatment in chronic colonisation the night with a temperature of 38.3°C.
Urinalysis is negative but blood testing reveals
17.50. Acute coryza is most commonly caused raised inflammatoryr-harkers. A CXR clearly
by which of the following? shows a new right-sided infiltrate.
A. Bordetel/a pertussis Which of the following approaches is
B. Haemophilus inf/uenzae appropriate? '
C. Mycoplasma pneumoniae A. A CTPA should be ordered
D. Rhinovirus B. Blood cultures should be taken and a
E. Streptococcus pneumoniae watch-and-wait policy favoured /
c. Local antibiotic guidelines for CAP should be rifampicin. He is receiving the standard
followed treatment regimen. Two weeks into therapy, he
D. Local antibiotic policy for hospital-acquired phones the specialist nursing team as he has
pneumonia (HAP) should be followed painful eyes and is worried that the therapy is
E. Local antibiotic policy for not working.
ventilator-associated pneumonia (VAP) What is the likely cause of this presentation?
should be followed A. Drug resistance to ethambutol and
pyrazinamide
17.54. A 72 year old man initially improves B. Ethambutol
following treatment for an exacerbation of C. Immune reconstitution
COPD. He has been in hospital for I 0 days D. Intercurrent viral infection
when he spikes a temperature of 39°C, his E. Non-tuberculous Mycobacterium
oxygen saturations drop and he starts to
expectorate green sputum with blood-streaking. 17.58. A 54 year old man is due to start a
A CXR reveals dense left-sided consolidation. monoclonal antibody-based therapy for active
Late-onset HAP is often attributable to which Crohn's disease but the radiologist has noted a
of the following microorganisms? minor abnormality on the patient's recent CXR.
A. Acinetobacter The patient had a bacille Calmette-Guerin
B. Chlamydia (BCG) vaccine in childhood and has no known
C. Haemophilus TB contacts. He has no respiratory symptoms.
D. Legionella Local guidance suggests checking an
E. Streptococcus interferon-gamma release assay (IGRA) on a
peripheral blood sample.
17.55. The mortality from HAP is approximately Which one of the following statements is
which of the following? true with regard to the IGRA?
A.IO% A. A positive result should prompt the clinician
B. 20%
c. 30%
to start antituberculous chemotherapy
B. It is more specific than tuberculin skin testing
~
D.40% C. It is now the first-line test for diagnosis of / 1 I
E. 50% active TB
D. It is only positive where there is systemic I
17.56. A 34 year old woman has been unwell mycobacterial infection I
with high fever, pleuritic chest pain and cough E. It measures the release of interferon-alpha
productive of foul sputum. She is an from sensitised T cells
intravenous drug-user and has noted that her
usual injection site in the groin has developed a 17.59. A 64 year old woman presents with back
fluctuant swelling. pain, weight loss and a palpable mass in her
CXR shows multiple nodules and a CT loin that extends into the buttock. She is
shows a predominantly basal distribution and reviewed by the orthopaedic team and imaging
notes that some of the nodules are cavitating. suggests the mass is of fluid consistency.
What is the likely explanation for these findings? They aspirate pus easily and send it to the
A. Aspiration pneumonia laboratory for culture and cytopathological
B. Infective endocarditis examination. They ask for advice about further
C. Metastatic cancer testing.
D. Pulmonary thromboembolism Which of the following would be an important
E. Tuberculosis additional test?
A. Bronchoscopy
17.57. A 28 year old student of Chinese origin B. Echocardiogram to exclude septic embolus
has begun treatment for pulmonary tuberculosis C. Flow cytometry
that presented with a typical clinical picture and D. Fluid biochemistry
CXR. Sputum was positive for acid- and E. Mycobacterial testing.
alcohol-fast bacilli, and polymerase chain
reaction (PCR) for Mycobacterium tuberculosis 17.60. A 34 year old haematology patient has
has detected no resistance to isoniazid or been receiving cytotoxic chemotherapy for
subsequent CT scanning has identified diffuse physician arranges a CXR, below, and refers to
interstitial thickening radiating from the hilar the respiratory clinic.
regions.
What is the likely diagnosis?
A. Drug-induced pneumonitis
B. Lymphangitis carcinomatosa
c. Pneumocystis pneumonia
D. Pulmonary oedema
E. Venous thromboembolism
17.69. Respiratory bronchiGiitis-interstitial lung 17.12. A 72 year old woman has had
disease (RBILD) is more common in which of rheumatoid arthritis for 20 years. She recently
the following groups? had a chest infection but fully recovered. A
CXR was ordered to exclude pneumonia but
A. Non-smokers
revealed multiple smooth nodules. CT scanning
B. Patients > 65 years of age
also identifies four smoo;th nodules of varying
C. Patients with connective tissue diseases
size. A CXR recovered ·from storage shows that
D. Smokers
these nodules have been present for at least 5
E. Women
years. •
What is the likely cause of these nodules?
11.70. A 28 year old woman develops a painful
rash on her lower limbs, arthralgia and fever. A. Bronchiectasis
She feels run-down and unwell. Her family B. Metastatic cancer
C. Pulmonary embolism
D. Pulmonary fibrosis
CXR bilateral peripheral, especially upper-zone
consolidation.
What should the treatment be for this
T
E. Rheumatoid nodules
patient?
17.73. A 64 year old man presents with high A. Antibiotics to cover hospital-acquired
fever, left -sided pleuritic chest pain and pneumonia
shortness of breath. His CXR is below. B. Antituberculosis chemotherapy
C. Continue current therapy
D. Intravenous furosemide
E. Stop daptomycin and give prednisolone
catches an abnormality on the upper pole of 17.80. Which of the following statements is true
the right kidney, which is incompletely imaged with regard to progressive massive fibrosis
and the radiologist suggests an MRI for better (PMF)?
characterisation of the lesion. A. Characterised by small radiographic nodules
What diagnosis should be considered and B. Chyloptysis is associated
further investigated? C. Finger clubbing and basal crackles are
A. Alveolar microlithiasis characteristic
B. Alveolar proteinosis D. It has no impact on lung function
c. Lymphangioleiomyomatosis E. It may progress even after exposure ceases
D. Lymphocytic interstitial pneumonia
E. Pulmonary Langerhans cell histiocytosis 17.81. A 41 year old stonemason admits to
(histiocytosis X) shortness of breath on exertion. A screening
CXR and pulmonary function testing are both
17.78. A 43 year old woman presents abnormal so he has been referred to the
with cough, shortness of breath and wheeze. respiratory clinic. Silicosis results from the
She is a smoker, has no past medical history inhalation of which of the following?
and no exposure to birds or animals. She had A. Coal
been off work for 2 weeks but made an B. Cotton
improvement after starting inhaled C. Quartz
beclometasone and a short -acting D. Silicone
bronchodilator as required. On return to work, E. Tin
things seemed to be fine but deteriorated after
about 3 weeks. She works behind the counter 17.82. A 72 year old man presents with
in a local bakery. progressive breathlessness over 6 months;
-
The patient would like to know if more recently he has had a vague ache in the
she has occupational asthma. Which right side of his chest that has kept him awake
test would be most helpful in making the at night.
diagnosis?
A. Histamine challenge test
B. Peak expiratory flow rate diary
His past medical history is significant for two
separate episodes of 'benign asbestos pleurisy'•
in his 50s. He has pleural plaques and receiVfld
I
C. Specifc lgE to flour compensation. He had worked in the J
D. Spirometry with reversibility construction industry and had frequent, heavy
E. Sputum eosinophils exposure to asbestos. He stopped smoking 20
years ago during a bout of pleurisy, having
17.79. A 55 year old geologist has been started age 12 years and smoked an average
coughing, breathless and experiencing of 20 cigarettes per day.
arthralgia since renovation started at her home. CXR reveals a right -sided pleural effusion
The work was started because of damp and and pleural plaques. It is not possible to see
has involved some structural work. Her home the right-sided costophrenic angle.
always seems to be dusty currently. Her CT scanning reveals pleural plaques,
husband is a stonemason and has been right-sided pleural effusion and mild thickening
working on a new piece at home in their of the pleura that extends onto the
garage. At work she has been preparing mediastinum anteriorly.
beryllium samples for a PhD project, which has What is the most likely reason for his
been quite stressful as deadlines for submission presentation?
approach. A. Asbestos pleural plaques
CXR shows bilateral hilar lymphadenopathy B. Asbestosis
with some soft nodularity in the mid-zones. C. Benign asbestos pleurisy
What is the most likely diagnosis? D. Diffuse pleural thickening
A. Berylliosis E. Mesothelioma
B. Dysfunctional breathing
C. Hypersensitivity pneumonitis 17.83. A 69 year old wo~an has progressive
D. Sarcoidosis breathlessness on exertion. Because she
E. Silicosis described a vague feeling of her chest
tightening during one of these episodes, her spontaneous VTE (treated with 6 months of
family physician started aspirin and glyceryl warfarin) and a family history of VTE (mother
trinitrate spray and referred to cardiology. She and uncle).
underwent CT coronary angiogram. This Observations: oxygen saturations 88%
identified no coronary artery disease but diffuse on room air, respiratory rate 22 breaths/min,
ground glass and some centrilobular nodules pulse 110 beats/min, BP 110/65 mmHg. Chest
were picked up incidentally in the lungs. is clear. Right calf is greater in circumference
The patient has no past medical history, than left by 3 em. Heart sounds dual, no
worked as a secretary and was a non-smoker. murmurs.
She has kept a pet parrot at home for the last Investigations: CXR reveals marginally
year. elevated right hemidiaphragm; EGG: sinus
What is the likely diagnosis? tachycardia; CRP 35 mg/L, 0-dimer 200 ng/
A. Aspirin sensitivity ml.
B. Breathing artefact What should the next test be for this
C. Hypersensitivity pneumonitis patient?
D. Idiopathic pulmonary fibrosis A. CT pulmonary angiogram
E. Sarcoidosis B. Echocardiogram
C. Fluoroscopy of the diaphragm
17.84. A 72 year old man presents with cough D. Respiratory virus throat swab
and weight loss. He smoked 20 cigarettes per E. Sputum microscopy culture and sensitivity
day until 5 years ago. In addition, he worked
lagging pipes with 'monkey dung' during his 1.7.87. A 28 year old woman has an anterior
apprenticeship. cruciate ligament repair and is recovering at
Examination reveals a supraclavicular lymph home in an above-knee cast when she starts
node but no significant chest findings. His CT to feel like she will pass out every time she
scan notes the supraclavicular lymph node but stands up. She attends the emergency
also suggests there is a peripheral 5 em department.
peripheral mass in the left lung and an enlarged Examination reveals BP 80/45 mmHg, pulse
left-sided hilar lymph node. There is an 11 0 beats/min, oxygen saturations 92% on/.' air,
indeterminate lesion in the liver and MRI is respiratory rate 22 breaths/min, apyrexial.
suggested for clarification. Chest is clear. /
What should the next diagnostic test be? Investigations: CXR is clear. Bloods arrl as
A. CT-guided biopsy follows: haemoglobin 100 g/L, WCC
B. Endobronchial ultrasound 11 x 109/L, platelets 200 x 109/L, 0-dif)ler
C. Flexible bronchoscopy 1200 ng/ml, urea 10 mmoi/L (60 mg/dl),
D. Liver biopsy creatinine 92 11moi/L (1.04 mg/dl). EGG reveals
E. Supraclavicular lymph node biopsy sinus tachycardia. As the investigations are
being reviewed the patient has a cardiac arrest.
17.85. Which of the following associations in What should the immediate management
relation to lung disease is correct? include?
A. Anthrax and inadequately pasteurised milk A. Apixaban
B. Chlamydia psittaci and hide factory workers B. Intravenous heparin infusion
C. Coxiella burnetii and sewage workers C. LMWH
D. Francisella tularensis and muskrat contact D. Thrombolysis
E. Leptospiral pneumonia and welding E. Warfarin
17.86. A 45 year old man presents to the acute 17.88. A 26 year old w9man has been
receiving unit with sudden-onset right-sided increasingly short of _9feath over 2 years. She
pleuritic chest pain, shortness of breath and a attends the emergency department and is
swollen, painful right calf. He recently had noted to be hypoxaemic with swollen ankles.
right-sided anterior cruciate ligament Her EGG shows right bundle branch block. An
reconstruction abroad (following a skiing echocardiogram is arranged.
accident) and flew home from Canada in the Pulmonary hypertension is defined a~ a
last week. He has a past medical history of mean pulmonary artery pressure measured at
right heart catheterisation of at least which of 17.92. Which of the following statements is true
the following? with regard to breathing during sleep?
~I
involvement. She receives radiotherapy
17.90. A 23 year old woman has been following a mediastinoscopy. She has a hoarse
diagnosed with primary pulmonary voice and is worried this is because of her lung
hypertension following right heart turnour. Bronchoscopy reveals no vocal cord
catheterisation and extensive investigation to paralysis.
exclude alternative causes of her presentation What is the likely cause?
at a specialist unit. A. Chronic laryngitis
Which of the following therapies rnay B. Endotracheal intubation during
be indicated in primary pulmonary mediastinoscopy
hypertension? C. Laryngeal tuberculosis
A. Bosentan D. Left recurrent laryngeal nerve involvement by
B. Cyclizine the turnour
C. Etanercept E. Psychogenic aphonia
D. lnflixirnab
E. lsosorbide rnononitrate 17.95. A 34 year old man presents with
acute-onset shortness of breath and left -sided
17.91. A 45 year old wornan presents pleuritic chest pain. Examination reveals oxygen
with cough that appears in May and saturations of 94% breathing roorn air,
is gone by auturnn. In addition, she decreased air entry on the left side of the chest
experiences nasal discharge and watering with hyper-resonant percussion note. CXR
eyes. Examination is unremarkable and reveals large left-sided pneumothorax. A
spirometry is normal. therapeutic aspiration is performed and 2.5 L of
What is the likely diagnosis? air is aspirated with no change in the X-ray
A. Allergic asthrna appearance.
B. Allergic rhinitis What should be the n_ext step?
C. Bordete/la pertussis A. Adrnit for observation and oxygen
D. Perennial rhinitis B. Bronchoscopy
E. Viral upper respiratory tract infection C. Cardiothoracic surgery
Answers
17.1. Answer: A. mismatch and would be more likely to cause
The examination findings point towards type I respiratory failure. There are no
collapse of the right lung because the trachea examination findings in keeping with COPD and
is pulled to that side (the opposite would be the the oxygen involved (although delivered in an
case with pleural effusion). The collapse must uncontrolled fashion) is low flow.
be significant because the apex beat is not
palpable, suggesting the heart is pulled towards 17.3. Answer: C.
the right side by mediastinal shift. The patient's In COPD, loss of elastin fibres results in small
diagnosis was made at bronchoscopy, airway collapse and air trapping during /
suggesting a central tumour. Pneumothorax is expiration. This dynamic hyperinflation is ,Initially
less likely than if the patient had a peripheral noticed on exertion because expiration ti'me is
tumour that had been biopsied using computed shortened during exercise. Exercise-induced
tomography (CT) guidance. Pericardia! effusion bronchospasm would be more likely in asthma.
would not explain the respiratory examination There are no examination findings that suggest
findings. The presentation is too acute for sufficient pulmonary hypertension to cause
pneumonia and the patient is apyrexial. An breathlessness. There is no reason for the
urgent chest X-ray (CXR) would be an diaphragm to move paradoxically in this case.
important test and the patient may require Central chemoreceptors are stimulated by a
urgent radiotherapy or interventional rise in C0 2 , which might be expected in more
bronchoscopy to re-inflate the lung. advanced disease.
effusion. Given the age of the patient, the function testing, she should be referred to the
imaging and the subacute presentation, the cardiothoracic surgery team.
likely diagnosis is lymphoma and CT scanning
is required to identify the extent of disease and 17.9. Answer: C.
identify a possible site for obtaining a tissue The CXR shows total collapse of the right lung
diagnosis. Echocardiogram might be helpful if with the heart and mediastinum shifted to the
aortic dissection or pericardia! effusion were right and tracheal deviation. This appearance is
suspected. PET scan might be useful in staging likely to have been caused by a proximal
or to assess treatment response. D-dimer is obstructing lesion such as a tumour.
less relevant with the obvious CXR abnormality.
Bronchoscopy is unlikely to be a useful test, 17.10. Answer: A.
although endoscopic ultrasound/endobronchial The CT scan shows evidence of bilateral,
ultrasound would allow nodal sampling. proximal bronchiectasis and an area of varicose
bronchiectasis in the right upper lobe and
17.6. Answer: B. non-specific inflammatory change. The clinical
The CXR shows the classic D-shaped picture and radiology point towards allergic
appearance of an empyema. Thoracic bronchopulmonary aspergillosis, although
ultrasound and diagnostic aspiration should be further investigation (e.g. peripheral blood
undertaken as an emergency. Insertion of an eosinophilia, total immunoglobulin E (lgE),
intercostal chest drain is a priority and CT Aspergillus precipitins - lgE specific to
scanning to plan an insertion site may be Aspergillus) would be required to confirm this.
required if the ultrasound scan appearance is
very complicated. Mesothelioma and bronchial 17.11. Answer: E.
carcinoma are less likely because of the acute The CXR shows right-sided pleural effusion
presentation. There is no abdominal element to with a meniscus appreciable. The trachea
the presentation on this occasion, although is relatively central as the right lung is
pancreatitis can cause large (usually left-sided) compressed by the pleural effusion. The
pleural effusion. Hepatic hydrothorax usually meniscus and homogenous opacification make
causes a simple, right-sided effusion, so the consolidation unlikely. This is not collapse
D-shape configuration would be very unusual. because the trachea is not pulled towards the
opacification and there is a meniscus. ;
17.7. Answer: E. Right -sided bronchial carcinoma might cause /
We do not have measurements for the small pleural effusion but the CXR does not give us
pulmonary nodule at the apex of the right lung this diagnosis. Right-sided mesothelioma
but repeat CT scanning is not an option, so we cannot be diagnosed based on CXR but is a•
must presume it is > 8 mm in maximum cause of pleural effusion.
diameter, and we note the patient is an
asymptomatic smoker, so a PET scan to 17.12. Answer: D.
assess nodule activity is the best answer. The The CXR shows an isolated right-sided pleural
patient is asymptomatic (the initial pain was on effusion. It seems unlikely that this relates to
the left and the lesion is on the right), so cardiac failure given the normal
commencing antibiotics and interferon-gamma echocardiogram. It will be important to further
release assay (IGRA) is irrelevant. Further risk investigate this with a diagnostic aspiration but
assessment prior to an invasive test is required this cannot be performed safely given the
as CT-guided biopsy is difficult in this area and apixaban therapy.
the nodule is likely to be too small to allow this.
Standard flexible bronchoscopy would not 17.13. Answer: E.
allow access to the nodule. The CXR shows a left-sided pneumothorax.
It seems likely the patient h<;ts a concurrent
17.8. Answer: E. respiratory tract infection that may be viral but I,
I I
The PET scan image reveals a fludeoxyglucose requires further investigation.
(FOG) avid right upper lobe pulmonary nodule i
''
that must be presumed to be an early-stage 17.14. Answer: E.
bronchial carcinoma. Given the patient's The patient has a large left -sided pneumothorax
performance status and normal pulmonary (> 2 em depth measured at hilum) and is
symptomatic. He probably has a concurrent might have been expected to improve his
1
I
respiratory infection that may require symptoms if pneumonia was related to a more
investigation. The first step in management of a common pneumonia-causing organism (e.g. S.
primary spontaneous pneumothorax would be pneumoniae).
therapeutic aspiration.
17.20. Answer: B.
17.15. Answer: D. The patient presents with classic symptoms of
The CT-PET shows significant uptake in the pneumonia and might be expected to· isolate S.
right upper lobe cancer and in an ipsilateral pneumoniae on sputum examination given the
right hilar node, suggesting T4N2MO disease. rusty sputum, pleuritic chest pain and cold
There is apparent uptake in the marrow of the sores. The CXR shows left-sided basal
spine and sternum but this is physiological and consolidation.
not typical of metastatic deposit. The CT-PET
has upstaged the patient as the hilar lymph 17.21. Answer: A.
node was not obviously pathologically enlarged A typical clinical presentation and CT
on standard CT scanning. appearance should allow an interstitial lung
disease multidisciplinary meeting to reach a
17.16. Answer: C. diagnosis of idiopathic pulmonary fibrosis (IPF)
The patient has finger clubbing and bi-basal without a tissue sample. Bronchoscopy has no
crackles and presents with shortness of breath specific diagnostic features but may be useful
and dry cough late in life. The CT scan shows in the setting of intercurrent infection or atypical
bilateral peripheral lung cysts in a honeycomb CT scans/presentations. Transbronchiallung
pattern with some traction bronchiectasis. This biopsy would be risky and likely to be
clinical presentation and CT pattern is typical of non-diagnostic. There are no diagnostic lymph
idiopathic pulmonary fibrosis but should be node features in IPF.
confirmed by the assessment of an interstitial
lung disease multidisciplinary team. 17.22. Answer: E.
Direct visualisation and targeted biopsy of any
17.17. Answer: A. pleural lesion provides the best chance of a
The CXR shows extensive left-sided tissue diagnosis. Mesothelioma cannot b~
consolidation. The left costophrenic angle is diagnosed on cytopathological examinatipn of
clear so pleural effusion is unlikely. Loculated pleural fluid. Bronchoscopy would not help with
pleural fluid could give this appearance but the pleural disease but may be helpful if there were
likeliest cause is a pneumonia given the an endobronchial lesion with pleural
examination findings. metastases. Echocardiogram is not c6nsidered
helpful because there is pleural thickening as
17.18. Answer: C. well as a right-sided pleural effusion, so heart
The CURB-65 score was originally developed failure is an unlikely cause.
to predict mortality in community-acquired
pneumonia and is now widely used for the 17.23. Answer: B.
assessment of disease severity. The The patient requires a diagnostic test to
components are C = confusion, U = urea confirm lung cancer, determine histological type
> 7 mmoi/L (42 mg/dl), R = respiratory rate and complete staging. It seems likely he has
2 30 breaths/min, B = blood pressure systolic T2a, N1, MO disease. EBUS-FNA will meet all
< 90 mmHg or diastolic s 60 mmHg, 65 = age these requirements. Flexible bronchoscopy
2 65 years. His CURB-65 score is 2. He scores might give histological type but would not
points for confusion and urea. confirm disease in the hilar lymph node.
CT -guided biopsy is perhaps more likely than
17.19. Answer: C. flexible bronchosc9py to confirm histological
The patient has pneumonia with delirium, type but would have an attendant risk of
hyponatraemia, deranged liver function tests pneumothorax. Thoracoscopy has no role as
(LFTs) and high fever. He requires investigation there is no evidence of pleural disease. Repeat
for legionella and antibiotics to cover this CT scanning would delay diagnosis in a
organism. It may be that his LFT derangement scenario where curative treatment m<:J.Y be
relates to amoxicillin therapy but this antibiotic possible.
~I
infected by legionella but would not be available 17.30. Answer: C.
in a timely fashion. Differential cell count would This is a very typical presentation of
not give a specific answer about the causative dysfunctional breathing. The patient had an
pathogen. initial illness, which may have altered the j
breathing pattern by preventing nasal breathin~,
17.26. Answer: C. and has a reasonable fear of lung cancer I
The patient has an obstructive defect that because a close relative died of it. A CTPA has
entirely resolves following nebulised ruled out an acute venous thromboembolism
bronchodilator; this is in keeping with asthma and parenchymal lung disease (including lung
despite the patient's smoking history. Inhaled cancer) as a cause. Echocardiogram might be
therapy taken on the morning of reversibility useful if there was a murmur, background of
testing can confound the test but in this congenital heart disease or if there were signs
instance there is a clear result with strong of right heart dysfunction (CTPA would not
evidence of reversibility. necessarily exclude chronic venous
thromboembolism (VTE) or pulmonary
17.27. Answer: C. hypertension). Normal CT scan makes ILD or
The gas transfer is reduced and partially emphysema unlikely. Arterial blood gas would
corrects for lung volume. There is no evidence not necessarily be abnormal in dysfunctional
of airways obstruction. The respiratory function breathing (although almost certainly would have
tests are non-diagnostic and further clinical shown respiratory alkalosis during the
details and, potentially, imaging studies are emergency department presentation).
likely to be required. FEV1 , FVG and FEV/FVC
are within normal limits. 17.31. Answer: C.
Although this woman has stopped smoking,
17.28. Answer: A. she accumulated a significant total number of
Chronic cough has many causes but it is pack years. Her history is of chronic
important not to miss parenchymal lung breathlessness, typical of COPD, and her CT
disease or bronchial carcinoma and a CXR scan shows emphysema. It is often difficult for
ought to be performed. Physicians should be patients to accept that although they have
stopped smoking, their lung function continues regularly attending with exacerbations of
to decline. Spirometry is within normal limits bronchiectasis is likely to have had sputum
because she has emphysema-dominant screened for mycobacteria intermittently. There
disease with no evidence of airways obstruction are no systemic symptoms to suggest a
on testing. She would have an abnormal gas pneumonia and the haemoptysis is solely fresh
transfer. blood (not mixed in with purulent sputum) and
of sudden onset. Pulmonary infarction is less
17.32. Answer: E. likely because of the lack of other symptoms
The most likely cause of this pain is pulmonary (pleuritic chest pain and shortness of breath)
thromboembolism because she has recently and the CXR changes.
been on a long-haul flight, is hypoxaemic,
tachycardic and has a positive D-dimer. 17.36. Answer: A.
Malignant pleural disease would be unlikely to Bronchial artery angiography will demonstrate
have such a sudden onset. Pneumothorax and abnormally dilated areas of bronchial
pneumonia are not supported by the X-ray vasculature and with active bleeding can isolate
findings. Bronchospasm can give a central the leaking point. This can be difficult to
chest tightness but not a peripheral pleuritic interpret in chronic suppurative lung disease as
chest pain. Central chest tightness is a the bronchial vasculature is often diffusely
common finding in e«acerbations of COPD abnormal. Sputum culture is unlikely to be
because of coughing and strain on costal helpful in isolated massive haemoptysis
cartilages and intercostal muscles. although infection may be a precipitant in
chronic lung disease (such as cystic fibrosis
17.33. Answer: C. ·(CF) bronchiectasis). Bronchoscopy may be
The most likely cause is mesothelioma because helpful in the presence of a central lung tumour
~··
of the patient's employment history (asbestos and can sometimes determine whether the
was often found in the boiler rooms of older bleeding point is in the right or left lung (CXR or
ships), the insidious nature of the pain and its CT can be helpful here too), but bronchial
nagging quality. It seems likely the patient has artery angiography is increasingly favoured
a pleural effusion or perhaps pleural thickening. because of the potential to perform
Chronic thromboembolic disease might present embolisation of the aberrant artery. A CTfA
with recurrent pleuritic chest pain but more may determine the source of bleeding (e)g.
commonly is associated with progressive tumour or pulmonary arteriovenous I
breathlessness. Pneumonia might be expected malformation) in some cases but is unlikely to
to present with more systemic symptoms over be helpful here. Coagulation studies should be
a shorter time period. Tietze's syndrome performed as CF patients may be deficient in
presents more acutely and is usually vitamin K and can have liver disease, but the
self-terminating with supportive measures. more likely cause is abnormal bronchial
vasculature.
17.34. Answer: C.
It seems very likely that this man has familial 17.37. Answer: E.
clubbing. There is documented evidence of the Nodules greater than 4 mm require careful
presence of finger clubbing for approximately follow-up unless they have benign
30 years and the patient is asymptomatic. characteristics such as central deposition of
Interestingly, his father probably has finger calcification (which may suggest hamartoma).
clubbing too. There is no need for further Spiculated margins are more typical of
investigation or onwards referral. malignant lesions. Malignant nodules are more
common in upper lobes; benign nodules
17.35. Answer: B. distribute evenly. Sm9king is a very strong risk
The likely cause of haemoptysis here is a factor for lung car1_9er.
mycetoma developing in an old cavity caused
by tuberculosis. Carcinoma is less likely than 17.38. Answer: D.
mycetoma in this scenario but scar carcinomas PET scanning is u~eful for nodules > I em in
can develop in areas of the lungs previously diameter. It detects metabolic activity, which is
damaged by infection. Tuberculosis is likely to usually higher in malignant disease. However,
have been adequately treated and a patient metabolic activity can be high in inflammatory
nodules, which can lead to false positives. nebulised bronchodilator and be admitted for
Tissue diagnosis must still be pursued even observation. Her therapy should not be
with a positive PET scan to identify the best reduced because the greater risk to patient and
treatment option. False-negative PET scans can fetus is uncontrolled asthma. Antibiotics would
occur in very slow-growing cancers or in only be considered where there was strong
neuroendocrine cancers. Metabolic activity is objective evidence of infection (fever, sputum
assessed by PET scan, which is not detected culture positive, CXR infiltrate). The presentation
by a single CT scan, although could be inferred is not suggestive of pulmonary
by nodule growth on serial CT scans. thromboembolism.
test relies on the release of interferon-gamma not associated with the usual features of the
from sensitised T cells. carcinoid syndrome.
Endocrinology
Multiple Choice Questions
18.1. A 22 year old woman presents with a D. Increased growth hormone (GH)
few weeks' history of malaise and weight loss. E. Increased transforming growth factor-alpha
On clinical examination she has palmar (TGF-a)
hyperpigmentation. With which investigation
should she be followed up? 18.3. A 28 year old woman presents with
A. Dexamethasone suppression test secondary amenorrhoea and galactorrhoea.
B. Magnetic resonance imaging (MRI) abdomen An MRI scan of her brain is likely to show a
C. MRI pituitary lesion in which area?
D. Synacthen test A. Anterior pituitary
E. Thyroid function tests B. Hypothalamus
C. Lactiferous ducts
18.2. A 52 year old South Asian man is found D. Pars intermedia ,Ir
E. Posterior pituitary
to have thickened pigmented skin at the back
of his neck and in the axillae. His body mass I
index (BMI) is elevated at 38 kg/m 2 . Acanthosis 18.4. A 38 year old man is referred with a
nigricans in this setting is due to which of the history of polydipsia and polyuria passing over
following pathology? 3 L of urine in 24 hours. He undergoes a water
A. Axillary perspiration and friction deprivation test, which shows the following
B. Hyperinsulinaemia results:
C. Increased fibroblast growth factor activation
18.6. A 21 year old student is found to have (0.46 ng/dL) and TSH <0.01 miU/L. TSH
hyperthyroidism. She is counselled on receptor antibody (TRAb) levels are not
treatment options including radioactive iodine elevated. What is the most appropriate
and antithyroid medications. Carbimazole acts management?
on which part of the thyroid hormone synthesis A. Commence propranolol
pathway? B. Consent for radioactive iodine
A. Cleavage of thyroglobulin by proteolysis C. Perform ultrasound scan
B. Coupling of monoiodotyrosine (MIT) and D. Screen the infant for hyperthyroidism
diiodotyrosine (DIT) forming triiodothyronine E. Treat with selenium
CTsl and thyroxine (T4 ) 18.10. A 40 year old male smoker presents
C. Dehalogenation of iodinated tyrosine to
with weight loss and blood tests suggesting
recycle iodide
biochemical primary hyperthyroidism. Which of
D. Organification of iodide by thyroid peroxidase
the following features would suggest that the
incorporating tyrosine forming MIT and DIT
hyperthyroidism is due to Graves' disease?
E. Thyroglobulin synthesis
A. Eyelid retraction
18.7. A 56 year old woman is reviewed in clinic. B. Gynaecomastia
She was diagnosed with hypothyroidism 15 C. Lack of orbitopathy
years previously and has been on levothyroxine D. Male gender
100 ~g once daily ever since. Recent thyroid E. Palpable smooth goitre with bruit
function tests have shown thyrotrophin 18.11. A 74 year old woman is admitted to
(thyroid-stimulating hormone; TSH) 8.2 miU/L .hospital with a 3-month history of lethargy,
and free thyroxine (free T4) of 15.6 pmoi/L weight gain and increasing shortness of breath.
(1.21 ng/dL). TSH secretion by the Hypothyroidism can result in which of the
hypothalamus is increased by which of the following cardiovascular effects?
following?
A. Diastolic hypertension
A. A decrease in thyroxine-binding globulin B. High cardiac output
levels C. Low cholesterol
B. A large increase in free T4 beyond the normal D. Reduced peripheral vascular resistance
reference range E. Systolic hypertension /
C. During early hours of the morning
D. A fall in free T4 of 5 pmoi/L (0.39 ng/dL) 18.12. A 34 year old woman presents tolher
E. An increase in circulating free T3 family physician with weight loss, palpitations
and amenorrhoea. Thyroid function tests
18.8. A 23 year old asymptomatic woman confirm thyrotoxicosis with free T4 30.2 pmoi/L
attends her family physician for thyroid function (2.35 ng/dL) and TSH <0.01 miU/L. TRAb
testing as her mother has recently been levels are not elevated. A thyroid scintigraphy
commenced on levothyroxine. Thyroid function scan is performed revealing the following
tests (TFTs) show TSH 6miU/L, and free pattern of uptake.
T4 of 12.4 pmoi/L (0.96 ng/dL). Her serum
thyroid peroxidase antibodies are strongly
positive. What is the most appropriate
management plan?
A. Arrange a scintigraphy scan
B. Check thyroglobulin antibodies
C. Reassure and discharge
D. Repeat TFTs in 4-6 months
E. Start levothyroxine and recheck TFTs in
6 weeks
What is the most likely diagnosis? 18.15. A 23 year old white woman presents
A. Exogenous thyroxine intake with a 6-month history of increasing neck
B. Graves' disease swelling and discomfort on swallowing.
C. Iodine deficiency On examination she has a smooth diffuse
D. Toxic multinodular goitre symmetrical goitre. Thyroid function tests
E. Transient thyroiditis are normal and thyroid antibody levels are
undetectable. Ultrasound shows a diffuse
18.13. A 28 year old man presents to his family and symmetrical echogenic pattern,
physician with a 6-month history of neck with no significant nodularity. Which
swelling. On examination he has a 2x3 em of the follow statements is correct in this
palpable lump on the left side of his neck, which scenario?
moves with swallowing. He has no associated
A. Associated lymphadenopathy is normal
clinical symptoms. He undergoes a scintigraphy
B. Radioactive iodine treatment should be used
scan that reveals the following image.
to shrink the gland
C. She is likely to experience symptoms of
lethargy and weight gain
D. The goitre may enlarge during pregnancy
E. There is a high risk of malignancy
A.
B.
C.
Non-thyroidal illness
Non-functioning pituitary tumour
Thyroiditis
18.21. A 72 year old man was commenced on
amiodarone for atrial fibrillation 6 months
previously. He is referred with a history of
r
D. Treatment with amiodarone weight loss, tremor and sweating. Blood tests
E. Variable treatment adherence reveal TSH <0.01 miU/L, free T4 26.1 pmoi/L
(2.03 ng/dl) and free T3 4.1 pmoi/L (0.27 ng/
18.19. A 32 year old woman attends her family dl). What is a scintigraphy scan likely
physician with symptoms of tremor and vague to show?
anterior neck discomfort. Initial blood tests A. Diffuse increased uptake
reveal a free T4 14 pmoi/L (1.09 ng/dl) and B. Diffuse low uptake
TSH 0.12miU/L. Subsequent TFTs 4 weeks C. Multinodular goitre
later show TSH 89.8miU/L and free D. Normal uptake
T4 <5 pmoi!L (0.39 ng/dl). Scintigraphy scan E. Solidary toxic nodule
shows the following:
18.22. What is the correct treatment for
type II thyrotoxicosis secondary to
amiodarone?
A. Carbirnazole
B. Discontinue amiodarone only and allow
resolution of thyroid function
C. Glucocorticoids
D. Levothyroxine
E. Radioactive iodine
A. Anaplastic carcinoma
What is the most likely underlying cause? B. Follicular cell carcinoma
A. Graves' disease C. Medullary carcinoma
B. Primary hypothyroidism D. Papillary cell carcinoma
C. Subacute thyroiditis E. Toxic adenoma
D. Toxic adenoma
E. Toxic multinodular goitre 18.24. A 34 year old woman is reviewed
in the thyroid cancer clinic following total
18.20. A 75 year old man with a past medical thyroidectomy and neck dissection with lymph
history of ischaemic heart disease is admitted node clearance for a confirmed (pT 4, N I , MO)
to hospital following a fall at home. He papillary thyroid cancer. Follow-up management
becomes increasingly delirious on the ward. post-surgery should include which of the
As part of his work-up, thyroid function is following?
checked showing TSH 0.2miU/L, free T4 A. Levothyroxine replacement aiming to keep
26.2 pmoi/L (2.04 ng/dl) and free T3 TSH within the normal range
3.3 pmoi/L (0.21 ng/dl). What is the most B. Radioactive iodine treatment when TSH is
appropriate management plan? fully suppressed
A. Check for TRAbs C. Regular computed tomography (CT) scans of
B. Commence carbimazole treatment the neck
C. Consent for radioactive iodine treatment D. Screening of family members for thyroid
D. Discontinue cardiac medications cancer
E. Repeat thyroid function tests when the E. Thyroglobulin measurement at regular
patient has fully recovered intervals ·
18.25. A 32 year old woman attends her family total testosterone 5.6 nmoi/L (162 ng/dl),
physician with a 12-month history of inability to SHBG 42.1 nmoi/L (4.00 Jlg/ml), FSH 2.1 IU/L
conceive. She has been having regular periods (0.5 Jlg/L) and LH 1.76 IU/L (0.2 Jlg/L). He has
every 28 days. Ovulation can be confirmed by no other past medical history of note and has
which of the following tests? not fathered any children. On examination
A. Day I 0 rise in follicle-stimulating hormone visual fields are normal, testes are 5 ml volume
(FSH) and soft on palpation. He has little in the way
B. Day 13 surge in oestradiol of pubic or axillary hair. He has not noticed· any
G. Day 14 surgein progesterone problem with his sense of smell. Which of
D. Day 14 surge in luteinising hormone (LH) the following is the most likely underlying
E. Regular menses diagnosis?
A. Kallmann's syndrome
18.26. You review a 21 year old woman in the B. Klinefelter's syndrome
reproductive endocrinology clinic. She has a G. Previous trauma to the testes
history of secondary amenorrhoea and anorexia D. Reduced testosterone secondary to obesity
since she was 18 years old. She is keen to E. Reduced testosterone with age
know why she has stopped having periods.
Functional hypothalamic amenorrhoea is 18.30. An 18 year old woman with a BM I of
underpinned by which process? 31 kg/m 2 attends her family physician with
A. A high LH-to-FSH ratio troublesome hirsutism, acne and irregular
B. Gonadotrophin-releasing hormone (GnRH) periods. Hyperandrogenism as a sequela of
resistance polycystic ovary syndrome (PCOS) may result
G. High circulating leptin from which of the following?
D. Hyperprolactinaemia A. Genetic mutation in 3~-hydroxysteroid
E. Reduced pulsatility and secretion of GnRH dehydrogenase
B. Higher FSH compared with LH synthesis by
18.27. A 16 year old girl presents to her the pituitary gland
family physician having never had a period. G. Increased pulsatility of GnRH
She is noted to be of short stature. Blood D. Reduced aromatisation of androgens by
tests reveal FSH 26.2 IU/L (5.9Jlg/L), LH theca cells
18.5 IU/L (2.0 Jlg/L) and oestradiol <50 pmoi/L E. Reduction in circulating SHBG
(13.6 pg/ml). What is the next most
appropriate investigation? 18.31. A 23 year old student with known
A. CT scan ovary and adrenal glands karyotype 45X attends the clinic seeking
B. Karyotype advice as she is wanting to achieve pregnancy.
G. MRI pituitary Which of the following should she be
D. Synacthen test counselled about?
E. Ultrasound scan ovaries A. Child is more likely to have low 10
B. Increased risk of ovarian cancer
18.28. A 12 year old boy attends his family G. She will require anti-androgen therapy
physician as it has been noticed that he is D. She will require screening for aortic
falling behind in school and is considerably dissection
shorter than his classmates. Which of the E. There is a high chance of her becoming
following is consistent with the diagnosis of pregnant spontaneously
constitutional delay?
A. Bone age consistent with chronological age 18.32. A 17 year old boy is referred with
B. More common in females ' delayed puberty. He has nQticed that he is
G. Occurs as young as 3-6 months of age taller than his classmate7!0n clinical
D. Smaller adult height than predicted examination he is found to have sparse facial
E. Upper-to-lower body ratio< 1 and body hair as well as small pre-pubertal-
sized testes and penis. Blood tests reveal
18.29. A 56 year old man is referred to the testosterone 7.5 nmoi/L (216 ng/dl), FSH
endocrinology clinic with a history of poor libido 12 IU/L (2.8 [Jg/L), LH II IU/L (1.2 11g/L). What
and erectile dysfunction. Blood tests reveal is the most appropriate next test?
and body odour, and her voice has become A. Bilateral lesions
deeper. A diagnosis of congenital adrenal B. Hounsfield units <I 0 HU
hyperplasia (CAH) is being considered. C. Retention of contrast
What is the commonest enzyme deficiency D. Size < 4 ern
in CAH? E. Smooth surface
A. II ~-hydroxysteroid dehydrogenase
B. ~?a-hydroxylase 18.45. A 24 year old man is admitted to the
c. 17~-hydroxysteroid dehydrogenase emergency department having collapsed at the
D. IS-hydroxylase gym. He describes symptoms of headache,
E. 21-hydroxylase feeling flushed with associated palpitations and
sweating. He was observed by his friends to
18.41. A 63 year old man presents to his family become pale before he collapsed. He is
physician with a 1-month history of weight gain persistently hypertensive and a 24-hour urine
and difficulty climbing stairs. On clinical collection shows elevated metadrenalines
examination he is found to have a blood (metanephrines). First-line treatment for this
pressure of 182/85 mmHg, abdominal striae condition should be with which of the
and bruising on his arms. An overnight following?
dexamethasone test reveals a morning serum A. Bisoprolol
cortisol level of 153 nmoi/L (5.55 f.!g/dl). Which B. Dexamethasone
of the following would be an appropriate next C. Fludrocortisone
investigation? D. Ketoconazole
A. 24-hour urine free cortisol E. Pheroxybenzamine
B. Adrenal vein sampling
C. Bilateral inferior petrosal sinus sampling 18.46. A 28 year old man is referred having
D. CT adrenals been found, on home blood pressure
E. High-dose dexamethasone suppression monitoring, to have hypertension. His serum
test potassium at diagnosis was 2.9 mmoi/L. He
has been commenced on antihypertensive
18.42. A 56 year old man with recently therapy and is referred in for investigation of
diagnosed lung cancer has noticed weight gain, mineralocorticoid excess. Which of the
easy bruising of his skin, increased thirst and following antihypertensive therapies may .
difficulty climbing stairs. Which type of lung interfere with these investigations by increasing.·
cancer is associated with this endocrinological plasma renin concentrations?
picture? A. Amlodipine
A. Adenocarcinoma B. Bendroflumethiazide
B. Carcinoid tumour C. Bisoprolol
C. Large cell carcinoma D. Diltiazem
D. Mesothelioma E. Doxazosin
E. Squamous cell carcinoma
18.47. Glucose-stimulated insulin secretion by
18.43. Hypokalaemia associated with Cushing's the pancreas is augmented by which of the
syndrome is due to which underlying following?
mechanism? A. Dipeptidyl peptidase-4
A. Activation of mineralocorticoid receptors B. Glucagon-like peptide- I
B. Adipocyte proliferation C. Insulin-like growth factor-1
C. Increased glycogen synthesis D. Leptin
D. Increased protein breakdown E. Somatostatin
E. Insulin resistance /
18.48. An 18 year old woman with no past
18.44. An incidental finding of an adrenal mass medical history and on no regular medications
is discovered when a 72 year woman has a CT is admitted to hospital following a collapse at
scan. Which of the following parameters is home. She describes prodromal symptoms of
associated with an increased likelihood of palpitations, weakness and diplopia. Plasma
malignancy? glucose concentration is measured at
often the first to be affected due to mass effect She attends for a water deprivation test. Which
by a pituitary macroadenoma? of the following confirms a diagnosis of
diabetes insipidus?
A. ACTH
B. FSH A. 24-hour urine volume of 3 L
C. GH B. Plasma osmolality < 280 mOsm/kg at the
D. LH start of the test
E. TSH C. Plasma osmolality > 300 mOsm/kg and urine
osmolality < 600 mOsm/kg
18.56. A 55 year old woman is found to have a D. Plasma sodium concentration 145 mmoi!L
significant pituitary mass on MRI scanning. High E. Reduction in body weight of 1% over the
circulating levels of which hormone would direct test period
treatment for a pituitary macroadenoma down a
primarily medical, rather than surgical, route? 18.58. A 32 year old man is referred having
A.ACTH been found to have hypercalcaemia and a high
PTH level. He has recently been investigated
B. GH
C. LH for episodes of sweating, lightheadedness and
D. Prolactin confusion, which were helped by eating sugary
E. TSH foods. Which of the following is associated with
MEN 1?
18.57. 52 year old woman is referred to the A. Acromegaly
clinic with a 3-month history of polyuria. She B. Cerebellar haemangioblastoma
additionally complains of increased thirst, C. Marfinoid habitus
drinking up to 5 L per day. Fasting plasma D. Medullary thyroid carcinoma
glucose is normal at 4.2 mmoi/L (76 mg/dl). E. Phaeochromocytoma
Answers
~~
~I
18.1. Answer: D. 18.2. Answer: B.
Primary hypoadrenalism results in increased
synthesis and secretion of adrenocorticotrophic
High concentrations of insulin
(hyperinsulinaemia) exert proliferative effects
I
hormone (ACTH) from the pituitary gland. Due through the insulin-like growth factor-1 (IGF-1) I·
to the co-secretion of melanocyte-stimulating receptors, stimulating epidermal keratinocyte
hormone as part of the larger prohormone and dermal fibroblast proliferation in
(pro-opiomelanocortin; POMC), the axillae.
hyperpigmentation occurs, classically of the
palmar creases. Primary adrenal failure 18.3. Answer: A.
(Addison's disease) is usually autoimmune in Hyperprolactinaemia (often due to a
aetiology and this can be confirmed with the microprolactinoma) is a common cause of
detection of anti-adrenal autoantibodies. If secondary amenorrhoea in this age group.
diagnosed, potential coexisting autoimmune Prolactin is synthesised by lactotrophs in the
conditions should be looked for. Alternative anterior pituitary gland. Synthesis and release
causes of Addison's disease include of prolactin is under the tonic inhibition of
tuberculous adrenalitis, which should be dopamine, which is released from the
strongly considered in endemic areas and hypothalamus and passes down capillaries
when autoantibodies are negative. Abdominal surrounding the pituitary stalk to the anterior
imaging in such cases may reveal calcification pituitary.
of the adrenal glands. Secondary
hypoadrenalism due to pituitary pathology, with 18.4. Answer: A.
resultant low ACTH levels, is associated with Following overnight water deprivation, you
skin pallor. The dexamethasone suppression would expect urine to be.more concentrated,
test forms part of the workup for suspected with an osmolality of >600 mOsm/kg,
Cushing's syndrome. Imaging should not be particularly given that the plasma sodium level
done until the biochemical diagnosis is made. is at the upper end of the normal range and
plasma osmolality is >300 mOsm/kg. This deafness). Thyroid peroxidase catalyses the
therefore confirms diabetes insipidus. The conversion of iodide ions into organic iodine
concentrating ability of the kidney is improved and couples it with tyrosine to form MIT and
following the administration of desmopressin DIT. This later step is inhibited by thionamides
(DDAVP), providing evidence of a central cranial such as carbimazole. DIT and MIT combine
cause. In nephrogenic diabetes insipidus, urine forming T4 and T3 . The organification of iodide
osmolality would show little improvement and coupling of iodinated tyrosine molecules
following administration of DDAVP. occurs on the surface of thyroglobulin. This is
subsequently cleaved, releasing thyroid
18.5. Answer: A. hormone. Uncoupled iodinated tyrosine can be
Arginine vasopressin acts via V2 receptors in dehalogenated, allowing recycling of the iodine.
the renal collecting ducts to cause the insertion The majority of T4 circulates bound to
of aquaporin-2 that allows increased water thyroxine-binding globulin (TBG).
permeability across the collecting ducts with
subsequent reabsorption of water, leading to 18.7. Answer: D.
the production of more concentrated urine. Through a classical negative feedback loop,
TSH secretion will increase with a reduction in
18.6. Answer: D. circulating free T4 or Ts. TSH synthesis follows
Iodide is actively transported into follicular cells a circadian rhythm with a peak at 0100 hrs
by a sodium/iodide transporter (Fig. 18.6). and nadir at 1100 hrs. Free T4 circulates at
Pendrin is found at the apical membrane, concentrations around three times that of free
where it transports iodide into colloid. A defect T3 , although Ts is a more potent activator of
in this transporter underlies Pend red's thyroid hormone receptors. Both play a role in
syndrome (congenital hypothyroidism and feeding back to the hypothalamus. Small
Target tissues
Blood
Negative
feedback
--
this stage. She is likely to develop This is the classic image of a toxic adenoma
hypothyroidism, and close monitoring of her with increased uptake in the adenoma and
thyroid function to allow identification and early suppressed uptake in the remaining gland. The
treatment is advocated. Oral selenium is used presence of multiple nodules with high uptake /
for the treatment of mild to moderate of 99 mtechnetium would be consistent with toxic, 1
dysthyroid eye disease and is not appropriate multinodular goitre. 'Cold nodules' on · ~'
II
here. scintigraphy have a much greater likelihood of
18.1 o. Answer: E.
malignancy. Thyroglossal duct cysts are
typically located in the midline and are cold,
I
Exopthalmus but not lid retraction is specific whilst thyroiditis displays widespread reduced
to Graves' disease. Lid retraction is a uptake of tracer.
consequence of adrenergic stimulation
of the levator palpebrae muscles and may be 18.14. Answer: E.
seen in any form of thyrotoxicosis. Radioactive iodine is administered orally as a
Thyrotoxicosis can result in an increase capsule or liquid. The doses used for the
in sex hormone-binding globulin (SHBG), treatment of Graves' disease are much smaller
altering the ratio of free testosterone to than for the follow-up management of thyroid
oestradiol and, as such, result in cancer at 400-600 M Bq (approximately
gynaecomastia. Females have a greater 10-15 mCi). There is a significant risk of
susceptibility to autoimmune disease in general, hypothyroidism when using 131 1for the
including Graves' disease. Smoking is a treatment of Graves' disease; this is
significant risk factor for the development of approximately 40% after 1 year and 80% after
eye disease. The presence of a goitre in the 15 years. Failure to adjust energy consumption
setting of clinical and biochemical to the reduced metabolic rate associated with
hyperthydroidism is common with Graves' correction of hyperthyroidism may precipitate
disease but not universal or diagnostic. The weight gain. With a potential adverse effect on
presence of TRAbs or a classical picture of developing sperm, male individuals are advised
diffuse increased uptake on a to refrain from conceiving for a minimum of 6
scintigraphy scan are diagnostic. months post-treatment. There are reports that
radioactive iodine can exacerbate active TSH both at the lower end of the reference
Graves' ophthalmopathy and so it is best range. Thyroiditis typically causes an initial
avoided in this situation if alternative treatment thyrotoxic phase followed on by a period of
options carry less risk. High-dose hypothyroidism, which may resolve or persist.
glucocorticoids can be used to reduce the risk Non-thyroidal illness results in reduced
of potentiating eye disease. peripheral conversion of T4 to T3 with reduced
secretion of TSH. The differential diagnosis for
18.15. Answer: D. this pattern would include a TSH-secreting
Simple diffuse goitre is a benign condition with pituitary tumour or thyroid hormone resistance,
hypertrophy of thyroid tissue. Thyroid function but in this scenario it is most likely that the
is normal and it will therefore not shrink patient has not been reliably taking
significantly with radioactive iodine treatment. levothyroxine for several weeks (causing the
Surgery is a better option if there is concern TSH to rise) and then in the few days prior to
about cosmetic appearance. It may enlarge in the blood test has taken an increased dose of
response to alterations in circulating oestrogens levothyroxine (resulting in the borderline
such as during pregnancy. The goitre usually elevated free T4).
regresses over time but may develop into a
multinodular goitre with autonomous function. 18.19. Answer: G.
In areas of endemic iodine deficiency, iodine In subacute thyroiditis, inflammation results in
supplementation may cause some regression of the release of colloid and stored thyroid
the goitre. hormone, resulting in thyrotoxicosis. Damage to
follicular cells impairs retention of iodine,
18.16. Answer: E. resulting in subsequent hypothyroidism and
Intestinal absorption of levothyroxine is impaired produces the classic picture of a 'cold' image
by co-ingestion of iron, colestyramine and on scintigraphy. Acute thyroiditis usually results
calcium supplements, but enhanced by vitamin from bacterial infection such as Staphylococcus
C. Increased clearance occurs with a variety of aureus and Streptococcus haemolyticus, whilst
medications, including antiepileptic medications subacute thyroiditis often follows a viral illness.
and rifampicin. Clearance is reduced with Management of hypothyroidism resulting from
increasing age, potentially necessitating smaller thyroiditis may involve at least temporary i
doses for replacement. replacement with levothyroxine and clos1
monitoring of thyroid function tests. After 4
18.17. Answer: E. months of TSH being within the reference
After commencement of levothyroxine for range, reduction in levothyroxine dose to 50 ~g
hypothyroidism, symptoms of dry skin and hair may be tried with further TSH monitoring after
can take 3-6 months to improve. Reduction in 6 weeks. If TSH remains within the normal
periorbital oedema occurs more rapidly. The range, a trial of levothyroxine can be attempted,
dose of levothyroxine should be adjusted to with repeat thyroid function testing after a
keep TSH within the reference range, with further 6 weeks.
serum T4 in the upper reference range.
