Professional Documents
Culture Documents
@ebookmedicin 2018 Davidson's Self Assessment in Medicine 1st Edition
@ebookmedicin 2018 Davidson's Self Assessment in Medicine 1st Edition
Self-assessment in
Medicine
This page intentionally left blank
Davidson’s
Self-assessment in
Edited by
Deborah Wake
MB ChB (Hons), BSc, PhD, Diploma Clin Ed, MRCPE
Clinical Reader, University of Edinburgh; Honorary Consultant
Physician, NHS Lothian, Edinburgh, UK
Patricia Cantley
MB ChB, FRCP, BSc Hons (Med Sci)
Medicine
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
Edinburgh London New York Oxford Philadelphia
St Louis Sydney 2018
© 2018, Elsevier Limited All rights reserved.
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
Printed in China
Last digit is the print number: 9 8 7 6 5 4 3 2 1
Dominic J Culligan BSc, MBBS, MD, FRCP, Sally H Ibbotson BSc (Hons), MBChB (Hons),
FRCPath MD, FRCP (Edin)
Consultant Haematologist and Honorary Professor of Photodermatology, Photobiology
Senior Lecturer, Aberdeen Royal Infirmary, Unit, Dermatology Department, University of
Aberdeen, UK Dundee, Dundee, 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 Liver Immunology, Institute of Cellular
Medicine, Newcastle University; Consultant
David Dockrell MD, FRCPI, FRCP (Glas), Hepatologist, Freeman Hospital, Newcastle upon
FACP Tyne, UK
Professor of Infection Medicine, MRC/University of
Edinburgh Centre for Inflammation Research, Peter Langhorne MBChB, PhD, FRCP (Glas),
University of Edinburgh, Edinburgh, UK Hon FRCPI
Professor of Stroke Care, Institute of
Emad El-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 (Clin 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 DM, 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
Wellcome 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
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) × 100
likelihood ratios (LRs) for each clinical finding, B. A/(A + C) × 100
which of the following statements is true? C. A/(A + D) × 100
A. An LR greater than 1 decreases the D. D/(D + B) × 100
probability of disease E. D/(D + C) × 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 taking individual patient factors in
Positive test A B to account
Negative test C D 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) × 100 D. The probability of a disease after taking
B. A/(A + C) × 100 new information from a test result into
C. A/(A + D) × 100 account
D. D/(D + B) × 100 E. The proportion of patients with a test result
E. D/(D + C) × 100 who have the disease
2 • Clinical decision-making
1.6. A doctor is considering whether to treat a examination carries the most diagnostic weight
patient with antibiotics for a urinary tract in either a positive or negative direction?
infection. The term ‘treatment threshold’ A. Blood pressure greater than 120/80 mmHg
describes a situation in which various factors B. Heart rate less than 90 beats/min
are evenly weighted. What is the best C. Oxygen saturations greater than 94% on air
description of the factors involved? D. Respiratory rate less than 20 breaths/min
A. The cost of the treatment, and whether the E. Temperature less than 37.5°C
treatment is likely to succeed
B. The quality of life of the patient, and risks 1.11. Which of the following statements best
and benefits of treatment describes ‘patient-centred evidence-based
C. The risk and benefits of treatment medicine’?
D. The risks of the test, and risk and benefits of
A. The application of best available evidence
treatment
taking individual patient factors into account
E. The wishes of the patient, and whether the
B. The application of best available evidence to
treatment is likely to succeed
patient care
C. The application of clinical decision aids in
1.7. Dual process theory describes two distinct
decision-making
processes of human decision-making. What is
D. The implementation of a management plan
the accepted estimate of the proportion of time
based on patient wishes
we spend engaged in type 2 (analytical)
E. The use of evidence-based care bundles
thinking?
A. 5% 1.12. According to research, under what
B. 25% circumstances are patients more likely to
C. 50% comply with recommended treatment and less
D. 75% likely to re-attend?
E. 95%
A. If relative risk instead of absolute risk is used
in explanations
1.8. In terms of human thinking and
B. If the consultation is longer
decision-making, what tendency does
C. If the patient is male
confirmation bias describe?
D. If they feel that they have been listened to
A. To look for supporting evidence to confirm and understand the treatment plan
a theory and ignore evidence that E. If visual aids have been used instead of text
contradicts it to explain the treatment plan
B. To rely too much on the first piece of
information offered
1.13. Which of the following statements best
C. To stop searching because we have found
describes what is meant by the term ‘human
something that fits
factors’?
D. To subconsciously see what we expect to
see A. An understanding of diagnostic error
E. To want to confirm our diagnoses with B. How equipment is designed to take human
others before making a decision behaviour into account
C. How fatigue affects human thinking and
1.9. Which of these factors is most likely to lead decision-making
to an increased incidence of errors in clinical D. How healthcare professionals communicate
decision-making? in a team
E. The science of the limitations of human
A. Age
performance
B. Fatigue
C. Gender
D. Use of checklists 1.14. In terms of human thinking and
E. Working alone decision-making, anchoring describes what
tendency?
1.10. In a case of suspected pulmonary A. To look for supporting evidence to confirm
embolism in an ambulatory care setting, which a theory and ignore evidence that
of the following individual signs on physical contradicts it
Clinical decision-making • 3
B. To rely too much on the first piece of following statements is true regarding the
information offered interpretation of a D-dimer result?
1
C. To stop searching because we have found A. A negative D-dimer result in a high clinical
something that fits probability patient excludes acute VTE
D. To subconsciously see what we expect to B. A positive D-dimer result means that acute
see VTE is present
E. To want to confirm our diagnoses with C. D-dimer is a useful screening test in patients
others before making a decision presenting with breathlessness
D. D-dimer testing in suspected acute VTE
1.15. The D-dimer test has a sensitivity of at results in lots of false negatives
least 95% in detecting acute venous E. D-dimer testing in suspected acute VTE
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.
LR =
probability of finding in patients Positive predictive value = A (A + B) × 100
without disease
Predictive values combine sensitivity,
An LR greater than 1 increases the specificity and prevalence. Sensitivity and
probability of disease (the greater the value, the specificity are characteristics of the test; the
greater the probability). An LR less than 1 population does not change this. However, as
decreases the probability of disease. LRs are doctors, we are interested in the question,
developed against a diagnostic standard (in the ‘What is the probability that a person with a
case of meningitis, lumbar puncture results) so positive test actually has the disease?’ The
do not exist for all clinical findings. LRs illustrate positive predictive value is the proportion of
how a probability changes – but do not patients with a test result who have the disease
determine the prior probability of disease. If the and is calculated from a table of results in a
starting probability is high to begin with, an LR specific population. It is not possible to transfer
of around 1 does not affect this. this value to a different population.
1.3. Answer: B.
1.5. Answer: D.
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 1.10. Answer: B.
Human factors is the science of the limitations on the first piece of information offered (the
1
of human performance and how technology, ‘anchor’) when making decisions.
our work environment and team communication
can adapt for this to reduce diagnostic and 1.15. Answer: E.
other types of error. Analysis of serious adverse A very sensitive test will detect most disease
events in health care show that human factors but generate abnormal findings in healthy
and poor team communication play a people. A negative result therefore means the
significant role when things go wrong. Human disease is unlikely, but a positive result is likely
factors training is being introduced into to require further evaluation. As with all
undergraduate and postgraduate medical diagnostic tests, a low pre-test probability plus
curricula and multi-professional team training in a negative D-dimer virtually excludes acute
many countries. VTE. However, if the pre-test probability is
very high, a negative D-dimer still leaves a small
1.14. Answer: B.
but significant chance that acute VTE is
Cognitive biases are subconscious errors that present.
lead to inaccurate judgement and illogical D-dimer is commonly raised in conditions
interpretation of information. In evolutionary that have nothing to do with acute VTE: for
terms, it is thought that cognitive biases example, old age, pregnancy, heart failure,
developed because speed was often more sepsis and cancer. This is the reason for its low
important than accuracy. This property of specificity. It should be used only when the
human thinking is highly relevant to clinical history and physical examination are consistent
decision-making. Anchoring describes the with acute VTE.
S Maxwell
2
Clinical therapeutics and
good prescribing
Multiple Choice Questions
2.1. Which of the following drugs exerts its E. Reacting chemically with the agonist to
action directly at an enzyme target? reduce the agonist concentration available to
A. Aspirin bind to receptors
B. Hydrocortisone
C. Insulin 2.4. Which of the following drugs induce the
D. Lidocaine hepatic cytochrome P450 enzymes that are
E. Morphine responsible for drug metabolism?
A. Cimetidine
2.2. Which of the following statements best B. Ciprofloxacin
describes the term ‘potency’? C. Erythromycin
A. A less potent drug will always have a lower D. Rifampicin
efficacy than a more potent drug E. Valproate
B. More potent drugs have a lower ED50
C. The potency of a drug has no bearing on 2.5. Which of the following drugs may exhibit
recommended dose ranges zero-order drug kinetics at therapeutic drug
D. The potency of a drug is the extent to which concentrations?
the drug can produce a response when all A. Carbamazepine
of the available receptors are occupied B. Ciprofloxacin
E. The potency of a drug is unrelated to its C. Lamotrigine
affinity for a receptor D. Phenytoin
E. Vancomycin
2.3. Which of the following statements best
describes how a non-competitive antagonist 2.6. Which of the following statements about
drug affects the pharmacodynamic actions of the estimated volume of distribution (Vd) of a
an agonist? drug is true?
A. Binding irreversibly with the receptor to A. Drugs that are highly bound to albumin have
remove receptors as potential binding sites a lower Vd
for the agonist B. Drugs with a large Vd are eliminated more
B. Binding to a different population of receptors rapidly after discontinuation
that produce a response antagonistic to that C. Larger Vd is associated with a shorter
of the agonist half-life
C. Causing cell death so that it cannot function D. Vd cannot be greater than the volume of the
D. Increasing the total number of receptors for body
the agonist, thereby reducing the proportion E. Vd of lipid-soluble drugs is larger in males
that it can occupy than females (of equivalent mass)
Clinical therapeutics and good prescribing • 7
2.23. A 56 year old man is being treated with 2.24. A 78 year old woman is reviewed in the
intravenous gentamicin for Gram-negative emergency department of a hospital with
septicaemia that is presumed to be of urinary bruising. She is taking warfarin 3 mg and 4 mg 2
tract origin. He is well hydrated and his renal orally on alternate days as prophylaxis against
function is normal. He has had two previous recurrent pulmonary emboli. Her last 3-monthly
doses of gentamicin 360 mg as a 30-minute INR measurement was 2.7. She has been
intravenous infusion at 1000 hrs on Wednesday otherwise well with no other new symptoms
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 phytomenadione
1000 hrs). (vitamin K1) 1–3 mg by slow intravenous
When should the next plasma gentamicin injection
concentration be taken? B. Stop warfarin and give phytomenadione
A. 0400 hrs (Saturday) (vitamin K1) 1–5 mg by mouth
B. 1400 hrs (Friday) C. Stop warfarin and start apixaban
C. 1800 hrs (Friday) D. Stop warfarin and start low-molecular-weight
D. Immediately after the infusion is completed heparin injections
E. Immediately 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 enzyme cyclo-oxygenase irreversibly, or (iii) the antagonist interferes with
and is a non-selective and irreversible inhibitor. the signal transduction mechanism preventing
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.
higher doses. The lower potency of a drug can The clearance rate of most 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
small number of common medicines, their
2.3. Answer: A.
metabolism is ‘saturable’, meaning that the
The term ‘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 mechanism, to prevent the increases in exposure and the likelihood of
agonist activating the receptor. The common toxicity.
feature is that increasing the concentration of
agonist cannot outcompete the antagonist. 2.6. Answer: A.
The receptor is rendered inactive and so the The apparent volume of distribution (Vd) is the
maximal 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 intravenous injection. It is
ways: (i) the antagonist binds to an allosteric calculated from the equation Vd = D/C0, where
site of the receptor, (ii) the antagonist binds to D is the amount of drug given and C0 is the
1 0 • Clinical therapeutics and good prescribing
initial plasma concentration. Drugs that are CYP2D6 (‘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 CYP2D6 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.
2.11. Answer: E.
2.14. Answer: A.
Although there have been past suggestions New drugs are given a ‘market authorisation’
that broad-spectrum penicillins might interfere based on the evidence of quality, safety and 2
with gut flora to alter the enterohepatic efficacy presented by the manufacturer. The
recycling of oestrogens (reducing their regulator will not only approve the drug but will
bioavailability in the body), it is now thought also take great care to ensure that the
that the only types of antibiotic that interact accompanying information reflects the evidence
with hormonal contraception and make it less that has been presented. The summary of
effective are rifampicin-like antibiotics. The product characteristics (SPC), or ‘label’,
metabolism of oestrogens is accelerated by provides detailed information about
rifamycins, leading to a reduced contraceptive indications, dosage, adverse effects, warnings,
effect with combined oral contraceptives, monitoring, etc.
contraceptive patches and vaginal rings.
Erythromycin is a well-recognised inhibitor of 2.15. Answer: D.
the hepatic metabolism of many drugs The calculation of NNT can be undertaken in
(including oestrogens) but this will not result in two ways. First, the number of patients
contraceptive failure. prevented from suffering a stroke in the active
treatment compared to control arm was 100
2.12. Answer: B.
out of a total number at risk of 2500. Therefore,
Moxifloxacin is a quinolone antibiotic that the numbers treated for each one who
can be used to treat sinusitis, community- benefitted was 2500/100 = 25. An alternative
acquired pneumonia, exacerbations of chronic approach that works easily in less rounded
bronchitis, mild to moderate pelvic inflammatory numbers is to consider the difference in the
disease, or complicated skin and soft tissue percentage of patients in each group who had
infections. Along with other quinolones, it may a stroke, i.e. active treatment 150/2500 × 100
block cardiac potassium channels and delay = 6% and placebo 250/2500 × 100 = 10%.
the repolarisation phase of the action potential The difference is 4%, meaning that if a single
to prolong QT interval. This may potentiate at-risk group of just 100 patients were
the similar actions of amiodarone. Patients considered, then 4 would benefit and so the
with a prolonged QT interval are at risk of NNT is 100/4 = 25.
suffering episodes of torsades de pointes,
which may progress to cause cardiac 2.16. Answer: D.
2.18. Answer: C.
such medicines include diltiazem, lithium,
The UK National Institute for Health and Care theophylline, phenytoin and insulin.
Excellence (NICE) recommends that the dose Non-proprietary names are also preferred in the
of metformin should be reviewed if the eGFR is case of many compound and modified-release
less than 45 mL/min/1.73 m2 and that it should preparations.
be avoided if the eGFR is less than 30 mL/
min/1.73 m2. (Type 2 diabetes in adults: 2.22. Answer: D.
management. NICE guideline [NG28]. Published The patient has excellent control of her
December 2015.) ventricular rate and so digoxin appears to be
very effective. However, she is complaining of
2.19. Answer: A.
nausea, which is a very common toxic effect of
This patient has severe liver disease digoxin although there could be numerous
demonstrated by the failure to synthesise other explanations. The plasma digoxin
clotting factors and albumin, and is showing concentration is at the top end of the normal
features of hepatic encephalopathy. In severe ‘target’ range. Although within that range it is
liver disease many drugs can further impair perfectly possible (and likely) that, because of
cerebral function and may precipitate hepatic natural inter-patient variation, this patient’s
encephalopathy. These include all sedative nausea is indeed caused by digoxin. Given that
drugs, opioid analgesics (e.g. codeine the rate control is so good, the optimal course
phosphate), those diuretics that produce of action is to keep this patient on digoxin but
hypokalaemia and drugs that cause reduce the dosage in the hope of relieving the
constipation (e.g. codeine phosphate). Patients symptoms but maintaining the therapeutic
with hepatic encephalopathy must avoid effect. In other words, be guided by the
constipation, and lactulose is a preferred beneficial and adverse effects of the medicine
laxative. Spironolactone is indicated in the for your specific patient rather than the
management of ascites. B vitamins are published reference ranges alone.
important in avoiding Wernicke’s
encephalopathy in chronically malnourished 2.23. Answer: C.
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 2
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
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
A Frost
3
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, progesterone 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 BRCA1 mutation
calcitonin-gene-related peptide. Which of the carriers. Genetic testing of the BRCA1 and
mechanisms of controlling gene expression BRCA2 genes reveals a heterozygous BRCA1
listed below is responsible for this mutation (BRCA1 c.3748G>T). This mutation
multi-functionality? substitutes a G for a T, resulting in the creation
Clinical genetics • 15
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?
1 6 • Clinical genetics
Fig. 3.14
Clinical genetics • 17
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 female cancer and decided to undergo genetic testing
E. Variable expressivity through a private company offering a 3
next-generation sequencing (NGS) breast
cancer susceptibility gene panel test. They sent
3.15. You review a 39 year old woman 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 BRCA1 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 tumour
sequenced
suppressor gene
E. Successfully identifying a disease-causing
D. Loss-of-function mutation in an oncogene
variant
E. Passenger mutation
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 BRCA1 mutation. was successfully treated, and has now
Her oncologist has 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–Dubé 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 spindle
GC pair with an AT pair. fibres attach to the sister chromatids and pull
them apart.
3.2. Answer: C.
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
Clinical genetics • 19
expansion of a run of CTG repeats within the produces a shorter, non-functional protein and
DMPK 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. 3
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 monosomy 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 case
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
exome 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 joining 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 the condition has
rearrangements that may be found 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 condition 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.
20 • Clinical genetics
3.14. Answer: A.
either of them also carried the CNV it would be
X-linked conditions are not passed from father unlikely that it was contributing significantly to
to son, as the mutation is on the X his phenotype. It is not uncommon to identify
chromosome. Whilst X-linked conditions are benign inherited CNVs during array CGH
mostly restricted to males, occasionally female testing. If the CNV is not inherited from an
carriers may exhibit signs of an X-linked unaffected parent it is harder to assess its
disease due to skewed X-inactivation. Also, significance. You would need to carefully
when considering a pedigree, beware of the consider any genes that could be potentially
possible presence of phenocopies (i.e. disrupted. If you remain unconvinced that the
individuals with a similar phenotype who do not CNV provides an explanation for his difficulties
carry the mutation); with a phenotype as you may wish to proceed to further genetic
common and multifactorial as developmental testing, and consider an intellectual disability
delay/learning difficulties, this could be a gene panel or exome sequencing.
confounding factor in your analysis.
3.18. Answer: D.
3.15. Answer: B.
In NGS, ‘capture’ refers to the ‘pull-down’ of a
If a mutation results in activation of a growth targeted region of the genome for sequencing.
factor gene or receptor, then that cell will This may constitute a single gene, a number of
replicate more frequently as a result of genes associated with a given phenotype or
autocrine stimulation. Tumour formation is condition (a gene panel), the exons of all
promoted by gain-of-function mutations in coding genes known to be associated with
oncogenes and loss-of-function mutations in disease (a clinical exome) or the exons of all
tumour suppressor genes, not the other way known coding genes (an exome).
around. Passenger mutations accumulate
within cancer cells but do not in themselves 3.19. Answer: A.
promote growth (unlike ‘driver’ mutations). Whole-genome sequencing enables more even
Apoptosis is programmed cell death and does coverage of genes, allowing better identification
not have a role in tumour formation. (The BRCA of gene dosage anomalies than whole-exome
test result is not relevant here – the question is sequencing. (Gene dosage refers to the
simply testing knowledge of mechanisms number of copies of a gene that are present in
promoting tumourigenesis.) a genome, and anomalies may be caused by
CNVs such as deletions or duplications.)
3.16. Answer: A.
Whole-exome sequencing is, however, less
Array CGH provides a high-resolution expensive, and allows deeper sequencing and
genome-wide screen for chromosomal consequently better detection of mosaicism.
abnormalities. Mosaicism down to a 10% level Whole-genome sequencing will detect many
can often be detected. Since it relies on more variants, so it is associated with a greater
analysis of comparative dosage across the risk of incidental findings, and the likelihood of
genome, triploidy (all chromosomes present in any given variant detected being pathogenic is
an extra copy) may be missed. Similarly, reduced.
because with balanced translocations dosage
is unaffected, these may not be picked up and, 3.20. Answer: A.
3.21. Answer: C.
sarcoma, breast carcinoma, brain cancer
PARP inhibitors work by blocking the (especially glioblastoma) and adrenocortical
single-stranded DNA break-repair pathway. In a carcinoma. There are no additional clinical
BRCA1/2 mutation-positive tumour with an features other than the cancer susceptibility in
already compromised double-stranded DNA this syndrome. The other answers are also 3
break-repair pathway, the additional loss of the examples of other rare cancer predisposition
single-stranded break-repair pathway will drive syndromes, with different spectrums of tumour
the tumour cell towards apoptosis susceptibility, and in some cases additional
(programmed cell death). phenotypic clinical features.
3.22. Answer: D.
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-overlapping 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?
Clinical immunology • 23
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 IgG mediated has been shown to alter the course of
C. Type II hypersensitivity results in circulating disease progression in rheumatoid arthritis
immune complexes B. Biological agents are generally now
D. Type III hypersensitivity results in considered first-line therapy for inflammatory
complement activation bowel disease
24 • Clinical immunology
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 Moraxella
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 prior to
be informative transfer to her local hospital. She lives in a 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 should 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
5 × 6 cm 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)
Clinical immunology • 25
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.
microorganisms. They may cause damage to Primary immune deficiency often presents in
host tissue and have a short half-life. 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
26 • Clinical immunology
by B cells and predominantly protect against Bronchospasm, urticarial rash, vomiting and
extracellular infection. hypotension are well-recognised features of
type I hypersensitivity. Eczematous rash is
4.7. Answer: E.
more consistent with type IV hypersensitivity.