Treatment with T3 is controversial, but may be 18.20. Answer: E.
considered in selected cases. The half-life of These results are in keeping with non-thyroidal
levothyroxine is around 7 days and it therefore illness or 'sick euthyroidism'. This occurs due
takes around 6 weeks following to decreased peripheral conversion of T4 to T3
commencement of levothyroxine to see as well as altered circulating levels and binding
resolution of thyroid function tests. There is no of thyroid hormone to thyroxine-binding
indication to check the patient's TRAbs. globulin, with resultant altered feedback on the
Malabsorption can result in under-treatment of hypothalamic-pituitary-thyroid axis. During
hypothyroidism, although there is nothing in this recovery from the systemic illness, the TSH
clinical scenario to suggest coeliac disease. may increase to levels associated with
hypothyroidism. Over time these will, however,
18.18. Answer: E. normalise; hence, vnless there is clinical
Central hypothyroidism results in both low TSH evidence of concomitant thyroidal disease,
and T4 . Amiodarone treatment usually causes repeated measurements and monitoring is
a mild elevation in free T4 , with free T3 and advised.
~
surgery, with or without radio-iodine therapy.
These usually present as a single focus with or
without nodal involvement. Distant metastases,
greater age at presentation, nnale sex and ~::~ J\:.'. C\
certain histological subtypes have a worse
prognosis. The differential diagnosis in this case ~
0 Menses 7 14 21
Daysa!lerslarlollastmenslrualperiod
21!
'
is lymphoma.
Oestradiol OestradioiP~!~ed~e P~~j.:;.l'/
18.24. Answer: E.
With more extensive disease, levothyroxine
~ J., €) ~ &($
replacement is provided with an aim of
Fig. 18.25 Female reproductive physiology· and the normal
suppressing TSH, preventin@ stimulation of menstrual cycle. (FSH = follicle-stimulating hormone; LH =
any potential residual tissue. Studies have luteinising hormone.)
normal range and can result in a high testicular volumes are not reduced to the
FSH-to-LH ratio. Functional hypothalamic extent seen here. Testicular trauma would be
amenorrhoea can be caused by eating associated with hypergonadotrophic
disorders, mental or physical stress or hypogonadism. Klinefelter's syndrome due to
over-exercising. Circulating levels of the 'satiety' XX'( karyotype results in small under-developed
hormone leptin have been shown to be testes with resultant elevation in
reduced in hypothalamic amenorrhoea, which gonadotrophins.
may impact on the production of LH.
Gonadotrophin-releasing hormone insensitivity 18.30. Answer: E.
is a rare autosomal recessive condition A variety of theories exist as to the aetiology of
that would present in a similar manner hyperandrogenism associated with PCOS.
but would be detected on genetic testing. Disordered gonadotrophin secretion has been ·
Hyperprolactinaemia accounts for around 1 .9% observed with a higher ratio of LH to FSH.
of hypogonadotrophic hypogonadism, but Androgens are synthesised by theca cells in the
again would be detected through plasma ovary under the influence of LH, whilst FSH
measurements. stimulates aromatisation of androgens by
granulosa cells. Challenging the pituitary gland
18.27. Answer: B. with GnRH has shown a preponderance for the
High gonadotrophins in the context of low production of LH but no evidence exists for
oestradiol and secondary amenorrhoea disruption in hypothalamic function of GnRH.
implicate premature ovarian failure. The most Hyperinsulinaemia leads to a reduction in
likely causes are acquired injury to the ovaries SHBG and resultant increase in metabolically
(e.g. previous chemotherapy), autoimmune or active free androgens. Mutations in
genetic disorders such as Turner's syndrome. 3~-hydroxysteroid dehydrogenase cause a
Karyotype and genetic screening is therefore virilising form of congenital adrenal hyperplasia.
necessary. MRI pituitary would be the
investigation of choice for hypogonadotrophic 18.31. Answer: D.
hypogonadism. The karyotype in this scenario is consistent with
Turner's syndrome and usually presents with
18.28. Answer: C. short stature and amenorrhoea. There is ~o
Constitutional delay is observed more frequently increased risk of ovarian cancer. Excess 1
in boys. Reduced growth velocity is observed androgen is not usually a feature. '
as early as 3-6 months. Due to delay in age of Cardiovascular malformations (especially aortic
pubertal growth spurt, height can drift further root dilatation) may go undiagnosed until later
from the growth chart at this time but catches in life and present a high risk of morbidity and
up once puberty is achieved. Bone age is mortality, especially during pregnancy with
consistent with age appropriate for height increased circulatory volume, Only up to 5% of
rather than chronological age. In childhood individuals with Turner's syndrome become
when long bones are still developing, the ratio pregnant spontaneously, with the majority
of upper-to-lower body is > 1, which is then requiring intervention such as egg donation.
reversed by adulthood. Constitutional delay Turner's syndrome is not associated with
has no effect on final height and can therefore mental retardation but is associated with
be predicted based on mid-parental heights. degrees of learning disability later in life. As it is
not heritable, Turner's syndrome cannot be
18.29. Answer: A. passed on to future generations with
Hypogonadotrophic hypogonadism in the unassisted pregnar:~cies.
context of small testes suggests absent,
incomplete or partial pubertal development 18.32. Answer: C.
due to Kallmann's syndrome or idiopathic Delayed puberty in.the context of
hypogonadotrophic hypogonadism. Individuals hypergonadotrophb hypogonadism in males is
with Kallmann's syndrome may have either usually due to Klinefelter's syndrome with
anosmia or hyposmia. This may, however, not karyotype 47XXY, and testing for this should
be obvious to the individual until more formally therefore be part of the next -line investigation.
tested. A similar biochemical pattern is seen in The differential diagnosis is acquired gonadal
men in the context of central obesity, but damage due to chemotherapy/radiotherapy,
200 • ENDOCRINOLOGY
E. Recommend treatment with ascorbic acid for chest is clear to auscultation, her abdomen is
the prevention of kidney stones soft but mildly tender to palpation in the right
upper quadrant and she has no oedema.
19.9. A 58 year old woman from Angola is seen Blood tests show wee 23 X 109/L, platelets
in clinic after recently emigrating to the UK. Her 340x109/L, INR 1.5, alanine aminotransferase
husband states that she has been confused (ALT) 32 U/L, albumin 34 g/L. Extrahepatic
and at times disorientated. On further biliary dilatation is seen on abdominal
questioning, the patient states that she has ultrasound.
nausea and diarrhoea, with seven bowel Which of the following is the most likely
movements daily. On examination, she is factor leading to her mild coagulopathy?
afebrile, anicteric, without conjunctival pallor A. Hepatic synthetic dysfunction
or lymphadenopathy. Her tongue appears B. Intracerebral haemorrhage
enlarged; no cardiac murmurs are heard; and C. Medication effect
her abdomen is soft, mildly tender and D. Obstruction of the biliary tree
non-distended. A dry cracking rash is seen on E. Previously undiagnosed coeliac disease
the skin of her neck and upper extremities
bilaterally. 19.12. A 68 year old man is being discharged
Which of the following treatments is most from the hospital after experiencing palpitations.
likely to improve her symptoms? An EeG has revealed new-onset atrial
A. Ascorbic acid 250 mg orally 3 times daily fibrillation and he is started on warfarin for
B. Folate 500 J.Lg orally once daily anticoagulation and stroke prophylaxis. His
C. Nicotinamide 100 mg orally 3 times daily cardiologist explains that warfarin works by
D. Pyridoxine hydrochloride 50 mg orally 3 antagonising vitamin K and that the patient
times daily should not vary his vitamin K intake while on
E. Riboflavin 10 mg orally once daily warfarin. Which of the following foods is highest
in vitamin K and should be consumed with the
least amount of variation?
19.10. A 45 year old man with a history of
-
alcoholic cirrhosis presents to the emergency A. Egg yolk
department after being found unresponsive B. Kale
at home. On examination he is minimally C. Liver
responsive, disorientated, anicteric, cachectic D. Pork
and has restricted horizontal eye movement E. Sunflower oil II·
bilaterally. His lab results are notable for mildly
elevated transaminases and low albumin. 19.13. A 32 year old woman gives birth to a I
Treatment is initiated with parenteral baby boy weighing 4.2 kg. She defaulted from
multivitamin therapy. antenatal care and takes no medications or
Which of the following is true regarding his supplements. On examination of the child after
most clinically significant vitamin deficiency? 10 minutes, his pulse is 136 beats/min and
A. Adults have limited stores of thiamine in the he is crying vigorously with arms and legs
liver and may manifest deficiency after a held in flexion. The skin appears pink with a
short period protuberant mass on his back in the midline at
B. Thiamine deficiency commonly leads to the level of L4. Treatment with a water-soluble
coagulopathy vitamin may have prevented this birth defect
C. Hepatocytes are most vulnerable to damage through which of the following mechanisms?
as a result of thiamine deficiency A. Accepting and donating hydrogen in
D. Thiamine acts as a co-factor in folate nicotinamide adenine dinucleotide (NAD)
co-enzyme recycling B. Decarboxylation of pyru':ate to acetyl-co-
E. Thiamine is fat soluble enzyme A to initiate the Krebs cycle
C. Donating a methyl gr6up in DNA and protein
19.11. A 41 year old previously healthy woman synthesis
is brought to the hospital by her husband who D. Facilitating absorption.of calcium in the small
states she has been febrile to 39oe for the past intestine
2 days and jaundiced for the past 7 days. On E. Hydroxylation of proline and lysine in the
examination she is delirious and jaundiced. Her formation of mature collagen
food. The act of feeding is very tiring for him Which of the following is NOT a recognised
and is taking up much of the day. Increasingly, risk of gastrostomy insertion or gastrostomy
there are days when he may not eat or drink at feeding?
all and there are concerns that he is losing A. Aspiration pneumonia
weight and becoming dehydrated. After B. Colonic perforation
multidisciplinary assessment it is felt he should C. Insertion site infection
be fed by gastrostomy to allow adequate food D. Laceration of the liver
and fluid to be given on a daily basis. E. Pulmonary embolus
Answers
19.1. Answer: A. 19.2 WHD recommended population
This is an obese patient being evaluated for macronutrient goals
the first time with a history of weight gain
Target limits for
that has accelerated recently, along with average population
fatigue. This history suggests an underlying Nutrient (% of total energy intakes
disorder such as hypothyroidism or Cushing's unless indicated) Lower Upper
syndrome may be related to the weight gain Total fat 15 30
(Box 19.1). All obese patients should have Saturated fatty acids 0 10
thyroid function tests performed. Very-low- Polyunsaturated fatty acids 6 10
Trans 'tatty acids 0 2
calorie diets require the supervision of an
Dietary cholesterol (mg/day) 0 300
experienced physician and dietician and can be
Total carbohydrate 55 75
considered if short-term rapid weight loss is
Free sugars 0 10
required.
Complex carbohydrate 50 70
Dietary fibre (g/day):
As non-starch polysaccharides 16 24
As total dietary fibre 27 40
19.1 Potentially reversible causes of weight gain
Protein 10 15
Endocrine factors
Hypothyroidism
Cushing's syndrome 19.3. Answer: D.
lnsulinoma This female runner's presentation is concerning
Hypothalamic tumours or injury
for under-nutrition and the female athlete triad
Drug treatments
of disordered eating, amenorrhoea and
Atypical antipsychotics (e.g. olanzapine)
Sulphonylureas, thiazolidinediones, insulin decreased bone mineral density. Her foot pain
Pizotifen may be related to osteopenia and a stress
Glucocorticoids fracture. In a state of under-nutrition, her basal
Sodium valproate
metabolic rate will be decreased to minimise
~-blockers
further weight loss. In addition, she will have a
low-insulin state in order to promote liberation
of energy stores from tissues such as the liver,
19.2. Answer: A. muscle, and adipose tissue for systemic
Fats have the highest energy density of the utilisation (Fig. 19.3).
macronutrients and should represent 15-30%
of daily energy intake compared to 55-75% for 19.4. Answer: A.
carbohydrates and I 0-15% for proteins (Box This patient with a history of chronic alcoholism
19.2). High saturated fat consumption is is at risk for malnutrition ~rid refeeding
associated with higher levels of LDL syndrome due to restoration of carbohydrate
cholesterol. Whereas omega-3 fatty acids metabolism, insulin secretion and electrolyte
promote prostaglandin production and shifts into cells. Refeeding syndrome (Box 19.4)
anti-inflammatory cascade, trans fatty may present with nausea, vomiting, weakness,
acids are associated with cardiovascular seizures, respiratory depression, and cardiac
disease. arrhythmias or arrest. Initiation of nutrition
to damage from thiamin deficiency as they the synthesis of coagulation factors II, VII, IX
exclusively utilise glucose for energy and X. Deficiency can lead to coagulopathy.
requirements. The liver has very limited stores While cirrhosis, malabsorption and medications
of thiamin, so deficiency can manifest after only (e.g. warfarin) can also lead to coagulopathy,
1 month of a thiamin-free diet. this patient is previously healthy prior to this
acute episode.
19.11. Answer: D.
The patient is presenting with four features of 19.12. Answer: B.
Reynolds' pentad of ascending cholangitis Vitamin K is a fat-soluble vitamin produced by
(fever, right upper quadrant pain, jaundice, intestinal bacteria. Green leafy vegetables are
altered mental status), probably caused by rich sources of vitamin K, along with soya oil.
obstruction of the biliary tree. In obstructive Egg yolks represent a source of biotin and
jaundice, bile is unable to enter the gut lumen vitamin D. Liver is rich in vitamin A and
for fat digestion. As a result, the fat -soluble sunflower oil is rich in vitamin E (Box i 9. i 2).
vitamins, including vitamin K, are poorly
absorbed (Box i 9. i i ). Vitamin K is required in 19.13. Answer: C.
The child was born with a neural tube defect,
19.11 Gastrointestinal disorders that may be but is otherwise healthy. Folate deficiency in
associated with malabsorption of fat-soluble pregnancy is associated with spina bifida,
vitamins anencephaly and encephalocele due to
Biliary obstruction increased requirements during embryonic
Pancreatic exocrine insufficiency development. Pregnant women are advised to
Coeliac disease take folate supplements during the first
Ileal inflammation or resection
trimester. Mechanistically, folate acts as a
methyl donor in the synthesis of DNA, RNA and fluid intake should be restricted in such patients
protein, with increased requirements during to 500 ml per day. A further 1 000 mL of a
cellular division. glucose/electrolyte solution with a sodium
concentration of at least 90 mmoi/L should be
19.14. Answer: D. given (e.g. St Mark's solution or Glucodrate,
The residual length of jejunum following Nestle) but no oral fluids over and above this
massive small bowel resection or bypass is a limit. Any subsequent deficit between intake
powerful predictor of the need for parenteral and output should be made up by parenteral
fluid or nutritional support. Those left with an fluid administration.
intact colon that can be anastomosed at the
time of initial surgery or at some time 19.17. Answer: A.
subsequently tend to fare better than those Deficiency of the water-soluble vitamin C
where the colon is lost (due to the further (ascorbic acid) has been shown to be prevalent
capacity of the colon to absorb water and in those aged >65 years living independently in
electrolytes). However, most patients with the UK. Its clinical presentation may be
<200 em of jejunum remaining will require oral precipitated by events such as trauma, surgery,
fluid restriction and the use of a glucose/ burns or infections and it tends to be more
electrolyte solution (with sodium concentration prevalent in those who smoke or use drugs
of 90-120 mmoi/L) to minimise diarrhoea and such as glucocorticoids or non-steroidal
maximise absorption of fluid and electrolytes. anti-inflammatory drugs. Ascorbic acid is very
In addition, those with < 100 em of jejunum heat labile and many traditional cooking
remaining will require a variable volume of methods lead to its degradation.
parenterally administered sodium chloride to Patients may notice poor healing of wounds.
maintain an adequate balance between what It may present with petechial or perifollicular
they can absorb orally and their overall fluid bleeding or larger ecchymoses. Gingival
requirements. Those with <75 em of jejunum swelling or haemorrhage may occur and, less
will also be unable to maintain their overall commonly, haemarthrosis or gastrointestinal
energy requirements by oral means and will bleeding. Anaemia is recognised.
require a variable amount of calories
administered parenterally (parenteral nutrition) in 19.18. Answer: E. J
addition to the other treatments above. There are nine essential amino acids (Bof
19 .18) that cannot be synthesised by the body
19.15. Answer: B. (e.g. through transamination) and must
Where the intestine is largely intact, functionally therefore be obtained in the diet. They are
normally and accessible to an enteral tube, the required in order to synthesise other proteins,
proven benefits of enteral over parenteral which have a variety of important functions.
nutrition are that the overall health-care costs Five other amino acids can only be synthesised
are less, that it is associated with fewer if there is an adequate dietary supply of their
episodes of infection, more rapid restoration of precursors. These are known as 'conditionally
normal intestinal function and a reduced length essential' amino acids.
of hospital stay.
19.16. Answer: B.
Although it may appear initially counterintuitive, 19.18 Amino acids
it is absolutely vital in this situation that further
Essential amino acids
intestinal losses are not incurred by Tryptophan Valine
inappropriate advice to simply drink more fluid. Histidine Phenylalanine
The jejunum is inherently 'leaky', allowing rapid Methionine Lysine
fluxes of sodium (and water) across the Threonine Leucine
Isoleucine
epithelial barrier. Taking fluids with a sodium
Conditionally essential amino acids and their precursors
concentration of < 90 mmoi/L results in a net
Cysteine: methionine, serine
efflux of sodium and water into the intestinal Tyrosine: phenylalanin~
lumen (and therefore greater stomal fluid Arginine: glutamine/glutamate, .aspartate
losses). Drinking a larger volume of such 'dilute' Proline: glutamate
Glycine: serine, choline
fluids leads to even more stomal losses. Oral
Dementia Age-related
Frailty changes and
Cognitive
Sarcopenia impairment diseases
Intake!
Diabetes mellitus
Multiple Choice Questions
20.1. A 110-kg 57 year old man presents with 25 and is dominantly inherited. One form of
1-month history of lethargy, urinary frequency MODY is due to mutation in glucokinase. How
and increased thirst. He has been dieting for should these patients be managed?
years but only recently has managed to lose A. Basal insulin
10 kg with little effort. What would be the B. Biguanide (metformin) alone
simplest test that could make the diagnosis? C. Diet alone
A. Autoantibodies to glutamic acid D. No treatment required
decarboxylase (GAD), protein tyrosine E. Sulphonylurea with meals
phosphatase islet antigen-2 (IA-2) and zinc
transporter 8 (ZnT8) 20.4. The diabetes team were asked to review
B. Capillary blood glucose a hyperglycaemic 37 year old man on the
C. Fasting venous blood glucose surgical ward who presented with abdomir:ml
D. Oral glucose tolerance test (OGTT) pain, general lethargy, weight loss and pal~
E. Random venous blood glucose loose bowel motions. He has been in hodpital a
number of times with upper abdominal pain
20.2. A 49 year old black woman with a body with a normal abdominal ultrasound scan. He
mass index (BMI) of 42 kg/m 2 presents with a has a family history of type 2 diabetes mellitus.
6-month history of fatigue and lethargy. Over He recently lost his job as a taxi driver as there
the past few days she has become increasingly was concern after he came to work smelling
thirsty, is getting up at night to pass urine and strongly of alcohol and was found to be above
has experienced some dysuria. On admission, the legal limit to drive. Mean corpuscular
blood glucose was measured at 40 mmoi/L volume (MCV) was raised on blood tests from
(720 mg/dl) with ketones of 4 mmoi/L and 3 years ago. On admission he had a blood
bicarbonate 12 mmoi/L. She is treated for glucose of 20 rnmoi/L (360 mg/dl) with
diabetic ketoacidosis (DKA), but what is the ketones of 3 mrnoi/L .and bicarbonate
most likely underlying diagnosis? 20 mmoi/L. What is the most likely
A. Impaired glucose tolerance diagnosis?
B. Latent autoimmune diabetes of adulthood A. Impaired glucose tolerance
(LADA) B.LADA
C. Metabolic syndrome C. Monogenic diabete$
D. Type 1 diabetes mellitus D. Pancreatic insuffi9iency
E. Type 2 diabetes mellitus E. Type 2 diabetes mellitus
20.3. The most common monogenic forms of 20.5. DKA is a medical emergency in people
diabetes are caused by defects in insulin with type 1 diabetes. What is the most
secretion. Maturity-onset diabetes of the young common mechanism of death in DKA in
(MODY) commonly develops under the age of children and adolescents?
a day. Which of the following conditions has a 20.11. A 32 year old woman attends the
pathophysiological link and is more common in antenatal clinic for her booking scan. She is 12
individuals with type 2 diabetes? weeks pregnant with twins and has been
A. Coeliac disease struggling with 'morning sickness'. She has a
B. COPD BMI of 36 kg/m 2 and undergoes an OGTI, the
C. NAFLD results of which are: fasting plasma glucose
D. Optic atrophy 4.8 mmoi/L (86 mg/dl); 2-hour plasma glucose
E. Rheumatoid arthritis 7.0 mmoi/L (126 mg/dl).
As part of her routine checks the midwife
20.14. A 67 year old female has had type 1 dips her urine and she has 2+ ketones. What is
diabetes for 50 years. She has an HbA1c of the most likely diagnosis?
42 mmol/mol (6%) and is very strict about her A. Diabetic ketoacidosis
diet. She was admitted for an elective total hip B. Gestational diabetes
replacement. On the day of surgery, she was C. Hyperemesis gravidarum
found by the junior doctor to be very drowsy D. Normal physiological response in pregnancy
with a capillary blood glucose of 2.2 mmoi/L E. Undiagnosed type 2 diabetes
(40 mg/dl). What should ideally happen next?
A. Cancel theatre 20.18. A 51 year old man with type 1 diabetes
B. Intravenous (IV) access and 100 ml of 20% returns to the foot clinic. He attends for regular
dextrose and repeat blood glucose in 15 review as he has an ulcer on his left heel. He
minutes has been on a walking holiday to the Amalfi
C. IV access and 100 ml of 50% dextrose c;oast for 2 weeks. The podiatrist asks for a
D. IV access and 200 ml of 20% dextrose medical' review as he is concerned that the left
E. Withhold insulin for rest of day foot is now warm and swollen. The ulceration
looks much improved and the patient feels well.
20.15. A woman at 20 weeks' gestation X-ray does not reveal any obvious bony
undergoes a 75-g oral glucose tolerance test abnormality. What is the most likely diagnosis?
with the following results: 0 minutes = A. Acute Charcot arthropathy
5.6 mmoi/L (1 01 mg/dl); 120 minutes = B. Deep vein thrombosis (DVT)
9.2 mmoi/L (166 mg/dl). According to the C. Dry gangrene
National Institute for Clinical Excellence (NICE) D. Gout
guidelines, what should be the immediate E. Osteomyelitis
management?
A. Dietary modification 20.19. A 47 year old woman with type 1
B. GLP-1 receptor agonist diabetes attends for annual review. She denies
C. Insulin any significant hypoglycaemia. Her results are
D. Metformin as follows: HbA1c 46 mmol/mol (6.4%); blood
E. Sulphonylurea, e.g. glibenclamide pressure (BP) 152/98 mmHg (average of 3);
weight 61 kg (BMI 24 kg/m 2); urinalysis: +
20.16. A frail 93 year old man with type 1 glucose, trace nitrites, albumin: creatinine ratio
diabetes for 46 years attends for review. His (ACR) 5 mg/rnrnol (previously early morning
HbA1c is 69 mmol/mol (8.5%). Blood pressure sample 6.2 mg/mmol); total cholesterol
is 152/82 mmHg for which he is taking an 3.8 mmoi/L (147 mg/dl).
angiotensin-converting enzyme (ACE) inhibitor Current medication: basal analogue insulin
(ramipril) and a calcium channel blocker (glargine), bolus/rapid-acting analogue insulin
(amlodipine). He has mild background diabetic (NovoRapid), ACE inhibitor (lisinopril), statin
retinopathy. Which of these treatment targets is (simvastatin).
most appropriate in this scenario? Which result is it most important to act
A. Avoidance of hypoglycaemia upon? '
B. HbA1c of 48 mmol/mol (6.5%) or less A. Blood pressure
C. HbA1c of 58 mmol/mol (7.5%) or less B. Cholesterol
D. Microvascular disease prevention C. HbA,c
E. No need to monitor blood glucose in view of D. Urinalysis
his age E. Weight
20.20. James is a 19 year old man from Ireland; D. Stimulation of hepatic gluconeogenesis
he has a family history of diabetes. His mother E. Stimulation of hepatic glucose uptake
developed diabetes later in life; he is unsure if
she required insulin but she often attended the 20.23. A 59 year old man with a BMI of 29 kg/
hospital. She died suddenly when he was m 2 is admitted to hospital with pleuritic chest
young. James is an active man but has recently pain and a productive cough and is found to
been hindered by general malaise, lethargy and have pneumonia. He has no history of diabetes
pain in his knees. He has had a steroid injection and takes no regular medication. As part of his
into his left knee with little improvement. The admission investigations, a plasma glucose is
following tests have been carried out: found to be 10.0 mmoi/L (180 mg/dL). Which
Haemoglobin 145 g/L Anti-GAD antibody: of the following is the most appropriate
(14.5 g/dL) negative management?
White blood cell count Anti-IA-2 antibody: A. Blood glucose monitoring with fasting
9
6.2 x 10 /L negative plasma glucose after recovery from infection
Urea 5.2 mmoi/L Antineutrophil B. Commence treatment with liraglutide
(31 mg/dL) cytoplasmic C. Commence treatment with metformin
Creatinine 62 JJmoi/L antibody D. No further assessment of glycaemic control
(0.70 mg/dL) (ANCA): negative E. Variable-rate intravenous insulin infusion
Glucose 11.4 mmoi/L Ferritin 1137 j.Jg/L
(205 mg/dL) 20.24. A 70 year old woman attends her family
HbA1c 51 mmol/mol physician complaining of excessive thirst and
(6.8%) fatigue. A random venous glucose is
What is the most likely diagnosis? 13.2 mmoi/L (238 mg/dL), confirming a
A. Hereditary haemochromatosis diagnosis of diabetes. She takes a number of
B. MODY medications for hypertension, ischaemic heart
C. Steroid-induced diabetes disease and polymyalgia rheumatica. Which of
D. Type 1 diabetes the following medications can precipitate
E. Type 2 diabetes hyperglycaemia?
._.
A. ACE inhibitor (e.g. ramipril)
20.21. Insulin is the main regulator of glucose B. Aspirin
metabolism and storage. It is secreted from C. Calcium channel blocker (e.g. amlodipine)
pancreatic ~ cells. These cells regulate blood D. Nitrate (e.g. isosorbide mononitrate)
glucose concentrations by coupling glucose E. Steroid (e.g. prednisolone)
with insulin secretion. Glucose enters the
20.25. An 18 year old female with type 1
I
pancreatic ~ cells by facilitated diffusion down
its concentration gradient through cell diabetes is admitted with suspected
pyelonephritis. She has not taken any insulin for
I
membrane glucose transporters (GLUTs).
24 hours during her acute illness. Her initial I
Through which GLUT does glucose enter
pancreatic ~ cells? blood tests include: plasma glucose 24 mmoi/L
(432 mg/dL), bicarbonate 12 mmoi/L and
A. GLUT1
ketones 5.5 mmoi/L. Which electrolyte will most
B. GLUT2
likely require regular monitoring and aggressive
C. GLUT3
intravenous supplementation?
D. GLUT4
E. GLUT5 A. Bicarbonate
B. Calcium
C. Magnesium
20.22. Blood glucose is tightly regulated in order
D. Phosphate
to provide a constant supply of glucose to the
E. Potassium
central nervous system. Following ingestion of
a meal containing carbohydrate, which of the
20.26. A 75 year old male with no prior diagnosis
following is most likely to occur in the normal
of diabetes is admitted to hospital because he
physiological state?
has become progressively more drowsy and
A. Inhibition of GLP-1 release unwell since being started on oral amoxicillinby
B. Inhibition of insulin release his family physician for a suspected chest
C. Stimulation of glucagon release infection 2 weeks ago. He appears clinically
dehydrated. His initial blood tests include: A. Advise him to avoid exercise
l
plasma glucose 55 mmoi/L (991 mg/dl), B. Always omit the short-acting insulin dose
ketones 0.1 mmoi!L, sodium 149 mmoi/L and after exercise
I serum osmolality 368 mmol!kg. Which of the C. Reduce his total daily insulin dose to relax
I'
following statements is correct with regard to the his glycaemic control
management of this patient? D. Refer for structured diabetes education
A. A solution of 10% dextrose is the initial programme
intravenous fluid of choice E. Refer to a tertiary centre for consideration of
B. Close monitoring of fluid balance is pancreatic islet transplantation
unnecessary
20.30. A 58 year old man with type 2 diabetes
C. Intravenous insulin is not required initially in
of 10 years' duration and a BMI of 33 kg/m 2
the absence of significant ketonaemia
attends clinic for review of his diabetes
D. Serum osmolality should normalise within 4
management. He has a suboptimal HbA1c
hours of treatment
of 69 mmol/mol (8.5%) on metformin
E. Thromboprophylaxis is contraindicated
monotherapy 1 g twice daily and would like to
discuss the addition of a second-line agent.
20.27. A 28 year old female has recently been
Which of the following options are the most
found to have hepatocyte nuclear factor 1 ex
appropriate if he wishes a strategy that
(HNF1cx) MODY. It is decided to treat
promotes weight loss?
her diabetes with gliclazide. Gliclazide, a
sulphonyulrea drug, exerts its hypoglycaemic A. DPP-4 inhibitor (e.g. sitagliptin)
effect by enhancing endogenous insulin B. GLP-1 agonist (e.g. liraglutide)
secretion. By which mechanism is this achieved? C. Insulin
D. PPARy agonistlthiazolidinedione (e.g.
A. Activation of PPARy
pioglitazone)
B. Activation of the GLP-1 receptor
E. Sulphonylurea (e.g. glipizide)
C. Closure of the transmembrane J3-cell KATP
channel 20.31. A 50 year old woman with type 2
D. Inhibition of DPP-4 diabetes presents to her family physician
E. Inhibition of SGLT2 complaining of genital thrush, which has ~ot
settled with topical antifungal treatment. She
20.28. A 21 year old female with type 1 had been started on a new oral hypoglydaemic
diabetes since childhood attends the diabetes drug 4 months earlier. Which of the following
clinic for review. She has been symptomatic of drugs is most likely to be responsible for her
hypoglycaemia several times since her last presentation?
appointment 6 months ago. Which of the
A. DPP-4 inhibitor (e.g. sitagliptin)
following is classed as a neuroglycopenic
B. Glucosidase inhibitor (e.g. acarbose)
symptom of hypoglycaemia?
C. PPARy agonistlthiazolidinedione (e.g.
A. Anxiety pioglitazone)
B. Confusion D. SGLT2 inhibitor (e.g. empagliflozin)
C. Headache E. Sulphonylurea (e.g. glimepiride)
D. Hunger
E. Sweating 20.32. A 35 year old .woman with type 1
diabetes of 20 years: duration presents with
20.29. A 24 year old male with type 1 diabetes chronic nausea, early satiety and intermittent
of 12 years' duration presents with frequent vomiting after meals.l She has a history of poor
episodes of hypoglycaemia. He goes running glycaemic control, retinopathy and peripheral
for up to 60 minutes 4 times per week and the neuropathy. Which of the following
hypoglycaemic episodes occur after exercise. investigations will b~,most helpful in
He has good awareness of hypoglycaemia and establishing a diagnosis?
is able to take corrective action on each A. Abdominal ultrasonography
occasion. He is on a basal-bolus insulin B. Anti-tissue transgl!Jtaminase (anti-tTG) antibody
regimen and his latest HbA1c is 62 mmol/mol C. Barium swallow
(7.8%). Which of the following interventions is D. Gastric emptying study
the most appropriate management? E. Plain chest radiograph
20.33. A 21 year old women with type 1 D. Centrally acting antihypertensive (e.g.
diabetes of 8 years' duration with good moxonidine)
glycaemic control - HbA1c 48 mmol/mol (6.5%) E. Thiazide diuretic (e.g. bendroflumethiazide)
- on basal-bolus insulin presents to her young
adult specialist clinic for routine review. She has 20.36. A 65 year old man with type 2 diabetes
been experiencing intermittent abdominal of 20 years' duration is referred to the specialist
bloating, diarrhoea and weight loss over the last diabetes foot clinic by his family physician with
3 months. Recent urea and electrolytes, liver an ulcer of the plantar surface of the right foot.
function tests and thyroid function tests were all The ulcer has been present for approximately
within normal limits. Which of the following is 6 weeks and there is a history of peripheral
the best next investigation to perform? diabetic neuropathy. On examination, there is a
A. Abdominal ultrasonography 2-cm diameter ulcer in proximity to the first
B. Anti-tTG antibody metatarsal head. It has an offensive odour and
c. Flexible sigmoidoscopy discharge. The area around the ulcer is hot and
D. Gastric emptying study erythematous. Which of the following features,
E. Upper Gl endoscopy if present, would most strongly indicate the
presence of osteomyelitis (bone infection)?
20.34. A 19 year old male with type 1 diabetes A. A normal plain foot radiograph
is admitted to hospital complaining of B. Elevated blood white cell count
generalised abdominal pain and vomiting. He is C. Increased skin temperature compared to the
apyrexial, tachycardic and clinically dehydrated. contralateral foot
There is no peritonism in the abdomen. He has D. Peripheral oedema
the following blood results: blood glucose E. The ulcer probing to the depth of bone
22 mmoi/L (396 mg/dl), ketones 4.3 mmoi/L,
bicarbonate 11 mmoi/L, alkaline phosphatase 20.37. A 72 year old man is admitted to hospital
250 U/L, white cell count 19 x 109/L and by his family physician for urgent investigation
haemoglobin 182 g/L. Which of the following of weight loss. He has a progressive 3-month
statements regarding interpretation of these history of back pain, jaundice, dark urine and
results is correct? anorexia. He has lost approximately 15 kg in
A. He can safely be discharged home weight. In the last 4 weeks he has developed
B. Measurement of venous pH will be normal increased thirst and is drinking excessively.
C. The elevated alkaline phosphatase A random venous glucose is 16.0 mmoi/L
enzyme invariably indicates vitamin D (288 mg/dl). Which investigation is most likely
deficiency to reveal the cause of his diabetes?
D. The elevated haemoglobin concentration will A. Anti-GAD and anti-IA-2 antibodies
likely normalise after intravenous fluid B. CT scan of the pancreas
administration C. Dexamethasone suppression test
E. The elevated white cell count invariably D. Faecal elastase
indicates underlying infection E. Serum C-peptide
20.35. A 48 year old man with type 1 diabetes 20.38. A 29 year old woman with type 1
of 30 years' duration attends clinic for routine diabetes for 18 years attends clinic for routine
review. He is on a basal-bolus insulin regimen review. She has poor glycaemic control with an
and has an HbA1c of 70 mmol/mol (8.6%). He HbA1c of 90 mmol/mol (1 0.4%). She is keen to
is on no other medication. Blood pressure is embark on stricter glycaemic management in
155/92 mmHg (repeated 3• times with similar advance of planning pregnancy. Which of the
results) and he has microalbuminuria with an following complications of diabetes would be
ACR of 7.3 mg/mmol. Estimated glomerular the most likely to deteriora!e· significantly should
filtration (eGFR) rate is 54 mUmin/1.73 m 2 . her glycaemic control impfove suddenly?
Which of the following drugs would be most A. Foot ulceration
beneficial? 1
B. Gastroparesis
A. ACE inhibitor (e.g. lisinopril) C. Microalbuminuria
B. ~-blocker (e.g. atenolol) ' D. Peripheral vascular disease
C. Calcium channel blocker (e.g. amlodipine) E. Retinopathy
20.39. An 18 year old woman with type 1 20.40. A 45 year old man with diabetes
diabetes attends her diabetes clinic to discuss presents with a 4-week history of weight loss,
the possibility of continuous subcutaneous polyuria and polydipsia. His blood results
insulin therapy (insulin pump therapy). She has include: random plasma glucose 20 mmoi/L
a suboptimal HbA1c of 68 mmol/mol (8.4%) and (360 mg/dl), ketones 2 mmoi/L and HbA1c
takes multiple daily injections of insulin. Which 110 mmol/mol (12.2%). He was diagnosed with
of the following statements is correct with diabetes 6 months ago at which point his BMI
regard to insulin pump therapy? was 23 kg/m 2 and HbA1c 65 mmol/mol (8.1 %).
A. A continuous glucose monitoring system There is no family history of diabetes. Since
(CGMS) is mandatory for all patients diagnosis he has been treated with metformin
B. DKA does not occur as insulin administration and a sulphonylurea. p-cell antibodies are
is constant checked and he is found to have a very high
G. Patients have to inject long-acting insulin in titre of anti-GAD antibodies. Which of the
addition to the pump-delivered insulin following diagnoses best fits with this scenario?
D. The rate of insulin delivery can be adjusted A.LADA
depending on the time of day B. Mitochondrial diabetes
E. There is an increased risk of microvascular G. MODY
disease compared to multiple daily D. Pancreatic disease
injections E. Type 2 diabetes
Answers
20.1. Answer: E. glucose but a normal post-prandial response.
This patient has osmotic symptoms in keeping Therefore, patients with glucokinase MODY
with hyperglycaemia. Given that he is generally have stable, mild hyperglycaemia, do
symptomatic, a random venous blood glucose not require treatment or monitoring and are at
of 2 11 .1 mmoi/L (2 200 mg/dl) is sufficient to very low risk of developing any diabetes ,
give the diagnosis of diabetes. This test will be complications.
the least burdensome to the patient and most
cost-effective. 20.4. Answer: D.
This patient has symptoms and signs in
20.2. Answer: E. keeping with pancreatic insufficiency, both
This patient is correctly treated for DKA as she endocrine and exocrine. The history of alcohol
has elevated blood glucose in keeping with excess is helpful to aid diagnosis. Alcohol
diabetes, elevated ketones and a metabolic excess can cause recurrent bouts of acute
acidosis. Given her ethnicity, BMI and pancreatitis, which can lead to progressive
prodromal illness, a diagnosis of 'ketosis-prone' destruction of the pancreas. Diabetes due to
diabetes (which is more common in patients of pancreatic insufficiency can sometimes be
African origin) is likely with an underlying managed with oral therapy but often requires
diagnosis of type 2 diabetes. This is important treatment with insulin.
as initially patients require insulin treatment but
as glucose levels are controlled and p cells 20.5. Answer: B.
recover, patients may be able to transfer off The average fluid loss in an adult with
insulin to oral hypoglycaemic agents. moderately severe DKA is 6 L. Patients are
therefore aggressively fluid replaced in the
20.3. Answer: D. first few hours. Cau9c>n is required in fluid
MODY is defined as non-insulin-dependent replacement in children and young adults
diabetes that develops under the age of 25 in due to the risk of cerebral oedema (a
one family member. Glucokinase is a pancreatic paediatric-specific DJ<A protocol should be
glucose sensor and patients with glucokinase used). The osmolar gradient caused by the high
mutations have an altered set-point for glucose. blood glucose results in water shift from the
This results in a slightly high fasting blood intracellular fluid to extracellular fluid and
contraction of cell volume. Correction of the drive fetal growth, resulting in an increased
blood glucose with insulin and fluids can result birth weight.
in a rapid reduction in the osmolarity, which in
turn reverses the fluid shift and development of 20.10. Answer: B.
cerebral oedema. It is thought that the cerebral Diabetic mononeuropathy is loss of a sensory
oedema is related to cerebral vasoconstriction, or motor function within a single peripheral or
brain ischaemia and hypoxia. As children's cranial nerve, in this case the 6th cranial nerve
brains have higher oxygen requirements than -resulting in sudden-onset diplopia. Given.that
adults, this may explain their unique the CT brain is normal and there are no other
susceptibility. Hypokalaemia-related cardiac symptoms or signs, it is unlikely to be in
events used to be a major cause of death but keeping with brain tumour or stroke. He would
potassium monitoring and replacement is now be unlikely to present with Graves' eye disease
much improved. with no features in keeping with thyrotoxicosis.
Giant cell arteritis commonly presents with
20.6. Answer: A. temporal tenderness and amaurosis fugax not
Metformin is a potent blood glucose-lowering diplopia.
treatment that is weight-neutral or can lead to
weight loss. It is low cost and does not cause 20.11. Answer: D.
hypoglycaemia. It is used as first line for type Ketone bodies are organic acids that are
2 diabetes in all patients who can tolerate it. formed during fat metabolism. When the body
The long-term benefits were shown in the UK has insufficient insulin or depletes its own
Prospective Diabetes Study. It is usually carbohydrate stores it will metabolise fat for
maintained when other medications are energy. Ketonuria may be found in normal
added. people who have been fasting or exercising
strenuously for long periods, who have been
20.7. Answer: A. vomiting repeatedly or who have been eating a
Thiazolidinediones predominantly work in diet high in fat and low in carbohydrate (all of
adipose tissue. They bind and activate PPARy. these circumstances can cause glycogenic
--;
This nuclear receptor regulates the expressions depletion). The history and glucose level in this
of many genes involved in metabolism. case are not in keeping with diabetic ketosis. 1
Thiazolidinediones enhance the action of The history here suggests vomiting to be the 1
endogenous insulin in the adipose cells but also most likely cause of ketonuria.
alter the release of adipokines, which adjust
insulin sensitivity in the liver. 20.12. Answer: B.
In the UK, according to the Driver and Vehicle
I
20.8. Answer: D. Licensing Agency (DVLA) it is a legal
All incretin-acting drugs have been reported to requirement for people on insulin who drive
be associated with an increased risk of larger vehicles such as buses or heavy goods
pancreatitis. Unlike sulphonylureas they do not vehicles to have an annual examination by a
cause hypoglycaemia as they only promote diabetes specialist along with a review of 3
insulin secretion when there is a glucose months of glucose meter readings. This patient
trigger. Sulphonylureas can lead to weight gain, should keep a record of his blood glucose
as can pioglitazone and insulin, but GLP-1 readings and the team should consider
agonists usually cause weight loss. Pioglitazone advocating a blood glucose meter, which can
is associated with an increased risk of bladder be electronically downloaded to provide this
cancer. SGLT2 inhibitors cause increased data at his annual review.
glycosuria, resulting in genital fungal infections
and increased risk of urine tract infections. 20.13. Answer: C.
Hypertension, NAFLD and
20.9. Answer: D. hypercholesterolaemia are associated with type
Maternal hyperglycaernia .causes fetal 2 diabetes due to insulin resistance. This
hyperglycaemia due to transmission of glucose cluster of conditions has. been termed the
across the placenta. Fetal insulin levels will 'insulin resistance syndrome' ~r 'metabolic
consequently rise. Insulin is a major fetal growth syndrome' and is much more common in
factor, and high levels of fetal insulin therefore obese individuals. Coeliac disease - gluten
trauma may have occurred on his walking descent. The disease is inherited in an
holiday and repeated 'trauma' may have led to autosomal recessive pattern.
bonY destruction. In view of the recent ulcer,
osteomyelitis should be excluded (MRI should 20.21. Answer: B.
be considered), but there is some reassurance GLUT2 is present in renal tubular cells, liver
that the area of ulceration has improved and cells and pancreatic 13 cells. It is a bidirectional
the patient is systemically well. Although he has transporter, allowing glucose to flow in two
been on a flight, he has otherwise been active directions. This is required in pancreatic 13 cells
and has a swollen foot - not calf - making DVT so that the intracellular environment can
less likely. The history is not in keeping with accurately measure the serum glucose levels.
gout or gangrene. GLUT1 is expressed in erythrocytes and in the
endothelial cells of the blood-brain barrier. It is
20.19. Answer: A. responsible for the low level of basal glucose
Microalbuminuria is the presence of small uptake needed to maintain respiration in all
amounts of albumin in the urine at a cells. GLUT3 is mostly expressed in neurons
concentration not detected on standard and in the placenta. GLUT4 is found in adipose
urinalysis. Early morning urine is measured for tissue and striated muscle; it is regulated by
albumin: creatinine ratio. Microalburninuria is insulin and is responsible for insulin-regulated
present if ACR is 2.5-30 rng/mmol creatinine in glucose storage. GLUT5 is a fructose
men and 3.5-30 mg/mrnol creatinine in transporter expressed in enterocytes in the
women. False positives should be excluded small intestine.
and 2 out of 3 samples should be positive to
confirm the diagnosis (ideally an early morning 20.22. Answer: E.
sample on repeat). In the post -prandial period, there are rises in
Microalbuminuria is a good predictor of portal vein glucose and insulin and a fall in
progression to nephropathy in type 1 diabetes. glucagon. The production of glucose in the liver
The presence of established microalbuminuria is suppressed and the uptake of glucose in the
should prompt action to reduce the risk of liver and peripheral tissues is increased. The
progression of nephropathy and of incretin hormones - GLP-1 and gastric
cardiovascular disease. This should be done by inhibitory polypeptide (GIP) -augment insulin
aggressive reduction of blood pressure, secretion following oral glucose delivery.
optimising glycaemic control and cardiovascular
risk reduction. 20.23. Answer: A.
This patient has good glycaernic control The patient most likely has 'stress
and has a healthy BMI with normal level of hyperglycaernia' provoked by acute illness, in
cholesterol. Blood pressure rnay need further this case infection. Underlying impaired
validation in the first instance, but presuming it glycaemic control or diabetes, however, could
is persistently elevated, then it is diagnostic for also be present. A diagnosis of diabetes in the
hypertension and needs lowering for vascular asymptomatic individual requires follow-up
and renal protection. testing of plasma glucose. In this case, the
patient's capillary blood glucose levels should
20.20. Answer: A. be monitored and he ought to have a repeat
The raised ferritin in this case points to a assessment of his plasma glucose when
diagnosis of hereditary haemochromatosis, a recovered from the acute illness.
disease characterised by excessive intestinal
absorption of dietary iron, resulting in a 20.24. Answer: E.
pathological increase in total body iron stores. The only medication listed that may result in
Excess iron accumulates in tissues and organs, hyperglycaernia and the development of
disrupting their normal function. The most drug-induced diabetes is prednisolone, a
susceptible organs include liver, adrenal glands, glucocorticoid. There is a:n increased risk
heart, skin, gonads, joints and pancreas. of developing diabetes while taking
Patients can present with airrhosis, 13-adrenoceptor antagonis.ts (13-blockers) and
polyarthropathy, adrenal failure, heart failure or thiazide diuretics for blood pres~ure control, but
diabetes. The hereditary form is most common not with other antihypertensive agents. Other
in those of Northern European and Celtic groups of patients at risk of developing
patients taking the drug. Only if the problem appropriate antihypertensive agents in this
becomes recurrent or unacceptable to the case. These drugs confer additional benefit
patient is the drug withdrawn. The other drugs beyond simply lower blood pressure - they are
do not cause genitaltract infection but have associated with significantly reduced
their own class-specific side-effects. progression of nephropathy. Patients with
microalbuminuria benefit from aggressive
20.32. Answer: D. lowering of BP (often with multiple agents),
The most likely diagnosis is gastroparesis as a control of cardiovascular risk factors and
manifestation of autonomic dysfunction in optimisation of glycaemic control.
diabetes. An upper gastrointestinal (GI)
tract endoscopy is commonly performed 20.36. Answer: E.
as part of the diagnostic workup, but Features that potentially indicate osteomyelitis
definitive diagnosis is achieved by in the diabetic foot include: dactylitis (marked
demonstrating delayed gastric emptying by swelling of the entire digit), an ulcer that probes
oomtechnetium scintigraphy following a to the depth of bone and evidence of bony
solid-phase meal with imaging over 4 hours. destruction on a plain radiograph (X-ray). X-ray,
The other investigations will not provide a however, may be normal in 50% of cases. MRI
definitive diagnosis. is far more sensitive for osteomyelitis than a
plain X-ray. The presence of oedema, increased
20.33. Answer: B. heat and elevated inflammatory markers may
The most likely diagnosis is coeliac disease, occur in soft tissue infection alone and are not
which is strongly associated with type 1 specific for osteomyelitis. If there is clinical or
diabetes. Up to 1 in 20 people with type 1 radiological evidence of osteomyelitis, the
diabetes go on to develop coeliac disease. patient is typically treated with antibiotics for at
The best screening test for this condition is least 6 weeks.
anti-tTG antibody, which is typically present in
high titre in this condition, with the exception of 20.37. Answer: B.
concurrent immunoglobulin A deficiency. An The clinical scenario presented is that of
upper Gl endoscopy with 02 (second part of pancreatic carcinoma, which may present with
duodenum) biopsy is required to confirm the diabetes as a feature. Pancreatic insufficiency
diagnosis but only after initial anti-tTG testing. may also present with weight loss typically in a
Coeliac disease should be considered in those patient with a history of alcohol excess, but this
who present with weight loss, gastrointestinal condition is not associated with obstructive
symptoms, iron/folate deficiency anaemia, jaundice. This patient is likely to require insulin
infertility, osteoporosis/low bone mineral density therapy to control the osmotic symptoms of his
and malabsorption. diabetes.
E EI-Omar, F Clegg,
MH Mclean
Gastroenterology
Multiple Choice Questions
21.1. A 38 year old woman, para 2+0 consults C. In Europe and North America, most cases
her family physician on account of new-onset are caused by infestation with Trypanosoma
painful mouth ulcers. Which statement about cruzi
mouth ulcers is correct? D. Manometry demonstrates failure of relaxation
A. They are a common feature of inflammatory of the lower oesophageal sphincter on
bowel disease swallowing and absent or weak simultaneous
B. They are malignant in I 0% of cases contractions in the oesophageal body after
C. They are managed with antibiotics in swallowing
recurrent cases E. Peroral endoscopic myotomy (POEM) is the
D. They are more common in pregnancy treatment of choice
E. They are particularly common in patients
with diverticulitis 21.4. A 32 year old man with a body mass
index of 32 kg/m 2 consults his family physician
21.2. A 19 year old female consults her family with a long history of heartburn and frequent
physician with recurrent oral thrush. He takes a use of over-the-counter antacids. The family
detailed clinical history, checks a number of
routine blood tests, offers her advice and starts
physician prescribes a 1-month course of
omeprazole, which cures his symptoms but I
her on an oral medication. Which statement is
correct?
they soon return after stopping the omeprazole.
The family physician refers him for an upper
I
A. Asking about dysphagia is irrelevant because
this is not caused by fungal infections
gastrointestinal (GI) endoscopy, which shows
evidence of a small hiatus hernia and Barrett's
I
B. Oral fluconazole would be an appropriate oesophagus. Which statement is true?
treatment in this case A. Acid is the only refluxate that causes injury to
C. The correct treatment is broad-spectrum the lower oesophageal mucosa
antibiotics B. Gastro-oesophageal reflux disease (GOAD)
D. The doctor should not start any treatment can be reliably diagnosed by symptoms
before confirming the presence of Candida C. Most patients who develop oesophagitis,
albicans on brushings or biopsies Barrett's oesophagus or peptic strictures
E. The oral contraceptive pill is the commonest have a hiatus hernia
cause of oral thrush in young females D. Patients are invariably obese
E. The incidence of GOAD is decreasing in
21.3. Which of the following statements about most populations /
achalasia is correct?
A. Barrett's oesophagus is a common finding 21.5. The patient in OuestiQn 21 .4 returns to his
on endoscopy family physician after the endoscopy with
B. Chest pain and heartburn are the usual considerable anxiety. He was alarmed by the
presenting symptoms mention of 'Barrett's oesophagus' in his
endoscopy report, which his internet search settled on the highest dose of esorneprazole.
classified as a 'pre-malignant' condition. His Although he lives a very healthy lifestyle
maternal uncle died of 'gullet cancer' and he is (non-smoker, no alcohol), he is unwilling to
naturally very concerned about his own risks. abandon his body building and heavy exercise
Which statement about Barrett's oesophagus is regime. Which statement is correct?
correct? A. He should be referred for a POEM because
A. Annual surveillance endoscopy in all patients of his young age
with Barrett's oesophagus is mandatory B. He should be referred for an open 'Heller's
B. Barrett's oesophagus is a condition in which myotomy
the normal columnar mucosa of the lower C. He should be referred for oesophageal
oesophagus is replaced by squamous manometry and 24-hour pH studies with a
mucosa view to laparoscopic fundoplication
C. It is a pre-malignant condition with a D. His medical therapy should be optimised
1000-fold increased relative risk of with the addition of calcium channel
oesophageal cancer but with a lower blockers
absolute risk (5-1 0% per year) E. Long-term use of PPis is not a concern in
D. It is an entirely benign condition and his this young and healthy patient
family physician should reassure him that
it is not associated with oesophageal 21.8. A 56 year old man with no prior history of
cancer GORD presents with progressive dysphagia
E. Treatment of Barrett's oesophagus is only and weight loss of 10 kg over a 3-month
indicated for symptoms of reflux or period. He is a heavy smoker (40 pack years)
complications, such as stricture and consumes on average 40 units of alcohol
per week. He also complains of fits of coughing
21.6. A sprightly 82 year old woman with a past after swallowing. Which statement is correct?
history of a small hiatus hernia is recently A. He is likely suffering from a chronic food
diagnosed with osteoporosis and started on bolus obstruction
appropriate treatment. Three months later she B. He is more likely to have a squamous cell
complains to her family physician during a carcinoma than an oesophageal
routine visit of progressive dysphagia to solids, adenocarcinoma
especially to meat. The family physician notes C. He likely has 'Boerhaave's syndrome' ·
that she has lost 3 kg in weight although she D. He should be referred for an urgent barium
retains a good appetite. She has no other swallow
symptoms and clinical examination is otherwise E. The lack of GORD symptoms excludes
unremarkable. What is the most likely oesophageal adenocarcinoma arising on a
explanation? background of Barrett's oesophagus
A. She has an early oesophageal cancer
B. She has developed eosinophilic oesophagitis, 21.9. Considering oesophageal carcinoma,
a common condition at that age which statement is correct?
C. She has developed the Plummer-Vinson A. Approximately 70% of patients have
syndrome extensive disease at presentation
D. She is developing early dementia and B. Globally, adenocarcinoma is more common
forgetting to eat her meals than squamous cell carcinoma
E. She was started on bisphosphonates for the C. Metastases from oesophageal carcinoma are
osteoporosis usually localised to regional nodes adjacent
to the tumour
21.7. A 28 year old male body builder consults D. Oesophageal adenocarcinoma is particularly
his family physician on account of intractable common in the ?"iddle third of the
heartburn, severe regurgitation and retrosternal/ oesophagus
epigastric pain. An upper Gl endoscopy 2 years E. Risk factors for squamous cell carcinoma
previously confirmed the presence of moderate include achalasia, radiation oesophagitis,
oesophagitis. He had already received multiple caustic oesophageal stricture, Barrett's
courses of different proton pump inhibitors mucosa and Plummer-Vinson (Paterson-
(PPis) in escalating doses and symptoms have Brown-Kelly} syndrome
21.10. A 74 year old man with dysphagia and A. She should arrange for him to have an
weight loss is diagnosed with oesophageal urgent barium meal
adenocarcinoma on upper Gl endoscopy. He B. She should check his H. pylori serology and
has a past medical history of hypertension, start him on eradication therapy if positive.
diet-controlled type 2 diabetes and mild C. She should start him immediately on H.
asthma. Which statement concerning his pylori eradication therapy
investigations and management is correct? D. She should start him on a course of PPis
A. Endoscopic ultrasound (EUS) is particularly and review him in 2 months for repeat blood
useful in assessing distant metastasis tests
B. Invasion of the aorta, major airways or E. She should start him on PPis and refer him
coeliac axis usually precludes surgery for an urgent upper Gl endoscopy
c. Oesophageal adenocarcinoma is very
sensitive to radiotherapy 21.14. The above patient undergoes upper Gl
D. Staging is futile, as his past medical history endoscopy, which shows a 2-cm chronic ulcer
precludes any operative intervention on the lesser curve of the stomach with no
E. The overall 5-year survival of oesophageal stigmata of recent haemorrhage. The rest of
adenocarcinoma is 50% the upper Gl tract is normal. Which statement
regarding his management is the most
21.11. Which statement is true regarding appropriate?
Helicobacter pylori (H. pylori) infection? A. He must have biopsies of the gastric ulcer to
A. Asymptomatic subjects are rarely infected by rule out malignancy and must have a repeat
H. pylori endoscopy 6-8 weeks later to confirm full
B. It is always present in patients with healing after treatment
dyspepsia B. He should avoid eating citrus fruits as these
C. It is always present in patients with peptic may delay healing of peptic ulcers
ulcers C. He should be referred to a surgeon for
D. It is usually acquired during early adulthood consideration of highly selective vagotomy
E. When present, it is always associated with D. He should only have antral biopsies to check
gastritis for presence of H. pylori infection, as gastric
ulcers are usually benign
E. There is no strong indication to stop
-
21.12. A 55 year old man presents with
progressive anorexia, weight loss, diarrhoea, smoking, as this has no impact on healing
nausea and vomiting, and profound peripheral rates
oedema. Blood tests show evidence of
anaemia and hypoalbuminaemia. Upper Gl 21.15. The patient in Question 21 .14 is found to . 'I
endoscopy shows enlarged, nodular and have H. pylori infection. Which statement about
coarse gastric folds. What is the most likely eradication therapy is correct?
diagnosis? A. Erythromycin is the most useful component
A. Classic NSAID gastropathy of eradication regimens
B. Crohn's disease of the stomach B. If first -line eradication therapy fails, the
C. Cronkhite-Canada syndrome same course should be repeated for another
D. Gl manifestations of thyrotoxicosis week
E. Menetrier's disease C. Metronidazole is no longer of benefit in
eradication regimens due to the very high
21.13. A 57 year old man who is a heavy resistance rates
smoker presents to his family physician with D. The inclusion of high-dose, twice-daily PPI
epigastric pain, occasional vomiting, tiredness therapy in eradication regimens increases
and easy fatigability. Clinical examination efficacy of treatment 1 ·
reveals signs of anaemia and epigastric E. The rate of success of eradication therapy is
tenderness but no masses or organomegaly. strongly dependent on the rate of amoxicillin
Routine blood tests confirm mild iron deficiency resistance in the popul?tion
anaemia but no other abnormalities.
Which action by the family physician is the 21.16. A 78 year old woman with osteoarthritis
most appropriate? and long-term indometacin therapy presents as
21.22. Which statement regarding B. Check human leucocyte antigen (HLA) status
gastrointestinal stromal cell tumours (GISTs) C. Commence a gluten-free diet and monitor
is correct? for symptoms
A. They are differentiated from other D. Endoscopy for gastric and jejunal biopsies
mesenchymal tumours by expression of the E. Recheck anti-tTG and lgA on a
c-kit proto-oncogene gluten-containing diet for 7 days
B. They are invariably benign and do not require
any specific management 21.26. Of those listed below, which
c. They are particularly aggressive and require pathophysiological process most likely leads to
resection and treatment with imatinib (a coeliac disease?
tyrosine kinase inhibitor) A. H. pylori colonisation of the small bowel
D. They arise from the interstitial cells of mucosa
Lieberkuhn B. Ingestion of gluten-containing foods in
E. They only bleed if patients also take genetically susceptible individuals leading to
NSAIOs aT-cell-mediated mucosal response in the
small bowel, associated with microbial
21.23. A 23 year old woman presents with dysbiosis
8-month history of bloating, loose stool and C. Ingestion of gluten-containing foods in
bowel-opening frequency of 3 times per day. individuals with HLA-002/008 status
There is no weight loss. Blood tests reveal a D. Ingestion of gluten-containing foods leading
haemoglobin of 108 g/L, a ferritin of 7 11g/L and to microbial dysbiosis and microbial
a folate of 1 11g/L and are otherwise normal. seqretion of short-chain fatty acids
What is the next best investigation? E. Interrupted T-cell tolerance in the colon
A. Abdominal X-ray leading to activation ofTh17 immune cells that
B. Coeliac serology with serum immunoglobulin react with gluten in the proximal small bowel
A(lgA)
C. Colonoscopy 21.27. A 50 year old man presents with
D. Stool calprotectin diarrhoea, low-grade fever and joint pains.
E. Stool culture A colonoscopy is normal. Biopsies from the
terminal ileum reveal the presence of foamy
21.24. A 42 year old man from the Indian macrophages. What is the appropriate
subcontinent presents with right iliac fossa pain management?
~·
that has progressively increased in severity over A. Two weeks of intravenous ceftriaxone, then
the last few months. This is associated with
weight loss and low-grade fever. Blood analysis
oral antibiotics for 1 year
B. Seven days of oral metronidazole . I
reveals alkaline phosphatase (ALP) of 235 U/L C. Intravenous immunoglobulin
and y-glutamyl transferase (GG1) of 120 U/L. D. No treatment is re1 qui red - symptoms
Chest X-ray is normal. usually settle spontaneously
What is the most likely diagnosis? E. Oral omeprazole and restriction of dietary
A. Chronic appendicitis gluten
B. Crohn's disease
C. Human immunodeficiency virus (HIV) 21.28. An 82 year old man presents with
D. Ileocolonic tuberculosis (TB) persistent fresh rectal bleeding on passing
E. Whipple's disease stool. He has a past history of prostate cancer
diagnosed 2 years ago. Flexible sigmoidoscopy
21.25. A 25 year old woman, presents to the reveals a 10-cm segment of mucosal erythema
family physician requesting a test for coeliac associated with an abnormal vessel pattern and
disease as her sister has received a recent no ulceration. What is the most appropriate
diagnosis of this condition. Her blood management?
results show a mildly positive, anti-tissue A. 5-Aminosalicylate suppository
transglutaminase (tTG) with a low serum lgA. B. Endoscopic argon pla:;,ma coagulation
What is the next best investigation? C. Loperamide
A. Check anti-endomysia! antibody (anti-EMA) D. Predfoam enema
and immunoglobulin G (lgG) E. Sucralfate enema
A.
B.
Basal cell carcinoma
Crohn's disease
21.63. A 24 year old man presents with fresh
haematemesis the day after a night of heavy
l
C. Depression alcohol consumption, during which he had a
D. Hepatocellular carcinoma prolonged period of vomiting. Which of the
E. Type 2 diabetes mellitus following statements is correct?
A. A Mallory-Weiss tear never causes significant
21.59. Which of the following is a bleeding
defence mechanism that is unique to the B. In the absence of melaena, upper
stomach? gastrointestinal endoscopy is not indicated
A. Hydrochloric acid secretion C. Results showing urea 6 mmoi/L (36 mg/dl),
B. Immunoglobulins haemoglobin 131 g/L and blood pressure
C. Macrophages 112/65 mmHg mean the patient can be
D. Peyer's patches safely discharged
E. T lymphocytes D. The likely diagnosis is oesophageal varices
E. The majority of cases like this heal
21.60. A female patient with rheumatoid arthritis completely within 2 weeks
presents with dysphagia and is referred for
oesophago-gastroduodenoscopy (OGD). 21.64. A 60 year old with a background of
However, the endoscopist would prefer a non-alcoholic steatohepatitis with cirrhosis
barium swallow as this patient's first presents with fresh haematemesis, melaena
investigation. Of which complication of OGD and collapse. Endoscopy reveals oesophageal
might the patient be particularly at risk given ~;arices as the origin of bleeding. Which of the
her history? following is an appropriate treatment?
A. Acute severe colitis A. Band ligation
B. Atlantoaxial subluxation B. Clip placement
C. Cardiac arrhythmias C. Heater probe coagulation
D. Respiratory distress D. Injection of adrenaline (epinephrine)
E. Small bowel perforation E. Laparotomy
21.61. A 60 year old man presents with a 21.65. A 40 year old man presents with
history of dysphagia. Which of the following diarrhoea, weight loss, night sweats and multiple
features would suggest that the problem enlarged lymph nodes. He has recently had a
originates in the oesophagus? vesicular rash on his right torso. Which one
A. A sticking sensation retrosternally in investigation would give a unifying diagnosis?
response to oral intake A. Coeliac serology
B. Altered voice B. Colonoscopy
C. Drooling C. Faecal calprotectin
D. Nasal regurgitation D. HIV test
E. Symptoms worse with liquids E. Thyroid function tests
21.62. A 29 year patient with type 1 diabetes on 21.66. An individual with coeliac disease is
insulin with poor glycaemic control has a admitted to the high dependency unit with a
6-month history of vomiting around 1 hour pneumococcal bacteraemia. What disease
following food. What is the most likely associated with coeliac disease is likely
diagnosis? responsible?
A. Gastric outlet obstruction A. Primary biliary cirrhosis
B. Gastroparesis B. Sarcoidosis
C. H. pylori infection C. Small bowel lymphoma
D. Medication-induced vomiting D. Splenic atrophy
E. Raised intracranial pressure E. Type 1 diabetes mellitus
Answers
21.1. Answer: A. POEM is a new endoscopic technique that is
The incidence of mouth ulcers is not increased performed in very specialised units and has not
during pregnancy but it is higher in women replaced the more established treatment
prior to menstruation. Although mouth ulcers modalities of pneumatic dilatation, endoscopic
are very common in the general population (up botulinum toxin injection of the lower
to 30%), malignancy is relatively rare. Mouth oesophageal sphincter and surgery (Heller's
ulcers are not related to diverticulitis but they myotomy).
are common in inflammatory bowel diseases
such as Crohn's disease and ulcerative colitis. 21.4. Answer: C.
There is no evidence that antibiotic therapy is Hiatus hernia is very common in GORD and
particularly useful in the management of mouth its complications, and is implicated in the
ulcers but topical (and occasionally oral) pathogenesis of reflux. Symptoms are
glucocorticoids are useful. notoriously misleading in the diagnosis. Acid,
bile and pepsin all cause injury, although acid is
21.2. Answer: B. the main factor. The incidence is rising in most
Dysphagia and odynophagia should always be populations. GORD can occur in very lean
asked about in case there is oesophageal individuals, although it is more common in
candidiasis. There is no convincing evidence overweight and obese individuals.
that the oral contraceptive pill, particularly in
young females, is associated with oral thrush. 21.5. Answer: E.
First -line treatment is with nystatin or Barrett's oesophagus is a pre-malignant
amphotericin suspensions or lozenges. condition in which the normal squamous lining
Resistant cases (as likely in this case with of the lower oesophagus is replaced by
recurrent infection) or immunosuppressed columnar mucosa that may contain areas of
patients may require oral fluconazole. Antibiotic intestinal metaplasia. The relative risk of
use is associated with increased risk of oral oesophageal cancer is 40- to 120-fold
thrush. The diagnosis is largely clinical and increased but the absolute risk is low
treatment could be started on the basis of the (0.1-0.5% per year). Surveillance is expensive
-
history and examination alone. Mycological and cost -effectiveness studies have been
confirmation could be sought in brushings or conflicting, but it is currently recommended that
biopsies but is not usually necessary. patients with Barrett's oesophagus with
21.3. Answer: D.
intestinal metaplasia, but without dysplasia,
should undergo endoscopy at 3- to 5-yearly
.. I
In South America, infestation by the parasite intervals if the length of the Barrettic segment is
T. cruzi causes a condition (Chagas' disease) less than 3 ern and at 2- to 3-yearly intervals if
I
that is clinically indistinguishable from achalasia. the length is greater than 3 em. Those with
In Europe and North America, the cause of low-grade dysplasia should be endoscoped at
achalasia is largely unknown. The commonest 6-rnonthly intervals. Neither potent acid
presenting symptoms are dysphagia, suppression nor anti-reflux surgery stops
regurgitation (indigested food) and weight loss. progression or induces regression of Barrett's
Chest pain is uncommon and heartburn is not oesophagus, and thus treatment is only
a feature, as acid reflux does not occur against indicated for symptoms of reflux or
a closed sphincter. As such, patients do not complications, such as stricture.
develop Barrett's oesophagus. However,
achalasia is regarded as a pre-malignant 21.6. Answer: E.
condition with a small risk of oesophageal Elderly patients generally/have a higher
cancer (squamous cell and adenocarcinoma), prevalence of oesophageal motility disorders
usually after 20 years. The classic manometric that affect swallowing. In this case, she is very
findings of achalasia are failure of relaxation of likely to have been starte.d on bisphosphonates
the lower oesophageal sphincter on swallowing for her osteoporosis. Bisphosphonates cause
and absent or weak simultaneous contractions oesophageal ulceration and should be used
in the oesophageal body after swallowing. with caution in patients with known
21.9. Answer: A.
I I
oesophageal disorders. Patients should be
clearly instructed to always take their dose with The majority of oesophageal cancers worldwide
a full glass of water on an empty stomach, and are squamous cell carcinomas, but the
to stand or sit upright for at least 30 minutes incidence of adenocarcinoma in Western
after taking the dose. Eosinophilic oesophagitis countries now exceeds that of squamous
is much more common in children. This patient carcinoma. Unfortunately, oesophageal cancer
is less likely to have a cancer as she retains presents late and 70% of patients present with
her appetite and general well-being. The extensive and inoperable disease. All of the
Plummer-Vinson syndrome is a rare disease listed risk factors are pre-malignant lesions but
characterised by dysphagia, iron deficiency Barrett's metaplasia is associated with the
anaemia, angular stomatitis, atrophic glossitis, development of adenocarcinoma, not
cheilosis and oesophageal webs. She had none squamous carcinoma. Squamous carcinoma
of these features on clinical examination. can occur in any part of the oesophagus, and
almost all tumours in the upper oesophagus
21.7. Answer: C. are squamous cancers. Adenocarcinomas
Long-term PPI therapy is associated with typically arise in the lower third of the
reduced absorption of iron, vitamin B1 2 and oesophagus from Barrett's oesophagus or from
magnesium. The drugs also predispose to the cardia of the stomach. Oesophageal cancer
enteric infections with Salmonella, is very aggressive, invading locally and
Campylobacter and possibly Clostridium difficile metastasising to local and distant sites quite
and have recently been shown to have an early.
undesirable impact on the composition of the
gut microbiota. Heller's myotomy and POEM 21.10. Answer: B.
are procedures for treatment of achalasia not His past medical history is not unusual and
GORD. In this young and healthy patient, does not preclude surgical intervention. The
medical therapy has clearly failed and he patient should undergo extensive staging with
requires laparoscopic anti-reflux surgery. Some thoracic and abdominal CT, often combined
calcium channel blockers relax the lower with positron emission tomography (CT-PET).
oesophageal sphincter and can cause reflux This will identify metastatic spread and local
and heartburn. invasion. Patients with resectable disease o.n
imaging should undergo endoscopic ultrasound
21.8. Answer: B. (EUS) to determine the depth of penetration of
The diagnosis here is strongly in favour of a the tumour into the oesophageal wall and to
malignant oesophageal stricture. With such a detect locoregional lymph node involvement.
presentation, he should be referred for an EUS is clearly not suitable for assessing distant
urgent upper Gl endoscopy with biopsies in the metastasis. The overall 5-year survival of
first instance. Barium swallow demonstrates the oesophageal cancer is very poor (< 15%).
site and length of the stricture but adds little Squamous carcinoma is sensitive to
useful information. Food bolus obstruction radiotherapy, unlike adenocarcinoma, although
presents acutely and is an endoscopic radiotherapy could be used to palliate
emergency. Lack of GORD symptoms is obstructing tumours of both varieties.
frequently noted in patients who present with
oesophageal adenocarcinoma and Barrett's 21.11. Answer: E.
oesophagus, although GORD is a strong risk H. pylori is usually acquired during childhood;
factor for both. In this case, the combination of acquisition in adults is rare. Dyspeptic patients
lack of GORD symptoms, heavy smoking and have a higher prevalence of H. pylori compared
alcohol consumption favour a diagnosis of to asymptomatic subjects but many patients
oesophageal squamous cell cancer. with dyspepsia do not have the infection.
Boerhaave's syndrome is spontaneous Around 90% of duodenal ulcer patients and
oesophageal perforation that results from 70% of gastric ulcer patients are infected with
forceful vomiting and retching. In this case, the H. pylori. The remaining 30% of gastric ulcers
fits of coughing on swallowing are likely caused are caused by non-steroidal anti-inflammatory
by a fistula between the oesophagus and the drugs (NSAIDs)/aspirin. There are also more
trachea or bronchial tree. Fistulation can also rare causes of ulcers such as Zollinger-EIIison
lead to pneumonia and pleural effusion. syndrome and gastroduodenal Crohn's
disease. Half of the world's population is perforation. Once a peptic ulcer forms, it is
infected with H pylori and the majority are more likely to cause complications and less
asymptomatic. The hallmark of H pylori likely to heal if the patient continues to smoke.
infection is the induction of gastritis, which is There is no specific dietary advice and citrus
the pathognomonic histological consequence of fruits have no relevance in this situation.
the infection. This histological gastritis may or
may not be endoscopically visible and may or 21.15. Answer: D.
may not cause symptoms. The rate of success of treatment is dependent
on several factors, including medication
21.12. Answer: E. adherence and antibiotic resistance. The most
These features are very consistent with important is resistance to clarithromycin.
Menetrier's disease, which is a rare condition of Amoxicillin resistance is very rare. Treatment is
unknown aetiology characterised by excessive based on a PPI taken simultaneously with two
production of transforming growth factor-alpha antibiotics (from amoxicillin, clarithromycin and
(TGF-a). As a result, the mucosal folds of the metronidazole) for at least 7 days. High-dose,
body and fundus are greatly enlarged. Whilst twice-daily PPI therapy increases efficacy of
some patients have upper gastrointestinal treatment, as does extending treatment to
symptoms, the majority present in middle or old 10-14 days. Metronidazole is still useful in
age with protein-losing enteropathy due to eradication regimens because in vitro
exudation from the gastric mucosa. Endoscopy resistance to the antibiotic could be overcome
shows enlarged, nodular and coarse folds. in· vivo by combination with other effective
Crohn's disease of the stomach usually antibiotics, especially clarithromycin. If the
presents with deep ulcers. Hyperthyroidism is first -line therapy fails, the same course should
associated with gastrointestinal symptoms but not be repeated but quadruple therapy,
does not usually cause any endoscopic consisting of a PPI, bismuth subcitrate,
feature,s. Cronkhite-Canada syndrome may metronidazole and tetracycline (OBMT) for
present with generalised gastrointestinal polyps, 10-14 days, is recommended. Erythromycin is
cutaneous pigmentation, alopecia and never used in eradication regimens but
onychodystrophy. NSAID gastropathy presents clarithromycin, another macrolide, is one of the
with gastritis, erosions or single/multiple most effective in use.
superficial ulcers.
21.16. Answer: D.
21.13. Answer: E. She has a high urea but her creatinine level is
This patient clearly requires urgent upper Gl within the upper range of normal for women.
endoscopy to rule out significant pathology, NSAIDs cause renal damage but the most
particularly gastric neoplasia. The absence of serious abnormality in this case is the
weight loss and persistent vomiting is suspected Gl bleed. A silent myocardial
reassuring but the presence of anaemia is infarction is a possible complication of an acute
alarming and should trigger urgent referral for and significant Gl bleed but it is not the most
endoscopy. Barium meal is rarely used. The likely diagnosis here. NSAIDs cause ulceration
other options are inappropriate because urgent throughout the Gl tract but lesions that bleed
endoscopy is mandatory in this situation and are most likely in the upper part, including
over-rides the other suggestions. gastric and duodenal ulcers. Melaena (black
tarry stool) is characteristic of an upper Gl
21.14. Answer: A. bleed. Lower Gl bleeds present with fresh
Gastric ulcers may occasionally be malignant blood. Dieulafoy lesions are rare causes of
and therefore must always be biopsied and upper Gl bleeding and are caused by a single
followed up to ensure healing. He should, of tortuous small artery in the submucosa that
course, have antral biopsies to check for H may erode through the mucosa and cause
pylori and this should be eradicated if positive, significant bleeding. These lesions are
but he should also have the ulcer edge diagnosed endoscopically.
biopsied. Surgery is no longer an option in the
management of peptic ulcer 'disease unless 21.17. Answer: B.
there are severe complications such as gastric This patient is clearly haemodynamically
outlet obstruction, uncontrollable bleeding or compromised and in shock. The most
·~~'"""""""'""'''""."'~
~
Unrelaledtolnftamm"'oty
lnflammat~ .. bowe]dlsenoeactlvily
21.28. Answer: E. ~~~
Conjun~m:
-;;'k
<
The diagnosis is radiation proctitis. This Eplscl..rtll:3~
Mouthulce!S {- - _,, __ _
Jwloimmunehepatitls
~I
are ineffective. Endoscopic argon plasma
coagulation (APC) can be used for acute
bleeding but can increase risk of fistula
large·joinlarlhrilis
formation with repeated use. Evidence
suggests sucralfate enema is the best Erylhemanodosum
Pyodermogangrenosum
treatment and, if this fails, hyperbaric oxygen
therapy should be considered.
Fig. 21.31 Systemic complications of inflammatory bowel
disease.
21.29. Answer: D.
All these investigations can be considered in
this patient. Given the colour and consistency
of stool and previous cholecystectomy, the 21.32. Answer: B.
most likely diagnosis is bile acid malabsorption; Intravenous glucocorticoid therapy is indicated
therefore a radionuclide SeHCAT scan is the in this case of acute severe ulcerative colitis
correct answer in this scenario. (>6 bloody stools/24 hrs, raised CRP). Current
guidelines suggest revie';Y' at day 3 and then
21.30. Answer: C. day 5 for clinical and biochemical response. If
There is no evidence for use of antibiotics. non-response, rescue medical therapies with
Immunoglobulin is used for chronic Giardia anti-TNF biological therapy or ciclosporin can
infection associated with immunoglobulin be considered. Alternatively, nQn-response to
deficiency. Options B, C and E (all intravenous {IV) steroid therapy ± rescue
immunosuppressants) can be used in Grahn's medical therapies require a surgical review for
consideration of subtotal colectomy and from these cells. Grahn's disease can affect the
ileostomy. LMWH is required as these patients whole gastrointestinal tract and is associated
are at increased risk of thrombosis. Loperamide with a predominant Th1 adaptive response and
may precipitate toxic megacolon. There is no ulcerative colitis is associated with a Th2
evidence for antibiotic therapy. Vedolizumab response. There is ongoing research into the
(anti-a4~7 integrin biological therapy) can be pathogenesis of IBD, including alterations in the
considered for maintenance treatment of IBD; oral microbiome and the role of specific
it has a long onset of action and therefore has bacteria, including E. coli.
no role in the management of acute severe
colitis. 21.36. Answer: B.
The distribution and histology features of the
21.33. Answer: B. inflammation are in keeping with ulcerative
A complication of acute severe IBD is colitis. In mild disease, a high-dose oral 5-ASA
thrombosis. This presentation and clinical is appropriate first-line therapy, reducing to a
status suggest a pulmonary embolus and maintenance dose when symptoms are under
therefore CTPA is most likely to lead to control. If symptoms do not settle, then
the diagnosis. Whilst some of the other addition of topical (enema) treatment with either
investigations may be appropriate in the acute 5-ASA or steroid, or a course of oral
scenario, they will not necessarily lead to the glucocorticoids, can be considered. Anti-TNF
diagnosis. therapy is a treatment for moderate to severe
ulcerative colitis, refractory to other
21.34. Answer: C. i;nmunosuppression including thiopurines (such
Regular blood monitoring is required to assess as azathioprine). Clinical trial data suggest that
for bone marrow suppression and liver ustekinumab may be a new treatment choice in
dysfunction. The interval between blood severe Grahn's disease but it is still in
analysis increases as time passes from development and is not yet used as a standard
induction. Very rarely, azathioprine can cause of care.
acute pancreatitis; amylase should be tested
if a patient presents with acute abdominal 21.37. Answer: E.
pain and vomiting soon after starting this This patient's symptoms are consistent with
medication. If a patient is stable on active small bowel Grahn's disease with
azathioprine, advice is to continue throughout subacute obstruction precipitated by eating and
pregnancy, as risk of teratogenicity is very low he needs investigation to assess disease
and a greater risk is uncontrolled IBD. activity and presence of stricturing. MRI
The side-effects of thiopurines include a enterography is a sensitive modality to assess
small increased risk of malignancy with mucosal inflammation and calibre of small
extended use, particularly lymphoma and bowel lumen. A small bowel barium meal and
non-melanoma skin cancer. A chest X-ray and follow through will also show this information
hepatitis serology should be checked prior to but is less sensitive than MRI and exposes this
anti-TNF biological therapy to avoid reactivation young patient to ionising radiation. A capsule
of latent TB or worsening of hepatitis B/C enteroscopy is contraindicated here, given
infection. suspicion of stricturing with risk of impaction.
Small bowel disease is suspected in this case
21.35. Answer: E. and a barium enema would assess the colon. If
The pathogenesis of IBD is complex and colonic investigation is required, a colonoscopy
involves breakdown of the epithelial barrier and would be first choice in a patient of this age.
disordered mucosal immune responses, Stool calprotectin would likely be high, in
associated with microbial dysbiosis in keeping with intestina,l inflammation, but would
genetically susceptible individuals. not give additional jriformation on structural
Genome-wide association studies have aspects of disease activity.
identified multiple polymorphisms in genes,
including cytokine genes, but there. is no one 21.38. Answer: D. •
somatic mutation driver gene identified. The This woman is likely to have damage to the
immune response involves both innate and pelvic floor/anal sphincter from previous
adaptive aspects and the cytokines secreted childbirth. Exercises to strengthen the pelvic
floor along with biofeedback techniques to financial income to support her child and this
regulate bowel-opening pattern is the first may be impacting on these symptoms. In a
treatment to try. If unsuccessful, sacral nerve patient of this age, the main diagnostic
stimulators can be considered and some considerations are IBS and lBO. CRP and
patients require defunctioning colostomy. Botox platelet count may be elevated in the latter
injection and topical diltiazern cream are used but not always. A stool calprotectin is a
for relaxation of the anal sphincter to treat anal more sensitive marker of gastrointestinal
fissure. inflammation in this scenario to guide need for
further investigation and appropriate treatment.
21.39. Answer: B. Coeliac serology is negative, so there is
In a patient of this age with 'red flag' symptoms no indication for proceeding tci duodenal
of change in bowel-opening habit to loose stool biopsy.
and iron deficiency anaemia, the suspicion is
colorectal cancer and therefore colonoscopy is 21.43. Answer: E.
the best next investigation. CT scan will detect There is no evidence for the use of
large mass lesions and metastatic disease but benzodiazepines for IBS. An appropriate
is not sensitive for smaller localised mucosal next-line treatment would be a low-dose
lesions. Colonoscopy allows biopsies to be nocturnal tricyclic antidepressant such as
taken for histological analysis. amitriptyline. There is no evidence for the use
of probiotics. Peppermint capsules can often
21.40. Answer: B. help with bloating and flatus in IBS patients.
Most colorectal cancer is sporadic with no Prucalopride is used as a treatment in
identifiable genetic predisposition. Most constipation-predominant IBS that has
sporadic colorectal cancer arises from a benign failed to respond to laxative therapy. There
pre-malignant adenoma (polyp). Aetiology is is emerging evidence that a low-FODMAP
multifactorial, involving genetic and diet is effective in the treatment of IBS. This
environmental risk factors. The genetic risk should be supervised by a dietician and is
factors include acquired mutations of somatic initially very restrictive, with gradual
genes such as APC, TP53 and SMAD4, and reintroduction of food groups dependent on
these tend to occur sequentially over time, with symptom response.
APC mutations an early feature and TP53 a late
-
feature. Epigenetic changes can also lead to 21.44. Answer: C.
altered gene expression. These genetic Protein, fat and folic acid absorption occur in
changes are not mutually exclusive - not all the small bowel. The colonic luminal pH is
individuals with these mutations develop
colorectal cancer and not all colorectal
mildly acidic to neutral (5.5-7). The colonic
rnicrobiota is acquired at birth, matures to that
. !
tumours will contain all of these genetic
mutations. Approximately 5% of colorectal
of an adult by the age of 3 years and changes
over time as a natural part of ageing in the
I
cancers are attributable to genetic syndromes, elderly years. It can also change in relation to
the most common being FAP and environmental alterations such as use of
HNPCC. antibiotics. The colon acts to absorb water and
electrolytes from stool.
21.41. Answer: C.
Often patients with bacterial overgrowth are 21.45. Answer: E.
anaemic with a macrocytosis •and low vitamin The pancreatic body and tail receive supply
8,2 due to bacterial utilisation of the vitamin B 12 from the splenic artery derived from the coeliac
in the gastrointestinal lumen.· The other answers artery. The head of pancreas received supply
are not findings you would expect with this from the inferior pancreaticoduodenal artery
diagnosis. derived from the superio.~ mesenteric artery
(SMA). The SMA also supplies the ileum,
21.42. Answer: D. alongside jejunum, ascending and transverse
The history is consistent with irritable bowel colon. The left kidney is :;jupplied by the renal
syndrome (IBS). It is important to explore social artery, ovaries by the gonadal artery, the
history. She is experiencing stress in her life sigmoid colon by the inferior mesenteric artery
with regard to employment and worry of loss of and the psoas muscle by the lumbar arteries.
242 • GASTROENTEROLOGY
c: 21.56. Answer: E.
21.53B Features that predict severe pancreatitis
In any young female, it is essential to consider
Initial assessment
pregnancy as a cause of abdominal symptoms
Clinical impression of severity
or vomiting. This will dictate what further
Body mass index > 30 kg/m 2
Pleural effusion on chest X-ray investigations and medications can be given
APACHE II score > 8 safely.
24 hours after admission
Clinical impression of severity 21.57. Answer: A.
APACHE II score > 8 The removal of a large portion of the stomach
Glasgow score > 3
Persisting organ failure, especially if multiple leads to a significant reduction in chief cells
CRP > 150 mg/L responsible for production of intrinsic factor,
48 hours after admission required to absorb vitamin B12 in the terminal
Clinical impression of severity ileum. They also have a role in pepsinogen
Glasgow score > 3 production, although protein absorption tends
CRP > 150 mg/L
to be affected less.
Persisting organ failure for 48 hours
Multiple or progressive organ failure
21.58. Answer: A.
(CRP = C-reactive protein)
Basal cell carcinoma has not been
demonstrated to be associated with the
intestinal microbiome. All the others have been
shown to be associated with dysbiosis.
Hepatology
22.7. A 35 year old man is being considered 22.11. A 25 year old wornan with
for liver transplantation. Which of the following well-controlled, non-cirrhotic AIH attends your
is true? clinic to say she is pregnant. She is currently
A. Acute cellular rejection most commonly maintained on azathioprine monotherapy. What
occurs between days 2 and 5 advice would you give her?
B. At least partial human leucocyte antigen A. Disease flare-ups can occur following
(HLA) matching is essential for a good delivery
outcome B. Her child runs a significant risk of developing
C. Hepatorenal failure will typically improve AIH
following liver transplantation C. Her disease will deteriorate during pregnancy
D. Immunosuppression can be safely stopped D. She should immediately swap to MMF
in most patients at 5 years maintenance therapy
E. Mycophenolate mofetil (MMF) monotherapy E. She should undergo endoscopy
is a useful immunosuppression regime
22.12. A 53 year old man with known
22.8. A 42 year old man is in hospital with acute oesophageal varies presents with a large
liver failure. The team are considering his gastrointestinal (GI) bleed. You are the first
prognosis. In this situation, which of the attending clinician. What is the first step you
following liver functions, when deranged, has should take?
an important impact on outcome? A. Alert interventional radiology in case
A. Glucose regulation transjugular intrahepatic portosystemic stent
B. Innate immune response shunt (TIPSS) is required
C. Oxalate metabolism B. Arrange urgent cross-match
D. Red cell breakdown C. Arrange urgent endoscopy and banding
E. Steroid hormone clearance D. Insert large-bore cannula and give fluid
E. Organise bedside ultrasound to assess for
22.9. A 28 year old woman presents to her portal vein thrombosis
family physician with fatigue and itch. She has
obstructive LFTs. Which of the following is true 22.13. A patient with suspected variceal
about the autoimmune cholestatic liver disease bleeding cannot have an endoscopy because
primary biliary cholangitis? of lack of an available trained endoscopist. She
A. It is a different condition to primary biliary is becoming increasingly unstable. Which of
the following is a medical therapy appropriate
cirrhosis
B. It is commoner in men than in women for use in the first instance to establish
C. Patients usually show elevation of PT haemodynamic control?
D. The disease is more aggressive in younger A. Glypressin
patients B. Noradrenaline (norephinephrine)
E. Ursodeoxycholic acid (UDCA) is first-line C. Propranolol
therapy and should be used once the patient D. Subcutaneous octreotide
is symptomatic E. Tranexarnic acid'
22.10. A 20 year old student with no significant 22.14. A computed tomography (CT) scan
past medical history presents with a 1-week performed in a patient with chronic liver disease
history of acute lethargy and jaundice 2 weeks has identified a mass lesion suspicious of a
after returning from a week-long holiday in hepatocellular carcinoma. What is the next
Turkey. His alanine aminotransferase (AL1) is investigation you should consider?
A. A magnetic resonance imaging (MRI) scan suspected that he has primary sclerosing
B. Blood alpha-fetoprotein (AFP) measurement cholangitis. Which of the following statements
G. Laparoscopy about diagnosis and treatment is correct?
D. Liver biopsy A. First-line imaging technique for the bile ducts
E. Positron emission tomography (PEl} scan is endoscopic retrograde
cholangiopancreatography (ERCP)
22.15. A 45 year old woman presents with B. HCC is the characteristic complication
painful hepatomegaly and ascites. What G. The diagnosis is unlikely as the patient is
imaging findings would you predict when male
investigating? D. There is no proven therapy able to improve
A. An irregular liver on CT prognosis
B. Hepatic artery thrombosis E. UDCA is proven to reduce mortality
G. Hepatic venous thrombosis on triple-phase
CT 22.20. A 60 year old woman is being treated for
D. Isolated gastric varies cellulitis and has developed abnormal LFTs.
E. Reversal of portal blood flow on ultrasound Her family physician calls you for advice as she
suspects that the patient has flucloxacillin-
22.16. Twenty-four hours following liver induced liver injury. Which of the following
transplantation for autoimmune hepatitis, a statements is correct?
patient's ALT is climbing rapidly. What A. Characteristic blood test abnormalities are
diagnosis is the most likely? elevation in ALT and eosinophil count
A. Acute cellular rejection B. Loss of the small intrahepatic bile ducts can
B. Cytomegalovirus (CMV) infection occur
G. Delayed graft function G. Glucocorticoid therapy increases speed of
D. Hepatic artery thrombosis recovery
E. Recurrent AIH D. The patient is safe to take the drug again in
the future as the risk falls with repeat
22.17. A patient with primary biliary cholangitis exposure
is concerned about the prognosis of her E. The patient should avoid all penicillin-based
disease. Which of the following is predictive of drugs in the future
a poor outcome?
A. Alkaline phosphatase (ALP) level 22.21 An 18 year old medical student has his
B. AMA titre hepatitis B and C status checked as part of his
G. Large liver size on ultrasound occupational health screening for entrance to
D. Older age at disease onset medical school. His results are as follows:
LFTs:
~-
E. Presence of intercurrent autoimmune disease
Bilirubin 12 J.lmoi/L (0. 70 mg/dl) 1
22.18. A 38 year old woman presents in the ALT 19 U/L
third trimester of pregnancy with itch. She is HCV antibody not detected
found to have a rise in liver enzymes and serum Hepatitis B surface antigen (HBsAg) positive
bile acids. Which of the following statements is Antibody to HBsAg (anti-HBs) negative
correct? Antibody to hepatitis B core antigen
(anti-HBc) lgM negative
A. Acute viral hepatitis is a likely cause
Anti-HBc lgG positive
B. Fatty liver of pregnancy is the most likely
What is the next step in his management?
diagnosis
G. It is likely that the mother has underlying A. Check hepatitis B e antigen (HBeAg) and
chronic liver disease HBV DNA
D. There is a risk of intrauterine fetal death, B. Liver biopsy .
meaning that consideration should be given G. Repeat blood tests in '6 months
to early delivery D. Tenofovir
E. There is no effective drug treatment E. Vaccinate for hepatitis .B
22.19. A 76 year old man is referred to the 21.22. A 42 year old female with a new
outpatient clinic. His family physician has diagnosis of chronic hepatitis B has recently
_____________ ______________________
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from www.medicalbr.com
248 • HEPATOLOGY
adult member of staff) has been identified as 22.30. A 62 year old male with cirrhosis from
unwell or an index case. What advice do you non-alcoholic fatty liver disease (NAFLD)
give to her? undergoes 6-monthly ultrasound for Hee
A. Everyone in her primary school should be surveillance and AFP. His AFP is normal but
vaccinated ultrasound shows a 3.5-cm lesion in the liver.
B. Good hygiene practice is the cornerstone of What is the next appropriate management
prevention step?
c. HAVis not highly infectious A. earcinoembryonic antigen
D. Infected individuals will always have B. PET scan
symptoms C. Repeat ultrasound liver by consultant
E. There is a risk of becoming a chronic carrier radiologist
D. Repeat ultrasound liver in 3 months
22.28. A 49 year old male with chronic hepatitis E. Triple-phase eT scan
B who has cirrhosis and developed
hepatocellular carcinoma has a liver transplant. 22.31. A 52 year old male is referred to
What treatment should be prescribed in the hepatology clinic due to an abnormal
post-operative period? ultrasound scan. He was originally referred to
A. Hepatitis B immunoglobulin haematology to be investigated for
B. Hepatitis B immunoglobulin and oral thrombocytopenia. He has a past medical
nucleoside history of type 2 diabetes, hypertension and
C. Hepatitis B vaccjnation body mass index (BMI) 33 kg/m 2 . He has mildly
D. Interferon-alta deranged LFTs (which prompted the ultrasound
E. Ribavirin scan request). Below are his results from clinic:
Full blood count:
Haemoglobin 106 g/L
22.29. A 79 year old male is admitted to the
wee 5.3x109/L
emergency department with rigors and
Platelets 89 x 109 /L
abdominal pain. He has a past medical history
LFTs:
of hypertension with no history of travel abroad.
Bilirubin 33 11moi/L (1.93 mg/dL)
On examination he is febrile with a temperature
ALT 54 U/L
of 40oe and tachycardic. He is tender in the
ALP 72 U/L
right upper quadrant but without guarding or
AFP 892 kU/L
rebound.
Ultrasound: 5-cm lesion in liver. Liver is
His inflammatory markers are raised with
shrunken and nodular. Further imaging is
wee 24x 109/L and e-reactive protein (eRP) of
requested.
300 mg/L. He has deranged LFTs with bilirubin
What is the likely description of the lesion on
64 11moi/L (3.74 mg/dL), ALT 74 U/L, ALP
a eT scan?
320 U/L. A liver screen was sent. An
ultmsound abdomen showed three cystic A. Enhances in arterial phase with portal venous
lesions in the right lobe of the liver with a washout
dilated common bile duct and associated filling B. Fluid-filled cystic lesion
defect suggestive of gallstones and inflamed C. Focal central scar
gallbladder. D. Low-density lesion with delayed arterial filling
Intravenous antibiotics and fluids are started. E. Thick-walled cyst with calcification
Stool microscopy for ova/cysts and parasites
was negative. Blood cultures were positive for 22.32. A 37 year old female presents to the
Escherichia coli and subsequent aspirate emergency department with colicky right upper
of cyst was positive for the same bacteria. quadrant pain and nausea. This is her fourth
Which of the following is the most likely presentation in 6 months. Ultrasound confirms
diagnosis? gallstones and she is referred to the surgeons
A. Amoebic liver abscess for elective cholecystectomy. Which of the
B. Hepatocellular carcinoma following dietary recomme.ndations do you
C. Hydatid cyst advise her to adopt?
D. Polycystic liver disease A. Fermentable, oligo-, di-, monosaccharides
E. Pyogenic liver abscess and polyols (FODMAP) diet
pale stool. On examination she is jaundiced 22.41. A patient has suspected NAFLD. Which
with hepatomegaly and moderate-volume of the following statements about diagnosis
ascites. and treatment is correct?
LFTs: A. Statins should be discontinued due to the
Bilirubin 240 ~-tmoi/L (14.03 mg/dl) risk of drug-induced liver injury
ALT 84 U/L B. Testing for the PNPLA3 rs738409 genetic
ALP 1400 U/L variant is part of the routine clinical testing of
Albumin 31 g/L patients
Carcinoembryonic antigen (CEA) 230 ~-tg/L C. The FIB-4 Score distinguishes between
Ascitic fluid: blood-stained alcoholic liver disease and NAFLD
Ultrasound: multiple liver lesions compressing D. The presence of individual features of the
bile ducts metabolic syndrome should be sought and
Which of the following is the most likely treated to reduce cardiovascular risk
diagnosis? E. Venesection should be commenced
A. Cholangiocarcinoma immediately if ferritin levels are raised, as this
B. Colorectal cancer indicates haemochromatosis
C. Focal nodular hyperplasia
D. Hepatic adenoma 22.42. A 57 year old man is admitted with
E. HCC presumed alcoholic hepatitis. Which of the
following statements about diagnosis and
22.39. A hospital porter is seen in the treatment is correct?
occupational health clinic following a A. A 1\(laddrey 'discriminate function' of less
needlestick injury. Investigations taken in the than 32 is indicative of a poor prognosis
clinic show that the patient is HBsAg negative, B. Alcohol consumption may safely continue
anti-HBc negative and anti-HBs positive. What C. Patients should be fasted to avoid stressing
is the correct interpretation of these results? the liver
A. Acute infection with hepatitis B D. The Steroids or Pentoxifylline for Alcoholic
B. Chronic dual infection with hepatitis B and Hepatitis (STOPAH) trial showed that
delta virus pentoxyfilline should be the first -line
C. Chronic mono-infection with hepatitis B treatment for alcoholic hepatitis
D. Previous immunisation against hepatitis B E. The STOPAH trial showed that prednisolone
without prior infection 40 mg daily for 28 days leads to a modest
E. Previous infection to hepatitis B but the reduction in short-term mortality
patient has cleared the virus
22.43. A 54 year old male patient with
22.40. When assessing the severity of NAFLD in alcohol-related cirrhosis is admitted with a
an overweight 65 year old type 2 diabetic 3-week history of increasing abdominal swelling
patient with hypertension, which of the and discomfort. He is mildly jaundiced and has
following statements is correct? a low-grade pyrexia but is haemodynamically
stable. Routine blood tests and a chest X-ray
A. A normal ALT level indicates that the disease
have been requested. What test would you
is mild and that there is unlikely to be
perform next?
significant scarring of the 'liver
B. A raised y-glutamyl transferase (GGT) A. Diagnostic paracentesis
indicates that the patient is probably B. Electroencephalogram
dependent on alcohol C. ERCP
C. The AST: ALT ratio is a useful indicator D. Triple-phase CT liver
of progressive liver fibrosis towards E. Upper Gl endoscopy
cirrhosis
D. The presence of obesity; hypertension and 22.44. An otherwise healthy 35 year old nurse
type 2 diabetes is not associated with a and part -time tattoo artist is referred with a
greater likelihood of steatohepatitis and liver persistent, fluctuating tral'!saminitis (ALT
fibrosis 40-120 U/L) that has been present for several
E. The use of routine ultrasound can distinguish years. What viral infection would you consider
between simple steatosis and steatohepatitis most likely?
A. Epstein-Barr virus (EBV) 22.48. A 48 year old male has recently been
B. Hepatitis A diagnosed with hemochromatosis with
C. Hepatitis B homozygous mutation of the HFE C282Y gene.
D. Hepatitis C His blood tests show a ferritin of 1950 11g/L
E. Hepatitis E and a transferrin saturation of 88%. What
treatment would be the most appropriate to
22.45. A 38-year old man is referred by his commence?
family physician to the outpatient clinic. His A. Ferrous sulphate 200 mg 3 times daily
father had haemochromatosis and he is about B. Fortnightly venesection
to get married, so he is wondering whether he C. Propranolol 20 mg 3 times daily
is likely to be affected. What would be the best D. Spironolactone I 00 mg once daily
first -line screening test in this case? E. Vitamin C supplement twice daily
A. CT liver
B. Ferritin 22.49. A patient with NAFLD cirrhosis
C. HFE genetic analysis undergoes screening upper endoscopy and is
D. Liver biopsy noted to have moderate (grade 2} oesophageal
E. Transferrin saturation varices with no signs of recent bleeding. What
would be the best next step?
22.46. A 45 year old woman presents with a A. Admit for TIPSS placement
5-day history of pale stools and dark urine B. Admit to intensive care unit and place
associated with cramping epigastric and right Sengstaken-Biakemore tube immediately
upper quadrant pains. Blood tests show C. Repeat upper Gl endoscopy in 6 months
bilirubin 120 11moi/L (7.02 mg/dl}, ALT 65 U/L, D. Start non-selective ~-blocker (propranolol
ALP 580 U/L, GGT 640 U/L. What would be 20 mg 3 times daily}
your first-line imaging investigation? E. Variceal banding
A. CT pancreas
B. Endoscopic ultrasound 22.50. A 53 year old bank employee in the UK
C. ERCP is found at a routine check-up to have
D. PET-CT abnormal LFTs. What is the most common
E. Ultrasound abdomen aetiology for abnormal liver biochemistry in
developed countries?
22.47. A 54 year old man with alcoholic A. Alcoholic liver disease
cirrhosis presents with haematemesis. The B. Autoimmune hepatitis
patient is commenced on terlipressin and C. Hepatitis C
emergency upper Gl endoscopy is performed, D. NAFLD
which demonstrates large oesophageal varices E. Primary biliary cholangitis
with active bleeding. The varices are banded
with good haemostatic effect. What medicine 22.51. A 60 year old man is found to have
would you start as secondary prophylaxis to hepatitis C and undergoes a liver biopsy that
reduce the chance of further variceal confirms stage 4 fibrosis (cirrhosis). He is
haemorrhage in the future? asymptomatic and subsequently receives
A. Atenolol antiviral therapy and successfully clears the
B. lsosorbide mononitrate virus (a sustained viral response). What further
C. Losartan test will he need?
D. Propranolol A. Cardiac angiogram
E. Ramipril B. Chest X-ray
C. Electrocardiogram (ECG)
D. HCV RNA annually to check for recurrence
E. Ultrasound every 6 months as part of routine
HCC surveillance
Answers
22.1. Answer: C. again not have an obstructive pattern.
The liver has significant regenerative capacity, Autoimmune hepatitis causes hepatocellular
with stem cells within the canals of Hering jaundice in aggressive forms, but not
playing a key role. This regenerative capacity obstructive jaundice. Hypothyroidism can cause
plays an important role in recovery from liver skin pigmentation that can be mistaken for .
failure and from liver resection. It also jaundice (although characteristically the sclerae
contributes to the phenotype of cirrhosis. The remain normal colour, in contrast to jaundice
liver is on the right side of the upper abdomen where yellowing is characteristic).
crossing the midline and weighs 1-2 kg,
depending on body size. Although drawings 22.4. Answer: E.
can give the impression that the liver lobule is Pancreatitis can be a rare complication of
encapsulated, this is not the case in humans paracetamol overdose and typically has a very
(although it is in pigs). The portal tracts contain poor outcome (also frequently preventing liver
portal vein radicles and arterioles, together with transplantation). Paracetarnol overdose causes
small bile ducts. Sinusoids cross the liver lobule acute liver injury, but if the acute event is
to the hepatic vein radicle. survived, the liver typically returns to normal.
Once encephalopathy develops, deterioration is
22.2. Answer: E. typically very rapid (hours or even minutes).
Synthesis of clotting factors by the liver makes Encephalopathy typically occurs after PT
prothrombin time (PT) a useful and easily prolongation and prior to the onset of jaundice.
available marker of hepatocyte function The outcome of acute liver failure in
(although watch for vitamin K deficiency and paracetamol is typically better than other
patients on warfarin). Alanine transaminase is a causes of acute liver failure.
marker of hepatocyte injury not function.
Platelet count lowering and elevation of 22.5. Answer: D.
Fibroscan values are markers of fibrosis/ The commonest autoantibody in PBC is
cirrhosis (through hypersplenism and liver antimitochondrial antibody (AMA; present in
fibrosis, respectively). MEGX, a dynamic test of over 95% of patients). A minority of patients
lidocaine metabolism, is a direct, active test of (around 20%) have characteristic antinuclear
.-.I
hepatocyte function but toxicity can be an issue antibodies that are reactive with either nuclear
and it is not in widespread clinical use. dot or nuclear rim antibodies. Where present,
these carry the same degree of diagnostic
22.3. Answer: E. value as AMA (and may suggest a worse
Yellowing of the sclera and skin are features prognosis). Both AIH and lupus are associated
suggestive of jaundice. The presence of dark with antinuclear antibodies but with a diffuse
urine and pale stools suggest a post -hepatic or nuclear staining pattern. Low-titre diffuse
obstructive jaundice (conjugated bilirubin is nuclear antibodies are seen frequently in NASH.
leaking back into the circulation and being The 'characteristic' autoantibody in PSG is
excreted through the kidney, causing urine perinuclear antineutrophil cytoplasmic antibody
darkening, whilst bilirubin metabolites are not (pANCA), although this is seen in only around
reaching the bowel, causing stools to be pale). 30% of patients.
Pancreatic carcinoma is a common cause of
this form of jaundice. Haemolysis is a cause of 22.6. Answer: B. ·
pre-hepatic jaundice through increased red DILl can be difficult to distinguish on liver
blood cell breakdown and bilirubin generation in biopsy from autoimmune hepatitis due to a
the spleen and thus would not give an number of shared features, including
obstructive pattern. Gilbert's syndrome is an parenchymal inflammation and eosinophilia.
inherited abnormality of bilirubin transport that Clinical context needs to be considered (e.g.
gives rise to clinically non-significant elevation autoimmune disease histQry and drug
of bilirubin (other liver biochemistry is typically exposure) and other immunological features of
normal), particularly in times of physiological AIH (elevated lgG and autoantibodies) sought.
stress such as intercurrent illness, which would Opiates are not reported to cause DILl; in ,
offspring of mothers with AIH run a slightly situations, in particular to explore for the
increased risk of AIH later in life (because of the presence of metastasis.
genetic contribution to pathogenesis). This
small risk should not impact on plans for 22.15. Answer: C.
pregnancy. This clinical presentation is typical of Budd-
Chiari syndrome (hepatic venous thrombosis).
22.12. Answer: D. Cirrhosis is typically associated with a small,
Variceal bleeding can be high pressure and can painless shrunken liver and reversal of portal
lead to the patient exsanguinating rapidly. It is venous flow; pain would be very unusual.
therefore essential to secure venous access Hepatic artery thrombus is a specific
early and commence fluid resuscitation. Delay complication of liver transplantation.
can lead to later failure to gain access.
Cross-matching is clearly urgent but should be 22.16. Answer: D.
done once access is secured. However, the ALT elevation following liver transplantation is,
acute intervention of choice is endoscopy and as in other settings, a marker of liver injury. The
banding; this should only be undertaken once commonest aetiology is dependent on the time
the patient is haemodynamically stable. TIPSS point post-transplant. Immediately post-surgery,
is a radiological intervention that is appropriate the commonest causes are thrombosis of the
after failed endoscopy or early rebleed. hepatic artery (a specific complication of liver
Ultrasound scan is a part of the workup to transplant) and primary graft dysfunction
explore triggers for bleeding - portal venous (typically a consequence of preservation injury).
thrombosis or occult hepatocellular carcinoma Acute cellular rejection would typically not be
(HCC) being potential factors - but should be seen until days 5-10. CMV infection is another
undertaken once the acute bleeding state is characteristic post-transplant challenge,
under control. typically when there is a mismatch between the
CMV status of the donor and recipient.
22.13. Answer: A. Prophylactic regimes in at-risk individuals are
Glypressin is recognised to reduce the severity effective. AIH recurrence post -liver transplant is
of acute variceal bleeding and can act as a described but is typically a late phenomenon.
bridge to endoscopy and an adjunct to
endoscopy (helping a clearer endoscopic field). 22.17. Answer: A.