Symptomatic immunoglobulin deficiency may
require immunoglobulin replacement therapy. 4.13. Answer: E.
Secondary immunoglobulin deficiency can Mast cell tryptase is stable in serum at room
occur with myeloma. Opportunistic infection is temperature and is a more reliable marker of
not commonly seen without additional T-cell mast cell activation than plasma histamine. It
deficiency. End-organ damage such as has a half-life of 2.5 hours. Serial measurement
bronchiectasis can occur, as can autoimmune can be helpful in confirming a mast cell-
disease. activating event but a negative result does not
exclude anaphylaxis.
4.8. Answer: D.
as part of the acute phase response and can Anaphylaxis leads to increased vascular
be activated by three pathways, the classical, permeability, is typically rapid in onset following
alternate and lectin pathways. All three allergen exposure and can be fatal. It results
pathways end in the membrane attack from cross-linking of allergen-specific IgE on
complex, leading to bacterial lysis. Local mast cells. Desensitisation therapy is currently
inflammation is induced by complement not routinely recommended for food allergy.
breakdown products.
4.15. Answer: A.
4.9. Answer: C.
Autoimmune disease is generally not
Complement deficiency is associated with monogenic and is influenced by environmental
connective tissue disease and recurrent factors. Many autoimmune conditions are not
infection, late complement protein deficiency life-threatening, e.g. vitiligo or hypothyroidism.
being particularly associated with recurrent Not all conditions require immunosuppression:
neisserial infection. Complement deficiency is e.g. coeliac disease, where gluten withdrawal is
not routinely treated with complement required. It can affect multiple organs.
replacement therapy. C1 inhibitor deficiency
can, however, be treated with C1 inhibitor 4.16. Answer: A.
concentrate. Patients with this condition have a Anti-TNF therapy has been shown to alter the
low C4, even between attacks of angioedema. course of disease progression in rheumatoid
Complement control proteins have an important arthritis. Small-molecule inhibitors targeting
role in controlling complement activity. intracellular signalling pathways are in
development. Natalizumab, an integrin inhibitor,
4.10. Answer: A.
has proven efficacy in multiple sclerosis.
Secondary immune deficiency can be drug Monoclonal therapy is not without potentially
induced, for example with immunosuppressive serious side-effects (e.g. natalizumab and
agents. It is much more common than primary progressive multifocal leucoencephalopathy).
immune deficiency, can be associated with Biological agents are generally second line.
opportunistic infection and can be life-
threatening. Secondary immune deficiency may 4.17. Answer: D.
to be considered. Rituximab can lead to B-cell CNS lymphoma, driven by Epstein–Barr virus
depletion, usually transient, and can be infection, is seen in immune deficiency, typically
associated with antibody deficiency. late-stage HIV infection or following systemic
Paraprotein assessment should be undertaken immunosuppressive therapy. A previously well 9
for appropriate interpretation of immunoglobulin year old is unlikely to have a secondary
results. immune deficiency. Candida oesophagitis is
more consistent with T-cell immune deficiency,
4.19. Answer: C.
as is toxoplasmosis. Severe combined immune
An immune deficiency is likely; the patient’s age deficiency is likely to have presented before the
does not rule this out. With the family history, age of 6 years and the clinical findings
an X-linked condition should be considered. described are more consistent with a primary
With the organisms identified, X-linked chronic phagocyte deficiency.
granulomatous disease, a disorder of
phagocytes, rather than a T-cell defect, is most 4.23. Answer: D.
likely, in which case neutrophil function testing A type II cryoglobulinaemia in the context of
would be diagnostic. hepatitis C is most likely, from the clinical
history, raised ALT, elevated inflammatory
4.20. Answer: C.
markers and low C4. SLE is on the differential
The clinical history is most consistent with diagnosis but crypglobulinaemia typically
symptomatic antibody deficiency. This may be presents with rash, arthralgia and neuropathy.
primary or secondary, for example with chronic Warm separated serum is required for
lymphocytic leukaemia, and may be associated appropriate investigation. Genetic deficiency of
with end-organ damage. Neutrophil function C4 is less likely in this context.
testing is indicated in the investigation of
chronic granulamotous disease rather than 4.24. Answer: B.
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 5
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
bias 1-year of follow-up, 130 patients in the placebo
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%
5.8. In a case–control study examining the B. 23%
effect of coffee consumption on lung cancer, C. 0.77
which one of the following might lead to D. 1.30
confounding? E. 33.33
A. People with lung cancer are more likely to 5.12. A city has a population of 100 000. 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-years
of a cohort study, as used in epidemiological C. The incidence is 11 per 100 person-years
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), calculated 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
30 • Population health and epidemiology
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.
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
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 some
in 2013. Suboptimal breastfeeding is ranked 19 population, characterised according to their
in 2013, down from rank 11 in 1990, and baseline characteristics and followed up 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 absolute 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
Population health and epidemiology • 31
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.
5.11. Answer: A.
5.13. Answer: E.
There are many ways to represent the effect of Globally, the vast majority of countries use the
drug treatments. The other measures are, in World Health Organization International 5
order, (1) the number needed to treat, (2) the Classification of Diseases (ICD) system. For
risk ratio of the placebo versus the treatment psychiatric illnesses, the disease is also
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
reduction. and Statistical Manual of Mental Disorders is
used), ICD 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 ICD 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/).
JAT Sandoe, DH Dockrell
6
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 cervical
6.2. A 9 month old infant has a temperature of carcinoma. The use of which vaccine in
39.5°C 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
Principles of infectious disease • 33
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 a CT 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 β-lactamase
Travel to which of the following countries is
most likely to be associated with this virus?
B. mecA penicillin-binding protein 6
C. NDM-1 carbapenemase
A. Brazil D. TEM-12 β-lactamase
B. China E. vanA gene cluster
C. Saudi Arabia
D. United States of America 6.10. A 73 year old patient develops
E. Zambia Staphylococcus aureus bacteraemia 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
D. Trypanosoma brucei gambiense is placed on treatment with voriconazole. Which
E. Typhoid fever of the following is a recognised adverse effect
of voriconazole therapy that the patient should
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 Legionella 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 spread 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
34 • Principles of infectious disease
Answers
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 suspicion 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 and 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.
6.3. Answer: C.
6.5. Answer: E.
The symptoms in this case have come on after Live vaccines should, in general, be avoided in
therapy was commenced, which raises immunocompromised patients or only given
Principles of infectious disease • 35
cases. Yellow fever virus vaccine is a live virus Persistent bacteraemia increases the risk of
vaccine. The other vaccines are not live complications. When the strain is sensitive to
vaccines. antistaphylococcal penicillins (e.g. flucloxacillin)
these should be prescribed in preference
6.6. Answer: C.
to other agents. Penicillins work by
The symptoms of severe respiratory syndrome time-dependent killing so the efficacy is, in
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 6
Travel-related cases have been seen in many killing (e.g. aminoglycosides).
countries but the majority of cases have initially
been associated with travel to countries in the 6.11. Answer: B.
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.
6.15. Answer: B.
should always be considered. Of the
Although there are a range of potential antimicrobials listed, colistin is associated, in
causes of encephalopathy in a patient particular, with neurotoxicity including
who has received ventilation for critical illness encephalopathy.
including infection, medication-related causes
SHL Thomas
7
Poisoning
Multiple Choice Questions
7.1. Which one of the following is most likely to D. Isosorbide mononitrate
produce significant toxicity if ingested E. Paracetamol
accidentally by a child?
A. A 1 cm 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 H+
52.5 nmol/L (pH 7.28), PaCO2 2.7 kPa 7.6. A 54 year old man presents unconscious.
(20.3 mmHg), PaO2 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 µmol/L (1.14 mg/
agent? dL) and glucose 7.3 mmol/L (131.4 mg/dL).
A. Cocaine Arterial blood gases results include H+
B. Gamma hydroxybutyrate 81.3 nmol/L (pH 7.09), PaCO2 1.8 kPa
C. Isopropyl nitrite (13.5 mmHg), base excess of −13 mmol/L,
38 • Poisoning
Answers
7.1. Answer: C.
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, emollients and other skin creams,
These are all useful interventions for torsades baby lotion
de pointes except procainamide. Magnesium Miscellaneous: plasticine, silica gel, most household
plants, plant food, pet food, soil
sulphate reduces the risk of torsades without
40 • Poisoning
treatment (Box 7.2). Isoproterenol and pacing The clinical features could be consistent with
increase the underlying ventricular rate and options B or C but the association with eating
reduce the risk of recurrence, as torsades is a predator fish suggests ciguatera, which is
bradycardia-dependent arrhythmia, although prevalent in the Caribbean. These neurological
they are infrequently needed. Hypokalaemia features are not found with Salmonella
worsens the risk of torsades, so correction poisoning. Scombrotoxic fish poisoning causes
is beneficial. Procainamide is a class Ia symptoms associated with histamine release,
anti-dysrhythmic drug that further prolongs which may include gastrointestinal disturbance,
ventricular repolarisation and would worsen the but neurological features are not characteristic.
risk of torsades. Aconite can also cause gastrointestinal
disturbances and paraesthesia but a plant is
7.3. Answer: C.
less likely to be involved in this episode.
Methaemoglobinaemia is commonly caused by
organic nitrites, such as isopropyl nitrite, which 7.5. Answer: D
oxidise haemoglobin. Other causes are shown These are all characteristic features of serotonin
in Fig. 7.3. The other substances listed in syndrome (Box 7.5A). Inducible clonus and
the question do not have this effect directly. shivering are not characteristic of the
Note, however, that occasionally cocaine is anticholinergic or stimulant toxidromes or
contaminated with oxidising adulterants such gamma hydroxybutyrate (GHB) toxicity
as benzocaine or phenacetin, which may (although myoclonus may be seen after GHB;
occasionally produce unexpected Box 7.5B). Clonus would not suggest
methaemoglobinaemia. intercurrent infection.
Poisoning • 41
7
NADH Methaemoglobin (Fe3+) Methylthioninium NADP*
chloride (reduced)
Cytochrome b5 Methaemoglobin
reductase reductase
Fig. 7.3
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,
myoclonus, raised
other listed chelating agents include poisoning
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.
Use of this method gives the same answer for Paracetamol toxicity is characteristically
this question. associated with liver failure (including
hypoglycaemia and abnormal clotting) and renal
7.9. Answer: D.
failure. Paracetamol does not generally cause
Tachycardia, ataxia, conjunctival irritation and unconsciousness, although this can be a
psychosis can all be characteristic of exposure feature of late-stage liver failure. It may also be
to both cannabis and synthetic cannabinoid caused by co-ingestants.
receptor agonists. Seizures, however, are often
reported after use of SCRAs but rarely after use 7.15. Answer: D.
of cannabis. Unlike cannabis, SCRAs have also These could all be cholinergic effects, but
been reported to cause hypokalaemia, acute tachycardia, reduced ventilation, mydriasis and
kidney injury and coma with respiratory acidosis. fasciculation are all cholinergic nicotinic (rather
than muscarinic) effects (Box 7.15).
7.10. Answer: B.
that can sometimes cause OPIDN, but this The child has features consistent with an
complication is rare with nerve agents (e.g. anticholinergic toxidrome (Box 7.16A). Plants
sarin, tabun) and non-organophosphate with this effect include Atropa belladonna
carbamate insecticides (e.g. methomyl, (deadly nightshade), Datura stramonium (jimson
bendiocarb). Nerve agents would not be found weed, thorn apple) and Brugmansia spp.
on farms. (angel’s trumpet). While ingestion of jequirity
beans, wolf’s bane and laburnum could
7.11. Answer: E.
potentially also cause convulsions,
Mephedrone is a white powder commonly anticholinergic effects would not be expected.
taken by nasal insufflation (‘snorting’), and Autumn crocus causes gastrointestinal effects,
44 • Poisoning
hypotension and cardiogenic shock poisoning but are uncommon and likely to
(Box 7.16B). be associated with severe cardiovascular
effects.
7.17. Answer: D.
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.
Poisoning • 45
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
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 olfersii) 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) fragilis)
C. A grass snake (Natrix natrix)
8.8. You are working in a hospital in rural D. A smooth snake (Coronella austriaca)
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
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 jamesoni) 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 ocellatus) 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) fragilis)
C. None of these listed C. A grass snake (Natrix natrix)
D. Scarification of the bite site D. A smooth snake (Coronella austriaca)
E. Tourniquet E. An escaped exotic snake, most likely a small
mamba
8.10. 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
48 • Envenomation
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 snake
venomous animal will develop medically causes coagulopathy, plus other effects. In
significant envenoming, therefore not every some areas, such as Myanmar, Russell’s vipers
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 cause
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 precisely
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 tamulus).
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 adrenaline (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
Envenomation • 49
giving antivenom, but clinical trial evidence The saw-scaled vipers routinely cause both
does not support their use. Prazosin has, in the significant tissue damage around the bite site
past, been the recommended treatment for and a severe coagulopathy.
envenoming by the Indian red scorpion, but Forest cobras cause only minor local bite site
more recent clinical trial evidence indicates that effects, major flaccid paralysis and do not 8
specific antivenom is more effective. Dopamine cause coagulopathy. Black-necked spitting
might be required in managing intractable cobras can cause severe local tissue injury, but
hypotension, but is not an alternative to not coagulopathy. Puff adders cause severe
adrenaline as the drug of first choice in treating local tissue injury, but not a clear coagulopathy,
anaphylaxis. although there may be bruising and oozing of
blood around the bite site. Green mambas
8.5. Answer: A.
cause local and paralytic effects, not
In this setting it is likely that a simple urine coagulopathy.
dipstick test will be available and if this shows
proteinuria, in this clinical scenario, it is very 8.9. Answer: B.
likely the patient is developing renal failure. The forest cobra causes principally flaccid
A serum creatinine level may certainly help, neurotoxic paralysis, without major local tissue
but even if available, may take time to gain an damage around the bite site. Therefore, the
answer. Renal ultrasound is unlikely to be most important consideration is slowing venom
available and may not assist in diagnosis. Renal movement from the bite site to the rest of the
biopsy is inappropriate given the active body, a process that initially occurs particularly
coagulopathy. via the lymphatic system. The Australian-
developed PBI first aid is the most
8.6. Answer: E.
effective safe way of achieving this.
The combination of coagulopathy, renal failure Because the pressure is applied to the
and neurotoxic flaccid paralysis is classic for Sri bite area and bitten limb, it has the
Lankan Russell’s viper envenoming. It is rarely potential, for bites by snakes causing extensive
seen elsewhere within the range of this snake, bite site tissue injury, to worsen that injury.
although there are a few reports from part of Therefore, the PBI method is not recommended
southern India. If the hospital was in south for bites by snakes likely to cause such local
eastern Australia (not an option listed), then a tissue injury; for these snakes, simple
tiger snake (Notechis scutatus) bite should be immobilisation of the bitten limb is
considered. recommended instead.
Tourniquets, while effective in the short term
8.7. Answer: D.
in preventing venom movement, are painful and
Because of the likely snake fauna in Brazil, have a well-established reputation for
early development of paralysis (as evidenced by causing major ischaemic limb injury,
ptosis) plus coagulopathy is typical of a often necessitating amputation; therefore,
significant South American rattlesnake bite, tourniquets are not recommended first
quite different to rattlesnake bites in North aid for any snakebite. Electric shock treatment
America. for snakebite has been proven to cause injury
The jararaca and related Bothrops spp. are and provides no benefit; it should never be
the most common cause of significant used as first aid for any envenoming.
snakebites in Brazil and often cause Scarification of the bite site, although
coagulopathy plus significant local bite site commonly used as first aid for snakebite, has
injury, but not paralysis. Coral snakes mostly no benefit, causes significant harm and should
cause only minor local bite effects and never be used for snakebite.
50 • Envenomation
8.10. Answer: B.
children, it can cause severe, even
The ‘Million Death Study’ in India provided the life-threatening envenoming, characterised by
best available data on the impact of snakebite local pain, swelling, bruising and sometimes
in that country and estimated at least 45 000 shock and a coagulopathy. Kidney injury can
Indians die from snakebite every year, far higher occur, although is rare.
than official Indian Government data, which Legless lizards are harmless, non-venomous,
uses only hospital data. as are grass snakes. Mambas (Dendroaspis
The precise number of snakebite deaths spp.) cause a quite different clinical picture of
each year worldwide is unknown, with envenoming.
estimates varying from a low of about 25 000
(almost certainly far too low), to > 100 000, with 8.13. Answer: C.
some experts speculating that up to 200 000 The severe local pain following a bite from a
deaths may occur, although this latter figure is large spider could be caused by a number of
not yet supported by definitive data. exotic species, but is a particular feature of
Snakebite causes nearly 100 times bites by the Brazilian wandering spider
more limb injuries requiring amputation, (Phoneutria nigriventer), otherwise known as the
each year, than land mines. Fortunately banana spider because it is sometimes
most of those injuries caused by accidentally imported in containers of fruit,
snakebites require only amputation of digits or notably bananas.
parts of a limb – less commonly whole-limb The Australian funnel web spiders (there are
amputation. a number of genera and species; the best
known is the Sydney funnel web spider, Atrax
8.11. Answer: C.
robustus) can cause local severe pain, but the
The grass snake is a non-dangerous snake, major risk is systemic envenoming causing a
arguably the most common native snake in the catecholamine-storm-like clinical picture and
UK. The pale band or collar behind the head is this develops quickly within minutes to an hour
a useful diagnostic feature present in many or so after the bite. Your patient does not have
specimens, although not all. this clinical picture, so even if it was a funnel
There are legless lizards (‘slow worms’) in the web spider, he is out of the danger period.
UK, but they generally do not have this pattern Black widow spiders (Latrodectus spp.) are not
of coloration. The European northern adder large and, while they can cause local pain, it
(Vipera berus) is the only venomous snake progresses to more regional, then generalised
native to the UK. It is often grey in colour, with pain, plus features of neuroexcitation, so your
darker blotchy markings on the body. Mambas patient does not really fit this picture. Brown
are tree-dwelling snakes and do not accord recluse spiders (Loxosceles spp.) generally
with the description given. Consider the cause little or no pain initially and it is only
possibility of an escaped exotic venomous many hours to days after people are bitten that
snake (depending on the setting) if the patient local necrosis and sometimes a significant
develops envenoming inconsistent with a systemic envenoming can develop; they are not
European adder bite. large spiders, so do not fit the picture
presented by your patient. The Mexican
8.12. Answer: A.
orange-kneed tarantula (Brachypelma smithi)
The European northern adder does cause may cause locally painful bites, but more
snakebites in the UK, maybe as many as commonly causes skin or eye irritation from
70–100 cases per year and, particularly in shed abdominal hairs.
M Byers
9
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
than the world average potassium > 12 mmol/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
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 maintain 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 process of the body
hypertrophy adjusting to the decreased availability of oxygen
E. Ultraviolet therapy for psoriasis at high altitudes. This becomes noticeable
52 • Environmental medicine
above 2500 m. 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.
3800 m. 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 10 m
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 30 m of seawater
with symptoms of dry cough, exertional
and oxygen becoming toxic at inspired
dyspnoea and extreme fatigue
pressures above 40 kPa (0.4 ata)
D. Monge’s disease (chronic mountain sickness)
B. As divers descend, the partial pressures of
is characterised by polycythemia and
the gases they are breathing decrease and
hypoxia that does not improve if the patient
the blood and tissue concentrations of
moves to lower altitudes to live
dissolved gases change accordingly
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 has taken
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
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
Environmental medicine • 53
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.
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 40°C 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 occurs
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 2500 m, high-altitude illnesses may slow decompression that allows the gas load to
occur in previously healthy people, and above be excreted.
3500 m 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, leave a safe gap between a final dive and a
fatigue and headache. subsequent plane journey.
10
VR Tallentire,
MJ MacMahon, J Bain,
S Fadden
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 PaCO2, 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. 100% saturated
He has bilateral infiltrates on chest X-ray B. In capillaries with a high carbon dioxide
and a PaO2 of 10 kPa (75 mmHg) on an FiO2 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 PaO2 of shifted to the left
10 kPa (75 mmHg) on an FiO2 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 PaO2 of 10 kPa E. When core temperature drops, for a given
(75 mmHg) on an FiO2 of 0.5 blood content of carbon dioxide, the PaCO2
D. A woman with acute pancreatitis. She has will increase
bilateral chest infiltrates, pleural effusions, a
normal echocardiogram and a PaO2 of 10.13. A 45 year old man is admitted to the ICU
14 kPa (105 mmHg) on an FiO2 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. An ECG
a PaO2 of 10 kPa (75 mmHg) on an FiO2 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
Patient data Reference range
(malaise, fever, coryza). On admission, his ECG
Cardiac output 10.2 L/min 4–8 L/min
showed sinus rhythm with no acute ST
Cardiac index 5.42 L/min/m2 2.5–4 L/min/m2
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
10 mmol/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
Acute medicine and critical illness • 57
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
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 to
with left ventricular hypertrophy (by voltage unconsciousness and she was intubated to
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 up, 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 bleed
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)
58 • Acute medicine and critical illness
E. She should be cooled to 28°C to reduce 10.21. A 25 year old man presents to the
intracranial pressure emergency department with a 4-day history of
chest pain and mild shortness of breath. He
10.18. A 45 year old man arrives in the medical feels that the pain is worse on lying flat,
receiving unit complaining of headache, blurred coughing and deep breathing; it is relieved by
vision, nausea and vomiting. His blood pressure sitting forwards and has improved with
(BP) is 256/138 mmHg. A CT head scan is ibuprofen. He has no significant past medical
normal. Which of the following is true? history but was recently unwell with a
A. Chest pain in this context is likely to be non-specific viral infection. An ECG shows
anxiety related widespread saddle ST elevation.