Noradrenaline (norepinephrine) may be required Alkaline phosphatase level at presentation and
in the critical care setting to maintain in particular after therapy with ursodeoxycholic
cardiovascular status but is not primarily an acid is predictive of outcome, with clinically
~.
agent to reduce bleeding risk. Octreotide has relevant cut-offs identified and now in
benefits in variceal bleeding but its use has widespread clinical use. AMA is an important
been superseded by Glypressin: where used, it
has to be intravenous. Propranolol should never
diagnostic feature but titre is not predictive of
outcome. Intercurrent autoimmune disease is I
be used in acute bleeding but is an important common and requires management but has no
agent in the treatment of chronic portal impact of liver disease risk. Liver size is typically
hypertension. There is no clear evidence to increased in early PBC. Small liver size is a
support the use of tranexamic acid in Gl feature of cirrhosis with a worse outcome.
bleeding (including variceal bleeding) although Younger age is associated with a lower
trials are ongoing. likelihood of response to UDCA and thus
increased risk. PBC is typically benign in older
22.14. Answer: A. patients.
A second imaging modality is the key next
investigation in a case of suspected HCC. AFP 22.18. Answer: D.
has some use as a screening test in at-risk The combination of abnormal biochemistry,
patients but it can be normal in patients with pregnancy stage and, in/particular, elevation of
HCC, meaning it has no use in diagnosis. serum bile acids all point to cholestasis of
Laparoscopy and liver biopsy can be of use in pregnancy. The bile acid.elevation makes fatty
staging and planning therapy in specific cases, liver of pregnancy unlikely. UDCA therapy is
once the diagnosis is supported by dual effective and rifampicin has been used in
imaging. PET scan has utility in specific severe cases. There is no association with·
22.34. Answer: E.
The patient has SOD type I. The gold standard
to the virus in the past but has been immunised
to the virus.
I I
for diagnosis is sphincter of Oddi manometry.
All biliary SOD patients with type I disease are 22.40. Answer: C.
treated with endoscopic sphincterotomy. NAFLD is an increasingly common liver disease
Medical therapies can be tried in SOD type II that is associated with features of the metabolic
patients. syndrome; the more features that an individual
possesses, the more likely they are to have
22.35. Answer: D. progressive disease. NAFLD is often
The patient has polycythaemia vera causing asymptomatic and may be associated with
Budd-Chiari syndrome. The ascitic fluid is an normal liver biochemistry, even when disease is
exudate with a serum-ascites albumin gradient advanced. AST rises and ALT falls as disease
(SAAG) of < 11 g/L. The other causes listed progresses towards cirrhosis. The AST: ALT
would have a high SAAG. ratio is included in calculated scores such as
the NAFLD fibrosis score and PIB-4 score that
22.36. Answer: C. are used to risk -stratify patients for presence of
The MELD score is used to identify and advanced fibrosis. GGT levels may be raised in
prioritise patients for liver transplantation. The NAFLD and so cannot be used to discriminate
Maddrey score enables the clinician to assess between alcoholic and non-alcoholic liver
prognosis in alcoholic hepatitis. The King's disease. Routine imaging modalities cannot
College criteria identify indices associated with distinguish between steatosis and
poor prognosis in patients with acute liver steatohepatitis; at present this can only be
failure. The Rockall score identifies patients reliably performed histologically.
needing intervention in upper Gl bleeds.
22.41. Answer: D.
22.37. Answer: D. NAFLD is a common, progressive liver disease
Fibrolamellar HCC occurs in young adults in the that is also associated with an increased risk of
absence of cirrhosis. The treatment of choice is cardiovascular disease. In patients with NAFLD,
surgical resection. The tumour biology is liver-related mortality is the third most common
different to standard HCC and, in the absence cause of death, after cardiovascular disease
of cirrhosis, surgical resection is less likely to and extrahepatic malignancy. If a patient is
cause liver failure. TACE and RFA are treatment found to have NAFLD, other features of the
options for HCC. metabolic syndrome (including type 2 diabetes,
hypertension, dyslipidaemia) should be sought
22.38. Answer: B. and treated. NAFLD is not associated with an
This patient has secondary liver disease. Given increased risk of statin-related liver injury and
the recent change in bowel habit and raised so statins are generally considered safe. Raised
CEA, the primary is likely to be colorectal ferritin levels may be seen in patients with
cancer. She has biliary obstruction from tumour NAFLD and do not necessarily indicate the
burden in liver. Options D and E are benign presence of haemochromatosis, which can be
lesions that would not present this way. Serum excluded by checking transferrin saturation.
levels of the tumour marker CA 19-9 are Although carriage of the PNPLA3 gene
elevated in cholangiocarcinoma. rs738409 variant is associated with more
severe NAFLD, it is not currently used as part
22.39. Answer: D. of routine clinical testing. The FIB-4 score is
HBV surface antigen (HBsAg) is a marker of used to risk-stratify patients for presence of
current infection. HBV surface antibody advanced fibrosis in NAFLD; it should not be
(anti-HBs) may be positive following previous used in patients with alcoholic liver disease.
infection with HBV or if the patient has been
immunised against HBV but immunisation 22.42. Answer: E.
against HBV does not induce HBV anti-core A Maddrey discriminate function greater than
(anti-HBc) antibody production. As this patient 32 is indicative of severe disease. Cessation of
is HBsAg negative, he is not currently infected. all alcohol consumption is essential. Good
The absence of anti-HBc despite the presence nutrition is very important, and enteral feeding
of anti-HBs indicates he has not been exposed via a fine-bore nasogastric tube may be needed
in severely ill patients. The STOPAH study was or passive protection against HCV. HCV is
a large multicentre double-blind randomised usually identified in asymptomatic individuals
trial to evaluate the relative merits of steroids screened because they have risk factors for
and/or a weak anti-tumour necrosis factor infection, such as previous injecting drug use,
(anti-TNF) agent (pentoxifylline), alone or in tattoos, needlestick injury, etc.
combination. In a cohort of II 03 patients, no
significant benefit from pentoxifylline treatment 22.45. Answer: E.
was identified; however, treatment with In hereditary haemochromatosis, iron is
prednisolone 40 mg daily for 28 days led to a deposited throughout the body and causes
modest reduction in short-term mortality, from damage to several organs, including the liver.
17% in placebo-treated patients to 14% in the Serum iron studies show a greatly increased
prednisolone group. These findings were ferritin, a raised plasma iron and saturated
consistent with earlier studies, where an plasma iron-binding capacity. The differential
improvement in 28-day survival from 52% to diagnoses for elevated ferritin includes
78% was seen when steroids were given to inflammatory disease, NAFLD or excess ethanol
those with a Glasgow score of more than 9. consumption for modest elevations
However, neither steroids nor pentoxifylline (< 1000 [.Lg/L). Transferrin saturation of more
improved survival at 90 days or I year. Sepsis than 45% is highly suggestive of iron overload
is the main side-effect of steroids, and existing and not affected by inflammatory state and so
sepsis and variceal haemorrhage are the main is more specific than ferritin. Genetic testing
contraindications to their use. can be considered later, but in the first instance
tests for iron overload would be first line and
22.43. Answer: A. best value.
The most likely diagnosis would be
spontaneous bacterial peritonitis. Diagnostic 22.46. Answer: E.
paracentesis (ascetic tap) may show cloudy The patient presents with a painful obstructive
fluid, and an ascites neutrophil count above jaundice. The blood tests represent a typical
250x 106/L almost invariably indicates infection. cholestatic picture with elevated ALP and GGT,
The source of infection cannot usually be making viral hepatitis unlikely. In this setting,
determined, but most organisms isolated are of ultrasound would be the first-line investigation
enteric origin and E. coli is most frequently to seek evidence of biliary obstruction with
found. Ascitic culture in blood culture bottles dilated common bile duct due to, for example,
gives the highest yield of organisms. gallstone disease. Depending on the findings, it
Spontaneous bacterial peritonitis (SBP) needs may then be necessary to proceed to MRCP or
to be differentiated from other intra-abdominal endoscopic ultrasound prior to ERCP if an
emergencies, and the finding of multiple obstruction is identified. Pancreatic cancer is
organisms on culture should arouse suspicion more classically associated with a painless
of a perforated viscus. obstructive jaundice.
Haematology and
transfusion medicine
Multiple Choice Questions
23.1. In a patient with a vague history of weight 23.4. A 65 year old man presents with an
loss but little else on examination you find immul!e-mediated thrombocytopenia. He has
lymphadenopathy confined to the right axilla. been treated with antibiotics during a recent
Which of the following conditions is most likely? hospital admission. Which of the following is
A. Chronic lymphocytic leukaemia most likely implicated in the new development?
B. Follicular lymphoma A. Amoxicillin
C. Glandular fever B. Ciprofloxacin
D. Human immunodeficiency virus (HIV) C. Gentamicin
seroconversion illness D. Metronidazole
E. Metastatic breast cancer E. Vancomycin
23.2. In the investigation of a patient with 23.5. A patient with systemic lupus
suspected essential thrombocythaemia, in erythematosus (SLE) and immune
which of the following genes may you find thrombocytopenia (ITP) presents with a platelet
abnormalities? count of 5 x 109/L. Which of these is the most
A. BCL-2 likely presenting symptom?
B.BCR A. Haemarthrosis
C. c-MYC B. Intracranial haemorrhage
D. CAL-R C. Muscular haematoma
E. MYH-9 D. Oral mucosal bleeding
E. Retroperitoneal haematoma
23.3. Having made a new diagnosis of
polycythaemia rubra vera (PRV) you are 23.6. Which of the following anticoagulants
consulting with the patient regarding prognosis has a mechanism of action involving
and complications of the condition. He has antithrombin-dependent inhibition of thrombin
read the information booklet and wishes to and factor Xa?
know about common vascular complications of A. Apixaban
the condition. Which of the following is the B. Bivalirudin
most common vascular complication? C. Dabigatran
A. Budd-Chiari syndrome D. Dalteparin
B. lschaemic stroke E. Edoxaban
C. Livedo reticularis
D. Mesenteric vein thrombosis 23.7. A 72 year old woman who is on warfarin
E. Pulmonary embolism consults to ask if she can change to an
23.31. A 73 year old man is found to have 23.34. The first-line therapy for a 50 year old
some abnormalities in a full blood count taken man with severe aplastic anaemia is best
to investigate a symptom of fatigue. In patients described as follows?
with chronic lymphocytic leukaemia (CLL), A. A myeloablative allogeneic stem cell
which one of the following features is true? transplant from an unrelated donor
A. Most patients are symptomatic and require B. Immunosuppressive therapy with high-dose
treatment at presentation glucocorticoids
B. Patients with mutated immunoglobulin genes C. Immunosuppressive tperapy with horse
have a poorer prognosis than those with anti-thymocyte globulin (ATG) followed by
unmutated immunoglobulin genes ciclosporin
C. Signalling through the B-cell receptor complex D. Immunosuppressive tl:lerapy with rabbit
(BCR) is not a useful target for treatment ATG
D. The peripheral blood lymphocyte count is E. Supportive care only with red cells, platelets
persistently above 5x109/L and G-CSF
Answers
23.1. Answer: E. 23. 7. Answer: A.
Follicular lymphoma and chronic lymphocytic All of the other circumstances are licensed
leukaemia (CLL) are systemic malignancies with indications for the use of rivaroxaban except for
involvement of lymphoid tissue in many sites. the management of patients with prosthetic
HIV and Epstein-Barr virus (EBV) infection heart valves. CHA,DS2 -VASc is a well"known
produce generalised lymphadenopathy and scoring system to evaluate risk of thrombosis in
systemic illness. Cancers tend to metastasise a patient with atrial fibrillation.
to local regional nodes draining a specific
tissue and so breast cancer tends to present 23.8. Answer: A.
with localised unilateral axillary HIT is most commonly seen in surgical patients,
lymphadenopathy. especially following major orthopaedic and
cardiac surgery. HIT is more commonly seen
23.2. Answer: D. when UFH is used compared with low-
All of these mutated genes are associated with molecular-weight heparin (LMWH); it is
haematological conditions: BCR with chronic commonly associated with moderate as
myeloid leukaemia (CML), c-MYC and BCL-2 opposed to severe thrombocytopenia and it is
with lymphoma, and MYH-9 with congenital associated, somewhat paradoxically, with
thrombocytopathy. Only CAL-R, calreticulin, is thrombotic events. The key period for
associated with the myeloproliferative neoplasm .developing HIT is after 5-10 days of exposure,
essential thrombocythaemia. with longer exposures less likely to be
associated.
23.3. Answer: B.
The most common complications of PRV 23.9. Answer: D.
involve vascular occlusion. All of the conditions All of these conditions can present with a
listed are associated with PRV, but the most normal PT and a prolonged APTI. Lupus
common is ischaemic stroke. anticoagulant is very rarely associated with a
bleeding diathesis. Factor XII deficiency causes
23.4. Answer: E. a very marked prolongation of the APTI but is
Vancomycin is associated with never associated with bleeding. Severe XI
immune-mediated thrombocytopenia - the deficiency is associated with variable severity of
others are not. bleeding and is rare. Factor VIII and IX
deficiencies present with identical phenotypes
23.5. Answer: D. but severe haemophilia A is 5 times more
Haemarthrosis, muscular haematoma and common than severe haemophilia B. The
retroperitoneal haemorrhage more commonly scenario is classical of the first presentation of
complicate bleeding disorders associated with severe haemophilia A or B.
reduced levels of coagulation factors.
Intracranial haemorrhage can complicate 23.10. Answer: C.
severe thrombocytopenia or severe coagulation She has a low factor VIII level, which is
factor deficiency but oral mucosal bleeding compatible with all the diagnoses given.
is by far the most common feature of However, she has a level of functional vWF
severe thrombocytopenia along with skin (RiCO) that is out of keeping with her vWF
purpura. antigen level (ratio is 0.35). This suggests a
dysfunctional molecule and therefore type 2
23.6. Answer: D. vWD. Type 2N vWD is associated with isolated
Dalteparin is a low-molecular-weight heparin low factor VIII and so' the most likely diagnosis
(LMWH), the effect of which is mediated by here is type 2A vWD. This is a common
enhanced avidity of antithrombin for its natural presentation in affected young women.
substrates, thrombin and factor Xa. Apixaban
and edoxaban are direct-acting inhibitors of 23.11. Answer: E.
factor Xa, while dabigatran and bivalirudin are Epistaxis, easy bruising and bleeding after
direct thrombin inhibitors. shaving are all symptoms commonly reported
oxygen release to tissues less readily. HbS Splenomegaly is hardly ever massive, which is
does not have any affect on oxygen a feature of chronic myeloid leukaemia (CML).
dissociation. Bleeding is into skin and mucous membranes
because of thrombocytopenia, not joints as in
23.21. Answer: B. haemophilia.
Low measured vitamin B12 level is common in
pregnancy although vitamin B12 deficiency is 23.25. Answer: A.
rare - indeed decreased fertility is associated MDS are diseases of the elderly, with a median
with vitamin B12 deficiency. Protein C levels rise age of over 70 years. Anaemia is the
in pregnancy, protein S levels fall. Procoagulant commonest abnormality, occurring in 80% of
factors like factor VIII and fibrinogen increase as patients at some point, and is usually
pregnancy progresses. Pregnant patients tend macrocytic. Patients with anaemia and low
to have increased plasma volume and, if transfusion requirement and a baseline EPO
anything, tend to be anaemic rather than level of <200 U/L have a 70% chance of
polycythaemic. Lupus anticoagulant is never a responding to EPO therapy, independent of
normal finding. renal function. Dysplasia is present in more
than 10% of an affected bone marrow lineage
23.22. Answer: C. and ring sideroblasts are one form of dysplastic
The normal spleen is rarely if ever felt and a red cell. Mutations in SF381 (a splicing factor)
palpable spleen has the clinical features of are very strongly associated with the presence
moving down on inspiration as the diaphragm of ring sideroblasts. Progression to AML is
contracts and upwards (away from the hand) diagnosed when the blasts are over 20%.
on expiration. The examining hand cannot get
above the spleen and under the left costal 23.26. Answer: C.
margin. Inflammation of the splenic capsule In MGUS, the paraprotein is at a low level and
following infarction leads to an audible rub over with no evidence of end-organ damage, i.e. no
an acutely painful spleen. evidence of anaemia, bone disease or renal
disease. lgM paraproteins are associated with
23.23. Answer: D. low-grade lymphomas, most notably
Stem cells are rare, accounting for about 0.1% lymphoplasmacytic lymphoma, but can present
of marrow cells. They cannot be identified on as MGUS if there is no clinical evidence of
routine morphology and require immunological lymphoma. A normal serum free light chain
staining for identification. They have the ratio in MGUS carries a very good prognosis.
important characteristics of self-renewal
(daughter cells can remain as stem cells rather 23.27. Answer: B.
than differentiating into mature blood cells) and Myeloma is a disease of middle to old age. It is
pluripotency (they give rise to cells of different never seen in children and extremely rare under
lineages depending on requirements). Stem the age of 30 years. The diagnosis requires a
cells circulate in the blood in small numbers paraprotein (including light chain only as in
normally and these can be increased up to option B) with signs of end-organ damage and
I 000-fold by mobilisation procedures following usually with an increase in bone marrow
chemotherapy, G-CSF or plerixafor. In this way, monoclonal plasma cells. Option ·o is most
stem cells can be harvested from the blood for likely metastatic prostate cancer; option C is
transplantation. autoimmune disease, e.g. rheumatoid arthritis;
and option E would fit with HIV infection.
23.24. Answer: E. Normal light chains can appear in the urine in
The hallmark of acute leukaemia is bone acute renal failure because of failed
marrow failure: the presence of one or more of reabsorption by the renal tubules, as in
anaemia, thrombocytopenia and neutropenia. option A
This is because the leukaemic blast cells
proliferate but fail to differentiate normally. The 23.28. Answer: D.
disease is most common in older adults. The CML arises from a mutated stem cell
total white cell count can be low, normal or containing the Ph chromosome, which results
high, depending on how many of the blasts from the translocation t(9;22) and the resulting
escape the marrow into the blood. fusion gene BCR-ABL. The leukaemic clone
does not cause direct marrow toxicity. Chronic RhO-negative can safely be given to any patient
Gl tract bleeding leads to iron deficiency
anaemia, as does achlorhydria, e.g.
as it lacks isohaemoglutinins that can react
against the patient's red cell surface antigens.
I
post-gastrectomy. Option E describes
I
hypersplenism. 23.39. Answer: A. !
A female of child-bearing age would have
23.36. Answer: E. received RhO- and Kell-negative units. Routine
All have been recognised prognostic factors at antenatal anti-0 prophylaxis is administered at
one time or another but the presence of MRO 28 weeks. Anti-0 only occurs in RhO-negative
is now recognised as the most significant individuals exposed to exogenous 0 antigen,
prognostic factor and used to modify therapy and has clinical implications. She has not been
accordingly. pregnant before. It is most likely that her
partner is 0 antigen positive and the fetus has
23.37. Answer: D. inherited this antigen causing maternal
Nowadays the use of indwelling lines and allo-anti-0 to form.
antibiotic prophylaxis with quinolone antibiotics
(e.g. levofloxacin, ciprofloxacin) leads to more 23.40. Answer: C.
identified Gram-positive infections than Group 0 FFP contains both anti-A and anti-B,
Gram-negative, although Gram-negative which will react with the recipient's red cells
infections are still more life-threatening. expressing A or B antigens. Group 0 patients
Quinolone prophylaxis and posaconazole have anti-A and anti-B that will react with A
prophylaxis have both been shown to be and or B antigens expressed on transfused
beneficial and to reduce mortality during cells. Group A patients have anti-B, which will
induction therapy for AML. Indwelling plastic react with B antigens expressed on transfused
lines are more commonly infected with cells. The neonate immune system does not
Gram-positive organisms, e.g. Staphylococcus produce antibodies when exposed to
epidermidis. Neutropenic sepsis is a medical exogenous antigens and so neonates tolerate
emergency and must be treated empirically, ABO incompatibility better than adults.
e.g. with piperacillin/tazobactam with or without
aminoglycosides, whilst waiting for culture 23.41. Answer: E.
results. Positive cultures only occur in about A Kleihauer test or acid elution test is a blood
30% of episodes of neutropenic sepsis. test used to measure the amount of fetal
haemoglobin transferred from a fetus to a
23.38. Answer: D. mother's blood stream. It is vital not to miss
In an emergency, group 0 red cells can be this sensitising event. Implantation bleeds occur
given safely to any patient as the group 0 red in the first trimester. Although exclusion of
cells lack surface antigens against which the placental abnormality is required, the priority is
patient's isohaemoglutinins can react (Box to minimise the likelihood of RhO sensitisation
23.38}. There is a historic ABO and Rhesus 0 occurring. Normal pregnancy causes a fall in
type available; however, group-specific units the haemoglobin through haemodilution for
can only be issued when the group has been which transfusion is not indicated. Red cell
confirmed from a current sample. As this parameters will guide the need for iron
woman has child-bearing potential, she should replacement.
receive RhO-negative. Plasma of group AB
23.42. Answer: A.
It is good practice to explain and document the
reason for transfusion to the patient and to
23.38 ABO blood group antigens and antibodies obtain the patient's consent but this may
ABO blood Red cell. A or Antibodies UK frequency not always be possible. Key steps in the
group B antigens in plasma (%) transfusion process are to positively identify the
0 None Anti-A and 46 patient at the bedside prior to taking a blood
anti-B sample and before administering a blood
A A Anti-B 42 component. As he has evidence of
B B Anti-A 9 cardiorespiratory compromise, transfusion
AB A and B None 3
should not be withheld.
~
asynchrony. Iron deficiency results in anaemia microvascular occlusion. This puts them at risk
with small, pale red cells. Acute myeloid of life-threatening infections from capsulated
leukaemia can cause a pancytopenia but is organisms. Aplastic crises produce a very low
associated with circulating immature blast cells. haemoglobin with a reticulocytopenia. There is
Alcohol excess can result in a macrocytosis no history of joint pain or shortness of breath to I
and poor diet, usually leading to folate suggest a vasa-occlusive painful crisis or sickle
deficiency. Hypothyroidism can cause a chest syndrome.
macrocytosis and fatigue with normal neutrophil
appearances on film. 23.52. Answer: C.
This child has non-spherocytic haemolysis.
23.47. Answer: A. G6PD deficiency is the most common cause in
The blood film shows an increase in neutrophils this age group. The Donath-Landsteiner
with heavily staining granules consistent with antibody is found in paroxysmal cold
bacterial infection. There are no immature blast haemoglobinuria. The direct antiglobulin test
cells. Infectious mononucleosis is associated detects antibody-coated red cells found in
with a lymphocytosis. Whilst diabetic autoimmune haemolysis .•Parvovirus is
ketoacidosis can cause a neutrophilia, the associated with anaemia and reticulocytopenia.
blood glucose is normal. Autoimmune disease The urine discolouration is caused by
is associated with a neutropenia. haemosiderinuria.
Bacterial contamination?
o Blood pack discoloured or damaged
; Yes i o Rapid onset of hyper- or hypotension, rigors or collapse
o Temperature;;, 39'C or rise of;;, 2'C -
If acute dyspnoea/hypotension
o Monitor blood gases
o Perform chest X-ray , .Normal\
o Measure central venous/pulmonary ' CVP
capillary pressure
Fig. 23.43 Investigation and management of acute transfusion reactions. ·use size-appropriate dose in children. (ARDS ~ acute
respiratory distress syndrome; BP =blood pressure; CVP =central venous pressure; DIG~ disseminated intravascular coagulation; FBC
~ lull blood count; IV ~ intravenous)
Rheumatology and
bone disease
He has a history hypertension treated with (MCP) joints of the hands, gradually worsening
bendroflumethazide 2.5 mg daily. He drinks over a period of 6-8 weeks. On examination,
2-3 pints of beer each night and consumes 26 there is symmetrical swelling and tenderness of
units of alcohol per week. What is the most both wrists and the MCP and PIP joints of the
likely diagnosis? hands. Investigations show that anti-citrullinated
peptide antibodies (ACPAs) and rheumatoid
A. Gout
B. Osteoarthritis factor are negative, but that she has an elevated
c. Psoriatic arthritis ESR (25 rnrn/hr) and a raised CRP (65 rng/L). ·
D. Rheumatoid arthritis X-rays of the hands are normal. Which of the
E. Septic arthritis following statements is correct?
A. Magnetic resonance imaging (MRI) of the
24.7. A 77 year old woman with a history of hands should be done to clarify the diagnosis
generalised osteoarthritis (OA) is admitted to B. Rheumatoid arthritis is excluded by the
hospital with a delirious episode associated negative ACPA test and normal radiographs
with dehydration and a urinary tract infection. C. The joint pain and swelling is most likely due
During the admission, she develops pain, to generalised osteoarthritis
swelling and redness of the left wrist gradually D. The presentation is consistent with
worsening over a period of 4-6 hours. Blood polymyalgia rheurnatica (PMR)
tests reveal a neutrophilia (white cell count E. The presentation is typical of seronegative
12.5x109/L), a raised erythrocyte sedimentation rheumatoid arthritis
rate (ESR; 65 mm/hr) and a raised C-reactive
protein (CRP; 154 mg/L). 24.10. Which of the following is a common
What would be the most likely diagnosis? complication of seronegative (ACPA and
rheumatoid factor negative) rheumatoid
A. Calcium pyrophosphate deposition disease
arthritis?
B. Gout
C. Reactive arthritis A. Felty's syndrome
D. Septic arthritis B. Osteoporosis
E. Vasculitis C. Rheumatoid nodules
D. Uveitis
24.8. A 63 year old woman with a 10-year E. Vasculitis
history of rheumatoid arthritis presents with
gradually worsening pain and swelling of the left 24.11. A 36 year old woman presents with
knee joint over a period of 2-3 days. Her 3-month history of joint pain and swelling
arthritis has generally been under good control affecting the wrists, MCPJs and proximal
with methotrexate 20 mg weekly and the interphalangeal joints (PIPJs) of the hands, both
tumour necrosis factor alpha (TNF-a) inhibitor shoulders, both knees and the MCPJs of both
etanercept 50 mg weekly. On examination the feet. Laboratory investigations reveal an ACPA
knee is warm and swollen, with signs of an level of 145, an ESR of 68 rnm/hr and a CRP
effusion. What would be the most appropriate of 84 rng/L. On examination she has 22 tender
course of action? and 16 swollen joints and rates the activity of
A. Aspirate the knee and inject with 80 mg her arthritis as 65/100, giving a Disease Activity
methylprednisolone? Score 28 (DAS28) of 7.54. What would be the
B. Aspirate the knee and send the synovial fluid most appropriate initial treatment?
for culture and microscopy A. Adalimumab 40 rng every 2 weeks and
C. Commence treatment with a broad-spectrum prednisolone 5 mg daily
antibiotic B. Hydroxychloroquine 200 mg twice daily and
D. Commence treatment with diclofenac 75 mg ibuprofen 400 mg 3 times daily
twice daily C. Methotrexate 15 rng weekly, folic acid 5 rng
E. Increase the dose of methotrexate to 25 mg weekly and prednisolone 30 rng daily
weekly D. Prednisolone 30 rng daily, ibuprofen 400 mg
3 times daily and omepr~zole 30 mg daily
24.9. A 66 year old woman presents with pain E. Rituxirnab 1000 mg on two occasions a
and stiffness affecting the wrists, proximal fortnight apart combined with prednisolone
interphalangeal (PIP) and metacarpophalangeal 5 mg daily
24.12. Which one of the following statements 24.14. A 60 year old woman suffers a low
is true with respect to post-menopausal trauma fracture of the right wrist after a fall.
osteoporosis? She is a non-smoker and drinks 8 units of
A. Bone pain is the most common presenting alcohol per week. Her menopause occurred at
feature aged 52. She is on no current medication and
B. Calcium and vitamin D supplements can has no significant medical history but reports
prevent its development that her mother, aged 79, has recently suffered
C. It is a rare complication of polymyalgia a hip fracture.
rheumatica What would be the most appropriate course
D. Obesity is an important risk factor of action?
E. Patients are usually asymptomatic until a A. Advise her to stop drinking alcohol
fracture occurs completely
B. Commence treatment with alendronic acid
24.13. A 73 year old woman presents to her C. Commence treatment with calcium and
family physician with sudden onset of pain in vitamin D supplements
the lower back region that developed after D. Request a dual X-ray absorptiometry (DXA)
removing weeds in her garden. She has a scan
history of breast cancer treated 10 years E. Request a spine radiograph
previously with surgery and radiotherapy
followed by tamoxifen for 5 years. She has a 24.15. Which one of the following is a common
history of hypertension controlled with adverse effect of oral bisphosphonate therapy
bendroflumethazide 2.5 mg daily. Her height is ,in patients with osteoporosis?
154 em, weight 53 kg and physical examination A. Atypical subtrochanteric fractures
is unremarkable. A spine radiograph is shown B. Iritis
below. C. Leucopenia
D. Osteonecrosis of the jaw
E. Upper gastrointestinal upset
metatarsophalangeal (MTP) joint of the right (DIPJs) of both hands. Investigations show a
toot. Investigations show an elevated ESR haemoglobin of 118 g/L, white cell count
(35 mm/hr), CRP of 56 mg/L, a mild 6.3x 109/L, platelets 355 x 109/L and ESR
neutrophilia (12.1 x 109/L), serum creatinine 20 mm/hr. An X-ray of the hands and wrists is
75 J.Lmoi/L (0.85 mg/dL), estimated glomerular performed.
filtration rate (eGFR) >60 mUmin/1.73 m and
2 Which radiological features are typical of
a serum uric acid level of 450 J.Lmoi/L (7.6 mg/ osteoarthritis?
dL). Radiographs reveal evidence of erosions in A. Irregularity and fusion of the sacroiliac joints
the affected joint. B. Joint space narrowing and subchondral
What would be the most appropriate sclerosis of the PIPJ and DIPJ of the hands
treatment? G. Marginal erosions affecting the MCPJ of the
A. Allopurinol 100 mg daily initially gradually hands
increasing in dose until uric acid falls below D. Periarticular osteoporosis affecting the PIPJs
360 J.Lmoi/L (6.1 mg/dL) and DIPJs in the hands
B. Colchicine 500 mg 3 times daily until E. Punched-out erosions of the first MTP joint
symptoms settle followed by colchicine of the feet
500 mg daily on a long-term basis 24.20. A 65 year old man presents to his family
G. Colchicine 500 mg 3 times daily until physician complaining of pain in the left knee,
symptoms settle followed by long-term worse on ascending and descending stairs. He
diclofenac 75 mg twice daily smokes 15 cigarettes a day, and drinks about
D. Diclofenac 75 mg twice daily followed by 4 units of alcohol daily (28 units per week). He
long-term low-dose aspirin 75 mg/day is a former amateur soccer player who suffered
E. Etoricoxib 60 mg daily followed by allopurinol a cruciate ligament tear in his 30s. He has lived
starting at 100 mg daily, gradually increasing alone since his wife died 5 years previously. He
in dose until uric acid falls below 360 J.Lmoi/L has been avoiding dairy products since he
(6.1 mg/dL) thinks they cause gastrointestinal upset.
Which of the following risk factors predispose
24.18. A 35 year old woman with well-controlled
to the development of osteoarthritis?
RA states that she wishes to become pregnant.
Her medication consists of methotrexate 20 mg A. Alcohol intake >21 units per week
weekly, folic acid 5 mg weekly and ibuprofen B. Cigarette smoking
400 mg 3 times daily. What advice would you G. lmmobilisation
give with regard to her plans to conceive and D. Low dietary calcium intake
her medication? E. Previous anterior cruciate ligament tear
A. She can go ahead and try to conceive so 24.21. A 66 year old woman is referred to the
long as she reduces the dose of rheumatology clinic with pain in the right hip of
methotrexate to 10 mg weekly and ibuprofen gradual onset over the past 2 years, worse on
to 200 mg 3 times daily weight-bearing. Examination reveals limitation
B. She should stop the ibuprofen for at least 3 and pain on internal rotation of the right .hip.
months before trying to conceive but can Her height is 154 em and weight is 82 kg
continue the methotrexat~ (body mass index (BMI) 34.6 kg/m 2 ). A pelvic
G. She should stop the methotrexate and the X-ray shows joint space narrowing and
ibuprofen and then go ahead and try to osteophytes of the right hip joint, consistent
conceive with osteoarthritis.
D. She should stop the methotrexate for at Which one of the following statements is true
least 12 months before trying to conceive with regard to the treatment of osteoarthritis of
but can continue the ibuprofen the hip?
E. She should stop the methotrexate for at
A. A cyclo-oxygenase 2(COX-2) selective
least 3 months before trying to conceive but
NSAID is more likely to be effective than a
can continue the ibuprofen
non-selective NSAID in the treatment of pain
24.19. A 75 year old woman is referred to the B. Joint replacement surgery is indicated if the
rheumatology clinic complaining of pain and response to paracetamol is inadequate
swelling affecting the proximal interphalangeal G. Long-term prophylactic NSAID therapy has a
joints (PIPJs) and distal interphalangeal joints disease-modifying effect
deformities of the lower limbs. He was What is the most likely cause of the pain?
diagnosed as having childhood rickets and A. Osteoarthritis
treated with vitamin D metabolites but stopped B. Osteomalacia
treatment aged 16 years and was lost to C. Osteoporosis
follow-up. There is a family history of rickets D. Paget's disease
affecting his mother and brother. E. Renal osteodystrophy
Investigations reveal a serum calcium of
2.25 mmoi/L (9.0 mg/dL), phosphate 24.29. Which of the following clinical or
0.60 mmoi/L (1.86 mg/dL), PTH 12.5 pmoi/L radiographic features is consistent with a
(118 pg/mL), ALP 160 U/L and serum 25(0H)D diagnosis of Scheuermann's disease?
54 nmoi/L (22 ng/mL).
A. At least two wedge deformities in the
What is the most likely diagnosis?
thoracic spine with aT-score of <-2.5 at
A. Tumour-induced osteomalacia either spine or hip on DXA examination
B. Vitamin D-deficient rickets B. Crush deformity affecting at least three
c. Vitamin D-resistant rickets type I vertebrae in the lumbar spine
D. Vitamin D-resistant rickets type II c. Disc space narrowing in the lumbar spine
E. X-linked hypophosphataemic rickets with marked osteophyte formation
D. Two vertebral crush deformities in the
24.27. Which of the following statements is true
thoracic spine and one in the lumbar spine
with regard to Paget's disease of bone?
with evidence of osteopenia on radiographs
A. Dietary calcium deficiency and smoking are E. Wedge deformity affecting several adjacent
recognised risk factors vertebrae in the thoracic spine with disc
B. It can be inherited in families in association space narrowing
with mutations in the SQSTM1 gene
c. It is a focal skeletal disorder characterised by 24.30. A 32 year old man is referred to the
inhibition of bone formation and an increased rheumatology clinic having sustained a fracture
risk of fracture of the right femur after falling when he tripped
D. It is a systemic skeletal disorder characterised over an uneven pavement. Examination is
by a generalised increase in bone turnover unremarkable apart from the fact that he has
E. There is a strong genetic component blue sclerae. He is known to have osteogenesis
mediated by variants at the human leucocyte imperfecta (01) and has a history of low trauma
antigen (HLA) locus on chromosome 6 fractures dating back to childhood.
Which of the following statements is true with
24.28. A 68 year old man presents with gradually
regard to this condition?
worsening pain in the right hip region, which is
present at rest and worsens slightly on A. Bisphosphonates are highly effective at
weight-bearing. lnvestigations,reveal a creatinine preventing fractures in adults with 01
of 140 J.lmol/L (1 .58 mg/dL) and an eGFR of B. Fractures of the vertebrae are an uncommon
35 mUmin/1.73 m2 but otherwise normal urea complication
and electrolytes, normal serum calcium and C. The diagnosis can be excluded if the sclerae
phosphate, but an ALP of 350 U/L. The full are of normal colour
blood count is normal. A pelvic radiograph is D. The incidence of fractures increases
performed and is shown below. progressively with age
E. The incidence of fractures is highest in childhood
What is the most likely diagnosis? of fine touch on examination of the affected
A. Camurati-Engelmann disease digits in the right hand. Investigations are as
B. Fibrous dysplasia follows: haemoglobin 120 g/L, white cell count
C. Osteomyelitis 6.5x 109/L, platelets 456x 109/L, ESR 20 mm/
D. Osteopetrosis hr, CRP 6 mg/L.
E. Paget's disease of the tibia What is the most likely cause of the
symptoms?
24.32. A 58 year old man with haemochromatosis A. Bone erosions secondary to the
is referred to the rheumatology clinic with a long-standing RA
3-year history of pain mainly affecting the small B. Median nerve compression
joints of the hands and wrists. Four weeks C. Mononeuritis associated with rheumatoid
previously he had developed acute pain, swelling vasculitis
and redness of the right wrist, which had D. Osteoarthritis of the first CMC joint
responded to treatment with naproxen 500 mg E. Ulnar nerve compression
3 times daily. He has a history of type 2 diabetes
treated with diet and metformin and has been 24.34. Which one of the following statements is
treated with regular venesection for the previous true with regard to joint hypermobility?
3 years. A. Affected patients may experience episodes
Clinical examination of his hands is of postural hypotension accompanied by
unremarkable with no evidence of synovitis. tachycardia
Laboratory Investigations are as follows: B. It is a rare complication of osteogenesis
haemoglobin 115 g/L, white cell count imperfecta
8.2x109/L, platelets 345x10 9/L, ESR 20 mm/ C. Mutations in the FBN1 gene are the most
hr, serum iron 100 [!moi/L (558 [!g/dL), AST common cause
35 U/L, bilirubin 15 [.Lmoi/L (0.88 mg/dL) and D. The diagnosis can be confirmed by a
ALP 150 U/L. Beighton score of more than 4 in patents
Radiographs of the hands and wrists show who have dislocated at least one joint
joint space narrowing and subchondral cysts E. Treatment with NSAIDs is highly effective in
affecting the MCP and the radiocarpal joints controlling ligament and joint pain in affected
with no osteophyte formation. patients
Which of the following statements is true?
I A. The arthritis is an incidental finding unrelated 24.35. A 67 year old woman with a 15-year
I to the diagnosis of haemochromatosis
B. The clinical picture is consistent with
history of type 2 diabetes treated with diet,
metformin and sitagliptin presents with gradual
I rheumatoid arthritis
C. The most likely cause for his joint symptoms
onset of pain and deformity affecting the right
ankle and foot.
is diabetic cheiroarthropathy On general examination, blood pressure is
D. The most likely explanation for the acute flare 145/85 mmHg, pulse 85 beats/min, height
in his joint symptoms is calcium 153 em and weight 89 kg. Neurological
pyrophosphate deposition disease examination reveals absent ankle jerks and
E. The risk of further flares in symptoms can be impairment of fine touch and proprioception in
reduced by continued venesection and both feet. Peripheral pulses are absent below
restoration of serum iron levels to normal the femoral arteries. Examination of the ankle
joint reveals swelling and deformity of the ankle
24.33. A 64 year old woman with a 10-year joint and a severe valgus deformity.
. history of rheumatoid arthritis affecting the Investigations show moderate renal
hands and wrists, which is controlled with dysfunction with a serum creatinine of
sulfasalazine 3 g daily and hydroxychloroquine 165 [.Lmoi/L (1 .87 'mg/dL) and eGFR of 25 mU
200 mg twice daily, presents with a disturbance min/1 .73 m2 . Serum AST is 20 U/L, ALT
of sensation and tingling affecting the thumb 85 U/L, bilirubin 12 [.Lmoi/L (0. 70 mg/dL) and
and anterior aspects of the index and second serum uric acid 400 [!moi/L (6.7 mg/dL). Full
fingers of the right hand. blood count shows mild anaemia with a
On examination there is no evidence of haemoglobin of 11 0 g/L and an ESR of
active synovitis but there is altered perception 25 mm/hr.
I
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RHEUMATOLOGY AND BONE DISEASE • 285
Radiographs show severe destruction of the neutrophils and there are negatively birefringent
ankle and the mid-foot joints with bony crystals in the fluid.' What is the correct
fragments within the joint. management?
What is the most likely cause of the ankle A. Antibiotics and steroids should be used
pain? together
A. Calcium pyrophosphate deposition disease B. Intra-articular steroids can be given straight
B. Charcot joint away because the diagnosis is reactive
C. Diabetic cheiroarthropathy arthritis
D. Gout C. The patient can be treated for gout because
E. Osteoarthritis infection has been excluded
D. The joint should be drained and analgesia
24.36. A 17 year old male presents with pain given but steroids should be withheld until
and swelling of the middle of the right tibia the culture result is available
that has been gradually increasing in severity E. The results favour a diagnosis of
over a period of 6-8 weeks. An X-ray shows pseudogout
expansion of the bone and a soft tissue mass
containing islands of calcification. 24.40. Psoriatic arthopathy contains a number
What is the most likely diagnosis? of the radiographic signs in the answers below.
A. Fibrous dysplasia Which one of the following radiographic signs is
B. Hypertrophic pulmonary osteoarthropathy NOT typically recognised in psoriatic arthritis
C. Metastatic bone disease (PsA)?
D. Osteosarcoma A. Bone sclerosis
E. Paget's disease B. Calcification of peri-odontoid ligaments
C. Juxta-articular new bone formation
24.37. Which physiological process is primarily D. Sacroiliac erosions
responsible for the development of E. Syndesmophytes
osteoporosis in patients on long-term
glucocorticoid therapy? 24.41. A young man has a history of chronic
A. Increased degradation of 25(0H)D low back pain and stiffness, which disturbs his
B. Increased osteoclastic bone resorption sleep and takes time to wear off in the morning
C. Inhibition of 25(0H)D production after waking. In making a diagnosis, which is
D. Inhibition of bone formation the most appropriate combination of tests to
E. Secondary hyperparathyroidism do after clinical assessment?
A. HLA-827 and ESR
24.38. Which of the following environmental B. MRI lumbar spine and sacroiliac joints and
exposures has been associated with bone scintigraphy
susceptibility to, and severity of, rheumatoid C. MRI SIJs and ESR
arthritis? D. Pelvis radiograph and HLA-827
A. Cigarette smoking E. Pelvis radiograph, whole-spine and SIJs MRI,
B. Excessive alcohol intake (>21 units per and HLA-827
week)
C. Human immunodeficiency virus (HIV) 24.42. Which one of the following is a
infection recognised use of ultrasound in rheumatology
D. Obesity (BMI >30) practice?
E. Vitamin D insufficiency A. Adding information to the diagnostic workup
of patients with polyrnyalgia rheurnatica
24.39. In investigating the cause of an acute B. Detection of the vascularity of synovitis in
monoarthritis in a 50 year old man in a MCP joints
non-tuberculosis (TB) endemic region, synovial C. Diagnosing sacroiliac inflammation
fluid from the swollen joint is sent for Gram D. Discrimination of hip adductor tendonitis
stain, culture and polarised microscopy. The from symphysitis
laboratory staff call with the results: they say E. Guiding needle placement to a lumbar spine
'Gram stain negative; culture results are not facet joint in treating facet joint arthritis with
available for another 48 hours. There are many injectable steroid
24.50. Which of the following treatments has G. Enthesitis does not improve with
NOT shown efficacy in either ankylosing secukinumab (anti-IL-17 DMARD)
spondylitis or psoriatic arthritis? D. Enthesitis only occurs in SpA patients who
A. Anti-IL-l? A monoclonal (secukinumab) are HLA-827
B. Anti-IL-23/12 monoclonal (ustekinumab) E. Enthesitis only occurs in lower limbs
G. Anti-TNF-a
D. Apremilast (phosphodiesterase-4 inhibitor) 24.55. Apremilast - a treatment developed for
E. Rituximab (anti-CD20/anti-B-cell therapy) psoriatic arthritis - is a small molecule that ·
directly inhibits which of the following?
24.51. A 35 year old man develops low back, A. Mitogen-activated protein (MAP) kinases
posterior heel pain and a swollen knee and has B. Phosphodiesterase 4 (PDE4)
a pustular skin rash on the soles of his feet. G. RANK ligand
There are no preceding illnesses, no previous D. Signal transducer and activator of
psoriasis or family history of it. What is the transcription 3 (STAT3)
most likely diagnosis? E. T-cell CD80/86 binding
A. Ankylosing spondylitis
24.56. Which of the following interventions lack
B. Gout
evidence of efficacy in the treatment of any
G. Post -streptococcal arthritis
components of fibromyalgia (pain, fatigue,
D. Psoriatic arthritis
physical functioning)?
E. Sexually acquired reactive arthritis
A. Cannabis
24.52. Most of the genes below are implicated B. Cognitive behavioural therapy (CBT)
in influencing either susceptibility for, or severity
G. Gabapentin
of, ankylosing spondylitis. However, which of
D. Supervised aerobic exercise training
these genes below has NOT been implicated?
E. The serotonin and noradrenaline reuptake
inhibitor (SNRI) duloxetine
A. ERAP-1
B. HLA-827 24.57. Which of the following is thought to
G. ANK-H be a consequence of, or associated with,
D. /L -23 receptor constitutive substantial connective tissue laxity
E. STAT-3 (hypermobility syndrome (HMS)/
hypermobile-type Ehlers-Danlos)?
24.53. Which combination of features below
A. Enthesitis
is most likely to be relevant to a diagnosis
B. Fibromyalgia
of axSpA?
G. Hypertension
A. Achilles tendon enthesitis, anterior uveitis D. Plantar fasciitis
and pubic symphysitis E. Uterine fibroids
B. An aunt who has psoriasis, rheumatoid
factor and fatigue 24.58. The autoantibody profile: ANA positive,
G. Back pain, joint swelling and stiffness, DNA!Sm/Ro(SSA)/La(SSB) negative,
scleritis, fatigue and positive ACPA ribonucleoprotein (RNP) positive, is most likely
D. High ESR, anterior uveitis, ankle swelling, to be associated with which autoimmune
raised serum angiotensin-converting enzyme connective tissue disease?
(ACE)
A. Mixed connective tissue disease (MCTD)
E. Low back pain, rosacea, prostatism and
B. Polymyositis
diarrhoea
G. Primary Sjogren's syndrome (PSS)
D. Systemic lupus erythematosus (SLE)
24.54. Enthesitis is the hallmark musculoskeletal E. Systemic sclerosis (SScl)
lesion of all spondyloarthritides (SpAs). Which
one of the following is characteristic of 24.59. A 34 year old woman (currently
enthesitis in the context of an SpA condition? mid-menstrual cycle) pres.ents with small joint
A. Enthesitis can occur in PsA without causing pain and stiffness, a UV-sensitive erythematous
any symptoms skin rash on exposed skin surfaces, fatigue,
B. Enthesitis cannot be detected by US mouth ulcers, some ankle swelling and a
24.69. The abnormality on the wrist radiograph A. Barbotage for cutaneous calcinosis in
below (arrowed) suggests which condition? dermatomyositis
B. Local glucocorticoid injection for chronic
plantar fasciitis
C. Oral pilocarpine for primary Sjogren's
syndrome
D. Rituximab (anti-CD20 monoclonal) for
ANCA-associated vasculitis
E. Thalidomide for Beh<;:et's disease
A. A negative HLA-B27 rules out axSpA D. He may have sexually acquired reactive
B. A normal CRP rules out ankylosing arthritis
spondylitis E. SIJ radiographs will reveal the diagnosis
C. A previous diagnosis of sterile urethritis is
irrelevant information to making a diagnosis
Answers
24.1. Answer: E. single joint and risk factors of obesity,
Osteoclasts are responsible for resorbing bone thiazide therapy and excessive alcohol intake.
and osteoblasts for bone formation but The pattern of involvement and acute onset is
osteocytes are responsible for coordinating not consistent with rheumatoid arthritis,
osteoblast and osteoclast activity. psoriatic arthritis or OA. Septic arthritis is
possible but unlikely in·the absence of a
24.2. Answer: D. previous history of joint disease or site of
RANK and LRP5 are key receptors involved infection.
in the activation of osteoclastic bone
resorption and bone formation, respectively. 24.7. Answer: A.
Osteoprotegerin inhibits bone resorption. Wnt Calcium pyrophosphate deposition disease is
stimulates bone formation but is a ligand, not a strongly associated with OA and typically
receptor. RANKL is a ligand that stimulates affects those aged >65 years, affecting women
bone resorption. more commonly than men. The onset is
sudden with join pain and swelling developing
24.3. Answer: D. over a period of 4-6 hours. Dehydration is a
Paracetamol is the first-line systemic analgesic common precipitating factor, and investigations
for mild to moderate pain. Non-steroidal typically reveal a neutrophilia and a raised ESR
anti-inflammatory drugs (NSAIDs) such as and CRP. Gout and reactive arthritis can
diclofenac should be used with great caution in present in a similar manner but would be less
the elderly and there would be a higher risk of likely in a woman of this age. Septic arthritis is
adverse effects with co-codamol, gabapentin possible but usually has a subacute onset and
and tramadol. tends to develop more slowly, over a period of
24-48 hours.
24.4. Answer: E.
Obesity aggravates joint pain in osteoarthritis 24.8. Answer: B.
and weight loss is one of the most effective The history is suggesting of septic arthritis
therapies for osteoarthritis (OA) of the lower given the history of rheumatoid arthritis (RA)
limbs. Weight-bearing exercise is unlikely to and immunosuppressive therapy with
help and may worsen symptoms. Surgical methotrexate and a TN F-a inhibitor. Options A,
synovectomy is not indicated in OA and D and E would not be appropriate until
arthroplasty would only be indicated for infection had been excluded, nor would
advanced OA resistant to medical therapy. option C.
Cognitive behavioural therapy would be unlikely
to help. 24.9. Answer: E.
The negative ACPA and normal radiograph
24.5. Answer. B. does not exclude RA since ACPA and
Blood monitoring is not required for rheumatoid factor are negative in about
hydroxychloroquine but is required for all the one-third of patient~ and radiographs are
other drugs to screen for blood dyscrasias and normal in early RA. The presentation would not
abnormal liver function tests. be consistent with PMR and the distribution of
involvement (wrists,.metacarpophalangeal joint;
24.6. Answer: A. MCPJ) excludes OA. MRI.would not be
The clinical presentation is typical of gout, necessary since the patient has typical signs of
given the acute onset, involvement of a synovitis.
I
studied in hip OA. Joint replacement surgery is affected mother and brother.
a recognised treatment for OA, but would only
be indicated when optimal medical therapy was 24.27. Answer: B.
ineffective. In about I 0-15% of cases the disease is
inherited in families due to mutations in the
24.22. Answer: D. SQSTM1 gene. There is no proven association
Although diet accounts for a proportion of with the HLA locus. Paget's is a focal skeletal
circulating vitamin D, sunlight exposure is the disorder characterised by increased bone
most important source in most people. resorption and formation (not reduced bone
Synthesis of 25(0H)D in the skin under the formation). Although environmental factors play
influence of UV light accounts for the fact that a role in Paget's disease of bone, the triggers
circulating levels are highest in the summer and are unclear and there is no evidence that
lowest in the winter. It is very unlikely that this alcohol intake or smoking predispose to the
patient's symptoms are related to the level of disease.
vitamin D.
24.28. Answer: D.
24.23. Answer: D. The radiograph shows changes typical of
The inactive metabolite 25(0H) vitamin D Paget's disease with alternating areas of
(25(0H)D) is hydroxylated in the kidney at the osteosclerosis and osteolysis and expansion of
I a. position by the enzyme CYP27BI to give the femur. There is also a pseudofracture on
the active metabolite I ,25(0HhD. Although the lateral femoral cortex. The site of Paget's
25(0H)D is hydroxylated at the I and 24 corresponds with the location of the pain, and
positions, the 24,25(0HhD metabolite is not the elevated ALP level indicates increased
biologically active. metabolic activity, suggesting that the pain may
be caused by Paget's disease of bone. There
24.24. Answer: A. is no evidence of OA, which makes this unlikely
Osteomalacia is suggested by the symptoms, as the cause of the pain. The biochemistry
the patient's ethnic background, the low does not support a diagnosis of osteomalacia
25(0H)D, high PTH, low phosphate and high and renal osteodystrophy would not be
ALP. Vitamin D insufficiency is a biochemical expected in a patient with mild renal
diagnosis in patients with serum 25(0H)D levels impairment.
of 25-50 nmoi/L (I 0-20 ng/mL). Polymyalgia is
unlikely in view of the normal ESR, and 24.29. Answer: E.
statin-induced myopathy is unlikely in view of Scheuermann's is characteristically
the normal creatine kinase. The symptoms and accompanied by wedge deformities of several
biochemical abnormalities are not consistent adjacent thoracic vertebrae with disc space
with osteoporosis. narrowing. It typically results in contiguous
vertebral paramarginal syndesmophytes.
24.25. Answer: D. Options B, D and E would be consistent with
It is likely that the low 25(0H)D levels are osteoporosis. Option C would be consistent
secondary to fibromyalgia since vitamin D with osteoarthritis.
deficiency is common as a secondary feature
of many diseases due to lack of sunlight 24.30. Answer: E.
exposure and a poor diet. There is no evidence Fractures occur most commonly in childhood,
that vitamin D supplements help in fibromyalgia decrease during adolescence and adulthood
or that fibromyalgia is a complication of vitamin but increase again with ageing. Option A
D deficiency. is incorrect: it is un~nown whether
bisphosphonates reduce fracture risk in adults
24.26. Answer: E. with 01. Option B is imcorrect: vertebral
Option A is unlikely in view of the positive family fractures occur collJmonly. Option C is
history. Vitamin D-deficiency rickets is unlikely incorrect: blue sclerae are typical of type I 01
in view of the positive family history and the but normal sclerae do not exclude other
normal 25(0H)D level. Options C and D are subtypes.
third finger MCPJs are involved (RA often picks 24.49. Answer: C.
out the fifth MCPJ early on in the course of the All JIA patients should be referred for
disease). ophthalmological examination to rule out uveitis.
Both lBO and leukaemia can present with
24.46. Answer: D. oligoarthritis. Systemic JIA is regarded as an
The features are not unusual for a antibody-negative condition and is analogous to
rheumatology referral! The differential adult-onset Still's disease. The prevalence of
diagnosis can be wide and includes JIA (1 : 1000) is similar to the prevalence of
inflammatory and autoimmune disease. Also, diabetes in children and adolescents (1 : 700).
significant somatic and functional effects from
psychosocial triggers in a vulnerable person 24.50. Answer: E.
can provide such a symptom complex. Rituximab is 'B-cell depletion' therapy. B-cell
Rheumatology assessment requires a broad proliferation and B-cell antigen presentation are
approach and judicious use of investigations not a major part of the pathophysiology of
based on a stratified differential diagnosis either AS or PsA. Other therapies mentioned
based on clinical assessment. A 2-year history have alternatively been shown to have some
of an illness due to malignancy would be clinical effectiveness in one or both conditions.
expected to cause progressive clinical
deterioration. 24.51. Answer: E.