B. In this context, nausea and vomiting is What is the most likely cause of the chest
unlikely to represent raised intracranial pain?
pressure A. Aortic dissection
C. Shortness of breath in this context may be B. Musculoskeletal chest pain
the result of pulmonary oedema C. Pericarditis
D. The blood pressure should be reduced D. Pulmonary embolism
rapidly, aiming for a 50% reduction in the E. Type 1 myocardial infarction (MI)
mean arterial pressure in the first hour
E. The use of cannabis is a recognised 10.22. A 39 year old man is brought in by
precipitant ambulance to the emergency department. He
has a 3-day history of sore throat and feeling
10.19. An 87 year old woman presents to generally unwell. He is struggling to speak and
hospital with her daughter who found her in the swallow saliva and has marked stridor. He is
morning confused, incoherent and wearing distressed and does not want to lie down.
yesterday’s clothes. Initial examination reveals Observations show: heart rate of 115 beats/
normal observations. Which of the following min, respiratory rate of 25 breaths/min, BP
history and examination findings most likely 120/74 mmHg, SpO2 94% on 15 L oxygen,
suggest an alternative diagnosis other than temperature 39.4°C, blood glucose of
delirium? 4.7 mmol/L (84.6 mg/dL), GCS score 15. The
A. A history of progressive deterioration over patient is normally fit and well.
several months Which potential diagnosis requires most
B. A urine dipstick positive for leucocytes and urgent recognition and management?
nitrites A. Croup
C. Fluctuant course, with more florid confusion B. Epiglottitis
at night C. Lower respiratory tract infection
D. Periods of severe agitation requiring D. Nasal polyps
pharmacological management E. Tonsillitis
E. The inability to direct attention and sustain
conversation 10.23. Which one of these features is
associated with delirium but not dementia?
10.20. A woman is brought in the emergency A. Anxiety
department by the ambulance after being found B. Cognitive impairment
unconscious at home. Her pupils are equal and C. Disorientation
reactive. She does not open her eyes to a painful D. Reversibility
stimulus. She is making groaning noises but no E. Visual hallucinations
comprehensible words. She has no motor
response to supra-orbital pressure but she does 10.24. An 88 year old woman is referred to the
withdraw her arms briskly to nail-bed pressure. acute medical admissions ward by her family
How would you score her GCS? physician, who was asked to review her at
A. 5/14 home by a concerned carer. The patient has a
B. 6/15 medical history of frequent falls and mild
C. 7/15 cognitive impairment, but has become
D. 8/15 increasingly confused since suffering a fall in
E. 11/15 her garden 5 weeks ago. At that time, the
Acute medicine and critical illness • 59
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, SpO2 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, H+ is 51 nmol/L (pH 7.29), PCO2 7.0 kPa
what is the most likely cause of her current (52.5 mmHg), PO2 3.1 kPa (23.3 mmHg),
symptoms? HCO3− 25.5 mmol/L, base excess −2.0 mmol/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 10
C. Pneumonia
10.25. A 24 year old woman with a body mass D. Primary spontaneous pneumothorax
index (BMI) of 38 kg/m2 presents to the E. Secondary spontaneous pneumothorax
emergency department with a swollen and
tender right calf (3.5 cm 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 SpO2 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
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 PCO2 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
SpO2 of 88% on 2 L/min oxygen, which fell to seizure?
60 • Acute medicine and critical illness
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. SpO2 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 60 beats/min, respiratory rate of 6 breaths/
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 SpO2 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
SpO2 99% on 4 L/min oxygen. His GCS score B. Bacterial meningitis
is 15 with normal limb movements. You have C. First presentation of epilepsy
taken an arterial blood gas, full blood count, D. Hypoglycaemia
urea and electrolytes and a coagulation screen E. Subarachnoid haemorrhage
and are awaiting the results.
What is the next most useful investigation to 10.36. An 84 year old man is brought to
elucidate the cause of this man’s deterioration? hospital after a fall. He was found by his
A. CT abdomen daughter and had been lying on the floor for
B. CT head the previous 24 hours. He has a variety of
C. ECG soft tissue injuries but no serious head or
D. Renal ultrasound orthopaedic injuries. On catheterisation, his
E. V̇ /Q̇ scan urine is dark brown. Which one of these tests is
most suggestive of rhabdomyolysis?
10.33. In the general medical setting, what is A. 1+ blood on urine dipstick
the earliest and most sensitive sign of clinical B. Creatine kinase
deterioration? C. Haemoglobin
A. Blood pressure D. Renal ultrasound
B. Core temperature E. Urea
C. Heart rate
D. Respiratory rate 10.37. A 20 year old man is brought in by
E. Urine output ambulance to the emergency department,
complaining of moderate central chest pain
10.34. In the context of cardiac physiology, and feeling lightheaded. These symptoms came
which of the following is stroke volume most on acutely whilst he was playing football.
dependent on? Observations show: heart rate of 180 beats/
Acute medicine and critical illness • 61
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. 10 µg adrenaline (epinephrine) IV C. Extension of the original infarction
C. 50 µg adrenaline intramuscularly (IM) D. Neurogenic pulmonary oedema
D. 0.5 mL 1 : 1000 adrenaline IM E. Pulmonary embolism
E. 5 mL 1 : 10 000 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 3× DC shocks
kidney disease stage 4. His regular medication before return of spontaneous circulation, and
includes aspirin 75 mg once daily, bisoprolol had a total ‘downtime’ of 32 minutes. She was
5 mg once daily and ramipril 5 mg once daily. intubated and ventilated on arrival in the
On admission his observations are as follows: emergency department. Her best GCS prior to
heart rate of 60 beats/min, BP 90/45 mmHg, that was E1, V1, M2. Which of the following
respiratory rate of 16 breaths/min, SpO2 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 µg/L
ECG demonstrates peaked T waves. Blood B. Burst suppression on EEG
results include haemoglobin 101 g/L, white cell C. CT head with poor grey–white matter
count 16 × 109/L, platelets 190 × 109/L, urea differentiation
20.2 mmol/L (121 mg/dL), creatinine D. Extensor motor response
367 µmol/L (4.15 mg/dL), sodium 134 mmol/L, E. Immediate bystander CPR
potassium 8.3 mmol/L. He receives two
boluses of calcium gluconate and two infusions
of insulin/dextrose to manage his potassium. 10.49. Using checklists for interventions in the
After this, a venous blood gas demonstrates H+ ICU is a key component of good patient care.
84 nmol/L (pH 7.08) and potassium Which of the following forms part of the ‘FAST
8.2 mmol/L. HUG’ checklist?
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). Four 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 100/75 mmHg, specific for compartment syndrome
respiratory rate of 28 breaths/min, SpO2 96% B. Absent peripheral pulses are an early sign
on 15 L/min oxygen. His jugular venous suggestive of developing compartment
pressure (JVP) is elevated. He is pale and syndrome
Acute medicine and critical illness • 63
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 lateralising
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 10
manage his ICP? condition is most likely responsible for this
A. Administer mannitol bolus woman’s difficulty in weaning from ventilation?
B. Administer neuromuscular blockade A. Brainstem stroke
C. Increase propofol and alfentanil infusion rates B. Critical illness myopathy
D. Refer to neurosurgery for decompressive C. Critical illness polyneuropathy
craniectomy D. Guillain–Barré 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, and the clinical opinion is that
He is haemodynamically stable with good gas of brain death. His family say that he previously
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 mmol/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 survival 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
64 • Acute medicine and critical illness
mild asthma (well controlled). His observations count 5.7 × 109/L, platelets 41 × 109/L, sodium
are: heart rate of 100 beats/min, respiratory rate 132 mmol/L, potassium 5.6 mmol/L, urea
of 16 breaths/min, BP 85/40 mmHg 16 mmol/L (96 mg/dL), creatinine 75 µmol/L
(70/35 mmHg on standing), SaO2 95% on 6 L (0.85 mg/dL), lactate 4.5 mmol/L (40.5 mg/dL).
oxygen, temperature 36.5°C, blood glucose Which of the following would be your
4.2 mmol/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 GI 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–Blakemore 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 mL/kg 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 the
intravenous fluid will be beneficial. Furosemide process. An advance directive provides useful
and dopamine may improve the urine output, information about the values of the patient.
but have no effect on the GFR in this context. Once a decision has been made to withdraw
Renal replacement therapy is not required at treatment, it is an ethical obligation to provide
this stage and will not improve the renal palliative care (sedatives and analgesia) and
outcome. A noradrenaline (norepinephrine) extubation is a reasonable course of action. 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.
10.2. Answer: B.
10.4. Answer: C.
This man has orthodeoxia (arterial saturations This man has life-threatening asthma with type
reduce on standing). In the context of chronic II respiratory failure. The PaO2 is high as the
liver disease and a normal chest examination, it patient is receiving a high inspired oxygen
is likely that hepato-pulmonary syndrome is the concentration, and the pathology is air trapping
cause. The pathology involves inappropriate and alveolar hypoventilation. Even with very
dilation of the pulmonary capillaries so blood small amounts of ventilation, the PaO2 can be
flows through the lungs without becoming maintained if there is normal gas transfer
oxygenated. This is an example of shunt. The across the alveoli, but the PaCO2 rises.
only treatment known to be effective is liver Intubation and ventilation is indicated as he has
transplantation. become unconscious. Initial ventilator settings
should prioritise adequate minute volume while
10.3. Answer: B.
allowing sufficient expiratory time. High tidal
This is a very difficult situation and the right volumes and respiratory rates will lead to air
course of action will depend upon the legal trapping and a very high intrathoracic pressure:
Acute medicine and critical illness • 65
this can cause cardiovascular collapse. Whilst infarction or bilateral cerebral infarcts are the
pneumothorax is a consideration, inserting most likely causes. A CT 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.
10.11. Answer: E.
cardiac output, but have little or no role in this
The history and investigations are all suggestive scenario.
of viral myocarditis. This can cause hyperacute
cardiogenic shock. In this case, the use of 10.14. Answer: B.
of blood carbon dioxide is carried as The clinical picture here may be due to
bicarbonate ions, but significant quantities are pulmonary oedema or secretion retention with
bound to haemoglobin (carbamino compounds) exhaustion and septic shock. It is unlikely that
and dissolved in the plasma. This is significant, DC cardioversion will correct the underlying
as desaturated haemoglobin has a higher pathology. Critical care is not contraindicated
affinity for carbon dioxide than fully saturated on the basis of age; frailty is a more important
haemoglobin; hence the PaCO2 will be lower predictor of outcome. Intubation and ventilation
for a given carbon dioxide content if the oxygen can be performed with low doses of hypnotic
saturations are low (the Haldane effect). This agents, and awake intubation would be
partially explains why patients with type II challenging in an agitated patient. Escalation of
respiratory failure become more acidotic when antibiotics is not required unless there are
high levels of oxygen are administered. When specific risk factors for resistant organisms.
temperature drops, carbon dioxide solubility Peripheral noradrenaline (norepinephrine) via a
increases, so for a given content of carbon well-sited cannula may provide enough stability
dioxide, the partial pressure will be lower at to facilitate intubation and ventilation
lower temperatures. High capillary carbon (Box 10.15).
dioxide shifts the haemoglobin–oxygen
dissociation curve to the right, improving i 10.15 Optimising safety during intubation
oxygen offloading at the tissues (Bohr
Intervene early in the disease process (once it has become
effect). clear that the disease trajectory is downward)
Use a stable anaesthetic technique: low doses of sedative
10.13. Answer: E.
agents and rapidly acting paralytic agents
Remember that intubation should be performed by the
The data shows a high cardiac output with low
most experienced operator available
pulmonary arterial, left atrial (wedge pressure) Use techniques to optimise oxygenation and ventilation in
and central venous pressures. This pattern the period around intubation, e.g. keeping non-invasive
suggests vasodilatation, which is common ventilation in situ for pre-oxygenation, leaving high-flow
nasal cannulae on for the intubation process, and using
following cardiopulmonary bypass. Cardiac
a video-laryngoscope in an anticipated difficult
tamponade typically causes a low cardiac intubation
output and increased intracardiac pressures.
Graft occlusion is likely to reduce the cardiac 10.16. Answer: B.
output, and the pulmonary artery wedge The most likely diagnosis accounting for these
pressure is likely to increase. Inotropes and symptoms is critical illness myopathy (CIM).
intra-aortic balloon pumps may increase the There are no features of a central nervous
Acute medicine and critical illness • 67
10.17. Answer: B.
10.18. Answer: C.
people with or without pre-existing The GCS is the composite score of the best
hypertension. Precipitants may include drugs eyes (out of 4), verbal score (out of 5) and
that produce a hyperadrenergic state, such as motor (out of 6). This woman will score 1 point
cocaine, amphetamines or monoamine oxidase for eyes, 2 points for verbal (incomprehensible
inhibitors. Nausea and vomiting may be a sign sounds) and 4 points for flexion/withdrawal,
of raised intracranial pressure, whilst dyspnoea totalling 7/15.
may indicate pulmonary oedema. Chest
discomfort may represent either myocardial 10.21. Answer: C.
not explained by another pre-existing or Epiglottitis is the diagnosis most likely to lead to
evolving neurocognitive disorder, and airway obstruction and death. It requires
identification of a plausible cause such as a prompt recognition and specialist airway
medical condition, substance intoxication or management. Traditionally considered a
68 • Acute medicine and critical illness
10.23. Answer: D.
10.26. Answer: B.
100
93
87
Haemoglobin saturation (SaO2) %
75
Normal
P75 = 5.3 kPa
= 40 mmHg
50
Normal
P50 = 3.5 kPa
= 26 mmHg
25
0
kPa 0 1 2 3 4 5 6 7 8 9 10 11 12 13 14
mmHg 0 25 50 75 100
PO2 (kPa or mmHg)
Fig. 10.26
Acute medicine and critical illness • 69
absence of pulmonary vascular markings This man most likely has concealed bleeding
peripherally and a rim of air between lung and from an abdominal injury, given his mechanism
chest wall may be visible. of injury. His observations suggest
hypovolaemia and a liver or splenic injury is
10.28. Answer: A.
likely. This man requires fluid resuscitation, a
Carbon monoxide is a colourless, odourless, surgical opinion and appropriate imaging of his
tasteless, poisonous gas produced by abdomen. A chest X-ray to rule out thoracic
incomplete burning of carbon-based fuels. pathology and free air under the diaphragm
Carboxyhaemoglobin is a stable complex that would also be reasonable but would be highly
forms between haemoglobin and carbon unlikely to provide a definitive diagnosis.
monoxide molecules. This hinders the ability of
oxygen to bind to haemoglobin molecules, 10.33. Answer: D.
which will preferentially bind to carbon A raised respiratory rate (tachypnoea) is the
monoxide, resulting in tissue hypoxia even earliest and most sensitive sign of clinical
though the SpO2 reading may be normal. The deterioration. Tachypnoea may be primary (i.e. 10
half-life of carboxyhaemoglobin can be reduced a problem within the respiratory system) or
by administration of 100% oxygen or with secondary to pathology elsewhere in the body.
hyperbaric chamber therapy. All other parameters may also be affected but
tend to occur later as end-organ damage
10.29. Answer: D.
occurs.
Focal neurological symptoms, other than those
associated with migraine, may be indicative of 10.34. Answer: A.
an intracranial mass lesion. Other headache Stroke volume is dependent on cardiac filling
‘red flags’ include: sudden onset, constitutional (preload) and contractility. Stroke volume is the
symptoms (such as rash), signs of raised volume of blood ejected from the left ventricle
intracranial pressure (headache worse on lying per beat. An increased preload (i.e. increased
down), new onset in a person aged > 60 years. venous return) and an increase in contractility
(as a result of increased sympathetic
10.30. Answer: D.
stimulation, adrenaline infusion, increased
Premonitory symptoms associated with serum calcium, or glucagon infusion) will
syncope include nausea and lightheadedness, together increase stroke volume. Conversely,
whereas a seizure may present initially with an increase in afterload (as a result of increased
signs of confusion or symptoms of aura. The peripheral vascular resistance) will decrease
unconscious period of a seizure is also more stroke volume as the heart has to work harder
obviously symptomatic, including motor seizure against higher resistance. Heart rate has some
activity, tongue-biting or urinary incontinence effect on stroke volume as the time for
(but these are not discriminatory), and is likely ventricular filling is decreased at fast rates,
to entail a more prolonged recovery (post-ictal) decreasing the stroke volume; however, it is
phase. not the main factor. Cardiac index is a measure
that relates cardiac output (stroke volume ×
10.31. Answer: A.
heart rate) to body surface area; the unit of
Abnormalities in respiratory rate, SpO2, measurement is L/min/m2. Haemoglobin and
temperature, blood pressure, heart rate, oxygen saturation do not directly affect stroke
neurological response and urine output form volume, except in very extreme situations (e.g.
core components in common early warning extreme anaemia or cellular hypoxia).
systems. Each abnormality may be allocated a
score from 0 to 3, with the composite score 10.35. Answer: E.
10.36. Answer: B.
criteria are met (Box 10.39). All measurements
A creatine kinase level of greater than 1000 U/L should be taken on a minimum of 5 cmH2O of
is highly suggestive, although it can rise to tens PEEP or continuous positive airway pressure
of thousands in severe cases. The other tests (CPAP):
would not help in the specific diagnosis. • Mild ARDS: 40–26.6 kPa (300–200 mmHg)
• Moderate ARDS: 26.6–13.3 kPa
10.37. Answer: E.
(200–100 mmHg)
This patient has adverse signs relating to his
• Severe ARDS: ≤ 13.3 kPa (≤ 100 mmHg)
tachyarrhythmia (chest pain and hypotension).
Therefore DC cardioversion, rather than medical
management, is appropriate as per Adult Life i 10.39 Berlin definition of ARDS
Support guidelines. Onset within 1 week of a known clinical insult, or new or
worsening respiratory symptoms
10.38. Answer: A.
Bilateral opacities on chest X-ray, not fully explained by
effusions, lobar/lung collapse or nodules
To be diagnosed with sepsis, the patient must Respiratory failure not fully explained by cardiac failure or
have suspected infection and two or more of: fluid overload. Objective assessment (e.g. by
• Hypotension – systolic blood pressure echocardiography) must exclude hydrostatic oedema if
no risk factor is present
< 100 mmHg
Impaired oxygenation
• Altered mental status – GCS score ≤ 14
• Tachypnoea – respiratory rate ≥ 22 breaths/
10.40. Answer: B.
min
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/FiO2 ratio. This is a number calculated by other options may all be used to manage
the PaO2 from an arterial blood gas divided by sepsis; however, they are not first line and
the fraction of inspired oxygen (FiO2, expressed should only be used with critical care
as a fraction). For example, a patient with a oversight.
PaO2 of 10 kPa (75 mmHg) on 50% oxygen,
i.e. FiO2 of 0.5, would have a Pa/FiO2 ratio of 10.43. Answer: E.
20 kPa (150 mmHg). This would be defined as Non-invasive ventilation is the first-line therapy
moderately severe ARDS, if the other Berlin in patients with type II respiratory failure usually
Acute medicine and critical illness • 71
because it reduces the work of breathing and Compartment syndrome classically occurs
offloads the diaphragm, allowing it to recover following extrinsic compression of a limb due to
strength. trauma or reduced conscious level (especially
when caused by drugs or alcohol). It usually
10.44. Answer: D.
presents with a tense, firm and exquisitely
Volutrauma is the result of distending forces painful limb. The pain is characteristically
from the tidal volume; barotrauma results from exacerbated by passive muscle stretching or
excessive pressures required to inflate the lung; squeezing the compartment and altered
atelectotrauma results from alveolar collapse sensation is common. Absent peripheral pulses
and re-opening throughout the respiratory are a late sign, and their presence does not
cycle; the release of inflammatory cytokines in exclude the diagnosis. Clinical suspicion of
response to cyclical distension is termed compartment syndrome should prompt CK
biotrauma. Pulmotrauma is not used in invasive measurement and urgent surgical review – this
ventilation nomenclature currently. cannot wait until the next day. D-dimer
measurement is not indicated in suspected 10
10.45. Answer: D.
compartment syndrome.
A dose of 0.5 mL 1 : 1000 adrenaline
(epinephrine) IM forms part of the current Adult 10.51. Answer: C.
Life Support guidelines for anaphylaxis. IV Initial strategies to manage raised ICP include
adrenaline may be given by an experienced ensuring adequate sedation, sitting the patient
operator in anaesthesia or critical care but is up to ensure adequate venous drainage from
not a first-line management technique. the head, and ventilating to low-normal
end-tidal CO2. If this fails, further strategies
10.46. Answer: B.
include instituting neuromuscular blockade, and
This patient has hyperkalaemia refractory to administering mannitol or hypertonic saline. A
medical management and therefore the next neurosurgical opinion may be appropriate if the
step is renal replacement therapy. In view of his above strategies are unsuccessful.
ECG changes, and potential for significant
deterioration, this should take place in a critical 10.52. Answer: A.
10.48. Answer: E.
An IABP is commonly inserted via the femoral
Early bystander CPR and early defibrillation are artery. Despite its effectiveness in achieving
the two interventions most likely to improve predetermined physiological goals, there is no
survival after cardiac arrest. All other answers convincing evidence for increased survival in
are markers suggestive of poor prognosis. cardiogenic shock. The balloon is inflated with
helium and, even when inserted correctly under
10.49. Answer: E.
radiological screening, mesenteric ischaemia
The FAST HUG checklist for daily ward rounds remains a risk. The balloon is inflated in
includes: feeding, analgesia, sedation, diastole, augmenting the forward flow of blood
thromboprophylaxis, head of bed elevation (to to the abdominal organs and improving
reduce the incidence of passive aspiration), diastolic pressure proximal to the balloon, thus
ulcer prophylaxis and glucose control. optimising coronary perfusion.
72 • Acute medicine and critical illness
10.54. Answer: C.
of IV morphine 2 hours previously raises the
Critical illness polyneuropathy is due to possibility that the coma is secondary to a
peripheral nerve axonal loss and presents as narcotic drug and, therefore, brain-death
proximal muscle weakness with preserved testing cannot be carried out reliably.
sensation. Nerve conduction study results are
as described for this patient. The clinical history 10.56. Answer: A.
is not in keeping with multiple sclerosis or Wound site infection, tracheal stenosis and
brainstem stroke and, by definition, muscle tracheomalacia are late complications of
biopsy must be abnormal in critical illness percutaneous tracheostomy. Performed
myopathy. correctly, laryngeal damage should not be a
complication of percutaneous tracheostomy.
10.55. Answer: A.
In those patients where percutaneous
Preconditions for testing for brain death tracheostomy is anticipated to be difficult, ear,
include: the patient is deeply comatose, is not nose, and throat (ENT) referral should be made
hypothermic, has no profound electrolyte or for consideration of surgical tracheostomy.
metabolic disturbance and that the patient
is maintained on a ventilator because 10.57. Answer: D.
spontaneous respiration is inadequate or has Whilst all of the options may be applicable to a
ceased. Whilst atracurium is a muscle relaxant patient with upper GI haemorrhage, the first
that would lead to cessation of respiration, it is priority must be resuscitation and maintenance
short acting and would not cause effects 72 of adequate haemoglobin and thus
hours later. The administration of a large dose oxygen-carrying capacity.
DH Dockrell, BJ Angus
11
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
74 • Infectious disease
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 (IgG) 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 IgG 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 note a
pale pink macular rash over the abdomen.
A. Anterior uveitis
Initial blood tests show an increase in
B. Diabetes mellitus
polymorphonuclear leucocytes and a markedly
C. Hypothyroidism
elevated ferritin. Routine cultures and
D. Immune thrombocytopenic purpura
autoantibodies are negative and an HIV test is
E. Ulcerative colitis
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
transaminases. 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
A. Aciclovir central venous catheter (CVC) tunnel site
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 CVC 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
Infectious disease • 75
11.19. A 7 year old child presents with a 11.22. A 40 year old man from Turkey presents
short history of fever, tender cervical with a history of chronic back pain and fever. On
lymphadenopathy and pus on the tonsils. He is examination an MRI scan shows sacroiliitis. He
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. Imipenem 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 48 cells/mm3
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 A. β-D-glucan assay in serum
(BP) 90/60 mmHg. Which of the following is the B. Cryptococcal antibody measurement in
most appropriate initial investigation to promptly serum
establish a diagnosis? C. Cryptococcal antigen test on cerebrospinal
A. CT scan leg fluid (CSF)
B. Doppler leg D. Cryptococcal PCR on CSF
C. Inspection of muscles in theatre by a E. Galactomannan enzyme-linked
surgeon immunosorbent assay (ELISA) on CSF
D. MRI leg
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. What is a potential therapeutic
A. Enterobius vermicularis option to manage her relapsing infection?
B. Fasciola hepatica A. Ciprofloxacin
C. Gnathostoma spinigerum B. Glucocorticoids
Infectious disease • 77
tip but no other abnormalities. The full blood and meningism. He recently returned back to
count identifies a relative lymphocytosis and his home 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 some
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 D. Schistosoma japonicum
cultures and from the lumen of her tunnelled E. Taenia solium
11
central venous catheter, with the line cultures
turning positive 4 hours before the peripheral
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
rainforest, 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 from 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
E. Ophthalmological review performed some additional tests, including
xenodiagnostics with a triatomine bug, which
11.38. A 47 year old man with acute
resulted in a diagnosis. She was advised she
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
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
80 • Infectious disease
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 home 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 hospital
pressure. Chest X-ray shows multiple nodules complaining of abdominal pain radiating to 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 two 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 echocardiogram
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 further 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
Infectious disease • 81
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
a clinical diagnosis of leishmaniasis. The
develops a brain abscess, which is drained,
11
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. Intralesional 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 no
On biopsy these are Warthin–Starry silver stain history of monkey bites but had been working
positive. What is the likeliest diagnosis? close to primates. He complains of fever,
A. Bacillary angiomatosis headache and diarrhoea. Examination reveals
B. Kaposi’s sarcoma hepatosplenomegaly and his full blood count
C. Malignant melanoma shows mild anaemia, a mildly elevated white
D. Sporotrichosis cell count and a platelet count of 76 × 109/L.
E. Stevens–Johnson syndrome Malaria rapid diagnostic test is negative. What
is the likeliest diagnosis?
11.52. A 47 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 18.6 × 109/L, platelets 110 × 109/L; bilirubin
throat and fever; 2 days after the onset, he 98 µmol/L (5.73 mg/dL), aspartate
develops left-sided chest pain and haemoptysis aminotransferase (AST) 21 U/L, creatinine
82 • Infectious disease
Answers
11.1. Answer: D.
11.5. Answer: E.
11.2. Answer: D.
11.6. Answer: D.
they may have delayed symptoms. This Zika virus may be transmitted in semen for
patient’s blood film showed typical trophozoites prolonged periods after recovery. Condom use
of Plasmodium vivax. The incubation period is advised for those infected for at least 6
here would exclude the other infections. months and for those who have returned from
an endemic area for at least 2 months if they
11.4. Answer: C.
do not develop signs of infection. Alcohol and
The history of rash after fever resolution and dietary interventions have not been found to
the age of the child make roseala infantum the alter Zika virus infection to date. Strenuous
likely exanthem in this case. This is caused by exercise is not contraindicated, although in the
human herpesvirus 6 or 7. Parvovirus B19 also early recovery period of any serious virus
causes an exanthem, but typically with infection it is prudent to discontinue it. Infection
alternative features like a ‘slapped cheek’ rash. is not spread by body contact, so avoiding
Rubella is not likely as the efficacy of live rubella sharing towels is not necessary.
vaccine is very high. Coxsackie and enterovirus
infections can cause rashes, although 11.8. Answer: A.
enterovirus 71 has been primarily associated Late complications of Ebola virus disease
with neurological syndromes. include uveitis, sensineural deafness and
86 • Infectious disease
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.
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 abnormalities in the liver
compromise, haemolytic anaemia or tests and urinalysis. 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 may be undertaken, but its yield is
Infectious disease • 87
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 Behçet’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. 11
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 CVC 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 CVC In chronic diarrhoea – usually defined as
sample versus the peripheral blood sample or diarrhoea lasting at least 2–4 weeks – when
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, inflammatory
are frequently positive with CVC line infections bowel disease and malignancy should always
and a short time to culture positivity would be be considered.
suggestive of endovascular infection but not
specifically CVC line infection. Although 11.15. Answer: C.
right-sided endocarditis may complicate CVC 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.
11.17. Answer: D.
may have been contaminated with the parasite,
The World Health Organization has issued such as watercress and also the khat plant,
criteria for the identification of dengue with which is commonly chewed by people who live
warning signs. These mandate intensive in regions around the Horn of Africa or Arabian
medical management and monitoring. The Peninsula.
development of ascites, suggested by shifting
dullness or other signs of fluid accumulation, 11.22. Answer: A.
are one of these warning signs. The other signs The history of living in an endemic area and of
listed here are not regarded as warning signs. consuming unpasteurised milk makes
brucellosis a potential cause; it is an agent
11.18. Answer: E.
whose diagnosis involves confirmation by a
Parvovirus B19 is associated with transient serological test such as a serum agglutination
aplastic crisis in patients with test. The regime in option A would be
haemoglobinopathy or haemolytic anaemia. appropriate for this infection; the regimens in
Dengue and CMV cause anaemia but typically options B, C and D might be considered for
not aplastic crisis, while HTLV-1 tends to cause bone infection due to Staphylococcus aureus,
acute T-cell leukaemia/lymphoma. Candida spp. or in melioidosis, respectively;
streptomycin is usually used in infections like
11.19. Answer: E.
plague and tularaemia where bone infection is
Streptococcal infections are usually sensitive to less likely.
penicillin, which is the treatment of choice in
pharyngitis. Although clindamycin and 11.23. Answer: C.
erythromycin are alternatives and may be used The individual has a low CD4 T-cell count and is
in penicillin allergy, some strains show at risk of meningitis caused by an opportunistic
resistance. A work-up for immunodeficiency is infection. Cryptococcal meningitis is a leading
not indicated since there have been no prior consideration and should be excluded. The test
features of infection; however, since several of choice is a cryptococcal antigen test on the
family members appear to have developed CSF, which is highly sensitive and specific. PCR
pharyngitis, it would be appropriate to screen is not routinely performed and detection of
all family members at the same time, since blood antibody against cryptococci is not used
streptococci can be nasopharyngeal in the diagnosis of cryptococcal meningitis.
commensals and can be passed from one β-D-glucan and galactomannan assays are used
family member to another. Aspirin may be used in the diagnosis of Aspergillus spp. and in the
for rheumatic fever but there is no indication case of β-D-glucan some other fungi. Although
there are signs of rheumatic fever. cryptococcal infection can be detected at low
levels with the β-D-glucan, this test is not
11.20. Answer: C.
routinely used to diagnose cryptococcal
The scenario is suggestive of necrotising infection.
fasciitis, which is a medical emergency. In this
case there are signs suggestive of shock, and 11.24. Answer: C.
11.25. Answer: D.
addition to β-lactam antibiotics, clindamycin is
An incomplete vaccination history or waning usually added to decrease toxin production.
immunity can put young adults at risk of There is a low likelihood of CA-MRSA, so this
mumps, which can cause an aseptic or probably does not need to be added initially,
lymphocytic meningitis. Although multiple other but the decision on this would be governed by
viruses can cause aseptic meningitis, mumps is the risk of MRSA. The other antimicrobials
a potential consideration, especially when would be added in other settings, although
common causes such as enteroviruses, doxycycline is an alternative agent that may
HSV, HIV and geographically restricted also decrease protein synthesis.
mosquito-mediated viral infections are not
present and when there is no history of TB 11.29. Answer: A.
exposure, chronic medication use or medical The epidemiological setting and the appearance
comorbidity. of a severe illness with a groin swelling
suggestive of a bubo make plague a likely
11.26. Answer: B.
diagnosis. The causative agent Yersinia pestis
When vaccination has not been performed or gives the appearance of safety pins or bipolar
may have been unsuccessful due to drift in the staining with Gram stain. Staph. aureus
circulating strain from the vaccine strain, appears as a cluster on Gram stain and would 11
prophylaxis is indicated for high-risk patients be in the differential of any abscess. Other
such as heart and lung transplant recipients. characteristic appearances on Gram staining
Prophylaxis uses the neuraminidase inhibitors include Corynebacterium diphtheriae, which
oseltamivir or zanamivir rather than the M2 appear as rods at acute angles suggestive of
proton channel inhibitors amantadine and Chinese letters. A drumstick appearance due to
rimantidine, which were used in the past. the presence of a terminal spore is seen with
Ribavirin and tenofovir are not used in the Clostridium tetani. Candida albicans can appear
prophylaxis of influenza. as a filamentous form suggestive of a mould,
but this, in fact, is a pseudomycelium formed
11.27. Answer: E.
by the yeast.
The yellow fever vaccine is a live vaccine that
can cause viscerotropic disease in those with 11.30. Answer: B.
immunosuppression. The decision to give the A high bacterial index is associated with
vaccine is based on assessing the relative lepromatous leprosy. The presence of
balance of risks and benefits. In this case, widespread lesions and a ‘glove and stocking’
although both HIV and organ transplantation distribution sensory disturbance both suggest
are associated with immunosuppression, the lepromatous leprosy. The other findings of
relative risk is much greater in the scenario with clearly demarcated hypopigmented lesions with
liver transplantation only 18 months previously, early loss of sensation and sweating are all
due to its associated more significant degree of more in keeping with tuberculoid leprosy, where
immunosuppression due to tacrolimus (a a lower bacterial index would be expected.
calcineurin inhibitor) and mycophenolate. In
contrast, controlled HIV with a normal CD4 11.31. Answer: A.
count is not an absolute contraindication and The likely diagnosis is typhoid fever.
the vaccine may be considered if it is essential. Antimicrobial resistance is increasing, meaning
The other conditions are not associated with many agents formerly used are no longer active
significantly increased risk of side-effects from such as chloramphenicol, amoxicillin and
this vaccine, although they may influence other co-trimoxazole. Ciprofloxacin resistance has
medical considerations. For example also emerged as major problem, particularly in
mefloquine malaria prophylaxis would not be Asia, so ceftriaxone is the most reasonable
used with a seizure history and the initial choice.
antimicrobial linezolid should be avoided for
those on an SSRI. 11.32. Answer: D.
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 IgE 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.
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
Angiostrongylus 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.
11
used to treat other parasites. Radical cure of vivax malaria requires the use of
the 8-aminoquinoline drug primaquine. This
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.
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 Ivermectin 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.
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
92 • Infectious disease
often associated with a central venous catheter lesions on the palate usually indicates that
infection or endocarditis, certain organisms are there is deep-organ involvement, such as gut
associated with other foci and require specific and lung, which may lead to life-threatening
investigations, as in this case. bleeding. Treatment is with doxorubicin and
immune reconstitution.
11.48. Answer: E.
which detects the Bartonella species. Similarly, Haemolytic uraemic syndrome is usually
the histology does not show features of associated with infection with E. coli O157.
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 enterocolitica 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
immunocompromised hosts. The finding of after an incubation period of 3–7 days. It
Infectious disease • 93
give this clinical picture. Wound botulism results from the contamination
of a wound with the bacterial species
11.58. Answer: E.
Clostridium botulinum, which then secretes
Hantavirus is a ribonucleic acid (RNA) virus botulinum toxin into the bloodstream. It has
associated with pulmonary and renal failure become increasingly common in people who
mimicking pulmonary syndrome in leptospirosis, take drugs intradermally or subcutaneously
and is associated with a history of contact with (skin popping). Botulism is typically described
mice within a wide geographical area. Some as a ‘triad of bulbar palsy and descending
strains of hantaviruses cause the potentially paralysis, lack of fever, and clear senses’.
fatal diseases – hantavirus haemorrhagic fever Staphylococcal brain abscesses and tetanus
with renal syndrome and hantavirus pulmonary are also associated with drug injection but the
syndrome – while others have not been patient’s neurological symptoms with prominent
associated with known human disease. bulbar signs and ocular involvement make
Treatment is supportive. The other syndromes these less likely. Staphylococcal brain abscess
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 11
particularly associated with drug use.
11.59. Answer: D.
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 infection. 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 with
11.61. Answer: C.
an eschar and is more associated with dusky
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 problems but are less
thrombophlebitis, typically of the internal jugular consistent from the relatively 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 infection 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.
94 • Infectious disease
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 pallidum pertenue. Treponemal
serology cross-reacts and so is unreliable.
11.66. Answer: D.
Pinta is found mainly in South America and
Scombroid fish can produce histamines, which bejel is mainly in the Middle East and West
increase when bacteria metabolise histidine. Africa.
This rapidly causes symptoms. Uncooked tuna
steaks are a common cause. Ciguatera 11.71. 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 the
T-cell lymphoproliferation. It may be wild and treatment is with aminoglycosides or
smouldering or aggressive but should be ciprofloxacin or doxycycline. The other options
suspected in patients with T-cell are not associated with wild rodent contact
lymphoproliferation, particularly when from an leading to skin ulceration.
area where the virus is found. It is also
associated with hypercalcaemia. The other 11.73. Answer C.
viruses are not specifically associated with Enterococcal infection may occur in the urinary
T-cell lymphoproliferative disorders, although tract and in the biliary tract, which is particularly
HIV should always be excluded in the presence relevant in someone with a history suggestive
of lymphoproliferation. HIV-2, however, is not of gallstone disease. Thus imaging these sites
associated with the Caribbean and is mainly would be reasonable as part of the
found in West Africa. investigation. However, the presence of multiple
positive blood cultures and the rapid time to
11.69. Answer: C.
positivity suggests an endovascular focus;
There are a variety of influenza strains echocardiography is essential in this case and
associated with avian influenza but of those the test most likely to establish the source as
listed only H5N1 is an avian strain and has infective endocarditis. This man has a prior
caused outbreaks in the region around Hong history of a regurgitant murmur, which may or
Kong, while H7N9 has been implicated in cases may not be related to the current presentation
around Shanghai. H1N1 is a human strain and but this also increases his risk of having
the other viruses are not influenza A viruses. enterococcal endocarditis.
11.70. Answer: E.
11.74. Answer: A.
Non-venereal treponemal infections are Co-trimoxazole plus imipenem would work well
endemic in many tropical countries. Yaws for the treatment of Nocardia infection, but
Infectious disease • 95
11.76. Answer: D.
Herpes B is an endemic DNA virus of macaque
No antimicrobial indicated; there is monkeys, which can rarely cause encephalitis
some evidence that antibiotics may prolong in humans exposed through bites. Treatment
illness with E. coli O157. Treatment is with aciclovir is recommended as soon as
supportive. possible and may be life-saving.
G Maartens
12
HIV infection and AIDS
Multiple Choice Questions
12.1. What is human immunodeficiency virus A. HIV antibodies detected by enzyme-linked
(HIV) protease enzyme responsible for? immunosorbent assay
A. Budding of HIV from the cell B. HIV antibodies detected by western blot
B. Cleavage of post-translational regulatory C. p24 antigen detection
proteins D. Polymerase chain reaction (PCR) to detect
C. Fusion of HIV with the host cell surface HIV RNA
D. Integration of viral deoxyribonucleic acid E. Rapid point-of-care antibody test
(DNA) into the host genome
E. Reverse transcription of viral ribonucleic acid 12.5. A 35 year old HIV-positive man presents
(RNA) to DNA with diarrhoea of 4 weeks’ duration
accompanied by tenesmus. Blood and mucus
12.2. What is the risk of acquiring HIV during a is present in the stool. He is not on antiretroviral
single act of unprotected vaginal sexual therapy. His CD4 count is 17 cells/mm3. Which
intercourse when the male partner is HIV of the following is the most likely diagnosis?
infected and not on antiretroviral therapy, and A. Cryptosporidiosis
the female partner is HIV uninfected? B. Cystoisosporiasis
A. 0.001% C. Cytomegalovirus (CMV) colitis
B. 0.01% D. Giardiasis
C. 0.1% E. Microsporidiosis
D. 1%
E. 10% 12.6. Which one of the following non-acquired
immunodeficiency syndrome (non-AIDS)
12.3. Which of the following is a correct cancers has been shown to have an increased
statement regarding the features of primary HIV incidence in HIV-infected patients?
infection? A. Anal cancer
A. A maculopapular rash is a common B. Breast cancer
feature C. Melanoma
B. Atypical lymphocytosis occurs more D. Ovarian cancer
frequently than in Epstein–Barr virus (EBV) E. Prostate cancer
infection
C. Primary infection is asymptomatic in most 12.7. A 45 year old man with a CD4 count
people of 23 cells/mm3 presents with gradually
D. The incubation period is 5–7 days progressive spastic paraplegia and urinary
E. Transient CD4 lymphocytosis is usual incontinence. There is impaired short-term
memory. Plain X-ray of the spine is normal.
12.4. What is the most sensitive blood test for What is the most likely cause of the
diagnosing HIV during primary infection? paraplegia?
HIV infection and AIDS • 97
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
24 cells/mm3 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. krusei)
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 234 cells/mm3.
antiretroviral drugs raltegravir, dolutegravir and The largest node is 4 × 3 cm 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. Integrase 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 73 cells/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 human
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
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 0.2 log10) 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/mm3) C. Vaccination transiently decreases the viral
D. It usually presents within the first 3 months load
of initiating ART D. Viral load measures 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 34 cells/mm3 presents with headache and vomiting of 3 weeks’ duration.
dysphagia. There is no oral candidiasis. You His CD4 count is 62 cells/mm3. Computed
HIV infection and AIDS • 99
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 34 cmH2O. 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 mL/min 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 cmH2O failure
Answers 12
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),
Maturation
Attachment
to CD4 receptor
Binding
to co-receptor
CCR5 or CXCR4
Fusion
inhibitors
Viral
release
Fusion
Chemokine co-receptor
(CCR5 or CXCR4) Translation
Chemokine Cleavage
Reverse Reverse Viral of polypeptides
transcription receptor proteins
transcriptase antagonist and assembly
of viral RNA inhibitors
genome
Protease
Double-stranded inhibitors
Genomic DNA
RNA Viral mRNA
Reverse
transcription Integration
Integrase
inhibitors Cell nucleus
Fig. 12.1 Life cycle of HIV. Arrows indicate sites of action of antiretroviral drugs.