A pustular plantar foot rash occurring
24.47. Answer: C. simultaneously with inflammatory back pain,
Men do get osteoporosis and the commonest enthesitis and synovitis does suggest reactive
vertebral fracture sites are low thoracic spine or arthritis. A sexual history may not be
L1 or L2. Fracture pain can be mild to severe volunteered but should be sought - with direct
but often starts acutely or subacutely, and questions about new recent sexual encounters,
persists. It would be rare for axSpA to present penile discharge, dysuria and other genital
at this age for the first time. Disc prolapse symptoms, if necessary.
lesions occur mainly in younger people and are
rare in the thoracic spine - the commonest 24.52. Answer: C.
levels being L5/S1, L4/L5, L3/L4. The absence Ankylosing spondylitis (AS) and all
of systemic features is chiefly against this being spondyloarthropathies are generally
sepsis - patients with this diagnosis are often autoinflammatory conditions characterised by
generally quite unwell. Like prolapsed discs, the abnormalities in antigen processing (HLA-B27,
main sites of spondylolistheses are lumbar ERAP-1 ), antigen presentation (ERAP-1,
spine and sometimes in the neck, but very HLA-B27) and the stimulation and activity of
rarely in the thoracic spine. Malignancy is not type 17 T cells (IL-23r, STAT-3). ANK-H is
on the list but should be considered in anyone associated with calcium pyrophosphate
this age presenting with non-trivial/self-limiting deposition disease (CPPD). ANK-H codes
back pain for the first time. for a transmembrane protein important in
transporting inorganic pyrophosphate.
24.48. Answer: D.
Oligoarthritis is the most common form of JIA, 24.53. Answer: A.
accounting for 60% of cases. Monoarthritis is Scleritis and ACPAs are features of RA.
an unusual presentation of RA, especially if Uveitis, ankle swelling and raised ACE are
both rheumatoid factor and ACPA antibodies typical of sarcoid. Fatigue is a feature of all
are negative. Ophthalmological screening is autoinflammatory and autoimmune conditions.
recommended in all cases of JIA, regardless of A small minority of PsA patients may have a
whether ANA is positive or negative. As in positive rheumatoid factor. Achilles insertional
adults, PsA may be the cause of monoarthritis/ tendonitis (enthesitis) and symphysitis are
oligoarthritis, whether or not psoriasis is recognised axSpA lesions.
present, i.e. PsA has to be .considered
possible. Initial management should be 24.54. Answer: A.
with an NSAID and consider intra-articular Direct evidence from randomised. controlled trial
steroid injection (under light general data suggest TNF-a inhibitors ustekinumab
anaesthetic). (anti-IL-12/23 monoclonal) and secukinumab
malignancy so initially CT screening is helpful; headache and other cranial symptoms is not
however, the merit of regular yearly CT uncommon in the disease. Sarcoid is possible
monitoring in the absence of detecting - as the rash may be erythema nodosum,
malignancy thereafter has not been which is common to sarcoid and BD - but
substantiated. there is no hypercalcaemia or ankle joint
involvement here, which would be more typical
24.62. Answer: C. in sarcoid. Sinus thrombosis in BD can be
Even in severe disease, structurally normal detected by either head CT or MRI but sarcoid
parts of salivary glands can be seen. Their in the brain often affects meninges at the
sub-function may be a consequence of base of the brain and ideally requires
cytokine inhibition of neurotransmitter function. gadolinium-enhanced sequences on MRI to
Humidity, blink rate (and therefore tasks being disclose lesions adequately.
undertaken) and air conditioning all affect the
degree to which surface moisture from eyes 24.66. Answer: A.
and mucous membranes evaporates, and Cannabis use has been linked to causing an
therefore affects symptoms. Patients who have occlusive vascu/opathy similar to
previously failed to benefit from eye lubricants thromboarteritis obliterans. Hepatitis C is
managed to do so after a trial of topical eye associated most commonly with
drop steroids. PSS is significantly associated cryoglobulinaemic vasculitis. HIV and indeed
with the development of lymphoma. many different viruses are considered potential
triggers of vasculitis. HLA-851 is associated
24.63. Answer: D. with Behc;;et's disease -the main manifestation
In theory, all the features can conceivably occur of which is a vasculitis. lgA production and
in all the conditions but the likelihood of a deposition in vasculitis lesions is a characteristic
subacute, relapsing/remitting condition involving of Henoch-Schonlein purpura vasculitis.
different tissues arising at different times
supports the diagnosis of granulomatosis with 24.67. Answer: D.
polyangiitis (GPA; formerly Wegener's) here. Case examples and rationale exist to support
Fever and rash are generally temporally related an association of Propionibacterium acnes and
in post -streptococcal reactive arthritis, SAPHO syndrome but the level of proof that
adult-onset Still's disease and rheumatic fever. the organism is responsible for, or associated
Lung malignancy would not be common in a with, a substantial number of cases of SAPHO
non-smoker and features of it unlikely to remit is not high. SAPHO is thought to represent a
over time. spectrum of pathophysiological features
possibly contiguous with features seen in
24.64. Answer: B. childhood chronic relapsing multifocal
The diagnostic terminology for GPA and MPA osteomyelitis (CRMO). Associations between
have been subsumed under the new diagnostic the other microorganisms and their
classification 'ANCA-associated vasculitis autoinflammatory or autoimmune condition are
(AAV)', partly owing to their association with more robust, based on good epidemiological,
autoantibodies to neutrophil antigens clinical and immunological data or pathogenetic
(antineutrophil cytoplasmic antibody (ANCA) vs. principles.
intracellular antigens proteinase-3 (PR3) and
myeloperoxidase (MPO) for GPA and MPA, 24.68. Answer: C.
respectively). A substantial number of patients PSS is associated with about a 15% risk of
with polymyositis have antinuclear antibodies lymphoma (PSS with mucosa-associated
(ANAs) and myositis-specific antibodies. GCA is lymphoid tissue lymphoma; 'MALToma'). RA is
not associated with autoantibodies. associated with malignancy with a standardised
incidence ratio (SIR) of 1.1 . The risk is greatest
24.65. Answer: A. for Hodgkin lymphoma (SIR 3.21) and lung
The features are suggestive of Behc;;et's cancer (SIR 1.64). Relapsing polychondritis can
disease (BD). A history of genital lesions may be associated with coincident hematological
not be volunteered. Variollis inflammatory eye malignancy (particularly myelodysplasia) in a
lesions can occur in BD and cerebral venous small minority of cases. DISH is associated with
sinus thrombosis as a cause of non-specific diabetes and possibly with CPPD disease, but
not with malignancy. Giant cell arteritis occurs examining for crystals (urate-causing gout or
in the elderly, a population in which malignancy calcium-containing causing pseudogout). CKD
is not unusual but there is no known stage 3b-5 is associated with urate and
association. calcium-containing crystal-induced
musculoskeletal disease. Secondary joint
24.69. Answer: D. infection following incompletely treated urine
There is new bone formation at ligament infection is possible but also previous infection
attachments at the distal ulna (this is a can trigger subsequent bouts of crystal arthritis.
non-articular part of the carpus) typical of PsA.
The feature of juxta-articular ('fluffy') new bone 24. 71. Answer: A.
adjacent to joints is highlighted in the CASPAR Barbotage is a procedure usually done under
classification criteria for PsA (Box 24.69). The ultrasound guidance whereby needle disruption
radiocarpal joint space is reduced here from of calcific deposits in tendons is undertaken
PsA also. There is an absence of subchondral (e.g. calcific supraspinatus tendonitis). The
cysts or sclerosis and osteophytes (thus technique usually involves repeated
unlikely to be primary OA or CPPD), and no RA high-pressure fluid injection and aspiration. It
or gout erosions present, nor periarticular has not been shown beneficial for calcinosis
osteopenia, as seen in active RA. cutis. Thalidomide is an extremely effective
treatment for the severe mucosal ulcers
in Behr;:et's disease. Local glucocorticoid
24.69 The CASPAR criteria for psoriatic arthritis
injection is useful for treating a number of
Inflammatory articular disease ijoint, spine or enthesis) .non-inflammatory enthesopathic lesions (such
with ~ 3 points from the following (1 point each unless
stated):
as plantar fasciitis and elbow epicondylitis).
Current psoriasis (scores 2 points) Rituximab has now been shown useful in some
History of psoriasis in first- or second-degree relative patients with AAV, inducing as well as
Psoriatic nail dystrophy maintaining remission. Oral pilocarpine can
Negative lgM rheumatoid factor*
improve salivary and other glandular secretion
Current dactylitis
History of dactylitis in all but late PSS. A trial of therapy 5-1 0 mg 3
Juxta-articular new bone1 times daily can be attempted over a month.
*Established by any method except latex. 11/1-defined
ossification near joint margins (excluding osteophytes) on 24.72. Answer: D.
X-rays of hands or feet. Reactive arthritis can present like axSpA or AS
(CASPAR= ClASsification for Psoriatic ARthritis)
with low back axial symptoms. Radiographs are
frequently normal in early SpA conditions.
I 24.70. Answer: E.
The clinical features are fairly non-specific and
HLA-827 is positive in 95% of people with an
old (modified New York criteria) definition of AS
I gout, septic arthritis and pseudogout are but is less prevalent in cohorts of patients
-~
possible diagnoses. Indeed, severe gout or diagnosed with axSpA. In axSpA (and AS) and
pseudogout can cause systemic symptoms all SpA conditions, the acute phase response
identical to those caused by infection. The may be normal and associated clinical
diagnosis is made on knee fluid aspiration and problems (current or previous) include anterior
then Gram stain and culture of the fluid, but uveitis, psoriasis, inflammatory bowel disease,
also polarised light microscopy of joint fluid enthesitis and sterile urethritis.
Neurology
Multiple Choice Questions
25.1. A 44 year old woman is admitted with B. Dissociated sensory loss is always
abrupt onset of neurological deficit. The associated with reflex changes
referring physician suspects a brainstem stroke. C. Dissociated sensory loss is usually a sign of
Which of the following combinations of signs brainstem pathology
and symptoms would be most likely to originate D. Dissociated sensory loss means
from a brainstem lesion? loss of sensation over one-half of
A. Bilateral optic neuropathy the body
B. Cranial nerve signs with sensory and upper E. Dissociated sensory loss requires testing of
motor neuron signs in all four limbs pin-prick, light touch, proprioception and
C. Horner's syndrome with ipsilateral arm pain vibration in all four limbs
D. Lower motor signs in both arms only
E. Upper motor neuron signs in both legs only 25.4. A 25 year old woman presents to the
emergency department with a rapidly evolving
25.2. A 34 year old man is admitted with severe headache. She has a family history of
worsening weakness in both legs. Over the cerebral neoplasm and is worried that this is
course of 3 days he has found it increasingly the cause of her headaches.
difficult to walk upstairs. In the last 12 hours he Which of these accompanying features
complains of feeling mildly breathless. would suggest a diagnosis other than
The referring physician finds weakness in all migraine?
four limbs and cannot elicit reflexes. He can A. Asymmetrical reflexes
find no sensory problems. B. Exacerbation by exercise
Which diagnosis is most likely? C. Photophobia
A. Guillain-Barre syndrome (GBS) D. Unilateral site
B. Inflammatory myopathy E. Vomiting
C. Myasthenia gravis
D. Peripheral neuropathy 25.5. An 18 year old male presents with
E. Spinal stroke numbness in both legs evolving over a few
weeks. He reports some variable sensory
25.3. A 38 year old man presents with sensory alteration and is worried that this might
changes in both legs, which he finds difficult to represent multiple sclerosis. Gait is slower than
characterise. The referring physician asks you usual but there is no reported weakness.
to review him 'to assess him for a dissociated Which of the following would suggest a
sensory loss'. lesion outside the spinal cord?
Which of the following statements is true A. Band of hyperaesthesia across the trunk
about dissociated sensory loss? B. Loss of reflexes
A. Dissociated sensory loss is a sign of C. Preserved vibration but loss of pin-prick
peripheral nerve disease sensation over both legs
D. Puncture one of the purpuric lesions for Examination shows motor signs in the legs
microscopic analysis only with increased reflexes and upgoing
E. Take blood for viral polymerase chain plantars. All modalities of sensation are reduced
reaction (PCR) test below the costal margin.
What is the likely underlying process?
25.13. With regard to the patient in Question A. Cerebral metastasis
25.12, IV benzylpenicillin has now been B. Metastatic spinal cord compression
administered and his cerebral imaging has C. Paraneoplastic encephalopathy
been shown to be normal. A lumbar puncture D. Paraneoplastic Guillain-Barre syndrome
has been carried out. E. Paraneoplastic neuropathy
What is the most likely pattern of abnormality
to emerge in cerebrospinal fluid (CSF)? 25.16. A 33 year old female has had a severe
A. Normal white cells, normal protein, low pain over her left shoulder, which increased
glucose gradually over the initial 24 hours, corning on 2
B. Normal white cells, raised protein, normal weeks after an influenza vaccination. It is a dull
glucose unremitting ache for which she was given
C. Raised white cells (90% lymphocytes), raised opiate analgesia for several weeks.
protein, low glucose Since the pain subsided she has had some
D. Raised white cells (90% neutrophils), normal weakness of hand movements - most
protein, normal glucose particularly in holding and turning a door key.
E. Raised white cells (90% neutrophils), raised She has reduced reflexes in the left arm, with
protein, low glucose somE) subjective decrease in pin-prick sensation
over all dermatomes in the left arm.
25.14. A 38 year old man presents to his family What is the most likely diagnosis?
physician with a 3-rnonth history of a change in A. Brachial neuralgia
sensation in both arms. His wife has been B. Cervical radiculopathy
trying to get him to seek help for worsening C. Guillain-Barre syndrome
hand weakness and progressive gait D. Herpes zoster-related neuralgia
difficulties. E. Transverse myelitis
Examination shows him to have no cranial
nerve signs. He has marked wasting of intrinsic 25.17. An 18 year old female is referred by her
muscles of both hands and brisk leg reflexes optician after an abnormal visual field test. She
with upgoing plantar responses. Sensory had her vision checked after complaining of
examination shows him to have lost pin-prick headaches and formal perimetry has shown
sensation over both arms and the upper half of enlargement of both blind spots.
his trunk. Vibration and proprioception are Further clarification of her symptoms has
normal. revealed a 6-month history of worsening daily
What is the likely pathology? headaches, increased on bending and
coughing, sometimes accompanied by transient ~
A. Metastatic lesion in the upper spinal cord
flashing lights lasting seconds at a time. ~
B. Motor neuron disease
C. Peripheral neuropathy Neurological examination confirms the
D. Spinal cord stroke enlargement of blind spots with some
E. Syringomyelia accompanying papilloedema. No other focal
deficit was found.
What is the likely diagnosis?
25.15. A 64 year old man is referred to the
emergency department by his family physician. A. Cerebral venous sinus thrombosis
He has been undergoing radiotherapy for B. Idiopathic intracranial hypertension (IIH)
a small cell carcinoma of lung for the last C. Intracranial neoplasm
2 months. D. Migraine with aura
He sought help this morning for some back E. Optic neuritis
pain and gait difficulty evolving over the last
day. He has no symptoms in the arms. He 25.18. A 21 year old man was involved in a
reports some recent difficulty in initiating clash of heads while playing football. He was
urination. unconscious for about a minute but recovered
and was able to play on for the remaining half precipitated by rising from a lying position,
hour. He did not report any concussive building up over 4-5 minutes each time and
symptoms and was able to go out for a meal necessitating that she lie back down.
with a few friends where he consumed two She is distressed and cannot sit up for any
pints of beer. length of time. Examination shows no change
The next morning his friends cannot rouse in cranial nerves. Her reflexes are generally
him from sleep. An ambulance is called and brisk but plantar responses are downgoing,
takes him immediately to hospital. On and there is no other deficit in the limbs·.
admission he is apyrexial and has a Glasgow She has normal blood tests and a normal CT
Coma Scale (GCS) score of E2 V3 M2. His of brain but no other investigation.
pupils are symmetrical and reacting to light. What is the likely cause of her headache?
Plantar response is upgoing on the right. A. Cerebral venous sinus thrombosis
What is the likely diagnosis? B. Cluster migraine
A. Alcoholic coma C. Intracranial tumour
B. Extradural haernatorna D. Spontaneous intracranial hypotension
C. Post -traumatic tonic-clonic seizure E. Subarachnoid haemorrhage
D. Subdural haernatorna
E. Viral encephalitis 25.21. A 44 year old man has been in
hospital for 3 weeks for management of
25.19. A 75 year old woman had a diagnosis of decompensated alcoholic liver disease.
Alzheimer's disease made 3 years ago. He awakens with an inability to dorsiflex the
Recently her mobility has begun to deteriorate right ankle.
and she has had a number of falls, twice Examination shows normal movements
having her skull X-rayed in the emergency otherwise bilaterally. There is no wasting and
department as a result of her injuries. reflexes are intact. Sensory examination shows
She has a history of hypertension and reduced pin-prick sensation of the right lateral
transient ischaernic attacks and is on aspirin shin. He has slight tenderness over the lower
and rarnipril. Her daughter says that her back bilaterally but no other findings.
memory and concentration are much worse What is the likely cause of his weakness?
over the last 2 weeks and she can go for long A. Alcoholic neuropathy
spells where she is difficult to rouse. B. Cerebral infarct
On examination she is apyrexial and drowsy, C. Common peroneal nerve lesion
and she is disorientated in time and place. Her D. Sciatic nerve lesion
GCS score is E5 V4 M5. There are no cranial E. Tibial nerve lesion
nerve abnormalities, but she is weaker on the
left, with generally brisk reflexes and upgoing 25.22. A 23 year old woman presents havi11g
plantar reflexes. She has some frontal release had three generalised tonic-clonic seizures in
signs (pout and grasp reflexes) bilaterally. the previous 3 weeks. Which of the following
What is the most likely explanation for her would suggest a focal origin to her epilepsy?
decline? A. History of 'blank spells' in childhood
A. Alzheimer's disease B. History of morning myoclonus
B. Extradural haernatorna C. Prolonged post -ictal dysphasia
C. lschaernic stroke D. Prolonged seizure (lasting 2-3 hours)
D. Metabolic encephalopathy E. Seizures on awakening
E. Subdural haernatorna
25.23. A 56 year old right -handed man is
25.20. A 34 year old woman has a long history admitted with an abrupt onset of loss of
of migraine with aura happening three or four speech. Comprehension appears to be
times per year. After a recent episode where preserved and he can follow direction with no
she had visual aura, typical severe headache, difficulties. He cannot repeat words or phrases.
recurrent vomiting with photophobia and an Where is the abno~mality most likely to be
intolerance of noise, she is left with a different situated on imaging?
character of headache over the subsequent 10 A. Left and right frontal lobes
days. This is a severe pounding headache B. Left frontal lobe
periods for which she would take analgesia, but C. Functional sensory symptoms
these were different from the current D. Multiple sclerosis
symptoms. In between attacks, she is well and E. Ulnar entrapment neuropathy
on no medication.
Which of the following is the most likely 25.42. An 18 year old male presents to a
diagnosis? remote hospital 3 hours after being felled by a
A. Carotid artery dissection single punch. He was briefly knocked out,
B. Cluster headache seemed to recover, before becoming
C. Migraine increasingly drowsy, then losing
D. Temporal arteritis consciousness.
E. Tension-type headache On arrival in the emergency department,
his neurological examination shows: no eye
25.39. A 66 year old man presented with 6 opening, incomprehensible sounds, flexing to
weeks of intermittent diplopia, improved by pain on the right, extending on the left. His
closing one eye. His family physician has pulse is 50 beats/min, regular; blood pressure
checked a variety of blood tests - all were is 210/115 mmHg. His right pupil is fixed and
normal except antibodies to the acetylcholine dilated. His airway is compromised and he is
receptor (AChR), which returned strongly intubated and ventilated. The nearest hospital
positive with a high titre of antibodies. with a neurosurgeon and scanner is 6 hours
What is the next most relevant test? away by ambulance.
What is the best course of action?
A. Antibodies to muscle-specific kinase (MuSK)
B. CT chest A. Burr hole on the left side of the head
C. Electromyography (EMG) B. Burr hole on the right side of the head
D. MRI head C. Palliative care
E. Tensilon test D. Transfer him to the nearest hospital as soon
as possible
25.40. A 70 year old female presents with E. Treat him with mannitol and intensive care
variable weakness of her legs; she has lost a
significant amount of weight recently, complains 25.43. A 74 year old woman presents with a
of a dry mouth and, more recently, a cough, 12-month history of tremor affecting her right
occasionally with blood. There is little to find on arm only.
examination, and there is uncertainty about Which feature is the most supportive of a
whether her leg reflexes are present. There diagnosis of Parkinson's disease?
are no other signs, although she looks unwell A. Family history of learning disabilities
and thin. B. Her father had a tremor
Antibodies to which of the following are most C. Her husband reports that for the last few
likely to be present? years she has occasionally lashed out or
A. Acetylcholine receptor (AChR) grabbed him while asleep
D. Tremor improves with small amounts of
~.
B. Muscle-specific kinase (MuSK)
C. N-methyl-o-aspartate (NMDA) receptor alcohol
D. Thyroid peroxidase E. Tremor is most apparent when using the
E. Voltage-gated calcium channel (VGCC) arm
25.41. A 28 year old woman presents in the 25.44. A 65 year old man has been diagnosed
I
sixth month of her first pregnancy with with Parkinson's disease. He is reluctant to I
unpleasant tingling affecting the ring and little start treatment, as he has heard that such
fingers, mainly on the left hand and to a lesser treatment only lasts a short time before he will
extent the right, which keeps her awake at become immune to it.
night. She has developed gestational diabetes, Which statement is most correct?
but is otherwise well, with no previous A. He should avoid treatment as long as he
problems. She is on no medication. can, as there is a short therapeutic window
What is the most likely diagnosis? once he has started it
A. Carpal tunnel syndrome (CTS) B. He should delay treatment until his
B. Cervical spondylosis symptoms are interfering with everyday life
C. He should pursue deep brain stimulation otherwise well, and his only medication is
(DBS) surgery rather than medication, as this thyroxine.
is far more likely to be successful What is the likely diagnosis?
D. He should start a non-dopaminergic therapy A. Dystonic tremor
such as trihexyphenidyl B. Enhanced physiological tremor
E. He should start treatment now, as C. Essential tremor
dopaminergic therapies are disease D. Hyperthyroid-associated tremor
modifying E. Parkinson's disease
25.45. A 72 year old male presents with a 25.48. A 66 year old female is brought to the
12-month history of a right arm tremor at rest, emergency department by her worried husband .
micrographia and generalised slowness. He is in the late afternoon. She had been well when
finding it increasingly difficult to turn over in they got up that morning; he had left to do
bed. He is on no medication, and the some shopping at 1000 hrs, returning an hour
examination reveals mainly right-sided later, expecting her to be ready for a planned
parkinsonism. His grandmother was said visit to see old friends. However, she was still in
to have had Parkinson's disease, and died her dressing gown and seemed to have
aged 82. forgotten they were due to go out. Although he
What is the most appropriate next explained the proposed visit to her several
investigation? times, she kept asking him why he wanted her
A. CT head to get dressed. Shortly thereafter, their
B. Genetic testing for the known mutations neighbour knocked on the door to borrow a
associated with parkinsonism ladder- his wife did not recognise him, and
C. None when told it was their neighbour, she was
D. Serum caeruloplasmin adamant it was not, as she remembered their
E. Single-photon emission computed neighbour as someone quite different. Her
tomography (SPECT) imaging (DaTscan) husband realised she was referring to the
previous neighbour who had moved out 2
25.46. A 69 year old woman has developed odd years before. She got dressed unaided, they
involuntary chewing and 'gurning' movements visited their friends, whom she recognised, but
of her mouth and jaw over the last few months, she seemed to have forgotten a number of
which cause embarrassment. Three years recent events, and kept asking the same
previously, she suffered a minor stroke, but questions repeatedly. By the time she reached
made a good recovery. She has had hospital, she seemed to have recovered back
intermittent vertigo for many years. She takes to normal, although could not recall the
simvastatin, clopidogrel, lisinopril, previous few hours. The examination was
bendroflumethiazide and metoclopramide. normal.
What is the most likely cause? What is the likely diagnosis?
A. Drug-induced dyskinesia A. Early Alzheimer's disease
B. Functional (psychogenic) movement B. Functional (psychogenic) amnesia
disorder C. Post-ictal state following an unwitnessed
C. Huntington's disease seizure
D. Parkinson's disease D. Transient global amnesia (TGA)
E. Post -stroke chorea E. Transient ischaernic attack (TIA)
25.47. A 52 year old male describes a 10-year 25.49. A 45 year old man presents to his family
history of tremor affecting both arms, and more physician very worried about his memory. He
recently his head. His father has a similar but describes difficulty remembering words, making
more mild tremor, as does his older brother. silly errors whilst typing and occasionally
Although his brother claims that alcohol helps forgetting names, albeit transiently. His
his tremor, this patient has never noted such grandfather died in a nursing home having
an effect. It embarrasses him as he is a waiter, gone 'senile' at the age of.87. He is otherwise
and people notice him shaking as he tries to well. He is able to work, although worried
serve; he has, on occasion, split things. He is about his job as there have been recent
redundancies, and he has two young children lost weight. Her family have been alarmed by
and his wife does not work. her sudden bouts of laughing or crying, often
The doctor speaks to his wife (with his with little provocation, and this is apparent in
permission), who is surprised that her husband clinic. She was previously well. Examination is
was at the surgery, as she was unaware of any normal except for a small shrivelled tongue,
problems. She feels that he is stressed, no which moves slowly, barely intelligible speech
more than usual, and confirms that he is and a brisk jaw jerk.
sleeping well. He is on no medicatio11, does not What is the likely diagnosis?
smoke and drinks only occasionally. He A. Brainstern stroke
dropped 2 points on the Montreal Cognitive B. Motor neuron disease
Assessment, both on immediate recall. C. Myasthenia gravis
What is the likely explanation? D. Olfactory groove meningioma
A. Depression E. Polymyositis
B. Early Alzheimer's disease
C. Functional memory disturbance 25.52. A 59 year male has noted complete loss
D. Minimal cognitive impairment of smell and taste in the last few months. He is
E. Sleep apnoea sure this has only been present since he
slipped on ice outside a fishmongers and
25.50. A 79 year old male arrives in the banged the back of his head; he thinks he may
emergency department having developed an have briefly lost consciousness. He had a
acute movement disorder affecting his left arm headache for a few weeks after this and,
and leg that day. He is fully conscious but although he recovered well, he is pursuing legal
distressed. He has recurrent and apparently action against the fishmonger who he maintains
uncontrollable movements mainly of his left was negligent. He is a heavy smoker, but
arm, which suddenly shoots out at odd angles, otherwise well.
and flails, before being still for a few seconds, What is the most likely cause of his anosmia
then repeats the wild movements. There is a and ageusia?
similar but less dramatic pattern in his leg. He A. Idiopathic
does not appear weak, and has no other B. Malingering
symptoms or signs. He underwent triple C. Parkinson's disease
coronary artery bypass grafting 10 years D. Post-head injury
previously, and is on treatment for E. Smoking
hypertension. He is normally independent and
generally very well. He is seen by the stroke 25.53. A 32 year old woman with multiple
team who do not think this is the result of a sclerosis (MS) has developed urinary problems.
stroke, and a neurology consult is requested. She frequently feels she needs to pass urine,
Where is the likely lesion? although often passes only small amounts.
A. Brainstem She is intermittently incontinent, and has had
B. Left motor strip several proven urinary tract infections in the last ~
-
D. Meniere's disease work for the last 3 months and has now
E. Migraine become withdrawn, depressed and weepy.
Neurological examination is normal.
What is the likely diagnosis?
25.62. A 26 year old woman saw her optician
because of recent headaches. These are A. Chronic Daily Headache
present on stooping or coughing and often B. Chronic migraine
associated with visual symptoms (small flashing C. Functional headache disorder
dots or brief loss of vision). She has no history D. Intracranial space occupying lesion
of vomiting or other neurological symptoms. E. Subarachnoid haemorrhage
She has no cognitive or depressive symptoms.
Examination shows her body mass index to 25.65. A 28 year old man presents
be 40 kg/m 2 . She has bilateral papilloedema with episodes of unsteadiness lasting
and no venous pulsation on fundoscopy. Blind days to hours at a time on around 3-4
spots are enlarged in both eyes. Neurological occasions per year. The~e are not be
examination is otherwise normal. worsened by changes in position, and he is
What is the likely cause of her fundal not aware of any precipitants. There is no
abnormalities? accompanying pain or visual symptoms and in
-
right hand. weakness with preserved reflexes in all limbs.
You see her 24 hours later, at which point What is the likely cause of her symptoms?
she feels drained but otherwise back to normal. A. Botulism
Neurological examination is normal. B. Brainstem stroke
What is the most likely cause of her C. Miller Fisher syndrome
symptoms? D. Multiple sclerosis I
A. Cerebral venous sinus thrombosis E. Myasthenia gravis
B. Focal seizure arising in the occipital region I
C. Migraine with aura 25.74. A 34 year old woman was involved in a
D. Subarachnoid haemorrhage minor road traffic accident 24 hours previously.
E. Transient ischaemic attack Her car had been hit from behind but she had
not lost consciousness and had not suffered a
25.72. A 21 year old male has been working on direct blow to the head. On awakening the next
a farm for the summer. He has been on day she was aware of a 'ight-sided headache
treatment with flucloxacillin for jaw stiffness that with associated neck pain. She had no diplopia
had been diagnosed as an early dental or visual symptoms and no other focal
abscess. Over 5 days, he has become more neurological symptoms.
25.75. A 44 year old woman has a 5-year 25.77. A 54 year old man presents after a
history of progressive left-sided deafness. second bout of left-sided facial palsy in 4 years.
She has been travelling round Asia with her He is a gamekeeper in the Highlands of
work as an aid worker and has not sought Scotland but has been off work with increasing
medical help. fatigue for the last 4 months. He has had some
She has finally presented to her family increasing hyperacusis for the 3 days of his
physician after noticing some mild left-sided recent facial weakness.
clumsiness in her hand and severe headaches, His only other past history is of some
worse on exercising and stooping. She had no assessment at a rheumatology clinic for
family history of neurological disease. generalised aches and pains with worsening
Examination confirms the presence of blurred fatigue.
disc margins bilaterally, a left-sided Examination shows him to be apyrexial with
sensorineural deafness and cerebellar signs in a weakness involving the whole of the left face,
the left arm and leg. with normal fundi and normal eye movements.
What is the likely cause of her progressive Cranial nerve examination is otherwise normal
symptoms? and he has symmetrically normal reflexes and
A. Acoustic neuroma sensory examination.
B. Brainstem stroke What is the likely cause of his symptoms?
G. Meniere's disease A. Bell's palsy
D. Migraine without aura B. Lyme disease
E. Multiple sclerosis G. Multiple sclerosis
D. Stroke
25.76. A 68 year old man presents with E. Syphilis
progressive numbness over 6 months initially
affecting his feet, and spreading up his legs. 25.78. A 48 year old man complains of
Over the last 3 months, his hands have worsening gait difficulty over the last 3 months.
become affected with both numbness and Which of the following symptoms or signs
weakness. He admits to drinking around 12 would suggest that the cause is sited in the
units of alcohol per week. He has no cranial spinal cord?
nerve symptoms and sphincter function is A. Evolution of symptoms over seconds
normal. B. Progressively worsening urinary incontinence
Examination shows him to have reduced G. Sensory loss distally in upper and lower
power symmetrically in both legs distally and in limbs
finger abduction and adduction. Reflexes are D. Widespread upper and lower motor neuron
reduced in all four limbs with downgoing signs
plantars. Sensory testing shows symmetrically E. Worsening diplopia
reduced pin-prick sensation below both knees,
Answers
25.1. Answer: B. 25.5. Answer: E.
The brainstem is a packed centre from where Spinal cord lesions can cause upper motor
most cranial nerve nuclei originate (III-XII) and neuron findings, usually with some degree of
all long tracts pass through. Combination of all sensory change and sphincter dysfunction.
these signs will either signify widespread While reflexes can be lost in the immediate.
neurological disease or a lesion restricted to the aftermath of a spinal cord lesion (so-called
brainstem. 'spinal shock'), lower motor neuron changes
Horner's syndrome and arm pain would (wasting, areflexia) would not occur in isolation
suggest a brachial plexus lesion, while cervical with spinal cord pathology.
spine changes will cause lower motor neuron
signs in the arms (perhaps with upper motor 25.6. Answer: E.
neuron deficit in the legs). The optic nerves only The narcolepsy tetrad is excessive daytime
interact with the brainstem to serve the sleepiness, cataplexy, sleep paralysis and
pupillary light reflex. hypnagogic hallucinations. Hypnic jerks are a
normal phenomenon, while awakening
25.2. Answer: A. myoclonus is a feature of the generalised
Gradual onset of weakness without sensory epilepsy syndromes. Restless legs
signs and loss of reflexes is most in keeping can accompany a range of medical
with GBS. Strokes usually present abruptly and conditions (parkinsonism, iron deficiency,
would not cause lower motor neuron signs. neuropathy) and, like periodic limb movements
Breathlessness would be unusual in a peripheral in sleep, are not associated with narcolepsy/
neuropathy, even if onset is rapid. A myopathy cataplexy.
should not reduce reflexes. Myasthenia gravis
can cause weakness but onset is usually slower 25.7. Answer: B.
with some degree of fatigability. The scenario is highly suggestive of a
focal-onset epilepsy (previous head injury,
25.3. Answer: E. focal-onset seizures with altered awareness
Dissociation of sensory loss arises because of and automatisms). One of the first-line
the different decussation of dorsal columnar treatments is likely to be effective, and
pathways (vibration and proprioception) and lamotrigine is recognised as having an excellent
spinothalamic pathways (temperature/pin-prick). safety profile. Levetiracetam and sodium
Lesions can affect one pathway more than the valproate can be used in focal epilepsies but
other. It can occur in brainstem lesions, but is would not usually be first line. Clobazam and
usually a sign of spinal disease. Effects on pregabalin are considered adjunctive treatments
sensory pathways can be isolated and have no (used alongside other antiepileptic drugs).
effects on reflexes.
~I
25.8. Answer: B.
25.4. Answer: A. The story is highly suggestive of a genetic
Migraine is a recurrent condition that leads to generalised epilepsy, and treatment choice is
episodic headaches with or without warning. dictated by two issues. Firstly, genetic
The phase of severe headaches is usually
associated with heightened sensitivity to stimuli
generalised epilepsies (GGE) can be made
worse (particularly eliciting myoclonus) by the
I
I
(photophobia, phonophobia, •osmophobia). sodium channel blocking drugs, and
Avoidance of any stimuli is commonly carbamazepine and phenytoin should be
described by migraineurs (lying still in a dark, avoided in such cases. Lamotrigine's efficacy in
quiet room). Loss of function {dysarthria, Genetic Generalised Epilepsy is less than with
transient weakness, visual scotomata) can Valproate and this may deter first-line usage
occur but may merit investigation at the first here. Broad-spectrum antiepileptic drugs
occurrence, or if they emerge as an isolated should be used in these Qircumstances.
symptom. Abnormality of the reflexes (either Secondly, the possibility of future pregnancy
tendon reflexes of plantars) would not be (any drug will usually be required long term)
expected in migraine. should prompt avoidance of sodium valproate
I 25.11. Answer: B.
The pyrexia and evolving neurological deficit
prevent progression to destruction of the spinal
cord. Note that this should include the thoracic
f makes it likely that there is an encephalitic and spinal cord as there may be a 'dropped'
I
fifth nerve will cause sensory alteration over the (false-positive tests are very rare - the antibody
upper face. is very specific). Imaging his head will add
Pathology of the optic nerve will cause a nothing, as this is an autoimmune disease of
reduction in acuity in one eye, but this does not the neuromuscular junction. Antibodies to
pass through the superior orbital fissure. Any MuSK are rnuch less commonly found in
effect on acuity alongside some disturbance of myasthenia gravis, and never when the AChR
ocular motility would suggest pathology in the antibody is positive. Whilst he may have an
cavernous sinus. abnormal single-fibre EMG, the diagnosis is
already made with the antibody result, so the
25.36. Answer: D. EMG will add little or nothing; similarly, a
Labyrinthitis (also known as acute vestibular Tensilon test may well be positive, but
failure) presents with abrupt onset of vertigo adds nothing to what we already know.
that tends to be most severe for a few days, Myasthenia gravis is, however, associated with
severe enough to cause the patient to be thymic abnormalities and in older men
bed-bound. thymomas are not uncommon; hence, he
Meniere's disease is an idiopathic chronically requires imaging of his chest for this reason
recurring disorder involving episodic vertigo (either CT or MRI).
with tinnitus and a progressive deafness.
Benign paroxysmal positional vertigo can be 25.40. Answer: E.
precipitated by minor head injury and results in Whilst the differential on this limited history is
vertigo that is typically precipitated by specific wide, there are clues to suggest Lambert-
head positions (as in the Hallpike Test). This . Eaton myasthenic syndrome (LEMS). The
responds well in most cases to the Epley weakness is variable, in keeping with a
manoeuvre or more chronic rehabilitation. mysathenic syndrome, there are no sensory
features, and the dry rnouth suggests
25.37. Answer: E. autonomic involvement, which is common in
A lesion in the parietal region will cause a LEMS. LEMS may be paraneoplastic, and there
quadrantanopia - due to its effect on the are alarm bells for cancer, with weight loss,
superior fibres, the quadrantanopia will be in unwellness and haemoptysis (lung cancer is the
the contralateral inferior visual field. commonest malignancy seen with LEMS). The
Neglect will result frorn a parietal lesion but reflex uncertainty reflects the classic reflex
this is contralateral to the lesion. Reduced potentiation seen in LEMS, whereby reflexes
acuity results from a reduction in macular appear absent, but rnay return (potentiate) with
function and rnay be a manifestation of an optic exercise. The diagnosis is supported by the
neuropathy. presence of VGCC antibodies.
Diplopia results from a disturbance of ocular
motility - this is unlikely to be caused by a 25.41. Answer: E.
cortical abnormality. The symptoms conform to the distribution of
the ulnar nerve and, although carpal tunnel
25.38. Answer: G. syndrome (median nerve) is common in
1!'
'I This is a typical scenario for migraine without pregnancy, in this case the distribution
aura. The additional non-headache symptoms suggests ulnar not median. The most likely site
would not occur in tension-type headache, and of entrapment is at the elbow (as opposed to
neither temporal arteritis nor dissection behave the wrist in CTS).
in such a paroxysmal manner. (She is also too
young for temporal arteritis.) Although she gets 25.42. Answer: B.
occasional ptosis, the other autonomic features This is very suggestive of an extradural
of cluster are absent and the headache lasts haematoma, localising to the right side of his
too long; patients are usually very agitated with head. He is coning, and will not survive 6 hours
cluster and usually male. in ambulance. The immediate life-saving
procedure is a burr hole to evacuate the clot.
25.39. Answer: B.
The story of variable binocular diplopia is 25.43. Answer: G.
suggestive of myasthenia gravis, and the The sleep disturbance is very suggestive of an
positive AChR antibody confirms this REM sleep behavioural disturbance, now a
angular gyrus in the dominant parietal lobe are autonomic activation and agitation. Cluster
associated with Gerstmann's syndrome headaches typically awaken people from sleep,
(agraphia, acalculia, finger agnosia and inability clusters last weeks, with months to years of
to differentiate left from right). remission in between. They are more common
in male smokers. Migraine can awaken people
25.51. Answer: B. from sleep, but usually patients want- to lie
The symptoms and signs suggest a quietly in a dark room, the opposite of cluster
pseudobulbar palsy, but the progression over patients, and autonomic activation is rare.
several months excludes a stroke; a structural Hypnic headache also awakens people from
lesion could potentially cause this, but not in the sleep, but usually affects older women, and is·
frontal region. Polymyositis may affect not associated with agitation or autonomic
swallowing but not speech, and would not activation. Temporal arteritis does not occur
cause these signs or emotional incontinence. under the age of 50 years and does not
Whilst myasthenia gravis can present with produce such a paroxysmal history. Paroxysmal
bulbar symptoms, the upper motor neuron hemicrania is another form of TAG, but the
signs and emotionalism do not fit. Unfortunately, symptoms are much shorter and affect women
this sounds very likely to be a pseudobulbar more commonly.
presentation of motor neuron disease.
25.55. Answer: E.
25.52. Answer: D. This is a typical story for benign paroxysmal
Disturbance of sense of smell (and taste, which positional vertigo (BPPV), the clues being the
is crucially dependent upon smell) is common short-lasting vertigo induced by changes in
after minor head injury, most typically to the posture, typically in bed. About half of cases
occipital region, as the shearing forces cause are triggered by minor head trauma (there is no
disruption to the olfactory fibres as they pass indication for brain imaging). Treatment with an
through the cribriform plate in the anterior cranial Epley manoeuvre or similar is easy (there are
fossa. (Patients are often mystified as to why a plenty of examples on You Tube!) and highly
bang to the back of their head might affect their likely to be successful, unlike drug treatment.
nose.) It would be an unusual malingering Although he should be advised to reduce his
symptom, and malingering is a forensic rather alcohol intake, which might perhaps have
than medical diagnosis. Parkinson's disease is explained the initial accident, this is not directly
often preceded by hyposmia, although patients an alcohol-related problem.
rarely, if ever, present at this stage. Whilst
smokers often have less acute senses of smell 25.56. Answer: A.
and taste, they rarely notice this. For most The story of an episode of optic neuritis,
patients presenting with reduced sense of smell followed by a spinal cord syndrome, with an
and no apparent triggers, the causes are either extensive longitudinal inflammatory lesion in the
ENT related or idiopathic. spinal cord is very suggestive of neuromyelitis
optica (NMO), which is commonly associated
25.53. Answer: c. with the aquaporin-4 antibody. This does not
The scan confirms that she is retaining urine, sound like a paraneoplastic syndrome, and
with incomplete bladder emptying. Thus the whilst the other tests may add further
optimal treatment would be regular intermittent information, they are unlikely to be diagnostic.
self-catheterisation, providing that her arm/hand NMO is different from MS, and requires a
function is not compromised by her MS. different approach to treatment. Indeed some
Antibiotics would not affect her bladder MS treatments can make NMO worse, so
function, and anticholinergic drugs would distinction is important.
exacerbate the problem. A long-term catheter
would ideally be avoided. 25.57. Answer: B.
This is a non-disabling relapse, and thus there
25.54. Answer: A. is no immediate indication for treatment,
This is a typical scenario for cluster headache, although it should trigger reconsideration of
one of the trigeminal autonomic cephalalgias disease-modifying drugs. Although infection can
25.64. Answer: A. cause for her seizure. The event at the age of
Chronic Daily Headache (sometimes known 16 is removed enough to have little relevance,
as medication overuse headache) is an while the borderline hyponatraemia is not
increasingly common condition, made worse by severe enough to cause seizures. A neutrophilia
ease of access to paracetamol and compound is common after a seizure. While an EEG may
analgesics. The unrelenting nature of the slowly provide some prognostic information, the most
progressive pain with no neurological or important role of investigation is to exclude a
systemic features and associated high intake of primary intracerebral lesion.
analgesia will give good clues to the diagnosis.
While migraine headache syndromes can 25.68. Answer: A.
transform with time, many of this patient's People may develop a constellation of
painful episodes have no other migrainous symptoms after head injury, including
features. It would be an unusual person who headache, fatigue, dizziness, poor
was not rendered weepy or low by such severe concentration/memory, emotionalism and
headaches, and the concurrence of a mood numerous other symptoms. These are not
disorder should not allow the physician to specific to head injury. They are often persistent
make a hasty attribution of symptoms to and may get worse, especially if the diagnosis
psychological causes, particularly in the is not explained. The management requires a
presence of other diagnostic features. careful explanation of the diagnosis, as well as
Subarachnoid haemorrhage would cause an reassurance that they have not suffered any
abrupt -onset acute headache rather than a irreversible brain damage (http://www
relentless one. .headinjurysymptoms.orgl). Unfortunately, in
such scenarios, many (well-meaning) health-
25.65. Answer: C. care workers and other professionals may
The episodic ataxias are inherited exacerbate the situation by recommending
channelopathies that result in prolonged more intervention, as in this case. Neither a
paroxysms of ataxia in affected individuals, psychiatric nor neurosurgical consult will be of
usually with normal intervening neurological any value, and tramadol is a poor choice in this
examination (although some patients can situation.
develop a slowly progressive ataxia). The family
history is key in this case, suggesting an 25.69. Answer: E.
autosomal dominant disorder. The history is of a progressive degenerative
Peripheral neuropathies are unlikely to be disorder and, in this age, with evolution of
paroxysmal and would not cause an ataxia, choreiform movements, variant CJD would be
while migraine can cause episodic vertigo, but most likely. Myoclonus tends to be more
usually alongside other migrainous phenomena. prominent in sporadic CJD, but this involves
BPPV would usually have direct positional an older population, as does Alzheimer's
precipitants. disease (which has a slower course and
only shows neurological signs at a late
25.66. Answer: C. stage).
Cerebellar function can be acutely affected by a The presence of significant cognitive decline
number of medications including the older and upgoing plantars would not be in keeping
antiepileptic drugs (phenytoin, carbamazepine with a psychological cause. While age
and valproate), lithium and amiodarone. and gender would be in keeping with
Digoxin and diazepam at higher doses can hyperthyroidism, the presence of neurological
be associated with sedation and drowsiness signs and severity of the cognitive dysfunction
but not cerebellar ataxia. Antiemetics and would make this less likely.
antipsychotics can be associated with
movement disorders such as chorea and 25. 70. Answer: C.
athetosis but not usually ataxia; ~ 2 -agonists will The only localising features here are the
cause tremor in acute stage. symptoms of left sensory change and the
quadrantanopia, wf.lich would both suggest a
25.67. Answer: A. right parietal lesion. Seizures are more likely
At this age, the key investigation is brain with low-grade gliomas, while highly malignant
imaging (ideally MRI) to exclude a structural lesions such as glioblastomas will often have a
rapid onset of neurological symptoms with, for botulinum toxin from Clostridium botulinum.
reasons that are not entirely clear, a lower risk (Her cousin had obviously eaten the same
of seizures than low-grade lesions. poorly prepared food!)
Meningiomata, by definition, are situated Brainstem stroke would not arrive in such a
outside the brain, while medulloblastomas are progressive manner, and Miller Fisher syndrome
tumours more common in childhood, most would cause ataxia and areflexia along with any
likely to be situated in the posterior fossa ophthalmoplegia (nor is it contagious).
(cerebellum). Visual changes related to optic Myasthenia gravis would have an onset with
nerve problems will be monocular rather than some fatigability. Multiple sclerosis would be
homonymous. unlikely to cause isolated weakness in such a
progressive manner (although this can be
25.71. Answer: C. increased in family members, the simultaneous
Migraine is a common disorder, and preceding onset is a clue to a recent infection as the
visual symptoms that disappear with onset of cause).
headache are characteristic of migraine with
aura. Somatic sensations and dysarthria are 25.74. Answer: E.
common with migraine, but on a first Carotid dissection can be precipitated by a
occurrence would justify imaging to exclude a surprisingly minor trauma. Association of
primary structural cause. unilateral pain with Horner's syndrome is
Subarachnoid haemorrhage will not usually characteristic of this disorder.
have focal signs but may need excluding in Signs are too focal and would be expected
abrupt-onset headache as a first or worst to be more severe with subarachnoid
occurrence. TIAs are not usually associated haemorrhage. Subdural and extradural
with headache, while the prominent headache haematomas would be unlikely to cause an
and widespread other symptoms would not be isolated Horner's syndrome. A brachial
in keeping with focal seizure. Cerebral venous plexopathy would also be expected to
sinus thrombosis would not usually recover cause symptoms and signs in the
completely so quickly, and any focal signs or ipsilateral arm.
symptoms would tend to evolve with the
headache rather than precede it. 25.75. Answer: A.
Acoustic neuromas may be discovered
25.72. Answer: E. incidentally on imaging or on investigation of
The occurrence of jaw stiffness in advance of sensorineural deafness. If uncovered late, there
generalised stiffness and spasms would be may be compression of the brainstem,
characteristic of tetanus, in this case most sometimes with compression of the fourth
likely as the result of an infected wound. ventricle causing hydrocephalus and
Diagnosis and adequate treatment is raised ICP.
paramount as this disease can still be fatal Brainstem stroke would have a much more
even if treated. abrupt onset, and deafness is a very rare
Dental abscesses are usually very painful, feature of multiple sclerosis. Migraine would
and would be vanishingly unlikely to extend have a more episodic course, with no
intracranially. While the anxiety may make neurological deficit (and normal fundi). Most
doctors think of a functional illness, the acoustic neuromas are spontaneous and not
characteristic pattern of intermittent jaw related to neurofibromatosis.
symptoms followed by generalised symptoms
would be unlikely in functional disorders. 25.76. Answer: E.
Botulism is also caused by a bacterial toxin The symptoms of a rapidly progressive distal
(from Clostridium botulinum) but more usually sensorimotor loss would be most in keeping
causes ocular and bulbar weakness rather than with a neuropathy. The levels of alcohol intake
spasms. and random glucose are too modest to
account for an alcoholic or diabetic neuropathy,
25.73. Answer: A. respectively. A raised ES8 would highlight an
The rapidly progressive generalised weakness immune-related cause and, with no rash or
preceded by ocular and bulbar paralysis is arthropathy, such a raised level would be most
characteristic of weakness caused by in keeping with myeloma.
II
'
.,(.1
Stroke medicine
o. It reduces the risk of early death advise best medical therapy rather than carotid
E. It reduces the risk of early intracerebral endarterectomy?
haemorrhage A. Her age - she is too old to benefit
B. She has a history of diabetes
26.15. An 81 year old woman with diabetes, G. The carotid stenosis is on the asymptomatic
hypertension and a minor left hemisphere side
ischaemic stroke 1 week ago is found to have D. The stroke impact is only minor
a right carotid artery stenosis of 70%. Which of E. There has been too long a delay since h·er
the following features would cause you to stroke onset .
Answers .
26.1. Answer: B. haemorrhage will have a normal CT scan; in
The definition of a TIA is the rapid onset of a these cases, a lumbar puncture should be
focal neurological deficit, of presumed vascular performed 12 hours following the onset of
origin, that resolves within 24 hours. It also headache to look for xanthochromia
includes transient monocular blindness due to (breakdown products of red blood cells).
vascular occlusion in the retina (amaurosis
fugax). Dysphasia is caused by a deficit in the 26.4. Answer: G.
dominant cerebral hemisphere. Delirium, Carotid endarterectomy reduces the risk of
dizziness, lone dysarthria and loss of stroke in patients with severe stenosis of the
consciousness are not focal deficits when internal carotid artery but carries a significant
present on their own. Loss of consciousness risk of perioperative mortality and stroke.
can very rarely be caused by basilar ischaemia Decisions on whether to operate must,
but is rarely transient. As a general rule, the therefore, be based on a careful benefit/risk
diagnosis of TIA should not be made in patients analysis. The absolute reduction in risk of future
who present with episodes of syncope, stroke is greatest for symptomatic patients with
dizziness or delirium, as these do not reflect 70-99% stenosis and, in general, outweighs
focal cerebral dysfunction. the risk of surgical complications. Importantly,
symptomatic patients are defined as patients
26.2. Answer: E. with a TIA or non-disabling stroke in the
Early CT scanning is the ideal for all patients territory of the carotid artery on the same side
with suspected stroke to help plan acute
therapies and plan secondary prevention. This
as the stenosis in the preceding 6 months. The
evidence to support surgery in symptomatic
~
man is beyond the time window for acute patients with moderate (50-69%) stenosis and I
therapies. Patients who are anticoagulated with
warfarin or who have a non-iatrogenic
asymptomatic patients with severe stenosis is
less conclusive, as these patients have a I
coagulopathy require urgent imaging of the smaller benefit/risk ratio than patients with
brain to rule out the possibility of an severe symptomatic stenosis. Patients with
intracerebral haemorrhage. stenosis of less than 50% do not benefit from
carotid endarterectomy, irrespective of
26.3. Answer: G. symptoms. Finally, a patient with severe
The clinical signs and symptoms in this patient residual disability would Qain little benefit from
are suggestive of a subarachnoid haemorrhage. preventing a further stroke within the same
An emergency head CT scan is essential. territory and may have a greater risk of surgical
About 5-10% of patients with a subarachnoid complications.
Single
typical TIA
lschaemic Haemorrhagic I
Fig. 26.5 Strategies for secondary prevention of stroke. (1) Lower blood pressure with caution in patients with postural hypotension,
renal impairment or bilateral carotid stenosis. (2) Other statins can be used as an alternative to sirnvastatin in patients on warfarin or
digoxin. (3) Warfarin and aspirin have been used in combination in patients with prosthetic heart valves. (4) The combination of aspirin
and clopidogrel is indicated only in patients with unstable angina or those with a temporary high risk of recurrence (e.g. carotid stenosis).
(ACE= angiotensin-converting enzyme; BP =blood pressure; CT =computed tomography; EGG= electrocardiogram; INR = international
normalised ratio; MRI =magnetic resonance imaging; TIA =transient ischaemic attack; U&Es =urea and electrolytes)
I
f 26.5. Answer: E. mimic of stroke. For that reason, it scores -1
In addition to lifestyle modifications, anti platelet, on the ROSIER clinical stroke tool (Box 26.6),
lipid-lowering and antihypertensive therapy form as does loss of consciousness, whereas all the
the cornerstone of secondary prevention for other options score +1 .
most patients with an ischaemic stroke (Fig.
26.5). Recent large-scale randomised trials have 26.7. Answer: B.
demonstrated the benefit of statins and The main advantages of plain CT scanning are
antihypertensive medication in these patients, its speed and tolerability and it can rapidly
even with blood pressure and cholesterol levels detect intracranial bleeding plus some stroke
within the 'normal' range. Patients in atrial mimics. Magnetic resonance imaging (MRI) is
fibrillation benefit from anticoagulation with often needed to show more subtle ischaemia,
warfarin following ischaemic stroke, but there is while MR angiography or CT angiography are
no such benefit in those who are in sinus rhythm. usually required to show vessel occlusion.
~,
26.11. Answer: D.
26.6 Rapid assessment of suspected stroke
The main recognised risk factors for
ROSIER scale
intracerebral haemorrhage include high blood
can be used by emergency staff to indicate probability of
pressure, smoking, excess alcohol intake,
a stroke in acute presentations:
structural abnormalities, coagulopathies and
Unilateral facial weakness +1
drugs such as cocaine and amphetamines.
Unilateral grip weakness +1
Unilateral arm weakness
Raised cholesterol, antiphospholipid
+1
Unilateral leg weakness +1
abnormality, cardiac embolism and carotid
Speech loss +1 artery stenosis are recognised risk factors for
Visual field defect +1 ischaemic stroke.
Loss of consciousness -1
Seizure -1 26.12. Answer: B.
Total (-2 to +6); score of> 0 indicates stroke is Warfarin is a less expensive drug option but
possible cause does require regular monitoring. Also, at
Exclusion of hypoglycaemia present we cannot easily monitor and reverse
Bedside blood glucose testing with BMstix
anticoagulation levels with DOACs (although
Language deficit
new agents are being developed). DOACs have
History and examination may indicate a language deficit
simpler dosing regimes with fewer drug
Check comprehension ('lift your arms, close your eyes') to
identity a receptive dysphasia interactions and appear to have a better
Ask patient to name people/objects (e.g. nurse, watch, balance of effectiveness and safety than
pen) to identify a nominal dysphasia warfarin.
Check articulation (ask patient to repeat phrases after you)
for dysarthria
Motor deficit
26.13. Answer: B.
Subtle pyramidal signs: Cerebral venous sinus thrombosis usually
Check for pronator drift: ask patient to hold out arms and presents with symptoms of raised intracranial
maintain their position with eyes closed pressure, seizures and focal neurological
Check for clumsiness of fine finger movements symptoms. It often includes associated
Sensory and visual inattention
haemorrhage. MR venography demonstrates a
Establish that sensation/visual field is intact on testing one
filling defect in the affected vessel. About 10%
side at a time
Retest sensation/visual fields on simultaneous testing of of cerebral venous sinus thrombosis is
both sides; the affected side will no longer be feiVseen associated with infection requiring antibiotic
Perform clock drawing test treatment. Otherwise, the treatment of choice is
Truncal ataxia usually anticoagulation.
Check if patient can sit up or stand without support
26.14. Answer: C.
Intravenous thrombolysis with rt-PA increases
hypoglycaemia must be excluded. While the risk of early haemorrhagic transformation of
important, the other actions do not take priority the cerebral infarct with potentially fatal results.
over checking the blood glucose. However, if it is given within 4.5 hours of
symptom onset to carefully selected patients
26.9. Answer: B. (about 20% of ischaemic stroke patients), the
Classification of a stroke is helpful for both haemorrhagic risk is more than offset by an
clinical and research purposes. A total anterior improvement in overall outcome The earlier the
circulation stroke results in a mix of motor treatment is given, the greater the benefit.
deficit, higher cerebral dysfunction and
homonymous hemianopia caused by occlusion 26.15. Answer: C.
of a major cerebral artery. An embolic cause is To benefit from carotid artery surgery, the
often found. patient needs to have an expectation of several
years of reasonable quality of life to offset the
26.10. Answer: C. risks of surgery. The stroke impact being minor
Mechanical clot retrieval (thrombectomy) and her age and other risk factors would not
appears to be particularly effective in cerebral influence this decision. The key contraindication
ischaemia caused by large-vessel occlusion. is that the carotid artery stenosis is on the
However, it requires careful patien~selection opposite side from the patient's symptoms and
and considerable support from imaging so this is a lower-risk asymptomatic carotid
investigations and catheter laboratories. stenosis.
Medical ophthalmology
Multiple Choice Questions
27.1. A 23 year old male presents to the 27.4. A 53 year old man attends his family
emergency department following an alleged physician for ongoing neck pain, which has
assault. He is intoxicated, his nose is bleeding occurred since he was involved in a road traffic
and he has a large left periorbital haematoma accident 6 months ago. During the consultation
that prevents spontaneous eyelid opening. his wife mentions his left eyelid is drooping. On
Alongside assessment for traumatic brain injury, . examination, the pupil on this side is 1-2 mm
which of the following ocular conditions is it smaller. Which is the most appropriate
most important to exclude? investigation?
A. Hyphaema A. Chest X-ray
B. Medial orbital wall fracture B. Computed tomography (CT) angiogram of
C. Orbital floor fracture the aortic arch, carotid arteries and
D. Retinal detachment intracranial vessels
E. Retrobulbar haemorrhage C. CT head
D. Doppler ultrasound of the carotid artery
27.2. A 36 year old male primary school teacher E. Magnetic resonance imaging (MRI) head
presents with a 3-day history of bilateral red,
watery, painful eyes. His vision is 6/7.5 in both 27.5. A 34 year old female is admitted with a
eyes. He is usually fit and well with no past life-threatening attack of asthma. After
ocular history. He mentions one of the children stabilisation she is transferred to the
in his class had a similar condition a week ago. intensive care unit where she remains
What is the most likely diagnosis? intubated and ventilated. The admitting doctor
A. Allergic conjunctivitis notices the left pupil, is dilated and minimally
B. Bacterial conjunctivitis responsive to light. There is no other
C. Episcleritis neurological abnormality. What is the most
D. Microbial keratitis likely cause?
E. Viral conjunctivitis A. An Adie's pupil
B. Argyll Robertson syndrome
27.3. An 18 year old female presents with a C. Horner's syndrome
24-hour history of a severely photophobic, D. Pharmacological mydriasis
watery and injected right eye. Her visual acuity E. Physiological anisocoria
is reduced to 6/18 in the affected eye. Which
feature of the clinical history will most affect 27.6. An 18 year old female has been referred
immediate management? following a routine visit to her optician, who
A. Contact lens wear noted anisocoria. Pupil measurements are as
B. Foreign travel follows:
C. Other unwell contacts The direct and consensual reflex in the left
D. Previous cold sores around the nose or mouth pupil is sluggish and the pupil constricts slowly
E. Previous ocular history in response to accommodation. There is no
'
She attends the diabetic retinal screening
programme for annual retinal photographs.
The latest image is show below.
A. Control of hypertension
B. lntravitreal anti-vascular endothelial growth
factor (anti-VEGF) therapy
G. Smoking cessation What is the earliest feature of diabetic
D. Tighter glycaemic control retinopathy visible on fundus fluorescein
E. Vitamin supplementation with high-dose angiography (FFA)?
antioxidants and zinc
A. Capillary occlusion
B. lntraretinal microvascular anomalies
27.13. A 69 year old male presents with a 2-day
G. Microaneurysms
history of sudden-onset, painless blurred vision
D. Venous beading
in his left eye. His visual acuity is 6/18 in the
E. Venous reduplication
affected eye. His past medical history includes
hypercholesterolaemia, chronic obstructive
27.15. A 31 year old patient with poorly
pulmonary disease (COPD), osteoarthritis and
controlled type 1 diabetes attends the eye
gastro-oesophageal reflux disease (GORD). He
casualty department complaining of blurred
has no past ocular history of note. The fundal
vision and floaters in the left eye. She manages
image is shown below.
her diabetes on a basal-bolus injection regime
with insulin Lantus and NovoRapid, but admits
her blood sugar levels have been high recently.
Her left fundus is shown in the image below.
Answers
27.1. Answer: E. asthma attack. lpratropiurn is an antirnuscarinic
All of the above conditions may have occurred agent. This may therefore cause dilation of the
following the inciting injury. Retrobulbar pupil if vaporised drug leaks from the mask.
haemorrhage is a sight-threatening emergency. The effect may last up to 24 hours. The
Bleeding behind the globe, in the absence of diagnosis of a pharmacological mydriasis can
any decompressing fracture, raises intraorbital be confirmed if there is little or no pupillary
pressure, which irreversibly damages the optic constriction following instillation of 1%
nerve. Typical clinical features include: severe pilocarpine. The other answers would be less
pain, progressive proptosis, reducing visual likely given the timing and clinical
acuity, ophthalmoplegia, diplopia and an scenario.
unreactive pupil. Emergency decompression
surgery is required to preserve optic nerve 27.6. Answer: A.
function. An Adie's tonic pupil is caused by loss of the
parasympathetic innervation to the sphincter
27.2. Answer: E. pupillae muscle in the iris and ciliary body.
Viral conjunctivitis is most commonly caused by The direct and consensual pupillary light reflex
adenovirus, a non-enveloped double-stranded are sluggish. The pupil slowly constricts to
DNA virus. The clinical presentation varies from near focus. The syndrome typically occurs in
subclinical to severe inflammation. The young females after a viral illness. Application
condition is highly contagious. Classic features of dilute pilocarpine 0.125% (a muscarinic
include prominent conjunctival hyperaemia agonist agent) to both eyes has no effect in
and follicles, petechial haemorrhage and the normal eye but causes constriction of
pseudomembranes. Corneal involvement is the Adie's pupil due to denervation
characterised by epithelial microcysts, punctate hypersensitivity.
epithelial keratitis and focal subepithelial
infiltrates. 27.7. Answer: B.
With age, the vitreous progressively liquefies, a
27.3. Answer: A. process known as syneresis. When a break in
A presentation of red eye in a known contact the posterior hyaloid face occurs, escaping
lens wearer should prompt a same-day referral fluid separates the vitreous from the retina,
for ophthalmological assessment including causing a posterior vitreous detachment
slit-lamp biomicroscopy. The cornea must be (PVD). An impression where the posterior
examined in detail for any features of microbial hyaloid face was once attached to the optic
keratitis. nerve becomes visible to the patient as a
large central floater and to the clinician on
27.4. Answer: B. examination as a circular opacity or Weiss
This patient has Horner's syndrome. Horner's ring. PVD occurs earlier in myopia, collagen
syndrome is a triad of ptosis, miosis and and connective tissue disorders, and may be
anhydrosis of the affected side of the face and triggered by trauma or inflammation. PVD is a
neck. It can be caused by interruption of the risk factor for a retinal tear and subsequent
~I
sympathetic fibres at any point along their detachment. A thorough examination of the
protracted course from their origin in the retina is required.
posterior hypothalamus through to their
synapse in the superior cervical ganglion and 27.8. Answer: B.
then to the eye. This patient has a history of Although all of these complications are possible
significant trauma; therefore a dissection of the after cataract surgery, this is a presentation
internal carotid artery must be excluded by CT
or MR angiography in the first instance.
of endophthalrnitis until proven otherwise and
requires specialist review. The worrying features I
are the initial subjectively good vision, followed I
27.5. Answer: D. by rapid deterioration, new floaters, which may
Nebulised salbutarnol and ipratropiurn are suggest infection in the vitreous, and increasing
involved in the management of a life-threatening pain.
Medical psychiatry
Multiple Choice Questions
28.1. A psychiatric history differs from a general 28.4. You are working in an emergency
medical history in which of the following key department. An elderly woman who has
respects? presented with a pretibial laceration is loudly
A. 'Drug history' refers to recreational drugs demanding that she be given priority treatment
rather that prescribed medication on the grounds that she is a close personal
B. 'Family history' refers to relationships within friend of the Prime Minister. A psychiatric
the family rather than illnesses affecting diagnosis of 'persistent delusional disorder' is
first- and second-degree relatives that might recorded in her case notes. Which of the
indicate genetic risk following statements best describes a delusion?
C. 'Past medical history' is less important A. A recurrent and intrusive thought that enters
D. Much of the examination is conducted during the patient's mind against their conscious
the course of history taking resistance and is recognised by the patient
E. The psychiatric history does not include as being a product of their own mind
'history of presenting complaint' B. An understandable belief that a patient
becomes preoccupied with to an
28.2. You are working in an emergency unreasonable extent
department. A 30 year old man presents C. An unshakeable false belief that is not
with excoriations on both forearms and tells accepted by other members of the patient's
you that he is experiencing a sensation of culture
something crawling under his skin. When D. A patient's perception and/or belief that
documenting this patient's mental state, under thoughts are being implanted into his/her
which heading would you record his tactile own head by someone or something else
hallucinations? E. When a patient's stream of thought shifts
A. Cognition suddenly from one thought to another very
B. Insight loosely or entirely unrelated thought
C. Mood
D. Perception 28.5. When reviewing a patient's neurology
E. Thought case notes, you read that her temporal lobe
epilepsy is characterised by a prodrome
28.3. Which of the following psychiatric comprising olfactory hallucinations. Which of
presentations is rare amongst general medical the following most accurately describes an
inpatients? hallucination?
A. Adjustment reactions A. A belief that has no rational basis
B. Alcohol-related disorders B. A false perce[)tion experienced by the patient
C. Delirium as arising in his/her own mind
D. Depression C. A fixed, false belief out of keeping with a
E. Schizophrenia patient's cultural background
28.6. When on-call over the weekend in a large 28.1 0. A 28 year old businesswoman presents
general hospital, you are asked to attend the to the emergency department with chest pain
toxicology unit. Which of the following is true of and various other symptoms. She admits to the
self-harm? doctor that she has been taking cocaine and
A. Incidence increases with age some other recreational drugs. Which of the
B. It is more common in men than women following combination of features could be
C. It is the term psychiatrists use for 'attempted attributable to cocaine intoxication?
suicide' A. Auditory hallucinations and hypothermia
D. Methods that carry high risk of death are more B. Constricted pupils and sedation
likely to be associated with mental disorder C. Formication and auditory hallucinations
than are methods that carry low risk of death D. Hypothermia and constricted pupils
E. There is a lower incidence in lower E. Sedation and formication
socioeconomic groups
28.11. A 46 year old man is brought to the
28.7. An 80 year old retired lawyer who lives emergency department by emergency
independently is brought to the emergency ambulance. He says he is unable to breathe,
department by a neighbour who found him his hands and feet are tingling, he feels that he
wandering on the street in the early hours of is about to collapse and possibly die. On
the morning. He has no past psychiatric examination he has sinus tachycardia. Oxygen
history. As you attempt to interview him, the saturation is 100%. You notice that thi;:; is his
man says, 'This is a wonderful party. It is great fifth attendance at the emergency department
to see all those young people dancing.' Which in 3 months. Which is the most likely
is the most likely diagnosis? diagnosis?
A. Delirium A. Factitious disorder
B. Dementia B. Generalised anxiety disorder
C. Histrionic personality disorder C. Hypochondriacal disorder
D. Mania D. Obsessive-compulsive disorder
E. Schizophrenia E. Panic disorder
28.8. As a 35 year old man wakes from sleep 28.12. A 32 year old man with diabetes mellitus
he briefly sees a lion at the foot of his bed. survives an 8-day admission to critical care with
Which of the following most accurately overwhelming sepsis and ketoacidosis. On
describes his experience? discharge from hospital he appears happy and
A. Autoscopic hallucination glad to be alive. You review him at the diabetic
B. Functional hallucination clinic 2 months later and he tells you that he is
C. Hypnagogic hallucination waking in the middle of the night with vivid
D. Hypnopompic hallucination nightmares. He is now struggling to sleep, he
E. feels anxious and jumpy all of the time and
--
Kinaesthetic hallucination
finds himself bursting into tears very easily. His
28.9. A 48 year old barman is brought to the mother has been admitted to hospital but the
emergency department by his wife from whom thought of visiting her on a hospital ward
he has recently separated. She is concerned
that he is confused and 'talking nonsense'.
terrifies him. Which is the most likely diagnosis?
A. Acute stress reaction
1
He has an unsteady gait yet his breath B. Adjustment disorder
alcohol level is zero. On examination he has
ophthalmoplegia and is disorientated in time.
His liver function tests are deranged.
C.
D.
Delirium
Depression
I
E. Post -traumatic stress disorder
Which is the most likely diagnosis?
A. Alcohol withdrawal 28.13. You review a 55 year old man in the
B. Alcoholic dementia cardiology outpatient clinic. Two months ago
28.14. Which one of the following statements 28.17. A 19 year old female student is brought
about psychiatric treatment is true? to the emergency department at midnight by
A. Most patients treated with psychiatric her friends. They had been out drinking
medication suffer significant sedation as a together but when she became so intoxicated
side-effect that she was unable to walk they became
B. Psychotropic medications can be prescribed worried about her and took her to hospital.
by psychiatrists and psychologists She is admitted overnight for observation
C. The majority of psychiatric patients are given (temperature, blood pressure, heart rate and
treatment against their will respiratory rate are all normal) and you review
D. There is considerable randomised controlled her on the ward round the following day.
trial evidence to support use of cognitive Her urea and electrolytes, liver function tests,
behavioural therapy (CBT) for depression and thyroid function tests and full blood count are
anxiety disorders all normal. On examination she is extremely
E. There is little randomised controlled trial thin, weight 38 kg (body mass index 16 kg/m 2 )
evidence to support pharmacological with lanugo hair on her arms and back. You tell
interventions in psychiatry her you are concerned about her low weight
and ask her about her eating. She tearfully tells
28.15. A 43 year old woman attends your you that she started dieting 8 months ago but
general medical clinic for investigation of it now dominates her life and she thinks she
severe and persistent fatigue. No abnormalities has developed anorexia nervosa. Unfortunately
are evident on examination or investigation. the hospital has no psychiatric liaison service.
On reviewing her medical record you see What is the most appropriate immediate
f] that over the past 25 years she has had management?
,,.i numerous visits to hospital, including to A. Dietetic review and referral for urgent
the ear, nose and throat (ENT) department, psychiatric outpatient assessment
where she was diagnosed with B. Mental health act detention and compulsory
temporomandibular joint dysfunction; refeeding
psychiatry, where she was diagnosed with C. Prescribe rnirtazapine as an antidepressant
depression; gynaecology, where a and appetite enhancer
hysterectomy was performed for menorrhagia; D. Transfer to the local psychiatric hospital for
and gastroenterology, where she was specialist inpatient treatment
diagnosed with irritable bowel syndrome. What E. Voluntary refeeding as a medical inpatient
is the most likely diagnosis?
A. Factitious disorder 28.18. A 30 year old man brings his 27 year old
B. Fibromyalgia wife and 10 day old son to the emergency
C. Hypochondriacal disorder department He says that over the past 2 days
D. Malingering his wife has not been her normal self. Initially
E. Somatisation disorder she appeared unusually anxious about the
baby, unable to put him down for more than a D. Genetic mutations that cause frontotemporal
few minutes. Last night she stayed up through dementia are also associated with
the night and this morning she refused to amyotrophic lateral sclerosis
accept any of the food or drink that he offered E. The genetic basis of Alzheimer's disease is
her and will not let him hold the baby. She will unknown
not tell him what is wrong but agreed to come
to the hospital as she said she would 'feel safer 28.22. A 50 year old woman with alcohol
there'. What is the likely diagnosis? dependence syndrome is admitted to hospital
with cellulitis in her foot. When the nurse gives
A. Post-partum blues
her lunch, she comments that this is the first
B. Post-partum depression
meal she has had for weeks as she has been
C. Post-traumatic stress disorder
spending all of her money on cider. On
D. Puerperal psychosis
examination she is fully orientated and does not
E. Schizophrenia
appear confused. She has a tremor, is
28.19. Which of the following statements is true sweating and tachycardic. What would
about the biological basis of psychiatric appropriate management comprise?
disorders? A. Acarnprosate and diazepam
A. A large number of conditions have an B. Diazepam and parenteral vitamins (Pabrinex)
identified single genetic cause C. Disulfiram and acamprosate
B. Depression is associated with focal D. Haloperidol and disulfiram
reductions in 5-hydroxytryptamine (5-HT, E. Parenteral vitamins (Pabrinex) and haloperidol
serotonin) receptor binding
C. Most disorders have a discrete underlying
28.23. A 22 year old male is brought into the
emergency department. He is agitated, difficult
abnormality on neuroimaging
to converse with, smells of alcohol and says
D. Schizophrenia is associated with increased
post-synaptic dopamine D2 receptor binding that he is being persecuted by secret services;
E. Task-based functional magnetic resonance however, he is fully oriented. Which of the
following is the most likely diagnosis?
imaging (MRI) is the technique of choice for
analysing the interactions between multiple A. Alcohol withdrawal-
brain regions B. Bipolar affective disorder
C. Drug intoxication
28.20. Which of the following complaints are D. Drug-induced psychosis
later (as opposed to earlier) manifestations in E. Schizophrenia
the natural history of dementia?
A. Difficulty getting dressed
28.24. A patient with schizophrenia getting
B. Getting lost in familiar surroundings treated with clozapine wants to speak to you
C. Personality change about her treatment. Which of the following
D. Subjective memory problems statements are true of clozapine?
E. Disinhibited behaviour A. Electrocardiogram (ECG) monitoring is
mandatory as clozapine commonly causes
28.21. A 70 year old widowed woman is cardiac arrythmias
brought to your clinic with a history of memory B. It can cause dry mouth
impairment and aggressive behaviour for C. It is a first-line treatment for schizophrenia
investigation and treatment. Which of the D. It is associated with constipation
following statements is true of the E. It is associated with myeloproliferation
pathophysiology and management of
dementia? 28.25. A 30 year old woman with a history of
A. Anticholinesterase mediCation is indicated to bipolar disorder treated with lithium wants to
treat memory impairment in Pick's disease have a child and wonders if she should stay on
B. Anticholinesterases may of some benefit in the treatment. Which of the following
the late stages of Alzheimer's disease statements are true of lit~ium salts?
C. Creutzfeldt-Jakob disease has characteristic A. Hypopararathyroidism is a potential risk
electroencephalogram (EEG) abnormalities of B. They are contraindicated in pregnancy
generalised slow waves because of a risk of neural tube defects
Answers
28.1. Answer: D.
28.1 How to structure a psychiatric interview
'Drug hi?tory' refers to both recreational and
prescribed medication (and over-the-counter Presenting problem
and herbal preparations!). This is true of both a Reason for referral
Why the patient has been referred and by whom
general medical and a psychiatric history. In the
Presenting complaints
psychiatric history, 'family history' refers to both
The patient should be asked to describe the main
familial conditions and relationships. Much of problems for which help is requested and what they
the mental state examination is conducted want the doctor to do
during the course of psychiatric history taking, History of present illness
rather than as a separate set of procedures at The patient should be asked to describe the course of the
the end (Box 28.1). 'History of presenting illness from when symptoms were first noticed
The interviewer asks direct questions to determine the
complaint' is as prominent in a psychiatric
nature, duration and severity of symptoms, and any
history as it is in clinical histories taken in other associated factors
specialties, as is 'past medical history'. Background
Family history
28.2. Answer: D. Description of parents and siblings, and a record of any
A tactile hallucination is the experience of mental illness in relatives
perceiving touch in the absence of a touch Personal history
stimulus. It is an abnormality of perception. Birth and early developmental history, major events in
The mental state examination (MSE) is a childhood, education, occupational history,
relationship(s), marriage, children, current social
systematic examination of the patient's thinking, circumstances
emotion and behaviour. As with the clinical Previous medical and psychiatric history
examination in other areas of medicine, the aim Previous health, accidents and operations
is to elicit objective clinical signs. Whilst many Use of alcohol, tobacco and other drugs
aspects of the patient's mental state may be Direct questions may be needed concerning previous
psychiatric history since this may not be volunteered:
observed as the history is being taken, specific
'Have you ever been treated for depression or nerves?'
enquiries about important features should or 'Have you ever suffered a nervous breakdown?'
always be made. Previous personality
The patterns of behaviour and thinking that characterise a
28.3. Answer: E. person, including their relationships with other people
Adjustment reactions, alcohol-related disorders, and reactions to stress (useful information may be
obtained from an informant who has known the patient
delirium and depression are all very common well for many years)
within the general medical inpatient population
(Box 28.3). Rates of schizophrenia in the general
medical inpatient population are similar to rates in
the general population. The lifetime prevalence of
schizophrenia is approximately 1%.
serotonin re-uptake inhibitors; SSRls) do not few weeks after delivery. Post-partum
cause sedation. depression is depression arising following
childbirth. Post-traumatic stress disorder is a
28.15. Answer: E. delayed reaction to an extremely stressful
Somatisation disorder is the diagnostic term for event. It is characterised by flashbacks,
patients who, over many years, experience (and avoidance and hyper -arousal.
present to medical services with) somatoform
(medically unexplained) symptoms affecting 28.19. Answer: B.
more than one system. Such patients are not Very few psychiatric disorders have a single
faking their symptoms (in contrast to patients cause of any sort; most are multifactorial and
with factitious disorder or malingering) and they polygenic. Very few conditions have a discrete
are not usually worried about a possible serious underlying brain lesion: abnormalities on
underlying condition (hypochondriasis). When neuroimaging, even in dementia or
assessing patients with somatoform symptoms schizophrenia, occur in < 10% and most
it is important to recognise and acknowledge disorders are characterised by 'dysconnectivity'
that their symptoms are real, distressing and (abnormal interactions between brain regions).
disabling and to explain that doctors often see Schizophrenia is associated with increased
patients whose symptoms cannot be explained pre-synaptic dopamine synthesis and turnover.
by disease. Resting-state functional MRI is the technique of
choice for analysing the interactions between
28.16. Answer: D. multiple brain regions.
This is a typical description of obsessive-
compulsive disorder (OCD), and the thoughts 28.20: Answer: A.
are 'obsessions'. The repetitive hand washing Subjective memory complaints are a common
sustained by the temporary relief from anxiety is early manifestation of all dementias. Getting lost
the 'compulsion'. 'Rumination' refers to the in familiar surroundings is a common presenting
focusing of attention on one's symptoms. feature of Alzheimer's. Difficulty getting dressed
Catastrophising is viewing a situation as much and other dyspraxias are usually more of a
worse than it actually is (relatively common in problem in the later stages of Alzheimer's
depression and anxiety). disease. Behaviour and personality change are
common early manifestations of the
28.17. Answer: A. frontotemporal dementias.
Despite her low weight, this woman is not
acutely medically unwell: hence neither 28.21. Answer: D.
psychiatric nor ongoing medical admission are Creutzfeldt-Jakob disease is characterised by a
indicated. She needs to be supported to gain generalised periodic sharp wave pattern on
weight but this is best done collaboratively as EEG. Mutations in several genes have
an outpatient. Antidepressant medication does been described in Alzheimer's disease but
not have a major role to play in the most are rare and/or of small effect (such
management of anorexia nervosa. as apolipoprotein E epsilon 4; APOe4).
Anticholinesterases have been shown to be
28.18. Answer: D. of some benefit at slowing progression of
Puerperal psychosis affects approximately 1 in cognitive impairment, but only in the early
500 women, with a peak onset in the first 2 stages of the disease, while post-synaptic
weeks after birth. It usually takes the form of an cholinergic receptors are still available. Although
affective psychosis (manic, depressive or Alzheimer's and Pick's (as one of the
mixed) but can sometimes resemble frontotemporal dementias; FTDs) share certain
schizophrenia. The onset is often rapid, with symptoms, they cannot be treated with the
transition from normal mental state to same pharmacological agents because the
psychosis in a matter of days. Women often cholinergic systems are not affected in FTD.
conceal their symptoms, which can place both
the woman and her baby at significant risk. 28.22. Answer: B.
Post-partum blues is the term used to This woman is at risk of Wernicke-Korsakoff's
describe a transient, self-limiting period of syndrome as a consequence of alcohol
increased emotional reactivity during the first dependence and poor nutrition. She should be
I
:~
'i'f
i!:.
Dermatology
Multiple Choice Questions
29.1. A 23 year old woman presents with a 29.2. A 45 year old farmer is prescribed
history of an itchy papular rash (see below), doxycycline 200 mg orally daily for rosacea.
which developed on her chest and arms in the A week later he experiences a severe sunburn
evening, after sitting in the sun for 2 hours, reaction after being out one morning on his
earlier that day. The eruption lasts for 3 days tractor on a cloudy day (see below). What is
before fully resolving. What is the most likely the most likely finding on investigation?
diagnosis?
her daughter had more dandruff than usual and Which of the following statements is correct?
tried her with an over-the-counter anti-dandruff A. Examination with Wood's light will show areas
shampoo, which did not help. She then asked of fluorescence if the endothrix is involved
the advice of her family physician, who thought B. If the diagnosis is confirmed he should be
the daughter may have 'nits'. treated with topical terbinafine
Which of the following statements is correct? C. Oral griseofulvin is the antifungal agent of
A. 'Nits' are the active head louse Pediculus choice for children in the UK
humanus capitis and are easily seen on the D. Systemic glucocorticoids will prevent any
scalp and often confused with dandruff further hair loss
B. All cases of head lice need intensive E. Tinea capitis is a dermatophyte fungal
treatment with insecticides infection of the scalp hair bulb
C. Head lice infestation is highly contagious and
all members of the family and all classmates 29.13. A 62 year old woman presents with a
should be treated at the same time 6-week history of a rapidly enlarging lesion on
D. Malathion would be the insecticide of choice the right cheek, which is otherwise
for active treatment asymptomatic (see below). She lived in South
E. Thorough combing of wet, conditioned hair Africa until the age of 20 years and has
may be effective previously had three BCCs excised. What would
be the most appropriate course of action?
29.12. A 10 year old boy presents with a patch
of inflammation and hair loss in the scalp,
which was noticed when he went for a haircut.
He is otherwise well, with no medical history
and lives at home with his mother, brother and
pets. They have just returned home from a
holiday on a farm. On examination, there is a
boggy area of inflammation in the scalp, with
overlying pustules and hair loss (see below).
This is thought most likely to be tinea capitis.
CM
A. Biopsy and photodynamic therapy
B. Biopsy and topical irniquimod
C. Excisional surgery
D. Mohs' micrographic surgery
E. Observation
DERMATOLOGY • 349
found out through the internet that vitarnin D B. Non-sedating antihistamines are usually
deficiency can lead to irnpaired bone health, effective
rickets and osteomalacia. Which of the C. She is advised that she should be delivered
following statements is correct? early because of fetal risk
A. Dietary vitarnin D intake is effective for D. She is advised that this is unlikely to be a
vitarnin D deficiency problern in subsequent pregnancies
B. Skin fibroblasts are the rnain source of E. Topical glucocorticoids should be avoided
vitarnin D synthesis due to potential adverse fetal effects
C. UVA exposure is required for cutaneous
vitarnin D synthesis 29.23. A 63 year old wornan presents with a
D. UVB exposure is required for cutaneous pigmented lesion on the anterior chest noted
vitarnin D synthesis by her farnily physician during Well Wornan
E. Vitarnin D toxicity is a risk for patients with screening. She had been aware of the lesion
increased photosensitivity for I 0 years and did not think it had
significantly changed, although on closer
29.21. A 54 year old wornan with chronic questioning, she said it had enlarged over the
urticaria, without obvious history of trigger, last year. Excisional surgery confirrns a
is referred to dermatology for investigation diagnosis of invasive superficial spreading
and rnanagernent (see below). With the malignant rnelanorna (Breslow thickness
exception of hay fever and long-standing 0.8 rnrn).
vitiligo, she is otherwise well and is taking no
medications.
--
psoriasis, despite UVB, PUVA and C. Photodynamic therapy
methotrexate, is being considered for biological D. Radiotherapy
therapy. He has extensiv~ chronic plaque E. Topical imiquimod
psoriasis, nail and scalp involvement and
troublesome psoriatic art.hritis. On assessing 29.29. Which of the following is a normal variant
the Psoriasis Area and Severity Index (PASI), of nail growth?
which of the following is included in the A. Longitudinal ridging
1
assessment? B. Nail furrowing
A. Area of involvement C. Onycholysis
B. Degree of lichenification D. Pitting
C. Severity of joint involvement E. Transverse ridging
I E. Switch to PUVA plus acitretin hypertension. His medications are ramipril and
aspirin. On examination he has several tense,
Which of the following would you expect B. Oxygen is required for the photodynamic
to find? reaction
A. Mucosal involvement C. PDT should not be used for nodular BCC
B. Neutrophilia D. PDT should not be used in elderly frail
C. Positive circulating anti-epidermal antibodies patients
D. Positive Nikolsky sign E. Red laser light is required for irradiation
E. Subcomeal blister on histology during PDT
29.40. Which of the following statements is 29.42. A 32 year old man with chronic plaque
correct with respect to malignant melanoma? psoriasis has been attending for UVB
A. Acral melanoma is less common in phototherapy. He was starting to respond to
dark-skinned populations treatment but in the second week commented
B. Lentigo maligna melanoma usually occurs in that he had developed a new asymptomatic
younger patients rash on the back and chest. On examination,
C. Most patients with melanoma have a positive in addition to chronic plaque psoriasis affecting
family history of melanoma extensor surfaces, sacral area and buttocks,
D. Nodular melanoma is most common in a rash is evident on the upper trunk, consisting
men of oval scaly macules and hypopigmentation
E. The majority of melanomas arise from a (see image). What is the most likely
pre-existing naevus diagnosis?
I(:
·I
~,
I
A. Pityriasis rosea
B. Pityriasis versic;olor I
29.43. A 35 year old woman returns to clinic for history of relevance and she is not known to be
management of chronic atopic eczema (see atopic. What is the most likely diagnosis?
image). She has a life-long history of eczema A. Allergic contact dermatitis
with whole-body and facial activity over the B. Dermatophyte fungal infection
last 5 years, despite topical emollients, C. Irritant contact dermatitis
glucocorticoids, phototherapy and PUVA. She D. Late-onset atopic dermatitis
is otherwise in good health, works in an office E. Progesterone dermatitis
and does not smoke or drink. She needs a
considerable amount of time off work because
of her skin, which is adversely impacting on her 29.46. A 14 year old boy attends the paediatric
life, with a DLOI score of 24. What would be dermatology clinic with his mother who is
the next most appropriate management step to seeking a second opinion for treatment of
consider? long-standing chronic atopic eczema. On
examination he has extensive eczema affecting
the trunk and flexor and extensor surfaces of
the limbs, with chronic inflammation and
lichenification (see below). He is using
Eumovate ointment daily, approximately 100 g
per fortnight to the trunk and limbs, emulsifying
ointment as emollient and fexofenadine at night
to help with itch. Which of the following
changes to his management is likely to be most
effective?
A. Acitretin
B. Apremilast
C. Ciclosporin
D. Dupilumab
E. Methotrexate
-I
B. IL-13 inhibition
C. IL-17 inhibition
D. IL-23 inhibition
A. Changing from emulsifying ointment to
E. TNF-a inhibition
aqueous cream
B. Changing vehicle formulation to Eumovate
29.45. A 28 year old mother of 6 month old cream
twins presents with a rash on the back of C. Increasing the amount of topical
hands and between the fingers. Examination glucocorticoid use I
reveals erythema and scaling at these sites, D. lnc'reasing the dose of fexofer:Jadine
with bilateral involvement and a relatively sharp E. Increasing the potency of topical I
cut -off at the wrists. There is no previous glucocorticoid, e.g. to Betnovate ointment
A. Associated hypothyroidism
B. Facial involvement
C. Involvement of the distal limbs A. Adenovirus
D. The presence of a trichrome pattern B. Herpes simplex virus
E. The presence of leucotrichia C. Ibuprofen
D. Paracetamol
29.52. A 53 year old woman with a known E. Oral contraceptive
diagnosis of hepatitis C attends a general
medical clinic for routine review. On enquiry 29.54. A 66 year old woman was commenced
she comments that she has been aware of on carbamazepine and co-codamol 10 days
blistering occurring on the backs of her hands, previously for trigeminal neuralgia. She was
in particular when she had minor trauma to the otherwise well, having just returned from a
skin. On examination there is nothing much to holiday in the Caribbean. She presents to
see other than mild scarring and milia. What out-of-hours primary care with an acute onset
would be the most appropriate course of action? of extensive rash, systemic malaise and high
A. Check renal function, as this may indicate fever. Examination reveals a widespread
renal failure erythematous maculopapular and purpuric
B. Patch testing, as this may be allergic contact rash, with prominent facial involvement and
dermatitis facial oedema. She has generalised
C. Porphyrin investigations, as this may be a lymphadenopathy and a temperature of 40°C.
cutaneous porphyria Initial investigations show an eosinophilia and
D. Reassurance that this is likely due to the marked elevation of liver function tests. She is
hepatitis C infection admitted to an infectious disease department.
E. Skin biopsy and direct immunofluorescence What would be the most likely diagnosis?
to exclude immunobullous disease A. Carbamazepine-induced drug reaction
B. Co-codamol-induced drug reaction
-
29.53. A 25 year old woman presents to her C. Hepatitis
family physician with a 2-day history of a rash D. Leptospirosis
on her hands and forearms. On examination E. Meningococcal sepsis
Answers
I
I
at any age but typically presents in elderly but liver function tests would be most important
males and the morphology of rash is a diagnostically. In the absence of other relevant
dermatitis. It usually takes a few hours to days history, there would be no specific indication to
of sun exposure to develop and it persists check ANA and complement.
until treated. Lupus erythematosus is a
photo-aggravated autoimmune disorder and 29.4. Answer: C.
the skin features more typically develop a day, The scenario of the relatively recent introduction
or so, after sun exposure and persist for of compression bandaging a few weeks· earlier
weeks. Erythema multiforme is a raises the po.ssibility of allergic contact
photo-aggravated disease often triggered by dermatitis. Specifically, rubber additives or
herpes simplex virus infection and can be most preservatives in any of the topical preparations
prominent on sun-exposed sites although could be culprits. All of the other diagnoses
usually affects sun-protected sites as well. The should, of course, be considered and excluded
rash is usually more targetoid and less papular. but a bilateral symmetrical presentation of each
of these diagnoses would be extremely unlikely.
29.2. Answer: E.
Most drugs, including doxycycline, 29.5. Answer: B.
photosensitise maximally in the UVA region The Nikolsky sign is when gentle lateral
and this would usually be detected on pressure on stroking the skin results in
monochromator phototesting. Patch testing is epidermal detachment. Carbamazepine is a
not the investigation of choice for suspected drug that is associated with many cutaneous
systemic drug-induced photosensitivity. Both adverse effects and is one of the most
false-positive and false-negative results mean common culprits in TEN. Evidence relating to
that patch testing using topical delivery of a the use of IVIg in TEN is controversial at best
drug that has been used systemically is an and overall not advised (see British Association
unreliable investigation. It is usually not of Dermatology guidelines). The symptom of
indicated nor of clinical relevance. Positive ANA dysuria is much more likely to be due to
and ENA autoantibodies can be seen with inflammation and desquamation of the
some systemic drug photosensitisers: for uroepithelial tract due to involvement in the
example, thiazides or proton pump inhibitors. TEN process. Catheterisation should be
However, this is not typically the case with avoided unless necessary, such as for
doxycycline and, indeed, the most common monitoring fluid balance - and in that instance
presentation of drug-induced photosensitivity is should be performed with caution. A
through a phototoxic non-immunological mid-stream urine should be undertaken, but
mechanism. UVB provocation testing may be antibiotics should not be prescribed empirically.
positive in drug-induced photosensitivity but is Skin pain is a characteristic feature of TEN and
much less likely to be abnormal than UVA the prognosis is better for patients who are less
phototesting, which is the main part of the than 40 years of age, although other prognostic
ultraviolet spectrum implicated in drug-induced indicators need to be taken into account when
photosensitivity. Whilst some drugs can cause assessing the disease severity score
minor derangements of porphyrins, this is not (SCORTEN), which is predictive of risk of
the case with doxycycline and one would not mortality (Box 29.5).
expect abnormal porphyrins in doxycycline-
induced photosensitivity. 29.6. Answer: B.
Photodynamic therapy is approved for use in
29.3. Answer: C. Bowen's disease. Given its relative specificity of
Acute cholestasis of pregnancy is uncommon treatment and improved healing compared with
but usually presents in the third trimester of other treatments such· as cryotherapy and
pregnancy. It is essential to diagnose this 5-f\uorouracil, this would be the treatment of
promptly as there is increased fetal and choice on a lower leg site where there is
maternal risk; urgent diagnosis and treatment, coexistent oedema and vascular insufficiency,
which may include early delivery, are required. either venous and/oF arterial. Definitive surgical
The other investigations of full blood count, excision would be an option but in this instance
urinalysis and thyroid function tests would all be a non-surgical approach would usually be
important to undertake in this clinical setting advised in order to reduce morbidity, given the
-I
There is no evidence that PLE is more common would be unlikely to be effective. Minocycline is
either in patients taking the contraceptive pill not the first antibiotic of choice given the risk of
or in psoriasis. The prevalence of PLE is skin pigmentation and of drug-induced lupus.
approximately 18% in Northern Europe and, as Antibiotics will need to be continued for several
it most commonly occurs in young females of months, and a trial of at least 3 months is
child-bearing age, the contraceptive pill and required. Combined oestrogen/anti-androgen
PLE are commonly associated but there is no contraceptives, such as those including
evidence to indicate a causal relationship. PLE cyproterone acetate, may be appropriate but I
does commonly occur during a course of would usually only be consider(ld or added in if
phototherapy and, if this is the case, there there was an inadequate response to a trii:ll of
is concern that Ki:ibnerisation of psoriasis systemic antibiotics. lsotretinoin would not be
considered at this early stage in management regress. However, given that spontaneous
of a patient with papulopustular acne. The resolution of keratoacanthoma often leaves
hope would be that this case would respond cosmetically unacceptable scars and that it is
well to systemic antibiotics; systemic retinoids impossible to distinguish from invasive sec,
would only be required if there was a failure to active intervention and removal is important. An
respond to 3-6 months of antibiotic treatment. incisional biopsy may not clearly distinguish
between keratoacanthoma and invasive SCC:
29.11. Answer: E. the distinction often remains difficult; thus,
Scalp infestation with the head louse Pediculus usually these lesions are definitively excised. A
humanus capitis is very common. A diagnosis nodular lesion such as this would be unlikely to
is confirmed by identifying a living louse or respond to treatment with either topical
nymph. However, the 'nits' are actually empty imiquimod or photodynamic therapy.
egg cases, not the head lice themselves, and
are signs of there having been an infestation. 29.14. Answer: B.
'Nits' are yellowish in colour and can be Lentigo maligna may be very difficult to treat and
confused with dandruff. Not all cases require to achieve clinical and histological clearance. It is
treatment with insecticide, as regular wet not unusual for clinical response to occur but
combing of conditioned hair may be effective in abnormal cells to remain histologically.
physical removal of lice. Malathion would not Treatment of choice would be definitive surgical
be the insecticide of choice as resistance is excision although this can be difficult as
fairly common; alternatives such as dimeticone dysplastic cells often persist at the margins,
may be used. Whilst the infestation is highly ~rising as part of field change carcinogenesis.
contagious, treatment is only recommended for lmiquimod may be used if surgery is not
the affected individual and close contacts, such appropriate but the risk of recurrence is higher.
as family members or close school class Left untreated, there is a significant risk of
members where there has been direct invasive melanoma developing into lentigo
head-to-head contact. Treatment of all maligna. Pigmented lesions with metastatic
classmates is not required. potential would not be appropriately treated by
photodynamic therapy, and melanin absorbs red
29.12. Answer: G. light; thus efficacy would not be expected.
Fluorescence with Wood's light is only seen with
some species of dermatophyte infection and not 29.15. Answer: G.
with those involving the endothrix (within the hair Whilst some consider palmoplantar pustulosis
shaft). Dermatophyte infection of the scalp hair to be a variant of psoriasis, most patients with
affects the shaft as opposed to the bulb. Topical this condition do not have other features of
treatment will not be sufficient for clearance of chronic plaque psoriasis and there is increasing
inflammatory active fungal infection within the evidence to suggest that the two conditions are
hair-bearing scalp. Griseofulvin is the only distinct. Palmoplantar pustulosis is almost
systemic antifungal agent licensed for use in invariably associated with smoking but there is
children in the UK. There is no convincing no convincing evidence that stopping smoking
evidence that systemic glucocorticoids reduce results in disease improvement. Topical
hair loss associated with tinea capitis. glucocorticoids are usually a mainstay
treatment in palmoplantar pustulosis. Bacterial
29.13. Answer: G. swabs from the pustules are usually sterile.
From the history, this lesion is most likely a PUVA may be effective for disease suppression
benign keratoacanthoma, but it is impossible to in this condition.
distinguish this from a rapidly growing
squamous cell carcinoma (SCC). Given her 29.16. Answer: G.
history of significant sun exposure and previous Clustered painful vesicles recurring at the same
BCC, it would be important to excise in order site in association with the pre-menstrual period
to exclude invasive SCC. Mohs' micrographic are most likely to be extra-labial herpes simplex
surgery would not usually be required for this virus infection. Pain and clustered vesicles would
well-defined tumour and is most commonly not be expected in fixed drug eruption, although
used, in particular, for poorly defined BCC. this should certainly be something to be
Observation is an option, because if this is a considered, particularly if the patient is taking
benign keratoacanthoma, then it should paracetamol or non-steroidal anti-inflammatory
medication in the pre-menstrual phase. In tinea with chronic urticaria do not have an obvious
corporis or dermatophyte fungal infection, the trigger and total lgE and specific lgE testing are
most likely presentation would be a raised edge unlikely to be helpful in the absence of a history
with pustules and scaling and central clearing, suggestive of trigger factors. Prick testing would,
and it would be unlikely to clear and recur at the again, be unlikely to be contributory unless there
same site each month or be painful. In was a specific trigger identified in the history.
molluscum contagiosum, whilst these are due to
a pox virus infection, the lesions are not vesicular 29.22. Answer: D.
but are usually solid umbilicated papules and The condition is usually treated with topical
they are not usually painful or intermittent. Whilst glucocorticoids, which can be safely prescribed
an acute vesicular eczema can occur in in pregnancy. The condition is not known to be
association with contact allergy, the intermittent associated with any adverse effects to the fetus
and isolated nature of this would make this and early delivery is not generally required.
diagnosis unlikely. Abnormal liver function tests are not associated
with polymorphic eruption of pregnancy.
29.17. Answer: C. Sedating antihistamines, such as
A relatively common side-effect of chlorphenamine, may be required but as this is
angiotensin-converting enzyme (ACE) inhibitors not primarily a histamine-mediated disease,
is angioedema and this usually occurs without non-sedating antihistamines are not advised as
associated urticaria. Thiazide diuretics do not their safety in pregnancy is unproven.
typically cause angioedema. Patch testing is Polymorphic eruption of pregnancy usually
used to investigate type IV delayed persists until delivery and may even continue
hypersensitivity and not type I immunological for some time into the post-partum period
reactions. There is no evidence that angioedema before spontaneous resolution. It does not
is increased in patients with diabetes. usually occur in subsequent pregnancies.
-I
poor and vitamin D and calcium supplements disease. In this case it may be due to
are required in vitamin D deficiency. Vitamin D alcohol-induced liver disease. Skin biopsy and
deficiency is a potential concern for patients immunofluorescence may show characteristic
with photosensitivity diseases. changes of subepidermal blistering and periodic
acid-Schiff (PAS) staining but would not be the
29.21. Answer: D. investigation of choice. Patch testing, urinalysis
This patient is atopic and has autoimmune and lupus serology would not be specifically
disease. Urticaria may be a manifestation of indicated. I
autoimmune hypo- or hyperthyroidism. Patch
testing is the investigation of choice for delayed 29.25. Answer: D. I
type IV cell-mediated hypersensitivity but not Acitretin has a long half-life and high lipid
type I antibody-mediated allergy. Most patients bioavailability; pregnancy should be avoided for
3 years after the drug has been stopped, which 29.31. Answer: A.
is why it is not often used in women of As tumour necrosis factor alpha (TNF-a)
child-bearing age. Acitretin is at least as antagonists have efficacy both in psoriasis and
teratogenic as isotretinoin and the effect is of psoriatic arthritis, adalimumab would be the
longer duration. most appropriate next treatment approach to
consider. Ciclosporin could only be used
29.26. Answer: A. short-term and other treatment options would
The body is divided into four areas and each is not be effective for psoriatic arthritis.
scored individually based on area involved and
the redness, thickness and scaling of psoriatic 29.32. Answer: E.
plaques. Joint and nail involvement are not Given that this patient is 93 years old and has
assessed and neither is the type of psoriasis. other comorbidities, active treatment may result
Lichenification is taken into account in eczema in ulceration and poor healing. Given that these
severity scores. lesions have not significantly changed and are
asymptomatic and not bothering her, the most
29.27. Answer: B. appropriate treatment option would likely be to
The autoimmune bullous diseases are usually
leave these untreated, as the risk of significant
exacerbated by light-based therapies and change and development of invasive sec is
should be avoided. All of the other diseases very low (approximately 3%). This case
may respond therapeutically to PUVA. demonstrates how every patient must be
individually assessed in order to ascertain what
29.28. Answer: B.
i~ most appropriate in any clinical scenario.
The image is of a BCC. Mohs' surgery, if
available, would be preferred to excisional
29.33. Answer: D.
surgery at this site given the need for
Specific lgE testing is also known as the
preservation of normal tissue and structures.
radioallergosorbent test (RAST) and could be
Curettage and cautery may lead to
helpful in this situation, which is most likely to
unacceptable scarring at this site and is less
have been caused by type I latex rubber
likely to result in tumour clearance. Topical
allergy. Patch testing is used to investigate
imiquimod may cause significant inflammation,
delayed type IV cell-mediated hypersensitivity.
blepharitis and conjunctivitis at this site.
Prick testing may be positive and helpful in type
Photodynamic therapy, given the nodular
I allergy but is risky to undertake in a patient
nature of the tumour, would be unlikely to
who has already experienced angioedema as
result in complete clearance. Radiotherapy
this may trigger anaphylaxis and should not be
would be likely to result in poorer cosmetic
undertaken without anaesthetic support
outcome and risk damage to the medial
available. Thus, the specific lgE test would be a
canthus and lacrimal duct.
safe initial investigation. It is important to be
29.29. Answer: A. aware that both specific lgE and prick testing
Longitudinal ridging can be a normal part of the can be falsely positive or falsely negative. If
ageing process. Pitting, onycholysis, transverse specific lgE testing is negative but clinical
ridging and nail furrowing are associated with suspicion is high, further investigations with
pathological processes. prick testing in a controlled situation could be
indicated in order to try and clarify the
29.30. Answer: A. diagnosis. lgG antibodies are not elevated in
lntralesional corticosteroids are unlikely to be type I hypersensitivity reactions as the
effective in sudden-onset alopecia universalis mechanism is mediated via lgE immediate
;j and is mainly indicated for patchy alopecia antibody reactions. Oral challenge would not be
areata. There is no evidence for efficacy of appropriate and would, again, carry an
topical minoxidil, finasteride or UVB unnecessary risk of anaphylaxis.
phototherapy in the treatment of alopecia
areata. The most appropriate option is 29.34. Answer: A.
psychological support and discussion of As people get older ~here is reduced absorption
realistic expectations for hair regrowth, which and clearance of topical medications. Skin
may include whether she wishes to consider immune reactions are reduced with ageing.
use of a wig, given the complete alopecia. Photo-ageing is a different process to intrinsic
ageing but is superimposed on intrinsic ageing. evidence to suggest that regular sunscreen use
There is increased susceptibility to irritants and reduces the risk of actinic keratosis (AK) and
irritant dermatitis. The skin becomes thin and sec, although whilst assumed that it will
atrophic with ageing. reduce BCC risk, there is no good evidence to
support this. In most BCCs, the PTCH1 gene
29.35. Answer: C. mutations are somatic and not germline. SCC
Circulating anti-epidermal antibodies may be is a highly genetically heterogeneous tumour.
present in bullous pemphigoid. In this condition,
the split is below the basement membrane and 29.39. Answer: E.
therefore the subepidermal blisters are tense and Invasive SCC may arise de novo or from the
intact. Nikolsky sign is thus negative. Mucous background of AK. The risk of transformation of
membrane involvement is uncommon in bullous AK into invasive SCC is < 1%. A field-directed
pemphigoid. Eosinophilia is usually evident. approach, such as with 5-fluorouracil, PDT or
imiquimod, is required for multiple AK and
29.36. Answer: D. field-change carcinogenesis. Isolated lesions
Great caution needs to be taken with high may be treated with a lesion-directed approach
doses of antihistamines in elderly patients such as cryotherapy. Hyperkeratotic AK usually
because of the risk of over-sedation, delirium does not respond well to cryotherapy, and
and falls. Likewise, low-dose tricyclic curettage and cautery and preparations
antidepressants may be considered but a containing salicylic acid in combination with
high-dose approach would not be advisable. 5-fluorourcil are usually required. Spontaneous
In the absence of rash, very potent topical resolution of AK may occur.
glucocorticoids would be unlikely to be of
therapeutic benefit and, in the elderly, adverse 29.40. Answer: D.
effects of striae and purpura may occur. Most patients with melanoma do not have a
Topical capsaicin would be unlikely to be of positive family history for melanoma and
benefit for generalised pruritus as it can only be approximately 50% of melanomas arise from
applied to localised areas. pre-existing naevus. Lentigo maligna melanoma
tends to occur in the elderly, and acral
29.37. Answer: B. melanoma is more common in dark-skinned
Oxygen is required for the photodynamic populations. Nodular melanoma is more
therapy effect. The cream contains a common in men.
photosensitiser prodrug and not the
photosensitiser itself as the prodrug needs to 29.41. Answer: C.
be taken up and converted to the The description of the rash, the age of onset,
photosensitiser in the skin cells. Laser light is associated systemic features of irritability, fever,
not required for irradiation and most extensive areas of rash with erosions and
dermatological PDT is undertaken using blistering, and systemic upset are most in
broadband and light-emitting diode (LED) light keeping with staphylococcal scalded skin
sources. Nodular BCC can be treated with syndrome. Toxic epidermal necrolysis is much
PDT, particularly if surgery is contraindicated. less likely in this age group and usually occurs in
However, recurrence rates at 5 years are higher association with drug ingestion. Stevens-
following PDT for nodular BCC than for surgical Johnson syndrome typically has mucosal
excision. PDT is often the most appropriate involvement, lesions are more targetoid and
-I
treatment choice for elderly frail patients. It can often there is a precipitant of herpes simplex
be used to treat large areas, on an outpatient virus infection. Epidermolysis bullosa is a
basis, without the need for surgery and with genetically inherited blistering disease, which
improved healing. does occur in children but is not associated with
systemic upset. Impetigo is a localised form of
29.38. Answer: E. superficial bacterial infection, usually due to
Malignant melanoma usually occurs on Staphylococcus aureus.
intermittently sun-exposed sites. The I
immunosuppressed patient population is most
at risk of sec, with only a slight increased risk
29.42. Answer: B.
The description of the rash and its distribution I
of BCC. There is good epidemiological are consistent with pityriasis versicolor and it is
364 • DERMATOLOGY
likely that, as the patient has started to tan with dermatitis would be unusual, although not
phototherapy, the areas of hypopigmentation impossible at this age. The distribution, however,
have become more obvious, making him aware is more suggestive of external causes. The
of this second diagnosis. Pityriasis rosea would distribution would be unusual for dermatophyte
usually be more widespread, not just restricted fungal infection as this is usually unilateral.
to the central trunk, and would usually be Progesterone dermatitis is thought to be due to
associated with a herald patch. In addition, autoimmune sensitisation to progesterone and
lesions would be erythematous and not occurs cyclically with the menstrual cycle but
hypopigmented. Polymorphic light eruption this distribution would be unusual.
commonly occurs during phototherapy but is a
papulovesicular eruption. This is unlikely to be 29.46. Answer: E.
psoriasis because it is hypopigmented and also Moderate-strength topical glucocorticoid such
other sites of psoriasis are improving with as Eurnovate would usually not be sufficient to
phototherapy. Secondary syphilis should always gain adequate control of significant eczema
be considered with new development of activity on the trunk and limbs, and increasing
erythematous scaly rash, but lesions do not the potency of glucocorticoid to a potent agent
tend to be hypopigmented and are usually such as betamethasone 17 -valerate (Betnovate)
more prominently found on distal sites, would be likely to be more effective. Increasing
including palms and soles. the amount but not the potency would be
unlikely to suffice. For chronic lichenified
29.43. Answer: E. eczema, ointments are the preferred vehicle.
Methotrexate can be very effective for chronic Emulsifying ointment is a very good emollient
management of eczema, including atopic arid barrier for chronic lichenified eczema.
eczema. It would not be sensible to move to the Changing to aqueous cream, which can be
newer drugs - apremilast or the biological agent irritant, would not be advisable. Increasing the
dupilumab - without having a therapeutic trial of dose of fexofenadine would be unlikely to be
more conventional immunosuppressants such beneficial, as fexofenadine is a non-sedating
as methotrexate. Ciclosporin can be very antihistamine and, as atopic eczema is not
effective for clearing eczema; however, for primarily a histamine-mediated disease, the
chronic disease activity without acute flare, the beneficial effect of antihistamines would usually
use of a drug that can only be continued in the be via sedating antihistamines, in order to
short term would not be ideal. Acitretin would break the itch/scratch cycle at night.
not usually be used in a woman of child-bearing
age unless she had definitely completed her 29.47. Answer: D.
family, as there is a requirement for her to Pustular psoriasis can often be triggered as a
abstain from pregnancy for 3 years after rebound secondary to commencement and
cessation of drug because of teratogenicity. sudden cessation of systemic glucocorticoids.