100 • HIV infection and AIDS
1200 107
CD4+ T lymphocyte count (cells/mm3)
1100
cervical ectopy, uncircumcised male partner papilloma virus infection; the other cancers
and menstruation. listed are not caused by viruses.
12.3. Answer: A.
12.7. Answer: E.
Primary HIV is a glandular fever-type illness with This is a typical presentation of this HIV
an incubation period of 2–4 weeks. It differs disorder, which is usually accompanied by
from EBV infection with less prominent atypical features of AIDS dementia. Tuberculosis would
lymphocytosis and a rash is common (with EBV, usually cause abnormalities on spine X-rays.
rashes usually only occur when aminopenicillins CMV polyradiculopathy causes lower motor
are given). Typically CD4 lymphocytes are neuron signs and pain. Myelopathy from
transiently decreased (Fig. 12.3). HTLV-1 and multiple sclerosis are not HIV
associated and do not cause memory loss.
12.4. Answer: D.
sensitive, followed by p24 antigenaemia. This is the commonest infectious cause of red
Antibodies typically are detectable 2–6 weeks cell aplasia in HIV infection. The antiretroviral
later. drug lamivudine is another rare cause. CMV
and some other viruses may occasionally
12.5. Answer: C.
cause pancytopenia, but not pure red cell
The other diseases all present with small-bowel aplasia.
diarrhoea. The presence of blood and mucus in
the stool together with tenesmus is typical of 12.9. Answer: E.
large-bowel diarrhoea. CMV involvement of the This is a World Health Organization (WHO)
gastrointestinal tract typically causes ulceration stage 3/Centers for Disease Control and
and occurs mainly in the oesophagus and Prevention (CDC) B manifestation. The others
colon, but any part of the gastrointestinal tract are all WHO stage 2, which is not an indication
can be involved. to start co-trimoxazole. Note that in low-income
countries co-trimoxazole is given to all,
12.6. Answer: A.
irrespective of CD4 count or clinical stage, as it
HIV increases the incidence of virus-related is of benefit in high infectious diseases burden
cancers. Anal cancer is linked to human settings (including areas with malaria risk).
HIV infection and AIDS • 101
12.10. Answer: D.
i
12.15 Commonly used antiretroviral drugs
Pneumococcal pneumonia incidence is
Classes Drugs
markedly increased in HIV. Atypical bacteria
Nucleoside reverse Abacavir, emtricitabine,
can present in this way, but are less common
transcriptase inhibitors lamivudine, tenofovir,
causes. Pseudomonas pneumonia is rare. (NRTIs) zidovudine*
Tuberculosis can present acutely, but is usually Non-nucleoside reverse Efavirenz*, rilpivirine
a more subacute illness and the chest transcriptase inhibitors (only if viral load
radiograph is seldom that of dense lobar (NNRTIs) <100 000)
consolidation with no other features. Protease inhibitors (PIs) Atazanavir, darunavir,
lopinavir*
Integrase inhibitors Raltegravir, dolutegravir,
12.11. Answer: C.
elvitegravir
The duration of symptoms is too long for
Chemokine receptor inhibitor Maraviroc
bacterial pneumonia. The prominent dyspnoea
*These drugs are no longer recommended as first-line
and chest radiograph appearance is typical of options in high-income countries due to their toxicity.
Pneumocystis jirovecii pneumonia. Lymphoid
interstitial pneumonitis can have a similar
radiographic appearance but is a more chronic
illness and fever is uncommon. Pulmonary
tuberculosis with adult respiratory distress
syndrome is possible, but this is a rare
12
complication in tuberculosis.
12.12. Answer: C.
12.13. Answer: C.
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.
inhibitor (Box 12.15). Dual NRTI combinations IRIS is an exaggerated inflammatory 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 usual 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.
102 • HIV infection and AIDS
12.18. Answer: D.
12.21. Answer: B.
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 problem is
macular and may be difficult to diagnose. As not cerebral oedema.
the disease progresses, the skin lesions
become more numerous and larger. 12.23. Answer: A.
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 IgG EIA Negative
E. Oxytetracycline
RPR Negative
TPPA Positive – titre 160
13.7. Which of the following statements is true
Antitreponemal IgM 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 (IDU). 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
Test Result negative
Antitreponemal immunoglobulin G Positive – optical B. He can safely have sex with his wife if
(IgG) enzyme immunoassay (EIA) density 20.3 given treatment with a single dose of
Rapid plasma reagin (RPR) Positive – titre 4 azithromycin 1 g
Treponema pallidum particle Positive – titre C. He is at significant risk of acquiring hepatitis
agglutination assay (TPPA) > 5120 C (HCV)
Antitreponemal immunoglobulin M Negative D. He should be offered post-exposure
(IgM) 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 IgG EIA Positive – optical density 33
13.9. A 19 year old woman complains of RPR Negative
moderate lower abdominal pain that has been TPPA Positive – titre > 5120
present for 2 weeks, and is particularly Antitreponemal IgM EIA Positive – optical density 11.4
noticeable during sex. Which of the following
actively supports a diagnosis of chlamydial Which of the following is the most likely
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
Sexually transmitted infections • 105
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
C. 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
C. 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 1 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 13
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.
starting dose of famciclovir is 250 mg twice daily. Erythromycin and oxytetracycline were used
before the advent of azithromycin and
13.3. Answer: D.
doxycycline, respectively. Ofloxacin is a
Lymphogranuloma venereum is the likeliest quinolone with antichlamydial 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 was 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.
106 • Sexually transmitted infections
13.7. Answer: E.
13.11. Answer: E.
The percentage of infected patients who A rapid course of vaccination against hepatitis
develop visible warts is unknown, but is B – with inoculations today, and in 1 and 3
definitely a small minority. Although homosexual weeks’ time – would give good protection
men (MSM) are relatively more likely to get against this infection that is more common in
perianal warts, the majority of cases present in IDUs. PEP for HIV is only effective if given up to
heterosexual men. The mode of inoculation is 72 hours following risk. Female to male sexual
unclear. Liquid nitrogen destroys infected tissue transmission of HCV is extremely rare. One
but does not clear HPV infection. HPV types week after exposure is too soon to rely upon
6/11 are not associated with genital cancer negative tests for any STI. Negative tests for
– HPV types 16/18 are the most common Chlamydia and gonorrhoea become reliable at
oncogenic types. Cervarix vaccine only protects 2 weeks, negative fourth-generation HIV tests
against HPV types 16/18; Gardasil also become reliable at 4 weeks, and negative tests
protects against types 6/11. for HBV and HCV are reliable at 3 months.
Azithromycin is only reliably curative for
13.8. Answer: B.
chlamydial infection, less so for syphilis and
A diagnosis of primary or secondary syphilis is gonorrhoea, and would have no effect upon
based on typical clinical findings so cannot be viruses such as HIV or HBV.
applied to a symptomless individual. The
negative IgM makes early latent syphilis unlikely, 13.12. Answer: A.
and the RPR titre in untreated early or late Three of the four tests are positive, so this is
latent syphilis would be expected to be much not a false-positive scenario. The negative RPR
higher – at the very least 32. The titre here of 4 is almost certainly false and represents a
is more likely to represent accidental treatment prozone phenomenon where the very high
– in this case, antibiotics for a dental infection. antibody titre prevents formation of the
It would still be prudent to offer definitive antibody–antigen lattice necessary to observe
treatment, e.g. with a course of three injections flocculation in the test. Diluting the serum will
of benzathine penicillin at weekly intervals. allow this to be observed. The strongly positive
IgM test makes late infection extremely unlikely.
13.9. Answer: E.
possible ectopic pregnancy. Both HSV-1 and HSV-2 have a greater risk of
causing disseminated disease in pregnancy, so
13.10. Answer: C.
it is important that she is counselled effectively
The positive IgM is suggestive of early infection. to prevent acquisition. Symptomless shedding
False-positive IgM tests are possible, but a of virus can continue in the absence of clinical
second positive test, in this case the TPPA, episodes, so there is a risk of transmission in
makes that unlikely. The low TPPA titre is this scenario. Valaciclovir has been shown to
compatible with very early infection. Although reduce HSV transmission in sero-discordant
the chancre of primary syphilis is usually couples, is probably safe to take in pregnancy,
painless, this is not necessarily so for an anal but would be a suboptimal strategy. Caesarean
chancre, so primary infection is most likely. The section would only be considered if she
RPR would be strongly positive in secondary or developed primary infection around the time of
early latent syphilis. In treated infection, the IgG delivery. Avoidance of sex or consistent
EIA would remain positive, but the IgM would condom use represents the safest strategy in
become negative. this case.
A Mather, D Burnett,
DR Sullivan
14
Clinical biochemistry and
metabolic medicine
Multiple Choice Questions
14.1. What is a particular advantage of programmes. What is the most common form
obtaining a test analysis and result using a of inheritance of these LSDs?
point-of-care test (POCT) system rather than A. Autosomal dominant
using a traditional central laboratory? B. Autosomal recessive
A. POCT analysers often have a wider menu of C. Multifactorial
available tests than central laboratories D. X-linked dominant
B. POCTs avoid the need to use the laboratory E. X-linked recessive
or the medical records
C. POCTs provide test results at the time of 14.4. In the investigation of glycogen storage
seeing the patient diseases (glycogenoses), which of the following
D. POCTs are generally cheaper than traditional is a commonly used non-invasive test or finding
testing that may be useful in diagnosing this condition?
E. POCTs use newer technology and are A. Cataract in the lens of the eye
generally more accurate and precise B. ‘Cherry-red spot’ in the fundus of the eye
C. Dislocated lens (ectopia lentis) in the eye
14.2. Which of the following is an autosomal D. Exercise-induced fatigue or pain in muscles
recessive inherited disorder, often diagnosed E. Hypopigmentation of the skin
through newborn screening programmes
and treated with dietary modification, which 14.5. A 59 year old man presents for
can present with wide-ranging clinical cardiovascular risk assessment, but he has not
manifestations, including vascular disorders, fasted for the blood collection that was to be
skin hypopigmentation, ectopia lentis, and performed during his appointment. Which of
disorders of the central nervous or skeletal the following plasma lipid or lipoprotein levels is
systems? most likely to be affected by his recent
A. Cystathionuria consumption of food?
B. Cystinosis A. Calculated low-density lipoprotein (LDL)
C. Cystinuria cholesterol
D. Homocystinosis B. High-density lipoprotein (HDL) cholesterol
E. Homocystinuria C. Lipoprotein (a)
D. Non-HDL cholesterol
14.3. There have been many different lysosomal E. Total cholesterol
storage diseases (LSDs) discovered, and some
of these have been included in successful 14.6. The same 59 year old man returns with
population-wide community genetic screening a set of fasting results that include: total
108 • Clinical biochemistry and metabolic medicine
cholesterol 6.7 mmol/L (259 mg/dL), fasting blood. When she receives the results she is
triglyceride 3.3 mmol/L (292 mg/dL), HDL worried that the test is inaccurate due to
cholesterol 0.9 mmol/L (35 mg/dL), calculated haemolysis of the cells whilst performing
LDL cholesterol 4.3 mmol/L (166 mg/dL), venepuncture. What is the dominant
non-HDL cholesterol 5.8 mmol/L (224 mg/dL) intracellular cation that may be inaccurately
and fasting serum glucose 6.9 mmol/L (124 mg/ reported in this situation?
dL). What is the best indicator of the metabolic A. Bicarbonate
component of his cardiovascular risk? B. Calcium
A. Calculated LDL cholesterol C. Magnesium
B. Fasting plasma glucose D. Potassium
C. HDL cholesterol E. Sodium
D. Non-HDL cholesterol
E. Total cholesterol 14.10. One litre of normal saline is given to a
patient in the emergency department. How is
14.7. The same 59 year old man fails to this fluid likely to be distributed between the
improve his lipid profile following diet and fluid compartments?
exercise advice, and pharmacological treatment A. Intracellular fluid 0 mL, extracellular fluid
is deemed necessary. Which of the following 1000 mL, plasma volume 1000 mL
medications may have a detrimental effect on B. Intracellular fluid 0 mL, extracellular fluid
the triglyceride component of his lipid profile? 1000 mL, plasma volume 200 mL
A. An anti-PCSK9 monoclonal antibody C. Intracellular fluid 1000 mL, extracellular fluid
B. Cholestyramine 0 mL, plasma volume 0 mL
C. Ezetimibe D. Intracellular fluid 500 mL, extracellular fluid
D. Niacin 500 mL, plasma volume 500 mL
E. Rosuvastatin E. Intracellular fluid 666 mL, extracellular fluid
334 mL, plasma volume 68 mL
14.8. The same 59 year old man commences
atorvastatin 20 mg every evening. His follow-up 14.11. In comparison to the ultrafiltrate found in
lipid profile and glucose reveals: total Bowman’s capsule, which of these terms best
cholesterol 3.7 mmol/L (143 mg/dL), fasting describes the filtrate that leaves the proximal
triglyceride 1.1 mmol/L (97 mg/dL), HDL tubule?
cholesterol 1.1 mmol/L (42 mg/dL), calculated A. Hyperosmolar
LDL cholesterol 2.1 mmol/L (81 mg/dL), B. Hypertonic
non-HDL cholesterol 2.6 mmol/L (100 mg/dL) C. Hypo-osmolar
and fasting serum glucose 8.9 mmol/L (160 mg/ D. Hypotonic
dL). A subsequent glucose tolerance test is E. Isotonic
diagnostic of new-onset type 2 diabetes. What
best describes the relationship between the 14.12. Amino acids are almost entirely
onset of diabetes and the use of statins? reabsorbed from the glomerular filtrate via
A. Diabetes development is more likely in those active transport in which section of the
with pre-existing impaired fasting glucose nephron?
B. The development of diabetes is inconsistent A. Collecting duct
with the fact that fasting triglyceride has B. Early distal tubule
improved C. Late distal tubule
C. The development of diabetes is unrelated to D. Loop of Henle
the dose or potency of the statin E. Proximal tubule
D. The development of diabetes means that
statins are now contraindicated in that 14.13. A 35 year old man has been hiking in hot
individual weather. He collapses and is brought into the
E. The onset of diabetes and the use of statins emergency department. He is found to have a
are completely unrelated blood pressure of 95/62 mmHg with a postural
drop of 15 mmHg. His pulse rate is 112 beats/
14.9. A 57 year old man is having a blood test min, his jugular venous pressure is not visible
and the resident doctor finds it difficult to take and he has a dry tongue. Which statement
Clinical biochemistry and metabolic medicine • 109
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: H+ 57.5 nmol/L (pH
uncontrolled secretion of a hormone that is 7.24); PaO2 11.1 kPa (83 mmHg); PaCO2 4.3 kPa
responsible for his hypertension. (32 mmHg); bicarbonate 15 mmol/L. Serum
Which of the following would you expect to biochemistry: sodium 134 mmol/L; potassium
decrease in this scenario? 2.4 mmol/L; chloride 109 mmol/L. Urine pH 5.2;
A. Extracellular fluid volume following administration of intravenous sodium
B. Plasma concentration of bicarbonate bicarbonate, urine pH is 5.8.
C. Plasma concentration of potassium What is the likely underlying cause of these
D. Thyroid-stimulating hormone abnormalities?
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 mmol/L, potassium 3.1 mmol/L,
bicarbonate 35 mmol/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, haematuria
12 mmol/24 hrs (N < 7.5). and mild peripheral oedema. Blood tests taken
What is the most likely diagnosis? in the emergency department show that his
serum creatinine is 620 µmol/L (7.01 mg/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
D. Primary hyperaldosteronism A. Metabolic acidosis with no respiratory
E. Type 1 renal tubular acidosis (RTA) compensation
B. Metabolic acidosis with respiratory
14.22. Metabolic acidosis is seen in conjunction compensation
with which cause of hypokalaemia? C. Metabolic alkalosis with respiratory
compensation
A. Diarrhoea
D. Respiratory acidosis with metabolic
B. Gitelman’s syndrome
compensation
C. Loop diuretics
E. Respiratory alkalosis with metabolic
D. Primary hyperaldosteronism
compensation
E. Vomiting
14.27. A 42-year-old homeless man is brought
14.23. Hypokalaemia may be seen in into the emergency department. He is known
association with normal blood pressure in to have a history of alcohol abuse and presents
which of the following conditions? on this occasion with delirium, shortness of
A. Bartter’s syndrome breath and blurred vision. Initial investigations
B. Cushing’s syndrome show the following. Arterial blood gases (ABG):
C. Gordon’s syndrome H+ 58.9 nmol/L (pH 7.23); PaCO2 3.6 kPa
D. Liddle’s syndrome (27 mmHg); bicarbonate 12 mmol/L. Blood
E. Primary hyperaldosteronism results: sodium 130 mmol/L; potassium
Clinical biochemistry and metabolic medicine • 111
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. 14
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 syndrome, in which there is abnormal renal
requirement for portability or miniaturisation tubular function. Cystathionuria (also called
may involve design or engineering compromises cystathionase deficiency) is also an autosomal
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
environment or group of tests, and so their considered to be a benign biochemical
menu is usually more restrictive than standard anomaly.
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.
β-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 ischaemic 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 available, in the fundus is typically associated 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. Hypopigmentation, 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,
homocystinuria (see option E). Cystinuria is an but the glycogenoses are not typically part of
aminoaciduria, inherited in an autosomal this group.
112 • Clinical biochemistry and metabolic medicine
14.5. Answer: A.
body water, as in option E. Fluids that are rich
Calculated LDL cholesterol is correct because in proteins (such as concentrated albumin) will
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.
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.
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 rate in
14.8. Answer: A.
part by vasoconstriction of renal afferent
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.
potency of the statin, but the CVD benefit of Loop diuretics inhibit the Na,K,2Cl 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-transporter does transport
Total body water is about one-third extracellular potassium as in option 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 limb 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 water
proportion to the normal distribution of total permeability.
Clinical biochemistry and metabolic medicine • 113
14.15. Answer: A.
14.19. Answer: A.
In order to maximally dilute urine, there needs Acute diarrhoea would result in extrarenal
to be normal function of both the loop of Henle sodium and water loss and the normal renal
and the early distal tubule. Thiazide diuretics response of sodium conservation. In the other
inhibit the normal function of the early distal scenarios urine sodium would be high or
tubule by blocking the sodium–chloride normal due to effects of limited sodium
co-transporter. An inability to maximally dilute reabsorption in the nephron secondary to
urine can also result from options D and E but vasopressin, or lack of cortisol/thyroxine
this is not the mechanism of thiazide diuretics. response.
Absence of vasopressin is required for maximal
dilution of the urine. 14.20. Answer: C.
level of the collecting duct (rather than excess Metabolic alkalosis associated with
vasopressin), contributes to poor urinary hypokalaemia and urinary potassium wasting is 14
concentration. typical of diuretic use, or in this case Bartter’s
syndrome, which mimics loop diuretic use.
14.17. Answer: B.
Gitelman’s or thiazide diuretics would also
Hyperglycaemia causes osmotic shifts of present like this, but are associated with low,
water from the intracellular to the extracellular not high, urinary calcium. Laxative abuse would
space, causing a relative dilutional be associated with renal conservation of
hyponatraemia. The serum sodium corrects potassium and therefore low urinary potassium
to 131 mmol/L when using the correction level. Primary hyperaldosteronism is associated
factor of 1.6 mmol/L for every 5.5 mmol/L with hypertension and RTA with acidosis.
increase in serum glucose. The other causes
of hyponatraemia are possible but would 14.22. Answer: A.
result in a genuine reduction in sodium Loop and thiazide diuretics, Bartter’s syndrome
concentration and option D would cause and Gitelman’s syndrome, and primary
hypernatraemia. hyperaldosteronism are all associated with
metabolic alkalosis. As outlined in Fig. 14.22,
14.18. Answer: A.
vomiting is also associated with metabolic
These results are consistent with primary alkalosis while diarrhoea causes loss of
polydipsia which is the likely diagnosis here. bicarbonate thereby resulting in a normal anion
The serum osmolality is low, confirming gap acidosis.
hypotonic hyponatraemia and the urinary
osmolality is also low suggesting relative 14.23. Answer: A.
excess water intake. Option B, which Answers B–E are associated with hypertension
demonstrates low urinary sodium, is seen in while Bartter’s syndrome is associated with low
patients with low effective arterial volume due or normal blood pressure readings.
to either extrarenal losses or hypervolaemic
states. The high urinary sodium and osmolality 14.24. Answer: D.
seen in option C is consistent with SIADH or A number of factors alter potassium secretion
renal sodium loss. Option D is consistent with in the distal nephron segments. Increased distal
hyperosmotic hyponatraemia, as seen in sodium delivery and increased plasma
hyperglycaemia, and option E suggests aldosterone concentration will result in greater
isosmotic hyponatraemia such as with luminal sodium entry through epithelial sodium
hyperlipidaemia. channels, thereby increasing potassium
114 • Clinical biochemistry and metabolic medicine
complex effects on renal potassium excretion. As outlined in the above questions, the most
Alkalosis is generally associated with increased important buffer system in blood and tissues
potassium secretion while acute metabolic involves the reaction of hydrogen ions (H+) with
acidosis is associated with reduced renal bicarbonate (HCO3−) to form carbonic acid
potassium excretion. However, over time, (H2CO3) and ultimately CO2 and H2O. Hydrogen
acidosis will cause an increase in distal sodium phosphate (HPO4) and ammonia are important
delivery and an increase in aldosterone urinary buffers that associate with H+ ions
production that will result in an increase in secreted into the luminal space, thereby
potassium secretion. reducing luminal H+ concentration and allowing
for continued acid secretion.