It can also be triggered by topical use of
29.44. Answer: B. glucocorticoids and other irritants, which
Biological agents blocking and inhibiting include dithranol, coal tar and vitamin D
interleukin (IL)-4R and IL-13 are being trialled analogues. These should all be avoided in
for use in atopic dermatitis. TNF-a inhibition pustular psoriasis. Whilst PUVA light therapy
and inhibition of IL-12, IL-23 and IL-17 can often be effectively used in pustular
pathways by biological agents have been psoriasis, UVB, although highly effective for
shown to be effective in psoriasis. chronic plaque psoriasis, often causes further
flaring of unstable pustular disease. The effects
29.45. Answer: C. of methotrexate may take several weeks to
In the absence of a history of atopic dermatitis, become established as it does not have a rapid
bilateral dermatitis developing on the backs of onset of action.
hands and between the fingers in a young
woman on maternity leave and likely to have a 29.48. Answer: B.
lot of exposure to water and detergents is most There are many common culprits for
likely to be irritant contact dermatitis. Allergic drug-induced lichenoid reactions, which include
contact dermatitis is a possibility and if irritant gold, penicillamine, thiazides, [3-adrenoceptor
avoidance does not suffice then patch testing antagonists ([3-blockers), ACE inhibitors, proton
should be considered. Late-onset atopic pump inhibitors, non-steroidal anti-
L Mackillop, F Neuberger
Maternal medicine
Multiple Choice Questions
30.1. A 25 year old woman with a 5-year history C. She has stopped her medication for fear of
of rheumatoid arthritis is planning her first teratogenicity
pregnancy. Which of the following drugs should D. She is anxious about the pregnancy and is
be avoided in pregnancy? having pseudoseizures
A. Azathioprine E, Sleep deprivation has caused a worsening of
B. Hydroxychloroquine her epilepsy
C. Methotrexate
D. Prednisolone 30.4. A 35 year old primiparous woman attends
E. Sulfasalazine the antenatal day unit at 18 weeks' gestation
with a history of vomiting, dysuria, left loin pain
30.2. A 40 year old woman is 6 weeks pregnant. and rigors for 24 hours. A urine dipstick is
She has a diagnosis of epilepsy. Which of the positive for leucocytes and nitrites. Her
following pieces of advice is correct? C-reactive protein is 140 mg/L. Which of the
following findings on examination and
A. Drug doses should routinely be doubled in
investigation would require urgent attention?
the second trimester
B. Pregnancy reduces the frequency of seizures A. A decrease in urea and creatinine values
C. She should start high-dose folic acid from her pre-pregnancy levels
D. She should stop anticonvulsant therapy B. A mild respiratory alkalosis on the arterial
E. Sodium valproate is the antiepileptic drug of blood gas
choice in pregnancy C. A raised alkaline phosphatase result
D. A respiratory rate of 24 breaths/min
30.3. An 18 year old woman is admitted to the E. The presence of a systolic murmur
gynaecology ward at 8 weeks' gestation in her
first pregnancy. She has a known diagnosis of 30.5. A 22 year old woman is 9 weeks into her
epilepsy and takes levetiracetam. Her epilepsy first pregnancy, and presents with vomiting.
is usually well controlled but she has had three Which of the following is a feature of
seizures in the last 2 days. Four of the answers hyperemesis gravidarum?
below need to be considered as possible A. Abdominal pain
contributing factors; however, one is unlikely. B. Hyper-reflexia
I Which of the following factors is LEAST likely to C. Lactate >2 mmoi/L (18.0 mg/dL)
have contributed to the increasing frequency of D. Vomiting intermittently
seizures? E. Weight loss >5%
A. Serum drug levels have reduced due to
increased renal clearance and increased 30.6. A 34 year old primiparous woman is
plasma volume admitted to hospital at 32 weeks' gestation
B. She has nausea and vomiting of pregnancy with central crushing chest pain, ST segment
and cannot keep her tablets down elevation on her electrocardiogram (EGG) and a
30.9. A 17 year old woman who is 30 weeks 30.13. A 25 year old woman with ulcerative colitis
into her first pregnancy is admitted to hospital is planning her first pregnancy, and attends clinic
with acute severe asthma. Which of the for pre-pJregnancy counselling. Which of the
following statements is TRUE? following pieces of advicejs TRUE?
A. Chest X-ray is generally avoided in this A. She should be advised against pregnancy
situation B. She should stop taking sulfasalazine during
B. Inhalers should be stopped in pregnancy the first trimester
G. She should deliver by caesarean section irritability. On examination she has a fine
D. She should stop infliximab once she has tremor. What is the most likely diagnosis?
conceived A. Anxiety
E. She should stop taking methotrexate 3 B. Graves' disease
months prior to conception G. Hashimotos's thyroiditis
D. Post-partum depression
30.14. A 42 year old woman presents at 12 E. Post-partum thyroiditis
weeks post-partum with palpitations and
Answers
30.1. Answer: G. levetiracetam. Non-adherence is common
Methotrexate should be stopped 3 months due to concerns over teratogencity and
before pregnancy and throughout pregnancy non-reassurance or reticence to prescribe by
and breastfeeding. All other medications can be health-care professionals. Nausea and vomiting
taken during pregnancy and breastfeeding. is very common in early pregnancy and
Women taking sulfasalazine should also receive antiemetics may be used safely to allow regular
high-dose (5 mg daily) folic acid from medication to be given. All these factors need
pre-conception until at least 12 weeks' to be thought about and addressed to ensure
gestation. women feel confident and comfortable in
their decisions and their chronic condition
30.2. Answer: G. can be optimally managed in pregnancy.
Women with epilepsy should take high-dose Pseudoseizures in this scenario would be very
folic acid prior to conception and throughout uncommon.
the pregnancy. This is because women with
epilepsy who take antiepileptic drugs (AEDs) 30.4. Answer: D.
that induce cytochrome P450 (for example Pregnancy does not cause a significant
phenytoin, carbamazepine) are at risk of low increase in respiratory rate. A respiratory rate
levels of folic acid. Anticonvulsant therapy > 20 breaths/min is abnormal in pregnancy. All
should be reviewed prior to conception, and of the others are part of normal physiological
should not be stopped. Sodium valproate is changes of pregnancy.
associated with a higher risk of major
congenital malformations compared to other 30.5. Answer: E.
AEDs and there should be a discussion Hyperemesis gravidarurn (HG) can be
between the woman and her epilepsy specialist diagnosed in the first trimester of pregnancy,
about switching to another AED prior to when other causes of persistent nausea and
pregnancy. Pregnancy does not reduce the vomiting have been excluded. It is associated
frequency of seizures. Women with with > 5% pre-pregnancy weight loss,
well-controlled epilepsy are not more likely to electrolyte imbalance and dehydration. Nausea
have increased seizures in pregnancy, but and vomiting in pregnancy (NVP) is common,
those with poorly controlled epilepsy may find but not all of these women have HG.
their condition deteriorates. There is no
rationale for routinely doubling drug doses in 30.6. Answer: G.
I the second trimester, although some AEDs, for Myocardial infarction is more common in
example lamotrigine, may need a dose increase pregnancy compared to age-matched controls.
during pregnancy. PPCI is not contraindicated in pregnancy, and
should be carried out where benefits outweigh
30.3. Answer: D. risks. Both chest X-rays and EGGs are useful
Profound physiological changes in pregnancy investigations for chest pain in pregnancy.
can cause a significant reduction in serum Management of chest pain. where an acute
concentrations of some drugs - this is coronary syndrome is suspected should be the
particularly true for lamotrigine and same as in a non-pregnant woman.
R Mann
Adolescent and
transition medicine
31.2. In relation to the normal adolescent 31.4. On a global basis, what is the commonest
female, which of the following statements is cause of death in adolescents?
most correct? A. Complications of pregnancy
A. A fall in growth hormone levels is associated B. Infective gastroenteritis
with a climb in insulin-like growth factors 1 C. Late effects of childhood cancer treatment
and 2 (IGF-1 and IGF-2) D. Malaria
B. Breast bud development and the E. Road injury
development of pubic hair are seen around
the time of menarche 31.5. Which of the following characteristics are
C. Insulin levels fall by around 30%, coinciding particularly associated with risk-taking
with an increased risk of type 2 diabetes behaviours in teenagers?
31.16. A 16 year old boy presents with an B. Eighty per cent of adolescents follow their
8-week history of diarrhoea, weight loss and diet reasonably well
raised inflammatory markers. A biopsy is C. In females, concern about body image,
consistent with Grahn's disease. Which of the including the desire for weight loss, can be a
following is the most correct statement in significant factor in non-adherence to insulin
relation to this case? therapy
A. Anti-tumour necrosis factor (TNF) therapy, for D. Microvascular complications can begin from
example infliximab, is more commonly 20 years after diagnosis, and so can already
needed for adolescents, and he has about a be emerging in patients in their 20s and 30s
50% chance of needing treatment with a E. The majority of patients do not take their
biological agent. insulin injections reliably and this results in an
B. First-line treatment is with steroid therapy, increased admission rate with diabetic
most commonly oral prednisolone or pulsed ketoacidosis (DKA)
intravenous methylprednisolone
C. Methotrexate is a helpful first -line 31.18. When planning adult services for a young
maintenance therapy person with juvenile idiopathic arthritis (JIA),
D. There is a 50% chance of him requiring which one of the following statements is most
surgery in the next 5 years accurate?
E. When offering lifestyle advice, particular A. All children with oligoarticular juvenile arthritis
emphasis should be given to reducing will require long-term follow-up into adulthood
smoking, as smoking increases disease B. Antinuclear antibody (ANA)-positive patients
activity and reduces effectiveness of need ophthalmic screening for eye
biological agents involvement
C. Methotrexate is a first -line treatment if
31.17. Adherence with treatment is a particular multiple joints are affected, and it should be
challenge for teenagers and young adults with used early, particularly in polyarticular JIA
long-term medical conditions such as diabetes. D. Systemic JIA can often be treated with a
Which of the following statements is most combination of long-term NSAIDs and
correct in relation to studies in adolescents with systemic glucocorticoids
diabetes? E. When offering lifestyle advice, particular
A. About 15% of adolescents do not check emphasis should be given to reducing
blood glucose levels regularly and fabricate alcohol intake as it increases disease activity
results for the medical team looking after and reduces effectiveness of biological
them agents
Answers
31.1. Answer: D. changes are breast bud development and early
Puberty is initiated by pulsatile GnRH pubic hair growth, which can be seen from
production, which stimulates FSH and LH around 10 years of age. Menarche arises
production in the pituitary gland. LH stimulates relatively late in puberty, but an adolescent who
Leydig cells in the testis to produce has not started her periods by 16 years of age
testosterone, which causes androgenisation should be investigated for delayed puberty.
and skeletal growth. FSH acts on Sertoli cells Growth hormone levels, IGF-1 and IGF-2 levels
to stimulate spermatogenesis and not to climb steadily during puberty, as do insulin
increase androgenisation. levels by about 30%.
many conditions have been associated with a mycophenolate nor azathioprine are safe during
better long-term outlook. Younger patients find pregnancy. When pregnancy is diagnosed,
it harder to adhere to medicines where the angiotensin-converting enzyme (ACE) inhibitors
long-term health benefits are considerable if should be stopped immediately, and alternative
there is no short-term improvement in therapy commenced, due to human fetotoxicity.
symptoms. With careful monitoring, transplant survival rates
are good.
31.4. Answer: E.
Road injury/fatal road traffic accidents account 31.8. Answer: A.
for a significant proportion of adolescent deaths Illicit drugs have an adverse affect on seizure
on a worldwide basis. Death from road injury is control through both lowering seizure threshold
independently associated with alcohol and drug and adversely affecting adherence. Alcohol
ingestion. Whilst malaria and infective does not seem to independently increase
gastroenteritis are important causes of death in seizure activity, but binge drinking can be
younger children, teenagers have better associated with significant sleep disturbance
immune responses and these conditions are a and reduced AED compliance. In the UK,
common cause of morbidity but have a lower drivers are not permitted to drive unless they
mortality rate than in younger children. Lower have had no daytime seizures for 1 year, but if
respiratory tract infections and suicide are also seizures only occur during sleep then driving
important global causes of adolescent mortality. can be considered. There is no evidence of
teratogenicity in men taking sodium valproate
31.5. Answer: E. but it reduces sperm count in some. In most
The highest-risk adolescents, in terms of parts of the world there are restrictions on entry
risk-taking and self-harming behaviour such as to the armed forces, driving heavy goods
heavy alcohol intake, illicit drug ingestion and vehicles and driving emergency vehicles.
non-adherence to treatment regimes, are
males, older adolescents and those with 31.9. Answer: A.
serious long-term health conditions. It is The liver function tests (including raised alkaline
thought that maturation of the frontostriatal phosphatase) are normal for a male of this age,
reward circuits in early/mid-adolescence drives with the exception of the isolated raised
individuals towards impulsive and pleasure- bilirubin. Hypoalbuminaemia can be a marker of
seeking behaviours that place the adolescent at inflammatory bowel disease, but this albumin is
risk. With time, frontal lobe control of impulsivity normal. There is no need to check alkaline
improves and more stable and safe behaviour phosphatase isoenzymes as the GGT is
patterns develop. normal. Gilbert's syndrome affects 5-1 0% of
the Western European population, and is one
31.6. Answer: D. of the commonest causes of isolated elevation
The starting point in the development of an in bilirubin. It is autosomally recessively
effective transition policy is the local inherited and so his brother's jaundice is likely
development of a programme that meets the to also be due to Gilbert's syndrome.
medical, social and cultural needs of your local
population. The other measures may support 31.10. Answer: E.
the implementation of your transition All these issues may be important. However, in
programme, but often services overly focus a young person who has recently started a
upon a series of information-giving interventions sexual relationship, establishing his/her
rather than developing an ethos of patient understanding of the reproductive implications
autonomy and control. of his/her condition and treatment is of vital
importance - particularly with an agent as
31.7. Answer: E. teratogenic as sodium valproate.
There is an increased risk of hypertension
during pregnancy in all women with renal 31.11. Answer: C.
disease, so they require close monitoring Gastro-oesophageal wflux is common in
throughout - the pre-eclampsia rate is around patients with severe neurodisability. It places
30%. Prednisolone crosses the placenta poorly patients at significant risk of aspiration as they
and is not a particular risk to the fetus. Neither may not have adequate airway-protective
32.3. A 68 year old woman presents 32.5. Which of the following is an essential
complaining of dizziness. She says that this component of a successful rehabilitation
started 2 days ago, and that she cannot walk programme?
in a straight line. She feels sick and the room is A. A dedicated rehabilitation ward
spinning. What is the most likely cause? B. Clearly defined diagnoses
A. Fast atrial fibrillation G. Goal setting
B. Lumbar nerve root entrapment D. Medical leadership
G. Orthostatic hypotension E. The Barthel Index
examination, she has no nystagmus or past 32.18. An 82 year old woman with advanced
pointing, tone and power are normal, but dementia is noticed by the nursing home staff
Romberg's test is positive. What is the most to look rather pale. She does not complain of
likely cause for her unsteadiness? breathlessness or tiredness; she had a severe
A. Benign positional vertigo stroke 3 years ago and has been unable to
B. Cerebellar infarction walk since; she sits in a wheelchair during the
C. Parkinson's disease day and is helped into bed by two helpers at
D. Peripheral neuropathy night. Her bowels are open normally and she
E. Vestibular neuronitis does not complain of indigestion. She has been
in hospital twice. in the last 3 months and
32.15. A 93 year old man presents having fallen during her last admission stated a wish to be
three times in the last week. He has significant allowed to die. What is the most appropriate
bruising over the side of his face from the last investigation for this woman?
fall. His wife saw the last fall; she is sure that A. Abdominal ultrasonography
her husband lost consciousness for a few B. Full blood count
seconds, but came round after 2-3 minutes on C. No investigation
the ground. Lying and standing blood pressure D. Upper and lower gastrointestinal endoscopy
are 155/92 mmHg and 148/90 mmHg, E. Upper gastrointestinal endoscopy
respectively, and cardiac auscultation is normal.
Which course of action would be most 32.19. An 86 year old woman presents having
appropriate for this man? taken to her bed for the last 2 days. She is
A. 24-Hour electrocardiogram (ECG) monitoring normally mobile around the house using a walking
B. Echocardiography frame, but does not usually leave the house.
C. Referral to physiotherapist for strength and Carers come to help her wash and dress twice a
balance training day. On examination, her pulse is 110 beats/min,
D. Start calcium and vitamin D supplementation blood pressure 90/50 mmHg, respiratory rate
E. Tilt table testing 24 breaths/min, oxygen saturations 96% on air.
Her temperature is 37.0°C. Her chest is clear, she
32.16. An 85 year old woman presents with has a gallop rhythm on cardiac auscultation, and
diarrhoea and vomiting. Her blood tests show her jugular venous pressure is not elevated. She
acute kidney injury. Which one of the following is disoriented, drowsy, but able to move all her
changes in kidney structure is attributable to limbs. She opens her eyes when you raise your
ageing, rather than to an underlying disease voice. Her ECG shows deep T-wave inversion
process? across the anterior leads. What is the most likely
diagnosis?
A. Glomerulosclerosis
B. Porosity of the glomerular filtration barrier A. Depression
C. Reduction in nephron numbers B. Myocardial infarction
D. Renal arteriolar hyaline deposition C. Parkinson's disease
E. Stenosis of the renal arteries D. Pneumonia
E. Pulmonary embolism
32.17. A 94 year old man presents with three
falls over a 2-day period. On assessment, he is 32.20. A 77 year old man complains of difficulty
disoriented and dehydrated. His chest is clear walking. On inspection of his gait, he struggles to
to auscultation, temperature is 35.2°C, pulse start walking, but then accelerates into a series of
90 beats/min, blood pressure 11 0/50 mmHg. small steps, and fails to lift his feet very far from the
His respiratory rate is 18 breaths/min and his floor. He does not swing his arms when walking,
oxygen saturations are 89% on air. What is the and has difficulty turning at the end of the walk.
most likely cause for his falls? What is the most likely explanation for his gait?
A. Cerebral infarction A. Bilateral parietal lobe stroke disease
B. Pneumonia B. Cerebellar stroke
C. Poor fluid intake C. Hip osteoarthritis
D. Spinal cord compression D. Parkinson's disease
E. Subdural haematoma E. Peripheral neuropathy
Answers
32.1. Answer: E. Leadership is necessary, but does not have to
His falls do not occur at home: thus, home be medical or doctor leadership. Assessment of
modification is unlikely to help in this case. needs is necessary, but this does not have to
Calcium and vitamin D is effective only in be via the Barthel score. Rehabilitation can take
patients in institutional care, who are those with place in many settings, including the patient's
the lowest vitamin D levels. Hip protectors do home; a ward is not necessary. It is essential to
not reduce falls, and current evidence suggests define the patient's disabilities and functional
that they do not reduce fractures either. A capabilities; this is more important than the
pacemaker would help only if cardioinhibitory precise underlying diagnoses.
carotid sinus hypersensitivity was
demonstrated. 32.6. Answer: A.
CGA reduces short-term mortality or adverse
32.2. Answer: A. outcomes, but not these outcomes at 12
She is describing urge incontinence. months. CGA can improve cognition in the
Antimuscarinic medication can be helpful but medium term, but there is no evidence as to
carries a high burden of side-effects. Her whether it delays the onset of dementia or not.
symptoms have been continuous for 2 years; CGA might improve the speed of recovery from
they are not therefore due to infection and surgery, but there is no trial evidence to prove
antibiotic therapy is inappropriate. For most this. It is a key component, however, in
people, long-term catheters bring as much maximising function in older people recovering
harm as benefit. Tension-free vaginal tape from surgery. CGA is usually offered to those
and pelvic floor training are useful interventions patients who are already frail or pre-frail; thus it
for stress incontinence but not for urge is unlikely to affect time to onset of frailty.
incontinence.
32.7. Answer: C.
32.3. Answer: E. Hand grip strength forms part of the Fried frailty
She is describing vertigo, which may be due to phenotype, and is a powerful independent
either labyrinth or brainstem disease. As her predictor of frailty-related outcomes in older
symptoms have persisted for 2 days, a people. Blood pressure is not part of frailty
transient ischaemic brainstem attack is less syndromes. Although weight loss is part of
likely than vestibular neuronitis - although note frailty measurements, current body mass index
that a completed stroke involving the brainstem is not. Similarly, walk speed over a short
might produce similar symptoms. distance (4 or 5 m) is part of frailty assessment,
but 6-minute walk distance is not commonly
32.4. Answer: C. used; this is a measure of endurance exercise
This is a classic case of treating drug side- capacity and is more useful in assessing
effects with further drugs. The amlodipine has disease severity of cardiorespiratory illnesses
caused ankle oedema; the furosemide has then such as heart failure and chronic obstructive
caused intravascular volume depletion and pulmonary disease. Number of medications is
orthostatic hypotension. The safest course of related to multimorbidity, not to frailty.
action is to stop both agents, then reassess
the blood pressure (perhaps using a 24-hour 32.8. Answer: E.
blood pressure monitor). If the blood pressure All of the other changes are due to
is still high, an alternative agent (such as an cardiovascular pathology; all are more common
ACE inhibitor) could be considered. a-Blockers with age, but can be attributed to disease
are particularly likely to worsen orthostatic processes such as atherosclerosis,
hypotension. hypertension, obesity and myocardial
dysfunction.
32.5. Answer: C.
Goal setting (and regular review of goals) 32.9. Answer: E.
is an essential component of successful Timed 'get up and go' test is a good predictor
rehabilitation. The other components are not. of future falls risk, and also allows observation
of the gait for unsteadiness. Six-minute walk very unlikely that urinary infection is playing any
test measures endurance rather than part in her symptoms.
'fast-twitch' lower limb function (which is more
closely correlated with balance and falls risk). 32.13. Answer: E.
The Barthel Index measures dependency in She has 2 of the 5 Fried Frailty criteria - low
activities of daily living, and although hand grip grip strength and self-reported exhaustion.
is a good measure of overall physical status Three criteria are required to diagnose frailty,
(and forms part of the criteria for frailty), it is but the presence of 1 or 2 criteria is sometimes
less directly relevant to falls risk. categorised as 'pre-frail'. You are not given any
information to suggest that she has functional
32.10. Answer: C. impairment - she continues to undertake
Benign positional vertigo is common and activities of daily living. Similarly, you are not
amenable to treatment with simple positional told anything that suggests the presence of a
manoeuvres. Supine blood pressure alone will specific disability.
tell you little; postural blood pressure is more
important. Finding a reduced hip extension 32.13 How to assess a Fried Frailty score
range would be unsurprising after recent hip
Hand grip strength in bottom 20% of healthy elderly
surgery. Whilst depression is important, finding
distribution*
it will not directly influence your plans for Walking speed in bottom 20% of healthy elderly
reducing his falls risk. Cardiac auscultation may distribution*
uncover a murmur of aortic stenosis - a cause Self -reported exhaustion
Physical inactivity
of syncopal episodes potentially amenable to
At least 4.5 kg weight loss within 1 year
intervention - but this is less likely than option Patient is defined as frail if 3 or more factors are present;
C, and even if you find severe aortic stenosis, 1-2 factors indicate a 'pre-frail' state.
comorbid disease and frailty might prevent you *Varies between populations. Grip cut-off is 30 kg for men
from intervening successfully. and 18 kg for women in US adults; 5 m walk time cut-off is
7 seconds in US adults for both sexes.
32.11. Answer: B.
Drugs are the most common cause of 32.14. Answer: D.
hyponatraemia in older people - and thiazide The lack of nystagmus or past pointing argues
diuretics are one of the commonest drug against this being due to middle ear, brainstem
causes. Ibuprofen is a less likely cause, unless or cerebellar disease. The normal tone makes
acute kidney injury has been precipitated by its Parkinsonian syndromes less likely, although
use. Both carcinoma of the lung and Addison's you are not given specific information about
disease can cause hyponatraemia, but are both bradykinesia. A peripheral neuropathy or dorsal
much less common causes than drugs. column spinal cord disease would explain the
Inadequate salt intake is very unlikely to lead to unsteadiness and positive Romberg's test.
low serum sodium levels.
32.15. Answer: A.
32.12. Answer: E. The witness account suggests that this was a
Her dementia is likely to be severe enough that syncopal episode; this requires investigation.
she is unaware of needing to pass urine; the 24-Hour ECG monitoring is a reasonable first
normal inhibitory signals preventing bladder investigation; if this does not uncover a reason,
emptying are lost and the signals indicating that then further investigation (e.g. tilt table testing)
the bladder is full are either not processed or may be required. Echocardiography is likely to
not acted on. Regular toilet visits (e.g. every be less useful, especially given that no murmur
2-3 hours) can be helpful in ensuring that is audible.
voiding occurs before the bladder is full. Pelvic
floor exercises are useful in stress incontinence, 32.16. Answer: C.
but require active participation and The other structural changes are due to
understanding by the patient. Catheterisation is disease, not ageing. Glomerulosclerosis may be
not the first choice for any continence problem, caused by a range of dis~ases, including
and this woman is unlikely to have sufficient diabetes mellitus and infections; diabetes may
cognitive function to self-catheterise. The similarly cause porosity of the filtration barrier,
long-standing nature of the problem makes it leading to proteinuria. Hypertension leads to
arteriolar hyaline deposition, and renal artery decisions on her behalf should she lack
stenosis may be caused by atherosclerosis or capacity to make decisions about her medical
fibromuscular dysplasia. care.
Oncology
33.11. A 54 year old woman presents to the What factor is the most likely cause of this
emergency department complaining of severe problem in the UK?
lower abdominal pain and distension over a
24-hour period. Her bowels had not moved
over the same time period and her abdomen
has become visibly swollen with associated
nausea and vomiting. Over the previous 4
months, she has lost 9 kg in weight and has
noted progressive symptoms of constipation.
She reports that on several occasions she has
passed blood mixed in with her bowel
movements, which have become thinner in
calibre. She denies any recent travel, use of
antibiotics, or fevers.
On clinical examination, she appears acutely
uncomfortable and has a temperature of
38.3°C. Her abdomen is diffusely distended
and tender to palpation in the left lower
quadrant. There are hyperactive rushing bowel
sounds. On rectal examination, her stool is
brown and tests positive for blood. A plain A. Arsenic
abdominal X-ray film shows multiple small B. Benzene
bowel air fluid levels and a dilated colon C. Human papilloma virus (HPV)
proximal to the sigmoid colon. D. Ultraviolet (UV) radiation
What is the most likely diagnosis? E. Vinyl chloride
A. Amoebic abscess
33.14. A 42 year old man previously worked at
B. Colonic polyp
the Fukushima Daiichi Nuclear Power Plant
C~ Diverticulitis
and received radiation exposure as a result of
D. Diverticulosis
the damage to the reaCtor caused by an
E. Sigmoid carcinoma
earthquake and the subsequent leakage of
nuclear material. He has concerns about his
33.12. A 39 year old woman completed her last future cancer risk as a direct result of his
course of adjuvant chemotherapy for breast exposure.
cancer 2 years earlier. She presents to the What statement in relation to radiation
oncology clinic complaining of constant back exposure is the most accurate?
pain for 3 weeks. On clinical examination she is
tender to palpation over two well-circumscribed
A. Large exposure is required to develop the
most serious malignancies
areas in the thoracic and lumbar spine. There is
no neurological deficit.
B. Leukaemia has the shortest latency period of
all malignancies
What is the most appropriate next step
C. Malignancies always occur within 10 years of
in investigation, assuming rapid availability
exposure
of all?
D. Malignancy risk increases with advancing
A. Computed tomography (CT) scan of whole age at the time of exposure
spine
E. Therapeutic radiation therapy given without
B. Isotope bone scan
chemotherapy does not increase the risk of
C. Needle biopsy of the affected areas a second malignancy
D. Plain film X-rays of the affected areas
E. Ultrasour;Jd of the affected areas 33.15. A 22 year old man presents to his family
physician complaining of breathlessness
33.13. A 62 year old woman has noticed worsening over the previous 7 days. He has no
a lesion on her face that has persisted for cough and denies smoking. A chest X-ray is
more than a month. It appears as an performed, shown below.
ulcerated lesion with a raised, rolled edge
(see figure).
What is the most likely histological type of
malignancy? . .I
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386 • ONCOLOGY
Clinical examination reveals abdominal 33.23. A 44 year old woman presents to her
distension with shifting dullness. Pelvic family physician complaining of a severe
examination reveals a large, non-tender right headache that had been present for several
adnexal mass. weeks and had not responded to the usual
Abdominal CT scan shows masses arising over-the-counter headache remedies. She
on both ovaries, ascites and omental locates the headache to the centre of her head
thickening. Serum cancer antigen 125 (CA-125) and describes it as constant but worse in the
level is 2000 U/ml. Serum alpha-fetoprotein mornings. She has no other neurological signs
(AFP) and human chorionic gonadotrophin or symptoms. She has had 'tension headaches'
(hCG) are normal. previously but those were located in the back
What is the most likely diagnosis? of her head and felt different from the present
A. Choriocarcinoma pain. She has a past history of breast cancer 2
B. Dermoid cyst (cystic teratoma) years previously, which was treated with
G. Epithelial ovarian cancer surgery followed by adjuvant chemotherapy.
D. Ovarian sarcoma What is the most appropriate next step in
E. Sertoli stromal cell tumour diagnosis?
A. Carotid arteriogram
33.21. A 25 year old woman, gravida 2, para 2 B. CT scan of the head
presents to her family physician to discuss G. Lumbar puncture
contraception. She has no medical problems, D. Psychiatric evaluation
is on no medications and has no family history E. Skull X-rays
of cancer. All clinical examinations are normal.
After a discussion with the family physician, 33.24. A 43 year old woman presents to the
she chooses to take the oral contraceptive pill specialist breast clinic with a breast lump that
(OCP) and stays on the pill for the following she noticed on self-examination. She has a
5 years. 2-cm, firm, non-tender mass in the left breast,
What cancer' has the greatest reduction in which is movable from the chest wall, but not
risk as a result of this medication? movable within the breast. She has no prior
A. Bone sarcoma history of breast disease.
B. Breast cancer What is the most appropriate initial step?
G. Cervical cancer A. Arrange a mammogram to find any other
D. Endometrial cancer lesions that might also need to be addressed
E. Hepatocellular carcinoma B. Arrange an ultrasound scan and advise the
patient she is unlikely to need a biopsy
33.22. A 73 year old man presents to his family G. Discuss the surgical options in case cancer
physician complaining of a drooping right eye is found
lid. He has a 70-pack year history and his D. Obtain a fine needle aspirate and discharge
family physician has been seeing him for more the patient if no malignant cells are found
than 10 years for management of his E. Wait for two menstrual cycles to see whether
symptoms of chronic obstructive pulmonary there is spontaneous resolution
disease (COPD). On clinical examination, he
has ptosis of the right eye with a constricted 33.25. A 70 year old man presents to his family
right pupil. The remainder of the eye and physician with an episode of visible haematuria.
cranial nerve examination is normal. He denies prior episodes and had been
What is the most likely finding on a chest previously healthy. He is not on any medication.
X-ray of this patient? Urinalysis confirms gross haematuria without
A. A calcified granuloma in the left mid-lung proteinuria or casts. The patient denies any
field pain and all physical examination is normal.
B. A left-sided pleural effusion What is the most appropriate next step?
G. A right upper lobe pneumonia A. CT scan of the pelvis
D. An irregularly shaped mass at the apex of B. Cystoscopy
the left lung G. Renal angiogram -
E. An irregularly shaped mass at the apex of
the right lung
D. Transrectal prostatic biopsy
E. Trimethoprim-sulfamethoxazole I
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388 • ONCOLOGY
33.26. A 73 year old man presents to the chest 33.28. A 26 year old woman presents to her
clinic for annual review for asbestosis. He has a family physician complaining of facial hair on
long smoking history and was diagnosed with her upper lip. This has been present for many
asbestosis on biopsy 4 years previously. He years and has not bothered her before. She
has no change in his symptoms but continues has been trying to conceive for some time
to smoke cigarettes and denies any cough or without success and previously has taken the
shortness of breath. His chest X-ray shows left OCP for irregular periods.
lower lobe pleural thickening with calcifications On clinical examination, her body mass index
at the level of the diaphragm. (BMI) is 32 kg/rn 2 • Her blood pressure is
He has many questions about his disease 135/88 rnmHg, pulse is 72 beats/min and skin
and wants to discuss his risk for malignancy examination reveals acanthosis nigricans, mild
and long-term prognosis. What explanation is acne and scattered plucked chin with facial hair
most appropriate? on the upper lip. Abdominal examination is
A. Asbestosis itself (without smoking) is unlikely normal.
to progress to cancer This woman is at greatest risk for what
B. His risk of cancer is greater than 70 times condition?
that of the normal population A. Diabetes mellitus
C. Mesothelioma is the most common cancer B. Gastric cancer
associated with asbestosis and smoking C. Ovarian cancer
D. Small cell lung cancer is the most common D. Ovarian torsion
cancer associated with asbestosis and E. Uterine cancer
smoking
E. Steroids may slow progression of his disease 33.29. A 59 year old man presents to his family
physician with a 3-week history of dyspnoea,
33.27. A 42 year old woman presents to the particularly on exertion, and had an occasional
clinic to discuss her concerns regarding breast cough, which is dry and unproductive.
cancer. She has no symptoms at review, but He describes some chest tightness and
previously she had noted bilateral breast discomfort, which was mostly dull in
tenderness prior to her menses, which has nature.
since abated. She has had two caesarean On clinical examination there is nicotine
deliveries but no other operations. She is taking staining of the left index and second fingers.
a low-dose OCP and has no known drug There is no peripheral lymphadenopathy, no
allergies. She does not smoke and has no evidence of heart failure, the jugulovenous
family history of cancer. All clinical examinations pressure is not raised and heart sounds are
are normal. normal. On chest examination there is reduced
She wants to know whether BRCA 1 and expansion on the right, with decreased tactile
BRCA2 screening would be appropriate for her vocal fremitus, dullness to percussion and
in addition to routine screening starting at age diminished breath sounds. Examination of
50. What is the most appropriate response? the left hemithorax is unremarkable. Peak flow
A. BRCA 1 and BRCA2 screening is not rate is 450 Umin. Abdominal examination is
recommended normal.
B. BRCA 1 and BRCA2 screening should be What is the most likely diagnosis?
performed after age 50 A. Collapse of the right lung
C. BRCA 1 and BRCA2 screening should be B. Consolidation of the right lung
perfomied if breast pain recurs C. Interstitial fibrosis throughout right lung field
D. BRCA 1 screening is recommended D. Left tension pneumothorax
E. BRCA2 screening is recommended E. Right pleural effusion
Answers
33.1. Answer: A. and are then processed in the liver to become
Inhaled carcinogens are absorbed across the more water-soluble. The metabolised
bronchial mucosa and enter the blood stream carcinogens are then filtered by the kidney and
sit in the bladder for hours. After more than 10 aspiration, usually under echocardiograrn
years, the risk of bladder cancer is significantly guidance.
elevated. The same '1s true for breast cancer,
as carcinogens are secreted into the breast 33.7. Answer: A.
ducts, but the incidence of breast cancer This patient has no prior history of illness and
caused by this aetiology is not as great as that the fracture has occurred spontaneously, i.e.
for bladder cancer. without any trauma. In view of her gender and
Ovarian cancer is not affected by smoking age, of the options listed, this is most likely to
but the risk of endometrial cancer is lower in be due to breast cancer (1 in 8 lifetime risk).
smokers than non-smokers. Options C and D
have no significant linkage to smoking. The 33.8. Answer: B.
best answer is option A. The clinical indicators suggest that this patient
has Cushing's syndrome. There are four
33.2. Answer: C. possible causes of Cushing's. These are:
Options A and E would allow the cells to die exogenous steroids, adrenal adenoma, ectopic
and therefore be unsuitable for cytological ACTH and a pituitary adenoma. Only the latter
assessment. Option 8 results in cells sitting in two give a high ACTH and only ectopic
the bladder overnight with some also dying off. production does not fall on a high-dose
This is, however, the best option for suspected suppression test. Therefore, the clinical
Mycobacterium infection. Option Dis the scenario is describing Cushing's syndrome with
best sample for culture as it minimises ectopic ACTH production. The most likely
contamination at the start and end of stream. cau'le of that is small cell lung cancer (SCLC).
Option C gives the best yield for cytological LDH is an intracellular enzyme that is released
assessment. during necrosis as a pathological process;
therefore, in rapidly growing tumours (like
33.3. Answer: D. SCLC), this can be elevated in a serum sample.
The second growth phase precedes nuclear Patients with SCLC can develop the
division, which is in mitosis (M}, and is followed syndrome of inappropriate antidiuretic hormone
by cytokinesis, which is still in mitosis (M). (vasopressin) secretion, but that would
decrease plasma osmolality. Renin may be
33.4. Answer: A. increased in some tumours but not lung.
It is important to understand which drugs are Adrenaline is increased in neuroendocrine
safe in pregnancy, and vitamin A taken in large tumours of the adrenal gland
doses can cause fetal abnormalities. Other (phaeochromocytoma) but not neuroendocrine
vitamins mentioned are not thought to have any tumours of the lung (SCLC). Prolactin can be
teratogenic effect. produced as a result of an ACTH-producing
pituitary tumour causing loss of prolactin
33.5. Answer: B. inhibitory factor (due to pituitary stalk
This patient is likely to have a basal cell compression), but ACTH would fall with
carcinoma from the description. high-dose dexamethasone in that scenario.
Options D and E relate to management but
identification is required first, particularly before 33.9. Answer: E.
delivering invasive treatment. Option C would The clinical features do not suggest infection
be used for a fungal lesion. Option A would (option D) and option A would be more likely to
biopsy the central necrotic portion and may not cause a subarachnoid haemorrhage. Option B
yield a diagnosis, whereas option 8 would is more likely to have sudden onset. Option B,
sample the proliferative edge and therefore is C and E are possible from the clinical history
best for histological diagnosis. but the radiological description is more in
keeping with option E.
33.6. Answer: E.
The clinical presentation of this patient 33.10. Answer: A.
describes a pericardia! effusion resulting from A long smoking history increases the exposure
his malignancy: hence the increased cardiac of the urological epithelium to inflammatory
silhouette. His blood pressure is low as he is mediators such as carcinogens in tobacco.
developing cardiac tamponade. This requires After more than 1 0 years, this increases the
risk of developing a bladder cancer, which in myeloma. Vinyl chloride is hepatotoxic and has
turn is causing urinary retention. Given the time been associated with hepatic angiosarcoma.
course, it is most likely that bilateral
hydronephrosis will be present. 33.14. Answer: B.
The carcinogenic effect of radiation exposure is
33.11. Answer: E. related to the exposure rate. When we consider
This patient is in bowel obstruction and the this in relation to therapeutic radiation, larger
clinical history suggests many features to locate doses can be given in lots of small fractions
this to the sigmoid colon. Option A is unlikely in over more time to lessen the effect (55 Gy over
the absence of foreign travel and the symptoms 5 weeks on average for radiotherapy treatment,
would be right upper quadrant pain. Option B whereas 8 Gy to the whole body over 30
is unlikely to cause thin stools and obstruction. seconds could prove fatal). Second
Option C (-itis) has inflammation and could malignancies induced by radiotherapy usually
result in abscess formation, even perforation, take more than 10 years to manifest. Patients
but would not fully explain the stool history (thin that are young (< 18 years) have tissues that
calibre). Option D may explain the increasing are still developing and are therefore at highest
constipation over time but not the acute risk of transformation. Chemotherapy is
presentation. Option E is the best answer for all administered with radiotherapy to enhance the
symptoms and progression into an emergency biologically effective dose, i.e. it produces a
presentation to hospital in bowel obstruction. greater effect on tissue than the dose of
A high temperature can be seen in malignancy radiation on its own. This acts as a sensitiser
or when secondary infection is present. for the tissue and would therefore increase the
risk of malignant transformation. Leukaemia has
33.12. Answer: B. the shortest latency period.
This patient is likely to be pre-menopausal and
therefore osteoporosis is less likely. She has a 33.15. Answer: C.
diagnosis of breast cancer and could have This question is about understanding the
progressive recurrent disease and therefore the natural history of malignancy. Papillary serous
onset of back pain requires investigation. The carcinoma is mostcommonly associated with
first step in investigation is to assess the whole gynaecological cancers and is therefore unlikely
skeleton to see if this is isolated or widespread in a male patient, although it can arise in the
and that is best done with a radioisotope bone pancreas in older patients. Carcinosarcoma
scan. This will be followed with plain film contains malignant elements from epithelial
imaging of any hot spots and, if suspicious, tissue (carcinoma) and connective tissue
thereafter consider a biopsy of the (sarcoma) and is most commonly found in the
abnormalities. gynaecological system, although rarely it is
CT imaging can show bone detail but would found as a component of de-differentiated
be less sensitive than a bone scan. Ultrasound carcinoma of the lung, but not at this age.
would not be helpful. MRI would be best if Adenocarcinoma can develop from many
there was also a neurological deficit, to look for primary sites, including the lung, where it can
cord compression or to distinguish osteoporotic arise in the periphery or hilar region and is not
collapse from metastatic involvement. associated with tobacco products. This, too, is
less likely at this age. Testicular immature
33.13. Answer: D. teratoma is most likely to cause a large-volume
Each of these substances is associated with lung metastases in a young male.
malignancy but UV exposure is most
associated with a basal cell carcinoma. These 33.16. Answer: C.
tumours are therefore more common in According to the National Institute for Health
individuals that work outdoors. Although and Care Excellence (NICE) guidance, the lump
arsenic is associated with skin c~mcer, it is requires follow-up and investigation, not
most likely to be squamous cell carcinoma. reassessment in a month's time by the same
HPV is associated with head and neck cancer doctor. However, whilst one of the listed
and cervical cancer. Benzene is associated investigations is the most appropriate (option
with leukaemia, particularly acute myeloid A), it should be performed and interpreted by
leukaemia but also non-Hodgkin lymphoma and specialists and not in the primary care setting.
percentage of patients subsequently develop middle-aged patients and males more than
mesothelioma and the continued smoking will females. However, in younger patients it is
increase the risk of lung cancer. Moreover, more associated with insulin resistance and
smoking cessation will not negate the risk of thus an increased risk of diabetes mellitus and
malignancy. Steroid therapy may improve the polycystic ovary syndrome, which may explain
symptoms but does not alter the natural history some of the other signs and symptomatology.
of asbestosis. Her BMI will increase her risk of uterine
cancer but only after she has become
33.27. Answer: A. post -menopausal.
Screening of patients for breast and ovarian
susceptibility genes is indicated in individuals 33.29. Answer: E.
that have a personal history of both cancers, or The clinical features at presentation are those
that have a personal diagnosis of either breast of a pleural effusion: reduced expansion,
or ovarian cancer and a first -degree relative diminished tactile vocal fremitus (vocal
with either breast or ovarian cancer. Routine resonance), dullness to percussion and
screening of BRCA genes in a patient with no diminished breath sounds. Tracheal deviation
history would not be indicated. may be away from the side of the lesion in
massive effusion but shift of the lower
33.28. Answer: A. mediastinum (apex beat) is also likely to be
Acanthosis nigricans is a paraneoplastic away from the side of the effusion.
phenomenon associated with gastric cancer in
mother's memory is not as good as it used to B. Develop a management plan with the patient
be. What is the likeliest cause of the memory to support her in using self-management
impairment? strategies
A. Borderline cognitive impairment exacerbated C. Ensure she has a thorough assessment by a
by opioid medication dietician and advice on diet
B. Depression D. Increase oxycodone IR to 15 mg with an
C. Lack of sleep due to pain increase in frequency, as required for the
D. New onset of Alzheimer's disease pain, up to 8 times a day.
E. Undiagnosed malignant disease, with brain E. Stop her strong opioids, as they may be
metastases causing the constipation
34.7. A 27 year old man had a severe injury to 34.9. A 49 year old man with an advanced
his left arm in a motorcycle accident 4 years oropharyngeal tumour has severe pain in his
ago. He had extensive surgery, complicated by mouth and jaw, and is also struggling to eat.
post-operative infection, and required a high He is taking soluble co-codamol, which helped
dose of opioids to manage it at that time. He initially but is not really working now. He has a
has had persistent pain since then, being past history of peptic ulcer disease. What type
unable to return to his job as a builder. When of analgesic would you choose next?
assessed in the pain clinic he has very limited A. A strong opioid should be considered, with
movement, mechanical allodynia and appropriate formulation or route of
intermittent swelling (below). The affected limb administration (e.g. suspension or liquid;
is noticeably colder than the other arm, with transdermal)
increased sweating in his hand. B. Diazepam should be given to help with any
anxiety
C. Diclofenac should be started at maximum
dose to reduce any inflammation
D. Low-dose amitriptyline, or other tricyclic
antidepressant, should be started in case
there is any neuropathic pain
E. Paracetamol should be added in
A. Blood test, including full blood count, urea side-effects associated with the medication.
and electrolytes, calcium and albumin Which of the following pieces of advice is true?
B. Computed tomography (CT) scan of A. Drowsiness after a dose increase is common
abdomen and pelvis and may improve within a few days
C. CT scan of head B. Morphine is the opiate of choice regardless
D. Electrocardiogram (ECG) and of renal function
echocardiogram C. Once established on the right dose, furt~er
E. Endoscopy adjustments will not usually be necessary
D. The dry mouth associated with her morphine
34.12. A 68 year old patient with chronic prescription will improve within a week of
obstructive pulmonary disease (COPD) attends starting the drug
your outpatient clinic after a recent admission E. The nausea and vomiting are likely to persist
to the high dependency unit. He remains short and she should take long-term antiemetic
of breath on minimal exertion. His daughter medication in addition
asks whether he might be referred to the local
palliative care team. Which of the following 34.15. A 71 year old woman with lung cancer
statements applies? and end-stage COPD is becoming increasingly
A. He should be judged to be in the last 6 distressed by dyspnoea and is referred to the
months of his life in order to benefit from respiratory team for assessment. She is
specialist palliative care team input tachypnoeic and anxious. Her symptoms are
B. He should have a diagnosis of cancer to be no longer relieved by inhaled bronchodilators.
suitable for referral She has a cough productive of grey phlegm,
C. He should have up-to-date pulmonary which is unchanged from her normal situation.
function tests before referral Her husband supports her at home; both of
D. He would benefit from advice on anticipatory them continue to smoke.
planning for future exacerbations of his Her chest X-ray shows hyperinflation of both
disease lungs and the known tumour at the left apex.
E. Opiate medication is the likely treatment of Observations are unremarkable other than
choice for this patient oxygen saturations of 89%.
Which of the following might play a role in
34.13. A 79 year old man is in the ward. He has helping to manage her current condition?
presented with right flank pain and a sense of A. An oxygen concentrator, for use as required
abdominal fullness. His liver function tests are at home
abnormal and an ultrasound shows multiple B. Antibiotic therapy
lesions in the liver. He is tender over the right c. Initiation of citalopram medication
upper quadrant and tells the medical team that D. Oral diuretic therapy to treat any coexisting
his pain is not helped by paracetamol. cardiac failure
He has a past medical history of ischaemic E. Sublingual lorazepam, to be taken as
heart disease, gout, total hip replacement and required
a resection of a colonic cancer 2 years ago.
Which of the following would be a
34.16. A 76 year old woman is an inpatient in
reasonable strategy if his pain persists?
the general medical unit. She is known to have
A. A glucocorticoid such as prednisolone or multiple myeloma with bony metastases and
dexamethasone has presented with vomiting. Her bowels have
B. An NSAID not moved for 8 days. She is delirious and
C. Antispasmodic medication such as hyoscine looks as though she may be dying.
butyl bromide Her initial blood results are as follows:
D. Gabapentin haemoglobin 79 g/L, white cell count
E. Oral morphine solution 6.7x10 9/L, platelets 314x109/L; urea
18.3 mmoi/L (11 0 mg/dl), sodium 143 mmoi/L,
34.14. A 52 year old woman has metastatic potassium 4.2 mmoi/L, creatinine 213 11moi/L
cancer with bony metastases throughout her (2.4 mg/dl), calcium 2.94 mmoi/L (11.8 mg/
pelvis. She is requiring increasing doses of her dl), albumin 23 g/L, adjusted calcium
opiate medication, and is concerned about the 3.28 mmoi/L (13.1 mg/dl).
Which of the following initial treatments and is now unable to communicate his needs
would be most helpful to this patient? to his family or the nursing team caring for him.
A. A subcutaneous infusion of haloperidol for He is currently undistressed.
her delirium and nausea Which of the following statements applies to
B. Blood transfusion to bring haemoglobin his ongoing management?
above 100 g/L and addition of a proton A. As he is unconscious, there is now no need
pump inhibitor for religious or spiritual support in this
C. Intramuscular cyclizine situation
D. Intravenous fluids and bisphosphonate B. He should have his urea and electrolytes
therapy checked at least twice weekly to check for
E. Intravenous fluids and laxatives to address worsening of his renal function
the constipation C. If he is unable to swallow medication, then
he should receive his usual dose of diuretics
34.17. You are asked by hospital colleagues to by an intravenous route
undertake a palliative care review of a 77 year D. Parenteral medication should be available as
old man who is dying of end-stage cardiac required for any symptoms that might arise
failure in one of the general hospital wards. E. The family can be advised that he is likely to
He is no longer able to eat or drink and is die within the next 2-3 days
completely bed bound. He is now unconscious
Answers
34.1. Answer: B. such as CGRP. Spinal interneurons modulate
Normally, light touch and pressure cause input from peripheral nerves.
activation of specialised mechanoreceptors
such as Pacinian and Meissner's corpuscles, 34.2. Answer: B.
with transmission of sensation such as light A wide range of neurotransmitters are involved
touch being via large myelinated A~ fibres. in pain processing (Box 34.2), with changes
Painful stimuli activate high-threshold occurring in response to tissue injury.
nociceptors, found on small unmyelinated C Glutamate, acting via the N-methyl-o-aspartate
fibres. C fibres may contain a range of (NMDA) receptor plays a key role in central
neuropeptides involved in pain processing, sensitisation (Fig. 34.2), with increased neuronal
NMDA receptor
lll
Amplified
s1gnal
Regulation of
pain response
changes
Fig. 34.2 Mechanisms of central sensitisation. Post-synaptic activation of the N-methyl-0-aspartate (NMDA) receptor by the amino
acids glycine and glutamate, which bind to the NR1 and NR2 subunits, respectively, amplify pain signals at the level of the spinal cord.
In contrast, magnesium ions block receptor activation.
34.2 Neurotransmitters and receptors involved in pain processing in the spinal cord
Neurotransmitter Receptor(s) Receptor type Comments*
Amino acids
Glutamate AMPA ion channel Excitatory; permeable to cations: can be Ca'•, Na• or
K•, depending on subunit structure
NMDA lon channel Excitatory; blocked by Mg'+ at resting state; block can
be altered if membrane potential changes; permeable
to Ca'•, Na' and K'
Kainate lon channel Post synaptic - excitatory
Gp I GPCR Pre-synaptic - inhibitory through GABA release;
permeable to Na' and K'
Gp II GPCR Activates a range of signalling pathways; long-term
effects on synaptic excitability
(lp Ill GPCR Probably inhibitory; can decrease cAMP production;
pre-synaptic; decreases glutamate release
Glycine GlyR lon channel Mainly inhibitory; permeable to cl- blocked by
caffeine
y-aminobutyric acid GABA, lon channel Mainly inhibitory in spinal cord; permeable to Cl-;
indirectly modulated by benzodiazepines (increased
ion channel opening); not specifically involved in
nociception, generally depressant effect on spinal
cord activity
GABA, GPCR Predominantly inhibitory; activated by baclofen
Neuropeptides
Substance P Neurokinin receptors GPCR Mainly excitatory; increased in inflammation,
decreased in neuropathic pain
Cholecystokinin CCKRs1-8 GPCR Excitatory; clinical trials of antagonists in progress
Calcitonin gene-related CALCRL GPCR Excitatory; slows degradation of substance P;
peptide implicated in migraine
Opioids
Dynorphin OP1 (kappa) GPCR Excitatory??; may be pro-nociceptive
~-endorphin OP3 (mu) GPCR Inhibitory
Nociceptin ORL-1 GPCR Inhibitory; also expressed by immune cells
'Excitatory = increased pain; inhibitory= reduced pain.