14.25. Answer: D.
pH, low bicarbonate and compensatory low The student would have a respiratory alkalosis,
PaCO2. Acidosis with a low potassium, makes best represented by option C. Given the acute
type 1 or 2 renal tubular acidosis (RTA) the only nature of the respiratory alkalosis, a small
possible answers. Type 4 renal tubular acidosis change in bicarbonate concentration occurs,
would be associated with hyperkalaemia and but if respiratory alkalosis persists over days to
diuretic abuse is associated with metabolic weeks, the kidneys would have time to make
alkalosis. The urine pH is initially normal, but adjustments to acid secretion and produce
becomes alkalotic when bicarbonate is further compensation and reduction in
administered. This is consistent with poor HCO3− concentration.
B Conway, P Phelan,
GD Stewart
15
Nephrology and urology
Multiple Choice Questions
15.1. A 45 year old man presents with a 6-week formula-derived estimated glomerular filtration
history of bilateral ankle swelling. On rate (eGFR) of 40 mL/min/1.73 m2. Which
examination his pulse was 72 beats/min, blood person below is likely to have the lowest
pressure (BP) 126/68 mmHg, jugular venous measured (true) glomerular filtration rate (i.e. the
pressure (JVP) was not elevated and eGFR is falsely reassuring)?
auscultation of heart and lungs was A. A 25 year old male body builder
unremarkable. He had no stigmata of chronic B. A 40 year old African American man with
liver disease. Which of the following is the most hypertension
appropriate initial investigation? C. A 45 year old woman currently taking
A. Abdominal ultrasound scan trimethoprim for a urinary tract infection
B. D-dimer D. A 56 year old man with type 2 diabetes and
C. Echocardiogram an above-knee amputation
D. Urinalysis E. An 85 year old woman with hypertension
E. Urinary sodium and type 2 diabetes
15.2. A 72 year old man is found to have acute 15.5. A 46 year old man with a 10-year history
kidney injury (AKI). Urine microscopy reveals the of type 2 diabetes presents with a 6-week
presence of red cell casts. What is the most history of bilateral leg swelling. He reports
likely aetiology of his renal failure? that he had been taking non-steroidal
A. Acute tubular necrosis anti-inflammatory drugs (NSAIDs) for
B. Haemolytic uraemic syndrome osteoarthritis regularly for the past 3 months.
C. Microscopic polyangiitis Investigations reveal: eGFR > 60 mL/min/
D. Sclerodermic renal crisis 1.73 m2; urinalysis: protein 4+, blood negative;
E. Tubulointerstitial nephritis protein : creatinine ratio 1680 mg/mmol; and a
serum albumin of 14 g/L. Serum albumin and
15.3. Which of the following is maintained in the urinary albumin : creatinine ratios 4 months
circulation when transiting through the kidney previously were 36 g/L and 25 mg/mmol,
and not freely filtered across the normal respectively. What is the most likely diagnosis?
glomerular filtration barrier? A. Amyloidosis
A. Free light chains B. Diabetic nephropathy
B. Glucose C. IgA nephropathy
C. Glutamine D. Minimal change disease
D. Immunoglobulin A (IgA) E. Tubulointerstitial nephritis
E. Lithium
15.6. A 25 year old man presents with visible
15.4. The following subjects all have a haematuria. He reports that he had a very sore
Modification of Diet in Renal Disease (MDRD) throat 2 weeks previously, but is otherwise well.
116 • Nephrology and urology
His blood pressure and renal function are both of hydronephrosis. No urine is available for
normal. Protein : creatinine ratio was elevated urinalysis. What is the most appropriate initial
(100 mg/mmol). What is the most likely investigation from the list below?
diagnosis? A. Anti-glomerular basement membrane
A. Bladder cancer (GBM)/antineutrophil cytoplasmic antibody
B. IgA nephropathy (ANCA)/antinuclear antibody (ANA) serology
C. Polycystic kidney disease (PKD) B. Computed tomography (CT) pulmonary
D. Post-infectious glomerulonephritis angiography
E. Renal calculus C. Genetic testing for Alport’s disease
D. Plasma protein electrophoresis
15.7. A 69 year old man is diagnosed with E. Renal biopsy
streptococcal endocarditis and commenced on
benzylpenicillin and gentamicin. His renal 15.10. A 32 year old man is referred to the
function is normal on admission, but 1 week nephrology clinic for investigation of persistent
later it has deteriorated (eGFR 28 mL/ non-visible haematuria initially detected at an
min/1.73 m2). Investigations reveal: urinalysis: insurance medical examination. He is otherwise
blood 3+, protein 3+; ultrasound scan: well, with no personal or family history of renal
normal-sized kidneys with no hydronephrosis; disease. His BP is 126/68 mmHg. Preliminary
serum complement level (C3 and C4) is low. investigations reveal: urinalysis: blood 3+,
What is the most likely diagnosis? protein negative; creatinine 100 µmol/L
A. Acute interstitial nephritis (1.13 mg/dL); eGFR > 60 mL/min/1.73 m2.
B. Acute tubular necrosis What is the most likely diagnosis?
C. Infection-related glomerulonephritis A. Alport’s disease
D. Microscopic polyangiitis B. Bladder tumour
E. Pre-renal failure C. IgA nephropathy
D. Membranous nephropathy
15.8. A 76 year old woman attends her family E. Vesico-ureteric reflux
physician complaining of bilateral leg swelling
and vague aches and pains. Initial investigations 15.11. A 75 year old woman has peripheral
reveal: urinalysis: protein 4+, trace blood; vascular disease and stage 3 CKD with
haemoglobin 79 g/L; white cell count 1.9 × 109/L; proteinuria due to IgA nephropathy. Her BP is
platelet count 46 × 109/L; sodium 131 mmol/L; 136/80 mmHg on lisinopril 40 mg, amlodipine
potassium 4.6 mmol/L; urea 15 mmol/L 10 mg and bendroflumethiazide 2.5 mg (all
(90.1 mg/dL, BUN 42.0 mg/dL); creatinine once daily). Her renal function has been
176 µmol/L (1.99 mg/dL); albumin 23 g/L. relatively stable over the past 2 years with
What is the most likely finding on renal biopsy? current eGFR 39 mL/min/1.73 m2. Ultrasound
A. Amyloidosis scan revealed that her left kidney length at
B. Cast nephropathy 9 cm was smaller than the right kidney at
C. Interstitial nephritis 11.5 cm. Magnetic resonance angiography
D. Minimal change disease confirmed a 90% stenosis at the ostium of the
E. Thrombotic thrombocytopenic purpura (TTP) left renal artery. What is the most appropriate
management from the list below?
15.9. A 49 year old male presents with A. Check plasma renin activity
deafness, shortness of breath, haemoptysis, B. Commence a statin
reduced urinary output and ankle swelling. On C. Discontinue lisinopril
examination: BP is 170/100 mmHg; JVP is D. Perform angiography and stenting to her left
4 cm above the sternal angle, there are bibasal renal artery
crepitations in the lungs and he has bilateral leg E. Start warfarin
swelling to the mid-calves. Initial investigations
reveal: haemoglobin 92 g/L, white cell count 15.12. A 62 year old man presents with a large
9 × 109/L; platelet count 460 × 109/L; sodium myocardial infarction and undergoes primary
142 mmol/L; potassium 6.8 mmol/L; urea coronary angiography and stenting. Two days
45 mmol/L (270 mg/dL); creatinine later he develops a low-grade fever and dusky
1260 µmol/L (14.25 mg/dL); albumin 32 g/L. discolouration of the toes on both feet,
Chest X-ray: bi-basal air space shadowing; although peripheral pulses are palpable. eGFR
ultrasound: normal-sized kidneys, no evidence was 52 mL/min/1.73 m2 pre-procedure and
Nephrology and urology • 117
71
Creatinine micromolar, on reciprocal scale
100
125
150
175
200
250
300
400
500
700
1000
16.05.1991 11.05.1995 06.05.1999 01.05.2003 26.04.2007 21.04.2011
118 • Nephrology and urology
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 late
omeprazole, amlodipine and digoxin regularly presentation of CKD?
and takes ibuprofen intermittently. Urinalysis A. Anaemia
shows some leucocytes but no casts, B. Hyperphosphataemia
haematuria or proteinuria. She has a creatinine C. Hyponatraemia
of 320 µmol/L (3.62 mg/dL), which has been D. Renal biopsy showing interstitial fibrosis and
68 µmol/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 IgA 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 dropped to 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 looks 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 µmol/L (2.15 mg/ B. BK polyomavirus nephropathy
120 • Nephrology and urology
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-cm 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 inhibitor (TKI)
15.46. What is the most likely cause 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. Cystoscopy and transurethral
C. IgA nephropathy resection of bladder tumour provides tissue
D. Systemic lupus erythematosus that on pathological examination shows a
E. Upper urinary tract urothelial cancer G3pT2 urothelial cell cancer. What is the
Nephrology and urology • 123
optimal management for this muscle-invasive 15.55. In a 67 year old man with benign
cancer? prostatic hypertrophy (BPH) who has a large
A. Brachytherapy prostate (70 cc) and is already treated with an
B. Chemotherapy (gemcitabine and cisplatin) α-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. 5α-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 µmol/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 α-blocker, i.e. tamsulosin
D. Transurethral resection of the prostate
15.53. What is the most appropriate set of E. Urethral catheterisation 15
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. Intracavernosal 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
124 • Nephrology and urology
it will be inaccurate in patients whose muscle Acute tubular necrosis due to gentamicin and
bulk is atypical for someone of that sex and interstitial nephritis due to amoxicillin and
age. The body builder and African American pre-renal failure related to sepsis are all
male will have greater muscle bulk and hence common in this scenario; however, the 3+
higher creatinine for a given level of renal blood and 3+ protein on urinalysis would point
function compared to what would be expected towards a glomerulonephritis. Microscopic
for a sedentary Caucasian male; hence the polyangiitis is a possibility, but this is not
MDRD eGFR will underestimate the true GFR associated with low complement levels,
(for this reason a correction factor of 1.21 which are observed in infection-related
should be applied to the eGFR in those of glomerulonephritis.
African American descent). Trimethoprim
competes with creatinine for excretion in the 15.8. Answer: A.
distal tubule and hence will increase serum This is a presentation of nephrotic syndrome,
creatinine; thus the MDRD eGFR will which is consistent with amyloid or minimal
underestimate true GFR. Loss of muscle bulk change disease. The pancytopenia could not
following amputation will lead to a lower be explained by minimal change disease, but
creatinine and hence the MDRD equation raises suspicion of a bone marrow disorder
will overestimate the true GFR. The MDRD such as myeloma. While myeloma could cause
eGFR should approximate to true eGFR in the cast nephropathy, this would present with AKI
elderly woman with chronic kidney disease rather than nephrotic syndrome. While
(CKD). haemolytic uraemic syndrome (HUS)/TTP may
cause low platelets, they do not cause
15.5. Answer: D.
pancytopenia and do not present with
Minimal change disease classically presents nephrotic syndrome.
with sudden onset of nephrotic syndrome and
is associated with consumption of NSAIDs. 15.9. Answer: A.
Although NSAIDs may also cause The presence of haemoptysis and kidney injury
tubulo-interstitial nephritis, the heavy proteinuria indicates a pulmonary renal syndrome, most
Nephrology and urology • 125
polyangiitis (previously known as Wegener’s The dusky toes (sometimes called trash
granulomatosis), anti-glomerular basement foot) raise clinical suspicion of cholesterol
membrane disease or lupus. Pulmonary emboli in the microvasculature (especially
embolus may cause haemoptysis, but it would if peripheral pulses are intact) and this
not explain the renal failure in the context of diagnosis is supported by the low-grade
hypertension. While Alport’s disease can cause fever and eosinophilia. Contrast nephropathy
deafness, it does not account for the is the other main differential diagnosis;
haemoptysis, nor the acute nature of the however, it would not account for the trash
process. Renal biopsy is likely to be required, foot or eosinophilia, nor would renal artery
but the risk of bleeding is very high at this point thrombosis. Although the creatine kinase
due to hypertension and uraemia. Serological is elevated, either due to myocardial ischaemia
testing should be performed urgently given the or mild leg muscle damage, at this level
high risk of one of the above causes of there is likely to be insufficient myoglobinuria
pulmonary renal syndrome (most likely to cause AKI. While low platelets and
granulomatosis with polyangiitis given the AKI are consistent with haemolytic uraemic
deafness). syndrome, the haemoglobin is only mildly
reduced and this does not fit the clinical
15.10. Answer: C.
picture.
Asymptomatic non-visible haematuria is a
common presentation of IgA nephropathy. 15.13. Answer: A.
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, 15
Membranous nephropathy presents with which may be due to a number of conditions,
nephrotic syndrome and vesico-ureteric reflux including haemolytic uraemic syndrome or
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
tumour would need to be considered if he were consistent with HUS rather than TTP. The
over 40 years old. negative E. coli O157 stool cultures do not rule
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 D 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 hyperparathyroidism. 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 (secondary
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
126 • Nephrology and urology
counts are normal, rendering a bone marrow Pre-eclampsia is more common in first
problem or hypersplenism less likely. pregnancies or first pregnancy with a new
partner. Serum urate level may be elevated,
15.16. Answer: A.
which may be helpful in diagnosis.
The slow and very consistent rate of decline in Pre-eclampsia typically presents in the third
renal function illustrated here is consistent with trimester, and onset of hypertension prior to
polycystic kidney disease. Post-infectious this raises the possibility of pre-existing renal
glomerulonephritis is rapidly progressive, and disease. Maternal history of smoking may
microscopic polyangiitis is also typically more actually reduce the risk of pre-eclampsia.
rapidly progressive than here and may be Prolonged prothrombin time suggests the
associated with remissions and relapses. development of disseminated intravascular
Progression of renovascular disease typically coagulation.
occurs in a step-wise manner. Myeloma
typically affects an older age group and does 15.20. Answer: B.
not explain slow progression over 20 years. Unfortunately, the age group with the lowest
graft survival includes adolescence. The
15.17. Answer: A.
transition from paediatric to adult care and to
There is good evidence that ACE inhibitors more independent living away from the parental
are the drug of choice to treat hypertension home is a high-risk period for non-adherence.
and reduce proteinuria in patients with The rate of decline in renal function here is too
CKD and protein : creatinine ratio > 100 mg/mmol, rapid to be explained by chronic allograft
and initiation of lisinopril has been partially nephropathy. The absence of symptoms or
effective in this patient. The fall in eGFR of leucocytes in the urine makes acute
< 20% is acceptable and all alternative pyelonephritis in the graft unlikely. Graft
measures should be taken to reduce potassium thrombosis is rare outside of the early
before stopping the ACE inhibitor. Calcium transplant phase or during very severe
resonium is only suitable for short-term dehydration. Anti-GBM disease may
management of hyperkalaemia due to risk of occur in patients with Alport’s disease who
bowel perforation. While BP is suboptimal, receive a kidney with a normal collagen IV
increasing the lisinopril or adding a β-blocker isoform.
are not recommended at this level of
potassium. A thiazide would be more 15.21. Answer: C.
appropriate as this will have the combined A purpuric rash with renal impairment,
benefit of reducing BP and lowering potassium. abdominal and joint pain is typical of Henoch–
Schönlein purpura. Haemoglobin and platelets
15.18. Answer: B.
are normal; therefore haemolytic uraemic
Hyperkalaemia is less common than for syndrome is unlikely. Anti-glomerular basement
haemodialysis where potassium oscillates from membrane disease, post-streptococcal
high values pre-dialysis to low values glomerulonephritis and systemic lupus
Nephrology and urology • 127
failure and urinary findings, but not the Rhabdomyolysis is the most likely diagnosis
purpura. given the dark urine and risk factors, including
a statin, viral illness and alcohol use. Many
15.22. Answer: D.
cases will have several risk factors and
Anuria in this setting is probably caused by rhabdomyolysis may occur after being on a
bladder outflow obstruction: hence an statin for some time. The dipstick ‘haematuria’
ultrasound is the correct answer. A CT scan without red cells being visible is due to urine
would likely diagnose this too, but ultrasound is myoglobin. Intracellular ions (potassium,
the best, quickest and cheapest test. A phosphate) tend to be particularly high with
catastrophic vascular event is a less common rhabdomyolysis and calcium may be low
cause in which a contrast CT may be helpful. (precipitates with phosphate).
Red cell casts could indicate a rapidly
progressive glomerulonephritis, although this is 15.27. Answer: B.
much less common. Bloods for urea and The first dialysis is designed to be a short,
electrolytes will not be helpful in diagnosis, incomplete treatment due to the risks of dialysis
although they should obviously be performed, disequilibrium syndrome if the uraemia is
and a biopsy should not be needed if the corrected too quickly. Therefore a short session
cause is obstruction. is performed, using a small surface area
dialyser with low blood and dialysate flows.
15.23. Answer: B.
Anticoagulation is generally not used for the
A mesangiocapillary glomerulonephritis pattern first session, as a dialysis catheter will recently
of injury has two broad causes based on the have been placed, and in this case also due to
immunofluorescence findings: complement concerns regarding uraemic pericarditis, which 15
deposition, which is caused by inherited may be haemorrhagic precipitating tamponade.
alternative pathway complement gene
mutations with unregulated complement 15.28. Answer: E.
urine (high specific gravity). Dense granular Acute cellular rejection is commonest from day
casts would probably be present in ATN. 6–7 to week 12 post-transplant. Hyperacute
There is no particular reason she should be rejection is rare with modern cross-matching
hyponatraemic or hypercalcaemic. techniques and occurs immediately
post-transplant and this patient had no
15.25. Answer: A.
preformed anti-HLA antibodies. Renal artery
This patient likely has allergic acute interstitial stenosis manifests after several months with
nephritis due to her proton pump inhibitor hypertension and slowly deteriorating transplant
(omeprazole) as she has a mild fever and function. BK polyomavirus nephropathy may
her urine has some white cells but nothing occur as early as 1–2 months post-transplant
else to suggest glomerulonephritis. Pre-renal but not this early. Recurrent IgA nephropathy
injury/ATN is a possibility but, given happens often but is often not clinically
euvolaemia and lack of an apparent insult, it is significant and would perhaps be a late cause
unlikely. of transplant dysfunction. Causes not listed that
128 • Nephrology and urology
would need to be ruled out include a urine leak continuous treatments are better tolerated with
causing obstruction and a vascular thrombosis a reduced risk of precipitating encephalopathy.
(transplant artery or vein). IgA nephropathy is associated with chronic liver
disease but is not the cause of hepatorenal
15.30. Answer: A.
syndrome.
BK polyomavirus causes an interstitial nephritis
in renal transplant patients. It appears to be 15.34. Answer: E.
much less common in non-renal solid organ SGLT2 inhibitors work by inducing glycosuria
recipients. It appeared as an entity in the era of via impaired glucose reabsorption at the
modern immunosuppression with tacrolimus proximal tubule. Diabetic nephropathy is the
and mycophenolate. Risk factors are commonest cause of ESRD in the developed
augmented immunosuppression such as ATG world and likely worldwide. Biopsy is generally
or high-dose glucocorticoids given for acute not performed when the diagnosis is clear from
rejection. the patient history and the patient has overt
proteinuria, but may be performed if atypical
15.31. Answer: C.
features present (e.g. short history of
Cast nephropathy is a tubular injury as well-controlled diabetes, haematuria). ACE
described in option C and presenting with renal inhibitors generally decrease proteinuria and
impairment. Option A refers to monoclonal slow, but do not halt, progression of the
immunoglobulin deposition disease (usually light disease.
chain deposition disease). Option B refers to
amyloidosis, which may occur with multiple 15.35. Answer: B.
myeloma and presents with proteinuria or The presence of red cell casts and heavy
nephritic syndrome. Option D refers to proteinuria indicates severe glomerular injury
Fanconi’s syndrome, a proximal tubulopathy. and a likely proliferative lupus nephritis that
needs immunosuppression. Mycophenolate
15.32. Answer: A.
mofetil and glucocorticoids have been shown
Sarcoidosis typically causes a granulomatous to be as effective as the traditional treatment of
interstitial nephritis. It is not associated with the cyclophosphamide and steroids for both
FSGS lesion. Option D refers to a rapidly induction and maintenance treatment. As this
progressive glomerulonephritis such as ANCA woman likely wants to preserve her fertility,
vasculitis or anti-GBM disease. A chronic mycophenolate mofetil is a better choice for
interstitial nephritis may manifest as widespread her. Most patients who develop ESRD go into
‘scarring’ (interstitial fibrosis and tubular remission. If transplanted, recurrence may
atrophy) but the process described above is occur post-transplant, but usually does not
relatively acute and resolved with treatment. cause significant nephritis, possibly due to
While sarcoidosis frequently causes post-transplant immunosuppression.
hypercalcaemia, calcium does not deposit in
tubules, but larger-scale nephrocalcinosis may 15.36. Answer: B.
dangerous in a coagulopathic liver patient. HNF1-beta mutations may cause several renal
Hepatorenal syndrome portends a dismal phenotypes, which may differ within the same
prognosis and dialysis is only performed if the family (including interstitial nephritis, cystic
liver disorder is remediable or a liver transplant kidneys, vesico-ureteric reflux), maturity-onset
is likely. If dialysis is performed, slow diabetes of the young, pancreatic atrophy,
Nephrology and urology • 129
gout, hypomagnesaemia and abnormal liver glomerular perfusion. ACE inhibitors cause
function tests. COL4A5 mutations cause efferent arteriolar vasodilatation, further
X-linked Alport’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.
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
130 • Nephrology and urology
are: urinary tract infection, bladder cancer and This woman may be cured by a total
urinary tract stones. Ureteric stones are usually nephrectomy. In a tumour of this size, an open
painful rather than painless; nephrological approach is likely to be undertaken by most
causes of visible haematuria are less common surgeons. The lesion is too large for a partial
than urological causes. Upper urinary tract nephrectomy or ablative approach such as
urothelial cell cancer is rare relative to bladder cryotherapy. Radiotherapy is not a treatment
cancer. Of these choices, bladder cancer is the option for renal cancer. TKIs are used in
most likely pathology. metastatic disease.
15.47. Answer: C.
15.51. Answer: E.
This patient has an infected, obstructed left This fit patient is best managed with radical
kidney secondary to an obstructing ureteric cystectomy to try and cure the high-grade
stone. The critical step here is to unobstruct (G3) muscle-invasive (T2) bladder cancer.
the kidney and allow recovery of the sepsis The other options are not appropriate in this
with antibiotics and resuscitation. The key setting.
urological interventions to unobstruct the kidney
are a ureteric stent or percutaneous 15.52. Answer: C.
nephrostomy tube insertion. Definitive treatment This man’s grossly elevated PSA, DRE findings
options (ESWL, PCNL or ureteroscopy) are not and bone scan result indicate he has
appropriate at this time and should be deferred metastatic prostate cancer. This is incurable
to a later date when the patient has recovered but controllable with GnRH agonist injections
from sepsis. (androgen flare covered by initial androgen
receptor blocker treatment for 3–4 weeks).
15.48. Answer: C.
The other therapies are not appropriate for
Asymptomatic bacteriuria is defined as metastatic disease, nor is observation in a man
> 105 organisms/mL urine in healthy, with symptoms of metastatic disease.
asymptomatic patients. It is commonly
identified in patients with indwelling catheters 15.53. Answer: C.
and stents. This condition should be treated Persistent non-visible haematuria is 2 of 3 urine
with antibiotics in infants, pregnant women and dipstick tests positive for at least 1+ blood.
those with urinary tract abnormalities. Investigations should be undertaken in patients
who have associated symptoms (such as
15.49. Answer: E.
dysuria) that would indicate a possible
This man has lower urinary tract symptoms, intravesical lesion. Additionally, this man is a
most likely secondary to bladder outlet smoker, putting him at higher risk for bladder
obstruction. His family physician has correctly cancer. The most appropriate initial
trialled him on treatment with an α-blocker. On investigations are MSU to rule out infection,
attending the urology department he should cystoscopy and upper tract imaging to visualise
initially be assessed by digital rectal the urinary tract.
Nephrology and urology • 131
15.54. Answer: E.
self-catheterisation. Haemodialysis is not a
This man has a testicular cancer until proven curative treatment option in the setting of
otherwise. He should be seen urgently and, high-pressure urinary retention. Medical
following examination, undergo an urgent management, such as an α-blocker, is
ultrasound, which is the gold standard contraindicated.
investigation to rule out a testicular cancer.
Testicular cancer is almost always treated with 15.57. Answer: C.
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 ECG excludes myocardial infarction
C. Dissection of the femoral artery due to C. 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 ECG 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 C. Supraventricular tachycardia
C. 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,
16
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 A. Administration of intravenous drugs and
infarction. On examination she is tachycardic 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. C. 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 (ABCDE)
B. Left ventricular free wall rupture E. Support of airway, breathing and circulation,
C. Papillary muscle rupture and mitral and assessment of disability and exposure,
incompetence treatment of fibrillation (ABCDEF)
D. Post-infarction pericarditis with pericardial 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
C. A loud second heart sound B. Intravenous amiodarone will restore cardiac
D. A quiet first heart sound output
E. Fixed splitting of the second heart sound C. 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 hypothermia and
is true? hypoxia
134 • Cardiology
16.15. A 65 year old female presents with chest 16.19. β-Adrenoceptor antagonists (β-blockers)
pain, and the 12-lead ECG shows evidence of are used in which of the following situations?
acute inferior myocardial infarction complicated A. Acute left ventricular failure
by hypotension. An echocardiogram is B. Cardiac failure associated with bradycardia
performed and shows markedly reduced C. Cardiogenic shock
movement of the right ventricular walls, D. Chronic left ventricular systolic dysfunction
indicating that right ventricular infarction has E. High-output cardiac failure
occurred. Left ventricular function is only mildly
impaired. Which of the following physical signs 16.20. A 71 year old woman with a history of
would be expected in this situation? hypertension presents with fatigue and rapid,
A. Tachycardia, a late systolic murmur and irregular palpitations. She normally takes
ascites enalapril for blood pressure control. Clinical
B. Tachycardia, and absent jugular venous examination reveals an irregularly irregular
pulse because of inability to develop right pulse, rate 125 beats/min, and BP
heart pressure 128/86 mmHg. Cardiovascular examination is
C. Tachycardia, acute development of otherwise normal. A 12-lead ECG is performed,
peripheral oedema and acute ascites which shows atrial fibrillation with poor
D. Tachycardia, basal crepitations and a third ventricular rate control, but no other
heart sound abnormality. Which of the following drugs is the
E. Tachycardia, elevated jugular venous pulse most suitable agent to control heart rate in this
due to failure of right ventricular pump patient?
function, and hepatomegaly A. Adenosine
B. Amiodarone
16.16. What relationship does Starling’s Law of C. β-blocker
the heart describe? D. Flecainide
A. Between blood pressure and cardiac output E. Lidocaine
B. Between cardiac filling and blood pressure
C. Between cardiac filling and cardiac output 16.21. An 85 year old man presents with a
D. Between heart rate and blood pressure 6-month history of sudden episodes of
E. Between heart rate and cardiac output lightheadedness, which last up to 15 seconds.
He is admitted to hospital with an episode of
16.17. What underlying pathophysiological syncope resulting in facial injury. Examine the
changes is chronic cardiac failure associated rhythm strip below. Which conduction
with? abnormality does this show?
A. Activation of the renin–angiotensin– A. Complete (third-degree) AV block
aldosterone system (RAAS) B. Left bundle branch block
B. Inhibition of the RAAS C. Mobitz type II second-degree AV block
C. Inhibition of the sympathetic nervous system D. Sinus bradycardia
D. Reduced production of brain natriuretic E. Wenckebach (Mobitz type I) second-degree
peptide (BNP) AV block
E. Systemic vasodilatation
16.22. Which of the following rhythms is NOT
16.18. Loop diuretics such as furosemide and commonly associated with sick sinus syndrome
bumetanide have which of the following (sinoatrial disease)?
effects? A. Atrial fibrillation
A. Diuresis due to inhibition of potassium and B. Atrial tachycardia
water reabsorption C. Sinus bradycardia
B. Diuresis due to inhibition of sodium and D. Sinus pauses
water reabsorption E. Ventricular tachycardia
C. Diuresis due to inhibition of water
reabsorption only
D. Increased serum potassium levels due to
enhanced distal tubule function
E. Osmotic diuresis Fig. 16.21
Cardiology • 135
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 CHA2DS2-VASc occurring after cocaine use
score? B. A 48 year old man who presents with acute
A. 2 inferior myocardial infarction complicated
B. 3 within the first 6 hours by ventricular
C. 4 fibrillation
D. 5 C. A 55 year old woman with syncope; ECG
E. 6 monitoring shows sinus rhythm with
third-degree atrioventricular block
16.24. Which of the following drugs is known to D. A 75 year old man with syncope; ambulatory
be effective in preventing stroke in patients with ECG shows sinus bradycardia and daytime
atrial fibrillation? sinus pauses of up to 5 seconds
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. β-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. β-blocker (e.g. metoprolol) On examination, pulse is 100 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 pericardial
elevation on the 12-lead ECG. 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 pericardial rub is always heard if the
ventricular basal contraction. Which of the effusion is large
following factors is most likely to have C. An ECG 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 pericardial effusion
C. Excessive alcohol consumption E. In symptomatic patients, cardiac surgery is
D. Genetic factors required to remove the pericardial fluid
E. Viral infection
16.44. An 18 year old man presents with
16
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 ECG is recorded because the attending
E. Supraventricular tachycardia doctor suspects acute pericarditis. What
is the most specific ECG 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 ECG. What is the most
16.42. Which of the following conditions may common ECG change in patients with
result in chronic pericardial constriction? pulmonary embolism?
A. Acute myocardial infarction A. Anterior T-wave inversion
B. Dilated cardiomyopathy B. Atrial fibrillation
C. Excessive alcohol consumption C. ‘S1Q3T3’
D. Osteoarthritis D. Sinus tachycardia
E. Tuberculosis E. ST elevation
138 • Cardiology
16.46. In patients with a pericardial effusion, 16.51. An 80 year old woman presents with
what is the most important clinical sign to shortness of breath and swollen ankles. Her
determine whether there is cardiac tamponade? ECG showed some poor R-wave progression.
A. Cyanosis She was referred for an echocardiogram and
B. Haematuria was found to have a high ejection fraction.
C. Peripheral oedema Which of these conditions is the most likely
D. Pulsus paradoxus cause of her presentation?
E. Raised JVP A. Acute myocarditis
B. Aortic stenosis
16.47. The following medical treatments are all C. Dilated cardiomyopathy
associated with improved symptoms in patients D. Ischaemic cardiomyopathy with extensive
with heart failure due to left ventricular systolic infarction
dysfunction. However, which of the treatments E. Restrictive cardiomyopathy
has NOT been shown to also improve survival?
A. Bisoprolol 16.52. Neuroendocrine system activation is a
B. Enalapril feature of heart failure. Abnormalities of which
C. Furosemide hormone can cause heart failure rather than
D. Sacubitril–valsartan result from heart failure?
E. Spironolactone A. Aldosterone
B. Angiotensin II
16.48. Which of the following antiplatelet drugs C. Catecholamines
is a phosphodiesterase inhibitor? D. Thyroxine
A. Cangrelor E. Vasopressin (antidiuretic hormone, ADH)
B. Clopidogrel
C. Dipyridamole 16.53. Which of the following biomarkers is a
D. Prasugrel structural protein rather than a cardiac
E. Ticagrelor enzyme?
A. Aspartate aminotransferase
16.49. A 54 year old security guard who is B. Creatine kinase
obese and enjoys drinking alcohol and cigarette C. Creatine kinase MB
smoking with his friends has a diet high in D. Lactate dehydrogenase
saturated fats. He has an acute myocardial E. Troponin I
infarction. Which lifestyle risk factor has the
strongest association with myocardial 16.54. A patient has a stent placed in his right
infarction? coronary artery. On return to the ward, he gets
A. Excess alcohol severe chest pain and becomes very unwell.
B. High-saturated fat diet The nurse undertakes an ECG and calls the
C. Obesity interventional cardiologist to review the patient
D. Sedentary activity because she is concerned that he has a
E. Smoking thrombosed stent. What ECG features would
suggest the stent has become occluded?
16.50. A 36 year old smoker has sudden onset A. Anterior T-wave inversion
of chest pain whilst out walking in a remote B. Atrial fibrillation
island of Scotland. He attends the local hospital C. Atrioventricular block
and is found to have ST segment elevation D. ST elevation in I, aVL and V6
myocardial infarction. Which treatment has the E. ST elevation in V2–V5
strongest time-dependent benefit (i.e. the
quicker received, the better the outcome) for 16.55. A 72 year old woman has had
ST segment elevation myocardial infarction? ‘indigestion’ for 4 days with vomiting and
A. Aspirin sweating. She presents to the emergency
B. β-blocker department where a delayed presentation inferior
C. Heparin ST segment elevation myocardial infarction is
D. Percutaneous coronary intervention diagnosed. She has already developed Q
E. Tissue plasminogen activator waves in leads II, III and aVF. One day after
Cardiology • 139
B. Left main stem stenosis and significant left (reference range < 34 ng/L). Which of the
ventricular systolic dysfunction following treatments is likely to worsen his
C. Severe proximal disease of the left anterior prognosis?
descending coronary artery A. Aspirin
D. Three-vessel coronary heart disease with B. Fondaparinux
good left ventricular function C. Intravenous tissue plasminogen activator
E. Two-vessel coronary heart disease (tPA)
D. Metoprolol
16.80. The man with an extensive anterior E. Ticagrelor
myocardial infarction in Questions 16.78 and
16.79 has left main stem and triple-vessel 16.84. An anaesthetist is seeking advice
disease and is referred for coronary artery regarding a patient with coronary heart disease,
bypass graft surgery. However, the surgeon is diabetes mellitus and a murmur. Which of the
concerned that the anterior wall is completely following is NOT a significant risk factor for
infarcted and is no longer viable. The surgeon perioperative myocardial infarction during
wants to know if the anterior wall has significant non-cardiac surgery?
amounts of scar tissue. Which imaging modality
A. Aortic stenosis with a peak gradient of
is best to identify the scar of acute myocardial
25 mmHg
infarction?
B. Diabetes mellitus treated with insulin and
A. Computed tomography associated with renal failure
B. Coronary angiography C. Recent (within 4 weeks) stenting of a severe
C. Echocardiography proximal stenosis in the left anterior
D. MRI descending coronary artery
E. Stress echocardiography D. Recent acute coronary syndrome
E. Severe left ventricular dysfunction
16.81. An 83 year old woman presents
with acute pulmonary oedema, BP of 16.85. A 67 year old woman presents with
180/100 mmHg and a SaO2 of 85%. Which predictable exertional angina pectoris when
treatment is UNLIKELY to be helpful in this climbing steep inclines. She has been
setting? commenced on aspirin, statin and a β-blocker.
A. Furosemide She attends your clinic for assessment. Which
B. Intravenous dobutamine of the following suggests the patient is at low
C. Intravenous nitrates risk of future events?
D. Non-invasive ventilation A. Poor exercise tolerance
E. Supplementary oxygen therapy B. Poor left ventricular function
C. Post-infarct angina
16.82. A 43 year old woman with a past history D. Recent onset of symptoms
of breast cancer is referred with a gradual E. ST segment depression during stage 3 of
onset of breathlessness. An echocardiogram the Bruce Protocol
demonstrates a dilated poorly contracting left
ventricle. You wish to investigate potential 16.86. You review a 50 year old smoker 2
causes of her dilated cardiomyopathy. Which of months after successful treatment for a
the following would be an irreversible cause of myocardial infarction. Which intervention has
her dilated cardiomyopathy? the greatest benefit to prevent a recurrence of
A. Alcohol excess myocardial infarction?
B. Anthracycline chemotherapy A. ACE inhibitor therapy
C. Haemochromatosis B. Aspirin
D. Hypothyroidism C. Regular and frequent aerobic exercise
E. Thyrotoxicosis D. Smoking cessation
E. Statin therapy
16.83. A 56 year old man presents with sudden
onset of chest pain radiating down his left arm,
ST segment depression of the ECG and a
plasma troponin concentration of 4365 ng/L
Cardiology • 143
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 16
to atrioventricular block and ventricular
arrhythmias. Long QT 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, embolisation 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.
144 • Cardiology
16.8. Answer: C.
plasma troponin concentration takes time to
Infective endocarditis is often diagnosed become detectable. The admission troponin
relatively late in its clinical course. It may initially level may be normal if the patients attends
present with non-specific symptoms that lead soon after the onset of symptoms. If the
to a diagnosis of influenza or viral infection. Any 6-hour troponin level is normal then acute
patient with unexplained fever and a cardiac coronary syndrome is not likely to explain the
murmur, especially if changing, should be patient’s chest pain and other causes should
assessed for possible endocarditis, with then be considered. An elevated troponin level
urinalysis, an ECG, echocardiogram, blood is suspicious of myocardial infarction
cultures, and blood testing for white cell count but should be interpreted in the context of the
and C-reactive protein concentration. In this clinical presentation. Some non-cardiac
case the wide pulse pressure is suggestive of pathologies (e.g. sepsis, pulmonary embolism)
aortic incompetence which, if severe, may are also commonly associated with minimal
occur without a murmur. myocardial injury and therefore troponin
release.
16.9. Answer: E.
compromise associated with a new murmur Atrial fibrillation is the most common
may be caused by either papillary muscle tachyarrhythmia encountered in older patients
rupture, or rupture of the interventricular and is seen in approximately 2% of patients
septum (acquired ventricular septal defect; aged over 70 years, and in some studies up to
VSD). With acquired VSD the murmur often 10% of those aged over 80 years. Ventricular
radiates to the right sternal border because of ectopic beats would not produce episodic
left-to-right shunting across the interventricular symptoms of this type and sinus arrhythmia is
septum, whereas the murmur of acute mitral a normal variant and would not cause any
incompetence would be more likely to radiate symptoms. Supraventricular tachycardia
to the axilla or the back. Acute left ventricular normally causes regular palpitation.
free wall rupture is almost always fatal and
would not cause a murmur. While pericarditis 16.13. Answer: D.
may cause a sound that could be confused Basic life support describes the interventions
for a murmur, serious haemodynamic that can be carried out with minimal equipment
compromise is rare, as the associated in the event of a cardiac arrest. It does not
pericardial effusion is usually small. Aortic include defibrillation or administration of
incompetence is not a complication of intravenous drugs. It does include chest
myocardial infarction. compression and mouth-to-mouth
resuscitation, but the ABCDE mnemonic is a
16.10. Answer: B.
helpful aide mémoire for these and the other
Clinical signs of left ventricular failure are components of basic life support.
tachycardia, a gallop rhythm with a third heart
sound (which is the sound of abrupt left 16.14. Answer: E.
ventricular filling due to high left atrial pressure), Pulseless electrical activity means that
and bi-basal inspiratory fine crepitations at the there is an organised cardiac rhythm seen
lung bases. A fourth heart sound occurs on the ECG, but no discernible cardiac output.
during atrial systole because of increased left Defibrillation is not appropriate, as this is a
ventricular stiffness in patients with left treatment for ventricular fibrillation.
ventricular hypertrophy. A loud second heart Amiodarone can cause hypotension and is
sound is usually caused by systemic or not an appropriate treatment. In current
pulmonary hypertension. A quiet first heart resuscitation protocols, CPR should be carried
sound may accompany mitral out for 2 minutes before the rhythm is
regurgitation. reassessed. Reversible causes of PEA include
hypothermia, hypoxia, hypovolaemia, hypo-/
16.11. Answer: A.
hyperkalaemia (the four ‘H’s), and
Troponin testing is an important component in thrombosis (coronary or pulmonary), tension
the assessment of patients with chest pain. pneumothorax, tamponade and toxins
In patients with acute myocardial infarction, (the four ‘T’s).
Cardiology • 145
16.15. Answer: E.
16.20. Answer: C.
While peripheral oedema and ascites are First-line therapy for rate control in atrial
signs of right-sided cardiac failure, they typically fibrillation consists of β-blockade (or, if
take days or weeks to develop. Acute contraindicated, a rate-limiting calcium channel
right ventricular failure is characterised by blocker such as verapamil can be used). In this
hypotension, a compensatory sinus case, the β-blocker could be prescribed in
tachycardia, elevation of the jugular venous place of enalapril, as it may provide quite
pulse because of ineffective right ventricular effective blood pressure control, as well as
ejection, and hepatomegaly can develop quite limiting the heart rate. None of the other agents
quickly because of hepatic venous are appropriate for rate control in atrial
congestion. fibrillation. Lidocaine is used to treat ventricular
arrhythmias. Flecainide and amiodarone are
16.16. Answer: C.
used for rhythm control (i.e. maintenance of
Starling’s Law describes the relationship sinus rhythm) and not rate control, in atrial
between cardiac filling (preload) and cardiac fibrillation. Adenosine is an ultra-short-acting
output. Low preload causes inadequate atrioventricular (AV) node blocker and is not
ventricular filling and low output. Moderate used to treat atrial fibrillation.
preload causes optimal cardiac filling and
cardiac output. Very high preload causes 16.21. Answer: C.
ventricular stretch and reduces the efficiency of In Mobitz type II second-degree AV block, most
contraction, resulting in reduced cardiac output. P waves conduct normally to the ventricles and
Patients with decompensated cardiac failure are associated with a QRS complex. Some P
have high preload pressure, and diuretics and waves do not conduct and there is no
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
16.17. Answer: A.
‘all-or-nothing’. In contrast, Mobitz type I
Cardiac failure is associated with activation of second-degree AV block is characterised by
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 AV
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.
episodes but are not known to reduce stroke The only one of these conditions associated
risk. Apixaban is an oral factor Xa inhibitor, with a significant intracardiac shunt is tetralogy
which has been shown in large-scale clinical of Fallot. Central cyanosis occurs because of
trials to be effective at preventing stroke in shunting of blood through a ventricular septal
patients with atrial fibrillation and moderate-to- defect, and this is exacerbated by the
high stroke risk. over-riding aorta (i.e. the aorta over-rides the
defect, causing blood from the right ventricle to
16.25. Answer: E.
be ejected directly into the aorta) and by
This ECG shows a narrow, complex tachycardia muscular right ventricular outflow obstruction.
with no obvious P waves. The P waves may be Cyanotic episodes may be precipitated by fever
concealed in the QRS complex or ST segment. or by dehydration. In most cases the condition
The term ‘supraventricular tachycardia’ is used is recognised and corrected in infancy.
to describe this rhythm. The two most likely
mechanisms are atrioventricular nodal 16.29. Answer: D.