(AMPA = a-amino-3-hydroxy-5-methy/-4-isoxazolepropionic acid; CALCRL = calcitonin receptor-/ike receptor,· cAMP= cyclic
adenosine monophosphate; GABA = y-aminobutyric acid; Gp = group; GPCR = G-protein-coupled receptor,· NMDA = N-methy/-o-
aspartate; OP = opioid; ORL -1 = opioid receptor-/ike 1)
activity at the spinal cord level. Inhibitory amino is not controlled by the background analgesia.
acid neurotransmitters include glycine and Hyperalgesia occurs in a painful area when the
GABA, with neuropeptides such as j3-endorphin pain experienced is much greater than would
and galanin having inhibitory actions, although be expected from the painful stimulus. Pain
these may be altered in some chronic pain can also occur spontaneously without any
states. precipitating stimulus, and may be related to
spontaneously occurring electrical discharges in
34.3. Answer: D. injured nerves.
When normally non-painful stimuli become
painful (either thermal or mechanical), the term 34.4. Answer: A.
'allodynia' is used. This can occur in Assessment has shown features typical of
neuropathic pain, and may be associated with diabetic neuropathy: stocking distribution,
other sensory changes, resulting in other reduced sensation to pin-prick and mechanical
symptoms such as formication - the sensation allodynia. This man needs multidisciplinary
of insects crawling over the skin. Breakthrough management to address tl;le range of issues
pain tends to occur when the usual pain is that are affecting him. Psychosocial factors
controlled by analgesia and something (such as need to be considered with support in active
movement) precipitates an increase in pain that rehabilitation, and use of non-pharmacological
techniques to self-manage his pain. Support in assess physical and psychological effects of
managing his diabetes better will reduce the chronic pain in general (Box 34.5).
risk of worsening symptoms, and lifestyle/
dietary advice is needed to increase what he is 34.6. Answer: A.
able to do. The renal impairment means that While all of the above may impact on memory,
anti-neuropathic drugs such as pregabalin and the likeliest cause is borderline opioid toxicity.
duloxetine need to be used with care, as Elderly patients with limited reserve in terms of
toxicity may result on lower doses than cognitive function are much more sensitive to
expected. even low doses of opioids (Box 34.6).
I help. There is no evidence to suggest that vomiting. The other treatments may have a role
in due course, but would be of lower priority if they contribute to these ends. In the case of
than addressing her hypercalcaemia. this patient, he has no oral intake and is
undistressed; therefore diuretics are unlikely to
34.17. Answer: D. help and intravenous treatment will be
When patients with any advanced condition unnece~sarily burdensome. Religious and
become comatose and unable to take spiritual support are very important in this
medication or oral intake with no reversible situation, for the family as much as the patient.
cause, they are likely to be dying. Although Priority should be given to checking the
many will die within 2-3 days, this stage understanding of family members regarding
of life is often unpredictable and doctors should the situation and their wishes regarding
be cautious in any prognosis they give to care, visiting and how they wish to be
families. contacted.
Once the conclusion has been reached that Although the patient does not currently have
a patient is dying, there is a significant change any symptoms at present, it is possible that he
in management (Box 34.17). Symptom control, may develop them at some point in future. It is
relief of distress and care for the family become important to ensure availability of parenteral
the most important elements of care. medication for symptom relief so that it can be
Medication and investigation are only justifiable given without delay should the need arise.
I
I
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LABORATORY REFERENCE RANGES • 403
Analyte
a, -Antitrypsin
Alanine aminotransferase (ALT)
Albumin
Reference range
Sl units
1.1-2.1 g/L
10-50 U/L
35-50 gil
Non-SI units
11 0-21 0 mg/dl
-
3.5-5.0 g/dl
-
Alpha-fetoprotein <10 ng/ml 1000 ng/ dL
Alkaline phosphatase 40-125 U/L -
Amylase <100 U/L -
Aspartate aminotransferase (AST) 10-45 U/L -
Bilirubin (total) 3-16 j.!mOI/L 0.18-0.94 mg/dl
Calcium (total) 2.1-2.6 mmoi/L 4.2-5.2 mEq/L
or 8.5-10.5 mg/dl
Carboxyhaemoglobin 0.1-3.0% -
Levels of up to 8% may be found in
heavy smokers
Caeruloplasmin 0.16-0.47 g/L 16-47 mg/dl
Cholesterol Target cholesterol levels will vary according to individual cardiovascular
risk, with stricter goals for those most at risk. Normal ranges are
misleading as they cover both a healthy and unhealthy population. A
rough guide to treatment targets is given below, but further guidance,
e.g. National Cholesterol Education Programme Adult Treatment Panel Ill
(ATPIII) guidelines, should be used for individual case management. See
Box 35.15 for treatment guidelines in diabetes
Approx Treatment Targets:
Cholesterol (total) (see also Fig. 35.1) <5-5.2 mmol/1 <200 mg/dl
LDL -cholesterol <2-2.5 mmol/1 <100 mg/dL
HDL-cholesterol
Low <1.0 mmoi/L <40 mg/dl
High (desirable) ~1.5 mmoi/L ~60 mg/dl
Complement
C3 0.81-1.57 g/L -
C4 0.13-1.39 g/L -
Total haemolytic complement 0.086-0.410 g/L -
CA-125 <35 U/ml
CEA <3 ng/ml
Copper 10-22 j.!moi/L 64-140 j.!g/dl
C-reactive protein (CRP) <5 mg/L
Highly sensitive CRP assays also exist that measure lower values and
may be useful in estimating cardiovascular risk
Creatine kinase (CK; total)
Male 55-170 U/L -
Female 30-135 U/L -
Creatine kinase MB isoenzyme < 6% of total CK -
Ethanol Not normally detectable
Marked intoxication 65-87 mmoi/L 300-400 mg/dl
Stupor 87-109 mmoi/L 400-500 mg/dl
Coma >109 mmoi/L >500 mg/dl
y-glutamyl transferase (GGT) Male 10-55 U/L -
Female 5-35 U/L
Glucose (fasting) 3.6-5.8 mmoi/L 65-1 04 mg/dL
See Box 35.15 tor definitions of impaired glucose tolerance and diabetes
mellitus. Hypoglycaemia is defined as a blood glucose of less than
3.9 mmoi/L (70 mg/dl)
Glycated haemoglobin (HbA1,) 4.0-6.0% -
20-42 mmol/mol Hb
See Box 35.15 tor diagnosis of diabetes mellitus
Ketones <1 mg/dl
Note: levels can be mildly physiologically
elevated during periods of starvation
Continued
Stage of chronic
eGFR (mUmin/1.73 m') kidney disease (CKD) Description
>90 Stage 1 Normal
60-89 Stage 2 Mild reduction (not considered CKD)
45-59 CKD stage 3A Moderately reduced function
30-44 CKD stage 38 Moderately reduced function
15-29 CKD stage 4 Severely reduced function
<15 CKD stage 5 Very severely reduced function/end-stage
kidney failure
180
160
Non-smoker
Non-diabetic men
160
Smoker
-
SBP140 SBP140
120 120
100 100
345678910 345678910
TC:HDL TC:HDL
Age 5o-59 years
180 180
160 160
120 120
100 100
345678910 345678910
TC:HDL TC:HDL
Age 60 years and over
180 180
160 160
120 120
100 100
345678910 345678910
TC:HDL TC:HDL
10% 20%
Fig. 35.1
Urinalysis
Urinalysis is a point of care test normally
Calculated urine values
assessing the pH (normal range pH 4.6 to pH
8.0), specific gravity (normal range Urine Osmolality
1.005-1.030) and the prescence of Urine osmolality is a measure of the
components such as blood, protein, glucose, concentration of osmotically active particles,
ketones, nitrites, leukocyte esterase, bilirubin principally sodium, chloride, potassium and
and urobilirubin. A normal result is negative for urea; glucose can contribute significantly to the
all parameters. If present, a scale of + to ++++ osmolality when present in substantial
is used to describe the degree of positivity. amounts in urine
The levels of many analytes in blood vary appropriate and it is important for the clinician
during pregnancy, when many hormonal and reviewing the results to be aware of this to
metabolic changes occur. The standard adult enable appropriate interpretation and patient
reference ranges may therefore not be management.
35.13 Analytes that may be significantly affected by growth and puberty•- cont'd
Tanner
stage
Ill IV v
Female
Mature stage.
Elevation of breast Further enlargement Projection of Projection of papilla
Pre-adolescent and papilla as a of breast and areola areola and papilla with recession of
Breast
small mound with no separation to form mound areola to contour
of contours above breast of breast
y r r T T
Darker, coarse and
curled hair but Dark, coarse and
Pubic None Sparse, long and Darker, coarse and covering smaller curled hair
hair straight curled hair area than in adult. extending to inner
No spread to medial thighs
surface of thighs
Male
r
\_ / \ /
r l ) )
Genitalia
Pubic
hair
Pre-adolescent
None
Growth oftestes
and scrotum. Skin
on scrotum
reddens and
becomes wrinkled
Fig. 35.2
There are many national and international and local policy may differ. Targets given are
guidelines for diabetes. The targets/threshold according to the NICE 2015 diabetes guidelines
discussed below relate to current UK guidelines unless otherwise specified
Fig. 16.21
111!JI[[[[01
:UlLLLUJllilU
Fig. 13.5
v~
Fig. 16.25
Fig. 27.13
(")
3
Fig. 29.7
Fig. 29.1
Fig. 29.5
CM
Fig. 29.13 Fig. 29.28
Fig. 29.48
Fig. 29.42
Fig. 29.53
Fig. 29.46
Fig. 34.7
Aortic valve, infective endocarditis affecting, 133, 144 Autosomal dominant inheritance, feature of, 16, 19
Apixaban, 143, 157, 270 Autosomal dominant polycystic kidney disease (APKO), 121,
cessation of, for right-sided pleural effusion, 157, 175 129
for preventing stroke in patiens with atrial fibrillation, 135, AV block, second degree, Mobitz type II, 134, 145
146 Axial spondyloarthritis (axSpA), 287, 294-295
APKD. see Autosomal dominant polycystic kidney disease Azathioprine, 246, 254-255, 367, 371
Aplasia, parvovirus B19 and, 75-76, 88 for Crohn 's disease, 230, 239
Apremilast, 287, 291, 296 for inflammatory bowel disease, 230, 240
for eczema, 364 monotherapy, for autoimmune hepatitis in pregnancy, 246,
Aquaporin-4 antibody, in optic neuritis, 308, 320 254-255
Aqueduct of Sylvius, stenosis of, 309, 321 Azithromycin, 105
ARDS. see Acute respiratory distress syndrome for Campylobacter infection, 84- 85, 95
Arginine vasopressin (AVP), effect on kidney of, 185, 194
Array comparative genome hybridisation (CGH), 17, 20 8
for chromosomal abnormalities, 15, 19 Babesia microti, as causative agent of babesiosis, 84, 95
parental, 17, 20 Babesiosis, 84, 95
Arsenic, 390 Bacillary angiomatosis, 81, 92
Arterial blood, analytes in, 403b Bacillus Calmette-Guerin (BCG) vaccine, 167
Arterial blood gas, dysfunctional breathing and, 177 Bacterial contamination, of platelets, 269, 277
AS. see Ankylosing spondylitis Bacterial overgrowth, 231, 241
Asbestosis, 388, 391-392 Banana spider, 50
Ascending aorta, emergency repair of, 139, 150 Band ligation, for bleeding oesophageal varices, 234, 244
Ascitic fluid amylase, 232, 242 Barbiturates, 42b
Ascorbic acid. see Vitamin C Barbotage, 289, 298
Aspartate aminotransferase (AST), in venous blood, 405b-406b Bariatric surgery, pregnancy and, 204, 208
Aspergillosis, 165, 1651, 180 Barium swallow, for polymyositis, 288, 296
voriconazole for, 167-168, 181 Barotrauma, 71
Aspiration, in septic arthritis, 279, 290 Barrett's oesophagus, 225-226, 235
Aspirin, 132- 133, 143, 147, 170-172, 183, 236-237 Barthel Index, 380-381
for acute pericarditis, 136, 14 7 Bartter's syndrome, 11 0, 11 3
for diabetes, during pregnancy, 367, 369 Basal analogue insulin (glargine), 214
on enzyme target, 6--9 Basal cell carcinoma, nodular
for rheumatic fever, 140, 151 excisional surgery for, 347, 3471, 351, 3511, 359, 362
sensitivity, 183 photodynamic therapy for, 353, 3531, 363
Asthma, 30, 177 Basement membrane, 349, 361
exacerbation of, 132, 143 Basic life support, 133, 144
montelukast for, 165, 179 Basophil granulocytes, reference range of, 409b-41 Ob I
I,
pregnancy and, prednisolone for, 164- 165, 179 Bat bites, 82, 93 I
triggered by pollen, 160-161, 177 Bayes' Theorem, 3-4
1
ASTRAL. see Angioplasty and Stenting for Renal Artery B-blockers, 40b, 45b
Lesions Beck Depression Inventory, 398b
Asymmetrical reflexes, in migraine, 299, 313 Becker muscular dystrophy, genetic pedigrees and, 15-16, 19
Asymptomatic bacteriuria, in pregnant woman, 122, 130 Beclometasone, 171
Atazanavir, 101b Beh9et's disease, 288-289, 297
Atelectotrauma, 71 Belladonna, 41 b, 44b
Atherosclerosis, causing retinal vein occlusion, 332, 3321, 334 Bendroflumethiazide, 116, 190, 278-279, 378, 381
Atlantoaxial subluxation, rheumatoid arthritis and, 234, 243 causing lichenoid reaction, 356, 364-365
ATN. see Acute tubular necrosis plasma renin concentrations increased by, 191 , 200
Atopic dermatitis Benign paroxysmal positional vertigo (BPPV), 308, 320
IL-13 inhibition in, 355, 364 Benign positional vertigo, 381
late-onset, 364 Benzatropine, 40b-41b, 44b- 45b
Atorvastatin, 108, 119, 121 Benzene, 390
Atovaquone plus proguanil, 33-35 Benznidazole, 95
Atracurium, 72 Benzodiazepines, 40b-42b, 44b-45b, 241
Atrial fibrillation, 132-133, 143-144, 147 for acute alcohol withdrawal, 63, 71
excessive alcohol consumption and, 137, 148 for breathlessness, 400
limb ischaemia and, 150 Benzylpenicillin, 151 - 152
preventing stroke in patients with, apixaban for, 135, 146 intravenous (IV), for meningococcal sepsis, 300-301 , 314
Atrial myxoma, 137, 148 Benzylpiperazine, 42b
Atrial septal defect, 146-147 Berylliosis, 171, 182
myocardial infarction and, 149 Beta-thalassaemia trait, 268, 275
Atrioventricular block, 138, 149 Betnovate ointment, for eczema, 355, 3551, 364
Atropine, 42b Bicarbonate, 111, 114
Auditory hallucinations, cocaine intoxication causing, 337, 342 in arterial blood, 403b
Augmented immunosuppression (ATG and high-dose steroids), Biceps reflex, loss of, for magnetic resonance imaging (MRI),
120, 128 300, 314
Autism, CGH and, 17, 20 Biguanide, for type 2 diabetes mellitus, 213, 219
Autocrine stimulation, in tumour formation, 17, 20 Bilateral hydronephrosis, in genitourinary system, 384,
Autoimmune connective tissue disease, long-term management 389-390
of, 288, 296 Bilateral lower limb hypertonicity, 304, 317
Autoimmune disease, 23, 26 Bile acid malabsorption, SeHCAT for, 230, 239
disease-modifying therapy in, 23- 24, 26 Biliary colic, dietary recommendatiCl[ls for, 249-250, 257
Autoimmune gonadal failure, 198-199 Biliary tree obstruction, 205, 209, 209b
Autoimmune hepatitis (AIH), in pregnancy, azathioprine Bilirubin, in venous blood, 405b- 406b
monotherapy for, 246, 254-255 Bioassay, 402
Autoimmune pancreatitis, lgG4 in, 233, 243 Biopsy, bland urine sediment with interstitial fibrosis on, 121,
Autoscopic hallucination, 341-342 128
FODMAP (fermentable oligo-, di- and monosaccharides, and Giant cell arteritis (GCA), 288, 297
polyols) diet, for IBD, 232, 241 temporal artery biopsy for, 331, 334
Folate, 209b Gilbert's syndrome, 245, 253, 371, 374
deficiency, during pregnancy, 205, 209-210 GIST. see Gastrointestinal stromal cell tumour
reference range of, 409b-41 Ob Glargine. see Basal analogue insulin
Folic acid, for rheumatoid arthritis, 279, 291 Glasgow Coma Scale (GCS), 58, 67
Follicle-stimulating hormone (FSH) Glibenclamide, 220
in growth and puberty, 411b-412b Gliclazide, 216
in venous blood, 403b-404b Gliptins, 222
Follicular and papillary carcinoma, 197 Glomeruli, normal, 121-122, 129
Follicular lymphoma, 261-270 Glomerulosclerosis, 381-382
Fomepizole, 42b 'Glove and stocking' sensory disturbance, bacterial index and,
Formication, cocaine intoxication causing, 337, 342 77-78, 89
Foscarnet, 85 Glucagon, 242
Fracture, in post-menopausal osteoporosis, 280, 291 Glucagon-like peptide-1 , 191, 200
Francisefla tularensis analogues, 222
infection, 83-84, 94 Glucagon-like peptide-1 (GLP-1) agonist, pancreatitis and, 213,
muskrat contact and, 172, 183 219
FRAX, 294 Glucocorticoids, 88, 120-121, 128, 195-196,200, 239-240,
Free wall rupture, 149 298, 355
Fresh, full voided sample, for cytological assessment, 383, 389 for amiodarone-induced thyrotoxicosis, 188, 197
Fresh frozen plasma, for bleeding risk, 267, 275 for generalised itch, 363
Fried Frailty score, 381b for increased intracranial pressure, 400b
Frisen's scale, 334 intravenous therapy, for ulcerative colitis, 230-231 , 239-240
FSH. see Follicle-stimulating hormone for liver capsule pain, 395, 399, 400b
Full-thickness biopsy, of edge of the les1on, 383-384, 389 for palmoplantar pustulosis, 360
Functional hallucination, 341-342 for polymorphic eruption of pregnancy, 361
Functional hypothalamic amenorrhoea, 189, 197-198 systemic, for pemphigus, 365
Functional memory disturbance, 306-307, 319 for tinea capitis, 360
Furosemide, 64, 121, 148, 170, 377, 380 topical, for eczema, 355, 3551, 364
effects of, 134, 145 Glucodrate®, 210
Glucokinase, maturity-onset diabetes of the young, 212, 218
G Glucosamine, 291-292
Gabapentin, for neuropathic pain, 400b Glucose, in venous blood, 405b-406b
Gait, 382 Glucose-6-phosphate dehydrogenase (G6PD) assay, 269, 275
Gamma hydroxybutyrate (GHB), 38, 42b, 43 Glucose-6-phosphate dehydrogenase (G6PD) deficiency, 269,
I
Gas carriage, in blood, 56, 66 275
Gas gangrene, 93
Clostridium perfringens as causative agent of, 83, 93-94
test for, 80, 91
Glucose-related disorders, diagnostic cut-offs in, 413b
II
Gastric cancer, 228, 238 GLUT2, in pancreatic ~ cells, 215, 221
management options for, 228, 238 Glutamate, in central sensitisation, 393, 396-397, 3961, 397b
Gastric emptying study, for gastroparesis, 216, 223 Glutamine, 206, 210
Gastric lymphoma, 228, 238 y-glutamyl transferase (GGD, in venous blood, 405b-406b
Gastric ulcers, 227, 237 Glutathione repleters, 42b
Gastrin, in venous blood, 403b-404b Glycated haemoglobin (HbA,d, in venous blood, 405b-406b
Gastroenteritis, 10 Glyceryl trinitrate, 171-172
Gastroenterology, 225-244 Glycine, in pain processing, in spinal cord, 397b
Gastrointestinal stromal cell tumour (GISD. 229, 238 Glycogen storage diseases (glycogenoses), investigation of,
Gastro-oesophageal reflux 107, 111
cough from, 162, 177 Glypressin, for variceal bleeding, 246, 255
in severe neurodisability, 372, 374- 375 Gnathostomata spinigerum , 73-85
Gastroparesis, 234, 243 Goal setting, in rehabilitation programme, 377, 380
Gastrostomy, risk of, 206-207, 211 Goitre
GBS. see Guillain-Barre syndrome diffuse symmetrical, pregnancy and, 187, 196
GCA. see Giant cell arteritis Graves' disease and, 195
GCS. see Glasgow Coma Scale Gold, causing lichenoid reactions, 364-365
Gene expression, multi-functionality and, 14, 18 Gonadotrophin-releasing hormone (GnRH) agonist therapy,
Gene therapy, primary immune deficiency and, 25-26 123, 130
Generalised osteoarthritis, 294-295 Gonadotrophin-releasing hormone insensitivity, 197-198
Generalised tonic-clonic seizures Gout, 278-279, 290, 293-294
antiepileptic drug for, 303, 316 Grandiose delusion, 341
electroencephalogram (EEG) for, 308, 321 Granulomatous cerebral angiitis, 83, 94
in jerking of whole body, 303, 316-317 Granulomatous interstitial nephritis, 120, 128
Generic international non-proprietary name (INN), ciclosporin Granulomatous polyangiitis, 170, 182
and, 8, 12 Grass snake (Natrix natrix), 47, 50
Genes, ankylosing spondylitis and, 287, 295 Graves' disease, 186-187, 1861, 195
Genetic counselling, for myotonic dystrophy type 1, 15, 18- 19 hypothyroidism due to, 186, 195
Genetic defect, of alternative complement pathway, 118-119, radioactive iodine for, 187, 195-196
127 Griseofulvin, for tinea capitis, 348, 3481, 360
Genetic generalised epilepsy, 300, 313- 314 Group B streptococcal infection, in pregnancy, 86b
Genetic pedigrees, 15-16, 19 Group 0 fresh frozen plasma (FFP), 266, 274
Genioglossus, palatoglossus and, 173, 184 Group 0 red cells, 266, 274, 274b
Gentamicin, 151-152 Growth hormone (GH)
monitoring of, 9, 12 pituitary macroadenoma affecting, 192-193, 202
unpasteurised milk and, 76, 88 in venous blood, 403b-404b
Gestational diabetes, diagnostic cut-offs in, 413b Guillain-Barre syndrome (GBS), 299, 313
GHB. see Gamma hydroxybutyrate Gynaecomastia, finasteride and, 190, 199
Hyperandrogenism, polycystic ovarian syndrome and, 189, 198 Immunological reference ranges, 41 Ob
Hyperbaric oxygen therapy, for radiation proctitis, 229, 239 Impaired renal function, in peripheral diabetic neuropathy, 393,
Hypercalcaemia, 177 397-398
Hypercholesterolaemia, 147 Implantable cardiac defibrillator, 135, 146
Hyperemesis gravidarum, 214, 220, 366, 368 Incident pain, 400b
Hyperglycaemia, hyperosmotic hyponatraemia secondary to, Incontinence, treatment of, 377, 380
109, 113 Increased intracranial pressure, 400b
Hyperinsulinaemia, 198 Indomethacin, 227-228
Hyperlactaemia, in chronic renal failure , 61, 70 In-dwelling catheter, for urinary problems, in multiple sclerosis,
Hyperosmolar hyperglycaemic state (HHS), 215-216, 222 307, 320
Hyperprolactinaemia, 197-198 Infection-related glomerulonephritis, 116, 124
Hyper-reflexia, 304, 317 Infectious disease, 73~95
Hypersensitivity adverse drug reactions, 7, 10 principles of, 32-36
Hypersensitivity pneumonitis, 171-172, 183 Infective endocarditis, 167, 180
Hypersensitivity reactions, 23, 26 aortic valve affected by, 133, 144
due to allopurinol, 79, 9D-91 lnfiammatory back pain, 285, 294
Hypertension Inflammatory bowel disorder (lBO). 230, 239, 2391
essential, 132, 143 pathogenesis of, 23D-231, 240
poorly controlled, poor adherence to medication and, 140, Inflammatory polyarthritis, 286, 294-295
151 lnfliximab, 173
secondary, renal disease and, 140, 151 lngenol mebutate, 359
Hyperthermia, cocaine intoxication causing, 342 Inhaled carcinogens, 388-389
Hypertrophic cardiomyopathy, 136, 143, 147 Inhaled corticosteroid (ICS)/LABA combination inhaler, 165
inheritance of, 141, 152 Inhibiting interleukin (IL)-13, 355, 364
ventricular arrhythmia and, 136, 147 Inhibitory amino acid neurotransmitters, 396-397
Hypertrophic pulmonary osteoarthropathy (HPOA), 168, 181, 293 Innate immune response, acute liver failure and, 246, 254
Hyperventilation, 53 Innate immunity, key feature of, 22- 25
Hypnagogic hallucination, 341-342 Inotropic agents, 45b
Hypnopompic hallucination, 337, 341-342 Insulin, 9, 369
Hypoalbuminaemia, 10 exogenous, 191-192, 201
Hypochondriacal delusion, 341 in venous blood, 403b-404b
Hypoglycaemia Insulin pump therapy, 218, 223-224
patient education on, 216, 222 'Insulin resistance syndrome', 219-220
stroke and, 326, 328-329 Insulin-like growth factor 1, in growth and puberty, 411b-412b
type 1 diabetes and, 214, 220 Integ rase inhibitors, 98, 101, 101 b
Hypokalaemia, Cushing's syndrome associated with, 191, 200 Interferon-gamma release assay?, 167, 18D-181
Hypomania, 342 Intermittent short-acting opioids, for incident pain, 400b
Hypotension, postural, 143 Internal jugular vein thrombosis, Lemierre's syndrome and, 81,
Hypothyroidism 92
due to diastolic hypertension, 186, 195 International system of units (SI units), 402, 402b
due to Graves' disease, 186, 195 'International units' (IU/L), 402
transudative pleural effusion and, 164, 179 Interscapular pain, 143
weight gain and, 203-207 Interstitial pneumonia
Hypoxaemia bronchoscopy and, 176
severity of, 70 CT appearance of, 160, 176
shunt and, 54, 64 lymphocytic, 182
Interventricular septum, rupture of, 133, 144
Intra-aortic balloon pump (IABP), use of, 63, 71
lBO. see Inflammatory bowel disorder Intracellular fluid, 108, 112
Ibuprofen, 119, 121-122,381 Intracerebral blood, in acute stroke, 326, 328
arteriolar vasoconstriction with, 121, 129 Intracerebral haemorrhage, cocaine use and, 326, 329
Idiopathic intracranial hypertension (II H), 301, 309, 315, 321 Intracranial pressure (ICP). management of, 63, 71
IIH. see Idiopathic intracranial hypertension Intramural haematoma, aortic dissection and, 150
Ileocolonic tuberculosis (TB), 229, 238 lntraretinal microvascular anomalies, in diabetic retinopathy,
Illusion, 341 334-335
lmipenem, for Nocardia infection, 84, 94-95 Intrauterine fetal death, UDCA therapy for, 247, 255-256
lmiquimod, 363 Intravenous (IV) benzylpenicillin, for meningococcal sepsis,
for basal cell carcinoma, 359, 362 30D-301' 314
for lentigo maligna, 360 Intravenous fluid
Immature teratoma, 385-386, 3861, 390 in OKA, 217, 223
Immune deficiency for hypercalcaemia, 395-396, 400-401
primary, 22, 25-26 Intravenous glucocorticoid therapy, for ulcerative colitis,
secondary, 23, 26 23D-231' 239-240
Immune reconstitution inflammatory syndrome (IRIS), 32, 34, Intravenous normal saline, for hypercalcaemia, 386, 391
98, 101 Intubation
Immunoglobulin A (lgA), 115, 124 for asthma, 54-55, 64-65
nephropathy, 115-116, 124-125 noradrenaline and, 57, 66, 66b
Immunoglobulin E (lgE) testing lpratropium, 333
for latex rubber allergy, 352, 362 IRIS. see Immune reconstitution inflammatory syndrome
for urticaria, 361 Iron, 42b-43b
Immunoglobulin G (lgG) deficiency, 275
coeliac disease and, 229, 239 reference range of, 409b-41 Ob •
testing·, for latex rubber allergy, 362 Irritant dermatitis, 355, 364
Immunoglobulins (lg), 22, 26 lschaemic pain, 400b
deficiency, 22-23, 26 lschaemic stroke, in polycythaemia rubra vera, 261, 270
levels, bronchiectasis and, 179 Isoniazid, 167
reference range of, 41 Ob Isopropyl nitrite, 37, 40, 41 I
Lymphocytes, reference range of, 409b-41 Ob MERS. see Middle East respiratory syndrome
Lymphocytic interstitial pneumonia, 182 MERS-CoV. see Middle East respiratory syndrome coronavirus
Lymphogranuloma venereum, 103, 105 Mesalazine, 371
Lymphoma, 169, 181-182 Mesangiocapillary glomerulonephritis, 118-119, 127
Lymphoproliferative disorder, post-transplant, 372, 375 Mesenteric lymphadenopathy, Yersinia enterocofitica infection
Lynch's syndrome, autosomal dominant inheritance of, 16, 19 and, 82, 92-93
Lysosomal storage diseases (LSDs), 107, 111 Mesothelioma, 163, 171, 175, 178, 182-183
Metabolic acidosis, with respiratory compensation, 110, 114
M 'Metabolic syndrome', 219-220
M2 proton channel inhibitors, 89 Metacarpophalangeal joints (MCPJs), erosions at, 291
Macroadenoma, cabergoline for, 192, 201 Metadrenalines, in urine, 408b
Macroprolactin, 201 Metastatic spinal cord compression, 301, 314
Macular degeneration, age-related, smoking and, 331-332, Metformin, 369
3321, 334 estimated glomerular filtration rate and, 8, 12
Magnesium, in venous blood, 405b-406b for type 2 diabetes mellitus, 213, 219
Magnesium sulphate, 39-40, 40b, 45b Methadone, 42b
Magnetic resonance imaging (MRI) Methaemoglobinaemia, 40
loss of biceps reflex for, 300, 314 Methanol, 42b-43b
urinary incontinence for, 300, 314 ingestion, 110-111, 114
Malaria, in pregnancy, 86b Methotrexate, 24, 279, 352
Malathion, for head louse, 360 for eczema, 355, 3551, 364
Malignancy, 286, 295 increasing, 291
effusions as signs of, 137, 148 during pregnancy, 366-368
Malignant oesophageal stricture, 226, 236 for ulcerative colitis, 367-369
Malignant pleural disease, 178 in pregnancy, 281, 291
Malnutrition, in dementia, 206, 211, 211 I for rheumatoid arthritis, 279, 291
Mammogram, in breast lump, 387, 391 3,4-Methylene-dioxymethamphetamine, 42b
Mantle cell lymphoma, 265, 273 Methylthioninium chloride, 42b
MAOI. see Monoamine oxidase inhibitor Metoclopramide, 40b, 45b
Maraviroc, 101b Metolazone, 190
Marian's syndrome, 132, 143 Metronidazole, 88, 227, 237
aortic dissection and, 150 Mexican orange-kneed tarantula (Brachype/ma smithi), 50
mutations in fibrillin gene and, 141 , 152 MGUS. see Monoclonal gammopathy of uncertain
Market authorisation, granting of, 7, 11 significance
Mast cell tryptase, measurement of, 23, 26 Microalbuminuria, 214, 221
Maternal hyperglycaemia, fetal hyperglycaemia and, 213, 219 Microaneurysms, in diabetic retinopathy, 334-335
Maternal medicine, 366-369 Microangiopathic haemolytic anaemia, in thrombotic
Maturity-onset diabetes of the young (MODY), 212, 218 thrombocytopenic purpura (TTP), 263, 271
Maximum heart rate, reduced, ageing and, 378, 380 Microcephaly, investigations for, 15, 19
MCH. see Mean cell haemoglobin Microscopic polyangiitis, 115, 124
MCTD. see Mixed connective tissue disease Micturition, 122, 129
MCV. see Mean cell volume Middle East respiratory syndrome (MERS), 166, 180
MDRD. see Modification of Diet in Renal Disease Middle East respiratory syndrome coronavirus (MERS-Co\1), 80,
MOS. see Myelodysplastic syndromes 91
Mean cell haemoglobin (MCH), reference range of, 409b-41 Ob Mid-stream urine (MSU), 123, 130
Mean cell volume (MC\1), reference range of, 409b-41 Ob Migraine, 299, 304-305, 313, 318
Measles, in pregnancy, 86b with aura, 311 , 323
mecA penicillin-binding protein, 33, 35 'Million Death Study', 50
Mechanical clot retrieval, for cerebral ischaemia, 326, 329 Mineralocorticoids, 200
Median nerve compression, 284, 293 Minimal change disease, 115, 124
Medical ophthalmology, 330-335 Minocycline, papulopustular acne, 359-360
Medical psychiatry, 336-344 Minoxidil, 362
Medication reconciliation, errors and, 7, 11 20-Minute whole-blood clotting test (20WBC1), 46, 48
Medullary thyroid cancer, 197 Mitochondrial inheritance, 16, 19
Mefenamic acid, 44, 45b Mitosis (M), in cell cycle, 383, 389
Mefloquine, 35 Mitral stenosis, pre-systolic accentuation in, 140, 151
Melanoma Mitral valve prolapse, 143, 146-147
malignant Mixed connective tissue disease (MCTD), 287, 296
in men, 354, 363 Mobitz type I second-degree AV block, 145
prognosis of, 350, 3501, 361 Mobitz type II second-degree AV block, 134, 145
management of, 346-34 7, 359 Model for End-Stage Liver Disease (MELD), 250, 258
Melarsoprol, for trypanosomiasis, 84, 95 Modification of Diet in Renal Disease (MDRD), 115, 124
MELAS syndrome, 16, 19 MODY. see Maturity-onset diabetes of the young
MELD. see Model for End-Stage Liver Disease Mofetil, 371
MEN syndromes, 199 Mohs' micrographic surgery
MEN1 genes for benign keratoacanthoma, 360
acromegaly and, 1g3, 202 for nodular basal cell carcinoma, 359, 362
mutation of, 233, 243 Molluscum contagiosum, 360-361
Menaquinone. see Vitamin K Monkeypox, 82, 93
Menetrier's disease, 227, 237 Monoamine oxidase inhibitor (MAOI), 41b, 44b
Meningitis, mumps and, 77, 89 Monoclonal gammopathy of uncertain significance (MGUS),
Meningococcal meningitis, 304, 317 264, 272
Meningococcal sepsis, 300-301, 314 Monocytes, reference range of, 409b-41 Ob
sickle cell disease and, 268-269 Monoethylglycinexylidide (MEGX) test, 253
Mental state examination (MSE), 340 Mononeuritis, 293
Mephedrone, 38, 42b, 43 Montelukast, 164-165, 179,365
Meropenem, 34, 91 for asthma, 165, 179
Quadriceps, wasting of, in spinal cord, lesions outside, Respiratory rate, as sign of clinical deterioration, 60, 69
299-300, 313 Restrictive cardiomyopathy, 138, 149
Quartz, silicosis and, 171, 183 Retention of contrast, malignancy and, 191, 200
Quinidine, 40b, 45b Reticulocytes, reference range of, 409b-41 Ob
Quinine, 271 Retinal vein occlusion, atherosclerosis causing, 332, 332f, 334
Ouinolone, 27 4 Retinoids, systemic, for papulopustular acne, 359-360
with antichlamydial efficacy, 105 Retinol. see Vitamin A
Retrobulbar haemorrhage, 330-333
R Reversibility, delirium and, 58, 68
RAAS. see Renin-angiotensin-aldosterone system Reynolds' pentad of ascending cholangitis, 205, 209
Rabies vaccine, for bat bites, 82, 93 RFTs. see Respiratory function tests
Radiation, stochastic (random) effect of, 51-52 Rhabdomyolysis, 119, 127
Radical cystectomy, 122-123, 130 tests for, 60, 70
Radioactive iodine Rheumatic fever
for Graves' disease, 187, 195-196 acute, c-reactive protein and, 140, 151
post-thyroidectomy, 197 aspirin for, 140, 151
Radioallergosorbent testing (RAS1), 352, 362 Rheumatoid arthntis, 170, 1701, 182
Radiotherapy Rheumatoid nodules, 169-170, 182
for bone pain, 400b Rheumatology, 278-298
for increased intracranial pressure, 40Gb Rhinovrrus, acute coryza and, 166, 180
Raltegravi r, 98, 101 b Riboflavin. see Vitamin B2
Ramipril. see Angiotensin-converting enzyme (ACE) inhibrtor Richmond Agitation and Sedation Score (RASS), 55, 65
Random venous blood glucose, for diagnosis, 212-218 Ricinus communis (castor oil plant), 45b
Randomisation, 29-30 Rickets, X-linked hypophosphataemic, 282- 283, 292
Ranitidine, 365 Rickettsia alricae infection, tick bites and, 78, 90
RANK. see Receptor activator of nuclear factor kappa B Rifampicin, 167
Rash on contraceptive failure, 7, 11
monkeypox and, 82, 93 cytochrome P450 induced by, 6, 9
scabies and, 80, 91 unpasteurised milk and, 76, 88
RASS. see Richmond Agitation and Sedation Score Rifamycin, 11
RAST. see Radioallergosorbent testing Right arm weakness, headache and, 59, 69
Rathke's pouch, development of, into adenohypophysis, 192, Right lung, apex of, irregularly shaped mass at, 387, 391
201 Right pleural effusion, 388, 392
Raynaud's disease, 150 Right subthalamic nucleus, lesion in, 307, 319-320
RBILD. see Respiratory bronchiolitis-interstitial lung disease Right upper lobectomy, 156, 1561, 175
Reactive arthritis, 290, 294 Rilpivirine, 101b
Receptor activator of nuclear factor kappa B (RANK), 278, 290 Rimantidine, 89
Receptor antagonists, 42b Rituximab, 24, 287, 295, 298
Recombinant tissue plasminogen activator (rt-PA), intravenous Road injury, causing adolescent deaths, 370, 374
thrombolysis with, 326-327, 329 Rodents, Francisef!a tularensis infection from , 83-84, 94
Recompression, 53 ROSIER (Rule Out Stroke In Emergency Room) clinical stroke
Recurrent oral thrush, 225, 235 tool, 326, 328, 329b
Red cell count, reference range of, 409b-41 Ob Rubella, in pregnancy, 86b
Red cell lifespan, reference range of, 409b-41 Ob Ruminations, 338, 343
Red cell transfusion Ruptured berry aneurysm, 121, 129
for sickle cell disease, 268, 275 Russell's viper (Daboia russelii and Daboia siamensis), 46, 48
for upper Gl haemorrhage, 63-64, 72
Reducing agents, 42b s
5a-Reductase inhibitor, 123, 131 SABA. see Short-acting ~,-agonist
Refeeding syndrome, chronic alcoholism and, 203-204, Sacroiliac disease, 294
207-208, 208b Sacroiliac joints (SIJs)
Reference ranges, 402-414 irregularity and fusion of, 291
immunological, 41 Ob MRI, for inflammatory back pain, 285, 294
laboratory Salbutamol, 162, 165
in adolescence, 411 - 414 inhaler, 164-165
in adults, 403-409, 403b nebulised, 333
in chi ldhood, 411-414 Salicylates, 37-38, 43b
in pregnancy, 411 Salivation, 39, 43, 44b
Regular prompted toileting, for incontinence, 378, 381 Sarcoidosis, 128, 169, 1691, 181, 183
Renal artery stenosis, 381-382 stage IV, 169, 181-182
Renal disease, secondary hypertension and, 140, 151 Saudi Arabia, coronavirus and, 33, 35
Renal failure, chronic, hyperlactaemia in, 61, 70 Saw-scaled (carpet) viper (Echis ocellatus), 47, 49
Renal function, deterioration in, 118, 126 Scabies, 80, 91
Renal replacement therapy, for hyperkalaemia, 62, 71 Scanning speech, in dysarthria, 303, 315-316, 316b
Renal tubular acidosis, type 2, 110, 114 Scheuermann's disease, 283, 292
Renin, 38g Schistosoma haematobium infection, squamous cell bladder
in venous blood, 403b-404b carcinoma and, 78, 89-90
Renin-angiotensin-aldosterone system (RAAS), chronic cardiac Schizophrenia, 28, 30, 343
failure associated with, 134, 145 clozapine for, 339, 344
Respiratory alkalosis, 111, 114 diagnosis of, 339, 344
Respiratory bronchiolitis-interstitial lung disease (RBILD), 169, 181 prevalence of, 336, 340, 341 b
Respiratory failure , acute type I, lobar collapse and, 164, 179 Scombroid poisoning, uncoo~d tuna and, 83, 94
Respiratory function tests (RFTs) Scombrotoxic fish poisoning, 40
in autoimmune connective tissue disease, long-term Scopolamine, 41b, 44b
management of, 288, 296 SCORTEN, 358, 359b
interpretation of, 161 , 177 SCRAs. see Synthetic cannabinoid receptor agonists
reversible obstructive defect revealed by, 161, 177 Secondary immune deficiency, 23, 26
Quadriceps, wasting of, in spinal cord, lesions outside, Respiratory rate, as sign of clinical deterioration, 60, 69
299-300, 313 Restrictive cardiomyopathy, 138, 149
Quartz. silicosis and, 171 , 183 Retention of contrast, malignancy and. 191, 200
Quinidine, 40b, 45b Reticulocytes, reference range of, 409b-41 Ob
Quinine, 271 Retinal vein occlusion, atherosclerosis causing. 332, 3321, 334
Quinolone, 274 Retinoids, systemic, for papulopustular acne, 359-360
with antichlamydial efficacy, 105 Retinol. see Vitamin A
Retrobulbar haemorrhage, 33D-333
R Reversibility, delirium and, 58, 68
RAAS. see Renin-angiotensin-aldosterone system Reynolds' pentad of ascending cholangitis, 205, 209
Rabies vaccine, for bat bites, 82, 93 RFTs. see Respiratory function tests
Radiation, stochastic (random) effect of, 51-52 Rhabdomyolysis, 119, 127
Radical cystectomy, 122-123, 130 tests for, 60, 70.
Radioactive iodine Rheumatic fever
for Graves' disease, 187, 195-196 acute, c-reactive protein and, 140, 151
post-thyroidectomy, 197 aspirin for, 140, 151
Radioallergosorbent testing (RAST). 352. 362 Rheumatoid arthritis, 170, 1701, 182
Radiotherapy Rheumatoid nodules, 169-170, 182
for bone pain. 400b Rheumatology, 278-298
for increased intracranial pressure, 400b Rhinovirus, acute coryza and, 166, 180
Raltegravir, 98, 101 b Riboflavin. see Vitamin 8 2
Ramipril. see Angiotensin-converting enzyme (ACE) inhibitor Richmond Agitation and Sedation Score (RASS), 55, 65
Random venous blood glucose, for diagnosis, 212-218 Ricinus communis (castor oil plant), 45b
Randomisation, 29-30 Rickets, X-linked hypophosphataemic, 282-283, 292
Ranitidine, 365 Rickettsia alricae infection, tick bites and, 78, 90
RANK. see Receptor activator of nuclear factor kappa B Rifampicin, 167
Rash on contraceptive failure, 7, 11
monkeypox and, 82, 93 cytochrome P450 induced by, 6, 9
scabies and, 80, 91 unpasteurised milk and, 76, 88
RASS. see Richmond Agitation and Sedation Score Rifamycin, 11
RAST. see Radioallergosorbent testing Right arm weakness, headache and, 59, 69
Rathke's pouch, development of, into adenohypophysis. 192, Right lung, apex of, irregularly shaped mass at, 387, 391
201 Right pleural effusion, 388, 392
Raynaud's disease, 150 Right subthalamic nucleus, lesion in, 307, 319- 320
RBILD. see Respiratory bronchiolitis-interstitial lung disease Right upper lobectomy, 156, 1561, 175
Reactive arthritis, 290, 294 Rilpivirine, 101 b
Receptor activator of nuclear factor kappa B (RANK), 278, 290 Rimantidine, 89
Receptor antagonists. 42b Rituximab, 24, 287, 295, 298
Recombinant tissue plasminogen activator (rt-PA), intravenous Road injury, causing adolescent deaths, 370, 374
thrombolysis with, 326-327, 329 Rodents, Francisel/a tularensis infection from, 83-84, 94
Recompression, 53 ROSIER (Rule Out Stroke In Emergency Room) clinical stroke
Recurrent oral thrush, 225, 235 tool, 326, 328, 329b
Red cell count, reference range of, 409b-41 Db Rubella, in pregnancy, 86b
Red cell lifespan, reference range of, 409b-410b Ruminations, 338, 343
Red cell transfusion Ruptured berry aneurysm, 121 , 129
for sickle cell disease. 268, 275 Russell's viper (Daboia russe/ii and Daboia siamensis), 46, 48
for upper Gl haemorrhage, 63-64, 72
Reducing agents, 42b s
Sa-Reductase inhibitor, 123, 131 SABA. see Short-acting ~,-agoni st
Refeeding syndrome, chronic alcoholism and, 203-204, Sacroiliac disease, 294
207-208, 208b Sacroiliac joints (SIJs)
Reference ranges, 402-414 irregularity and fusion of, 291
immunological, 41 Ob MRI, for inflammatory back pain, 285, 294
laboratory Salbutamol, 162, 165
in adolescence, 411-414 inhaler, 164-165
in adults, 403-409, 403b nebulised, 333
in childhood, 411 - 414 Salicylates, 37-38, 43b
in pregnancy, 411 Salivation, 39, 43, 44b
Regular prompted toileting, for incontinence, 378, 381 Sarcoidosis, 128, 169, 1691, 181 , 183
Renal artery stenosis, 381-382 stage IV, 169, 181-182
Renal disease. secondary hypertension and, 140, 151 Saudi Arabia, coronavirus and, 33, 35
Renal failure, chronic, hyperlactaemia in, 61, 70 Saw-scaled (carpet) viper (Echis ocel/atus), 47, 49
Renal function, deterioration in, 118, 126 Scabies, 80, 91
Renal replacement therapy, for hyperkalaemia, 62, 71 Scanning speech, in dysarthria, 303, 315-316, 316b
Renal tubular acidosis, type 2, 110, 114 Scheuermann's disease, 283, 292 ·
Renin, 389 Schistosoma haematobium infection, squamous cell bladder
in venous blood, 403b-404b carcinoma and, 78, 89-90
Renin-angiotensin-aldosterone system (RAAS), chronic cardiac Schizophrenia, 28, 30, 343
failure associated with, 134, 145 clozapine for, 339, 344
Respiratory alkalosis, 111, 114 diagnosis of, 339, 344
Respiratory bronchiolitis-interstitial lung disease (RBILD), 169, 181 prevalence of, 336, 340, 341b
Respiratory failure, acute type I, lobar collapse and, 164. 179 Scombroid poisoning, unco.oked tuna and, 83, 94
Respiratory function tests (RFTs) Scombrotoxic fish poisoning, 40
in autoimmune connective tissue disease, long-term Scopolamine, 41b, 44b
management of, 288, 296 SCORTEN, 358, 359b
interpretation of, 161, 177 SCRAs. see Synthetic cannabinoid receptor agonists
reversible obstructive defect revealed by, 161 , 177 Secondary immune deficiency, 23, 26
Secondary spontaneous pneumothorax, 59, 68-69 SOD. see Sphincter of Oddi dysfunction
Secukinumab, 291, 295-296 Sodium
Sedation, in intensive care, 55, 65 fractional excretion of, 119, 121
Sedative agents, 40b, 45b in urine, 408b
Se-homocholic acid taurine (SeHCAT) scan, for bile acid in venous blood, 403b
malabsorption, 230, 239 Sodium bicarbonate, 40b , 45b
Seizures, 38, 43 Sodium calcium edetate, 42b
stroke and, 326, 328 Sodium channel blockers, 40b, 45b
Selective serotonin re-uptake inhibitor (SSRI), 41b, 44b Sodium valproate, 313, 368
Selenium, oral, 195 on pregnancy, 8, 11
Self-harm, 331, 341, 341b as teratogenic agent, 371, 374
Self-management strategies, for chronic abdominal pain, 394, SOFA see Sequential Organ Failure Assessment
399 Somatisation disorder, 338, 343
Self-selection bias, 28, 30 Somatoform disorders, prevalence of, 341b
Seminiferous tubules, dysgenesis of, Klinefelter's syndrome Somatostatin, 200, 242
and, 190, 199 Sotalol, 40b, 45b
Sensitivity, of test, 1, 1t, 3 Spastic quadriplegic cerebral palsy, gastro-oesophageal reflux
Sensory motor neuron signs, in brainstem stroke, 299- 313 in, 372, 374-375
Sensory nerves, delayed conduction in, in chronic inflammatory SPC. see Summary of product characteristics
demyelinating polyneuropathy (ClOP), 309, 321 Sphincter of Oddi dysfunction (SOD), management for, 250,
Sepsis, 294 258
definition of, 61, 10, lOb Spider naevi, during pregnancy, 361, 369
treatment for, 61, 10 Spinal cord, lesions outside, 299- 300, 313
typhoid and, 80, 92 Splenic atrophy, coeliac disease and, 234, 244
Septic arthritis, 219, 290 Splenomegaly, abdomen and, 263-264, 272
Sequential Organ Failure Assessment (SOFA), 61, 10, lOb Spontaneous bacterial peritonitis, diagnostic paracentesis for,
Seronegative rheumatoid arthritis, 219, 290 251' 259
Seropositive rheumatoid arthritis, 280, 291 Spontaneous intracranial hypotension, 302, 315
Serotonin syndrome, 31, 40, 4 1b-42b Spontaneous pain, 393, 391
Serum adrenocorticotrophic hormone (ACTH), 384 Sporothrix spp., 92
Serum allergen testing, reference range of, 41 Ob Sputum culture, haemoptysis and, 178
Serum cortisol, 384 SQSTMI gene, mutations of, in Paget's disease of bone, 283,
Serum iron studies, 111, 126 292
Serum osmolality, 109, 113,401-408 Squamous cell carcinoma
Severe haemophilia A (factor VIII deficiency), 262, 270 bladder, Schistosoma haematobium infection and, 78,
'Severe hypoglycaemia', 214, 2 19 89-90
Sex hormone-binding globulin (SHBG), in venous blood, genetic heterogeneity in, 353, 363
405b- 406b Sri Lanka, 47, 49
Sexually acquired reactive arthritis, 281, 289-290, 295, 298 SSRI. see Selective serotonin re-uptake inhibitor
Sexually transmitted infections, 103-106 SSSS. see Staphylococcal scalded skin syndrome
SGLT2 inhibitors, 222 St Mark's solution, 2 10
SHARP. see Study of Heart and Renal Protection ST segment elevation myocardial infarction, tissue plasminogen
Short Form 36 (SF-36), 398b activator for, 138, 149
Short-acting B2 -agonist (SABA), 164-165 Stamping gait, 382
Short-acting bronchodilator, 111 Standardised 'units' (U/ L), 402
Shortness of breath, due to pulmonary oedema, 58, 67 Staphylococcal scalded skin syndrome (SSSS), 354, 3541,
Shunt, hypoxaemia and, 54, 64 363
Sick euthyroidism, 188, 196 Staphylococcus aureus, 151
Sick sinus syndrome, 134, 145 Starling's law, 134, 145
permanent pacemaker for, 135, 146 Stalin-induced myopathy, 292
Sigmoid carcinoma, 385, 390 Statins, 150, 214
Silicosis, quartz and, 111, 183 cardiovascular events with, 116, 125
Simple coal worker's pneumoconiosis, 182- 183 Steroids, 128, 147
Simvastatin, 170 for asbestosis, 391-392
Sinoatrial disease. see Sick sinus syndrome causing drug-induced diabetes, 215, 221-222
Sinus tachycardia hepatocellular carcinoma from, 391
in pulmonary embolism, 131, 148 Stevens-Johnson syndrome, 363
vasodilation and, 55-57, 561, 66 Sticking sensation, 234, 243
Sister Joseph's nodule, 228, 238 Stochastic (random) effect, of radiation, 51-52
Six-minute walk distance, 380 Stomal losses, 206, 210
Skin ulceration, Francisel/a tularensis infection and , 83-84, 94 Stool calprotectin, for lBO, 231 - 232, 241
s-LANSS. see Leeds Assessment of Neuropathic Signs and Stool culture, in Yersinia enterocolitica infection identification,
' Symptoms 82, 92- 93
Slapping one foot, in peripheral nerve problem, 303, 316 Stop-gain mutation, other name for, 14- 15, 18
SLE. see Systemic lupus erythematosus Streptococcal infection, management of, 76, 88
Sleep, breathing during, 173, 184 Streptococcus pneumoniae, 97, 101, 166, 180
Sleep paralysis, in narcolepsy, 300, 3 13 'Stress hyperglycaemia', 215, 221
Small bowel magnetic resonance imaging (MRI) enterography, Stroke, 145-146
for Crohn's disease, 231, 240 atrial fibrillation and, 135, 146
Smoking direct oral anticoagulants for, 326, 329
cessation of medicine, 325-329
for abdominal aortic aneurysm rupture, 139, 150 prevention of, 7-8, 11
fer myocardial infarction, 142, 153 seizure and, 326, 328
in coffee drinkers, 29-30 total anterior circulation, 326, 329
Crohn's disease and, 373, 375 Stroke volume, dependence on, 60, 69
myocardial infarction and, 138, 149 Study of Heart and Renal Protection (SHARP), 125
Snakebite, 41, 50 Subacute thyroiditis, 188, 1881, 196