16.27. Answer: E.
Ventricular septal defect (VSD) causes a harsh
ICDs are indicated for primary prevention in systolic murmur that may radiate to the right
patients with previous myocardial infarction who side of the sternum. Small VSDs do not cause
have chronically impaired left ventricular significant shunting but can produce a loud
function. It is thought that the scar burden in murmur. Atrial septal defect might cause a
these patients predisposes them to ventricular quiet systolic flow murmur. Persistent ductus
arrhythmias, which, when they occur, are arteriosus causes a continuous murmur
poorly tolerated. As long as there are no throughout systole and diastole. Patent
Cardiology • 147
the context of flu-like illness and a viral Cardiac transplantation is limited by the
aetiology is common. Endocarditis is not availability of donor organs, the need for
associated with pleuritic chest pain. Persistent life-long immunosuppressive therapy to prevent
ductus arteriosus is a congenital (rather than rejection, and the risks of surgery and the
acute) condition, which is associated with a drugs used afterwards. Therefore it is only
continuous murmur. offered to patients with cardiac failure who
remain symptomatic despite adherence with
16.32. Answer: D.
optimal pharmacological therapy and, where
Aspirin, through its anti-inflammatory effects, is appropriate, cardiac resynchronisation therapy.
a very effective symptomatic treatment for
pericarditis. Non-steroidal anti-inflammatory 16.37. Answer: E.
16
drugs such as diclofenac can also be used Hypertrophic cardiomyopathy is associated with
orally. Steroids are rarely required. Amiodarone disorganisation and fibrosis of left ventricular
is an anti-arrhythmic drug and has no role in myocardial tissue. This can predispose patients
the management of acute pericarditis. to sudden ventricular arrhythmias, and these
may occur without warning during intense
16.33. Answer: A.
exercise. The risk is highest in patients with
Dilated cardiomyopathy is characterised by gross hypertrophy or left ventricular outflow
dilatation of the atria and ventricles, and tract obstruction. Some genetic variants are
thinning of ventricular walls. Hypertrophic also associated with high risk, such as troponin
cardiomyopathy causes disproportionate T mutations. Right ventricular failure and
thickening of myocardium, particularly the pulmonary embolism are not common in
interventricular septum. Myocardial infiltration patients with hypertrophic cardiomyopathy.
(e.g. with amyloid protein) can cause restrictive Atrial fibrillation occurs and may cause
cardiomyopathy, which does not cause cardiac symptoms but is rarely life-threatening.
dilatation but does restrict myocardial
contraction and relaxation. 16.38. Answer: B.
risk factor for coronary artery disease, not Takotsubo (stress) cardiomyopathy occurs
cardiomyopathy. Dilated cardiomyopathy can most often in females and is associated with
be caused by genetic defects of sarcomeric emotional stress. It can occur due to
148 • Cardiology
bereavement, acute non-cardiac illness, natural relieve symptoms and to obtain fluid for
disasters and other major life events. It is laboratory analysis. Patients with pericardial
characterised by chest pain and ECG changes effusion are very dependent on high preload
that mimic myocardial infarction. Troponin pressure to maintain cardiac output, so
elevation is common but coronary angiography diuretics may cause significant hypotension.
does not show occlusive coronary artery disease Large effusions may occur because of
or intracoronary thrombus. Echocardiography malignancy, usually metastatic disease from
shows a characteristic left ventricular lung or breast cancer.
appearance of apical dilatation, giving the
appearance of an octopus trap or takotsubo! 16.44. Answer: B.
16.43. Answer: A.
All of the agents listed except furosemide have
Large pericardial effusions are normally not been shown to improve survival in patients with
associated with a pericardial rub as the heart failure due to left ventricular systolic
pericardium and epicardium are well separated dysfunction. Loop diuretics such as furosemide
by pericardial fluid and friction does not occur. are important for symptom control, but so far,
The ECG may show small complexes but is not no large-scale randomised trial has shown
a sensitive test, and an echocardiogram is survival benefit.
required to make the diagnosis. The chest
X-ray may show a spherical or globular 16.48. Answer: C.
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.
fibrinolytic drug therapy are treatment If the patient has occluded his stent, then
modalities for acute ST elevation myocardial the ECG 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 16
administration of tPA or other fibronolytic drugs elevation in the inferior leads (II, III 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.
16.60. Answer: C.
16.63. Answer: C.
treat acute myocardial infarction but is an Mitral stenosis is characterised by the presence
effective treatment for some patients with of a tapping apex beat, reflecting a palpable
chronic coronary artery disease. opening snap, accompanied by a low-pitched
mid-diastolic murmur. If the patient is in sinus
16.64. Answer: A.
rhythm, pre-systolic accentuation of the
There is a strong association between age and murmur may occur because of atrial
risk of death after myocardial infarction. contraction. A loud second heart sound may
In-hospital mortality is three times greater in be heard due to secondary pulmonary
individuals aged over 80 years than it is in hypertension, which often accompanies mitral
those aged 60–65 years. While risk of stenosis.
myocardial infarction is much higher in smokers
than in non-smokers to start with, the risk of 16.70. Answer: A.
of hypertension, including those listed, but renal Aortic regurgitation is associated with a 16
disease is the most common cause. large-volume, collapsing pulse and an early
diastolic murmur associated with a systolic
16.66. Answer: D.
‘flow’ murmur. In severe aortic regurgitation,
All other options given apart from D describe the pulse pressure may be so large as to cause
recognised causes of secondary hypertension. prominent neck pulsation. A slow rising pulse,
Antihypertensive drug therapy, along with crescendo–decrescendo murmur, quiet second
lifestyle changes, effectively controls blood heart sound and palpable thrill in the aortic area
pressure in most patients with hypertension. are signs of aortic stenosis.
The most common cause of poor blood
pressure control is therefore poor adherence 16.72. Answer: E.
with antihypertensive therapy. This may be Viridans streptococci are the most common
because of side-effects, and also because of cause of endocarditis on a native heart valve.
the asymptomatic nature of the condition. Staphylococcus aureus is the most common
organism to infect prosthetic valves.
16.67. Answer: D.
16.68. Answer: A.
16.74. Answer: B.
Aspirin is the drug of choice in rheumatic fever Viridans streptococci are usually very sensitive
and is used in high doses compared with those to benzylpenicillin, and this agent works
used in common analgesia. Glucocorticoids are synergistically with gentamicin. Bactericidal
not used in this condition. blood concentrations can only be achieved with
152 • Cardiology
16.76. Answer: A.
16.81. Answer: B.
Mutations in myosin heavy chain, troponin and The main components in the management of
myosin-binding protein most often lead to acute pulmonary oedema are bed rest, oxygen
hypertrophic cardiomyopathy. Titan mutations therapy, intravenous nitrates and intravenous
(and some myosin-binding protein mutations) diuretics. Non-invasive continuous positive
may cause dilated cardiomyopathy. It is airway pressure (CPAP) ventilation is helpful in
mutations in fibrillin, a glycoprotein critical to resistant cases. Dobutamine is an inotrope that
production of elastic tissue, that most often increases cardiac work; it is sometimes used in
leads to Marfan’s syndrome. the management of cardiogenic shock, but is
not appropriate in a patient with high blood
16.77. Answer: B.
pressure and cardiac failure.
Atrial myxoma is the most common cardiac
tumour. It is a benign tumour that usually 16.82. Answer: B.
occurs in the left atrium and is associated with Endocrine causes of dilated cardiomyopathy,
increased risk of stroke and peripheral and alcohol-related cardiomyopathy, are often
embolism. reversible as long as the underlying problem
is treated early enough. Anthracycline
16.78. Answer: C.
chemotherapy can cause acute or late-onset
Transthoracic echocardiography is a form of dilated cardiomyopathy that responds only in a
ultrasound imaging that has limitations. It is limited manner to β-blockers and ACE inhibitors
good for assessing heart valve and myocardial and which may cause permanent cardiac
function but has limited value in characterising dysfunction.
tissues (e.g. for fibrosis). The left atrial
appendage is the most common site for 16.83. Answer: C.
thrombus formation in atrial fibrillation and this Non-ST segment myocardial infarction is
structure is not visible during transthoracic normally initially managed with dual antiplatelet
echocardiography. The electrocardiogram, not therapy (e.g. aspirin and ticagrelor), and an
echocardiogram, is used to assess cardiac antithrombotic agent (e.g. fondaparinux or
arrhythmias. Whilst poor left ventricular function enoxaparin). β-Blockade is often used as
is associated with a poor future prognosis, in prophylaxis against angina and arrhythmias.
isolation, echocardiography gives limited Intravenous tPA is a treatment for acute ST
information about prognosis. elevation myocardial infarction and has not
been shown to improve outcome in patients
16.79. Answer: B.
with non-ST segment elevation myocardial
The decision between percutaneous coronary infarction. Indeed, patients with ST segment
intervention (PCI) and coronary artery bypass depression have a worse outcome with
graft surgery is an important one in patients thrombolytic therapy.
with angina or after myocardial infarction. The
patients who have the most to gain from 16.84. Answer: A.
surgery are those with left main stem disease Surgery is associated with activation of platelets
and left ventricular impairment. and coagulation pathways, so patients who
have had recent myocardial infarction or recent
16.80. Answer: D.
percutaneous coronary intervention are at
Gadolinium-enhanced MRI is currently the most increased risk of thrombosis in the affected
sensitive imaging modality for the identification vessel, resulting in myocardial infarction.
Cardiology • 153
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.
16
A Leitch
17
Respiratory medicine
Multiple Choice Questions
17.1. A 46 year old woman has a recent diagnosis small vessel disease. Arterial blood gas: H+
of adenocarcinoma of the lung made at 60 nmol/L (pH 7.22), PaO2 8.7 kPa
bronchoscopy 1 week ago. She presents to the (65 mmHg), PaCO2 10 kPa (75 mmHg),
emergency department acutely short of breath HCO3− 26 mmol/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 (V̇ /Q̇ ) 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
the right side with dullness to percussion elastic recoil
throughout the right side. Her trachea is D. Opiate toxicity – suppression of the
deviated to the right and the apex beat is not respiratory centre
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. Pericardial 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 cricosternal 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 pathological change 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 L/min 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
Respiratory medicine • 155
A. Bronchoscopy
B. CT chest, abdomen, pelvis
C. D-dimer
D. Echocardiogram
E. Positron emission tomography
(PET) scan
A. Bronchial carcinoma
B. Empyema
C. Hepatic hydrothorax
D. Mesothelioma
E. Pleural effusion secondary to pancreatitis
156 • Respiratory medicine
17.7. A 63 year old woman had a CT pulmonary What should be the next step?
angiogram (CTPA) when she presented with A. Antituberculous chemotherapy
left-sided pleuritic chest pain to the medical B. Further follow-up scan in 3 months
assessment unit. There was no pulmonary C. Palliative chemotherapy
thromboembolism but the appearance below D. Palliative radiotherapy
was noted on CT scan. E. Right upper lobectomy
P
Respiratory medicine • 157
A 54
17.15.DFO 5 year
cm old woman attends the DFOV 50.0 cm
spinal metastasis
. m 3 p 3.3mm /3.3sp
C. Uptake in the right upper lobe lesion and
physiological uptake in Plarge
m=0.00 M=38 40 kBq/ml 250
vessels m=0.00 M=38.40 kBq/ml P 250
17.16. A 73 year old woman has struggled Blood tests reveal: haemoglobin 143 g/L,
with increasing shortness of breath on WCC 12 × 109/L (neutrophilia), platelets
exertion over the last year. In addition, she 435 × 109/L, urea 9 mmol/L (54 mg/dL),
has a dry cough. She worked in an office until creatinine 102 µmol/L (1.15 mg/dL), sodium
she retired. She has a pet dog. She has 128 mmol/L, bilirubin 12 µmol/L (0.70 mg/dL),
osteoarthritis, osteoporosis and hypothyroidism. alanine transaminase (ALT) 243 U/L, γ-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
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 10 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-smoker. Her medication includes: sinister cause. The image below is from the CT
omeprazole 20 mg 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 R
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 abnormality
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 LFTs, 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 she has an associated interstitial lung disease.
D. Referral to respiratory clinic She has mild basal interlobular septal
E. Sweat test to exclude cystic 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-diameter 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.
164 • Respiratory medicine
RT 18fps 13cm
A B
Respiratory medicine • 165
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
B. Oral amoxicillin unwell. Antibiotics seem to help but she only
C. Oral prednisolone feels better for 2–3 weeks.
D. Reduce high-dose ICS/LABA The patient is a non-smoker who works in an
E. Stop montelukast office. She finds her cough embarrassing and
work colleagues have been giving her a hard
17.44. A 48 year old asthmatic is referred to time. What would be the best investigation for
clinic because of increased frequency of this patient?
asthma exacerbations. He has been waking at A. α1-Antitrypsin levels
night with cough and breathlessness that B. Bronchoscopy
require extra doses of inhaled salbutamol. C. CXR
Spirometry reveals an obstructive defect and D. High-resolution CT chest
blood tests reveal an eosinophilia of E. Immunoglobulin levels
0.67 × 109/L. CXR is clear. The patient’s
current therapy includes Flixotide 500 µg/ 17.47. A patient who attends the asthma clinic
salmeterol 25 µg 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, WCC
A. Add amoxicillin 14 × 109/L (neutrophils 7 × 109/L, lymphocytes 17
B. Add montelukast 1.46 × 109/L, monocytes 0.8 × 109/L, eosinophils
C. Double prednisolone dose 4.7 × 109/L), platelets 340 × 109/L, CRP
D. Provide home nebuliser 120 mg/L. CXR is shown below.
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?
Ivacaftor 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. ΔF508 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 be
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)
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 confused 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 inflammatory markers. A CXR clearly
by which of the following? shows a new right-sided infiltrate.
A. Bordetella pertussis Which of the following approaches is
B. Haemophilus influenzae 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
Respiratory medicine • 167
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 10 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–Guérin
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. 10% A. A positive result should prompt the clinician
B. 20% to start antituberculous chemotherapy 17
C. 30% B. It is more specific than tuberculin skin testing
D. 40% C. It is now the first-line test for diagnosis of
E. 50% active TB
D. It is only positive where there is systemic
17.56. A 34 year old woman has been unwell mycobacterial infection
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
168 • Respiratory medicine
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 bronchiolitis–interstitial lung 17.72. 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
A. Non-smokers CXR was ordered to exclude pneumonia but
B. Patients > 65 years of age revealed multiple smooth nodules. CT scanning
C. Patients with connective tissue diseases also identifies four smooth nodules of varying
D. Smokers size. A CXR recovered from storage shows that
E. Women these nodules have been present for at least 5
years.
17.70. A 28 year old woman develops a painful What is the likely cause of these nodules?
rash on her lower limbs, arthralgia and fever. A. Bronchiectasis
She feels run-down and unwell. Her family B. Metastatic cancer
170 • Respiratory medicine
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. 17
diagnosis? His past medical history is significant for two
A. Histamine challenge test separate episodes of ‘benign asbestos pleurisy’
B. Peak expiratory flow rate diary in his 50s. He has pleural plaques and received
C. Specifc IgE to flour compensation. He had worked in the
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 woman has progressive
D. Sarcoidosis breathlessness on exertion. Because she
E. Silicosis described a vague feeling of her chest
172 • Respiratory medicine
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 cm. 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; ECG: sinus
What is the likely diagnosis? tachycardia; CRP 35 mg/L, D-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 17.87. 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 cm 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 110 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 are as
A. CT-guided biopsy follows: haemoglobin 100 g/L, WCC
B. Endobronchial ultrasound 11 × 109/L, platelets 200 × 109/L, D-dimer
C. Flexible bronchoscopy 1200 ng/mL, urea 10 mmol/L (60 mg/dL),
D. Liver biopsy creatinine 92 µmol/L (1.04 mg/dL). ECG 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 woman has been
receiving unit with sudden-onset right-sided increasingly short of breath 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 ECG 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 as a
last week. He has a past medical history of mean pulmonary artery pressure measured at
Respiratory medicine • 173
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?
A. 15 mmHg A. Abnormal ventilatory drive is present in
B. 25 mmHg obstructive sleep apnoea
C. 35 mmHg B. During sleep muscle tone increases
D. 45 mmHg C. Forty per cent of middle-aged women snore
E. 55 mmHg D. Hypoventilation accompanies normal sleep
E. Palatoglossus and genioglossus contract
17.89. A 24 year old woman presents with actively during expiration
breathlessness and palpitations that has
become worse over the preceding year. She 17.93. A 55 year old man has been increasingly
has had significant social stress because of the sleepy during the daytime. He is having trouble
end of a relationship and the death of her at work as he has been found asleep at his
mother. Examination reveals an elevated jugular desk and has taken to napping during his
venous pressure but no other abnormalities. An breaks. He had a near-miss in his car. His
ECG has a rate of 76 beats/min and a Epworth sleepiness score is 18. His BMI is 36.
rightward axis. CXR reveals a paucity of What is the result of his sleep study likely to
peripheral vasculature. be?
What would be the most appropriate next A. 5 apnoea/hypopneas per hour of sleep
investigation? B. 10 apnoea/hypopneas per hour of sleep
A. D-dimer C. 20 apnoea/hypopneas per hour of sleep
B. Dysfunctional breathing studies and D. Central sleep apnoea
Nijmegen questionnaire E. Narcolepsy
C. HRCT
D. Spirometry 17.94. A 55 year old woman has an apical lung
E. Transthoracic echocardiography cancer on the left side with lymph node
involvement. She receives radiotherapy 17
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 tumour. 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 may 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 tumour
C. Etanercept E. Psychogenic aphonia
D. Infliximab
E. Isosorbide mononitrate 17.95. A 34 year old man presents with
acute-onset shortness of breath and left-sided
17.91. A 45 year old woman presents pleuritic chest pain. Examination reveals oxygen
with cough that appears in May and saturations of 94% breathing room air,
is gone by autumn. 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 asthma appearance.
B. Allergic rhinitis What should be the next step?
C. Bordetella pertussis A. Admit for observation and oxygen
D. Perennial rhinitis B. Bronchoscopy
E. Viral upper respiratory tract infection C. Cardiothoracic surgery
174 • Respiratory medicine
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 time is
tumour that had been biopsied using computed shortened during exercise. Exercise-induced
tomography (CT) guidance. Pericardial 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 CO2, which might be expected in more
bronchoscopy to re-inflate the lung. advanced disease.
17.2. Answer: E.
17.4. Answer: A.
The patient has type II respiratory failure The CXR shows a large central cavitating mass
following a road traffic accident that caused with a smaller nodule immediately superior to
multiple fractures. It seems very likely that she the mass and a further nodule at the lower pole
would have sustained a whiplash-type injury to of the right hilum. There is a small left-sided
the neck. C3, 4 and 5 innervate the diaphragm pleural effusion. The possible answers given
via the phrenic nerve and a fracture at this level represent a reasonable differential diagnosis for
can cause respiratory failure. The patient has this appearance. The history strongly favours a
type II respiratory failure with a normal bronchial carcinoma.
alveolar–arterial gradient. Opiate toxicity is
unlikely given the dose involved. A flail segment 17.5. Answer: B.
requires multiple rib fractures. A normal The CXR shows significant widening of the
alveolar–arterial gradient is against V̇ /Q̇ mediastinum and a small right-sided pleural
Respiratory medicine • 175
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 pericardial 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.
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
17
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.
bronchial carcinoma. Given the patient’s The patient has a large left-sided pneumothorax
performance status and normal pulmonary (> 2 cm depth measured at hilum) and is
176 • Respiratory medicine
symptomatic. He probably has a concurrent might have been expected to improve his
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 T4N2M0 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. Transbronchial lung
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.
17.24. Answer: E.
very careful about attributing chronic cough to
Seasonal deterioration in asthma control is a ‘habit’. Reflux may be at the root of this cough
common presentation and it seems likely that but at this stage it is important to rule out
the patient encounters these allergens when parenchymal disease/bronchial carcinoma. A
she is out running. It will be important in future trial of steroid medication would usually be
to monitor the pollen counts and to avoid areas given if there was a suspicion of asthma or
of high antigen density (e.g. near oilseed rape eosinophilic bronchitis, but further testing would
fields). The patient may be allergic to cats and be useful prior to this. ENT surgeons may be
dogs but it would not explain this presentation. consulted when there is chronic rhinitis/sinusitis
It is possible to have positive specific IgEs but as part of a cough presentation, which does
no clinical phenotype on antigen exposure. The not respond to standard therapies.
history is as important as the serological
testing. Total IgE cannot be used to monitor 17.29. Answer: B.
medication adherence. Exercise-induced Given the CXR findings and history, reflux is the
asthma would not have such strong most likely cause even though the patient is
seasonality. asymptomatic (proton pump inhibitor started
following a duodenal ulcer, so no ongoing
17.25. Answer: C.
heartburn). TB is unlikely as the cough is
Nucleic acid amplification testing of sputum or non-productive and there are no systemic
throat swab would differentiate between symptoms. Asthma is less likely because there
legionella and influenza in this case. The test is no nocturnal element. Hypercalcaemia does
result would be available quickly. Sputum not cause cough, although if it were present
cytology has a limited role in respiratory alongside cough it should raise the suspicion of
diagnostics. HRCT would be unlikely to offer malignancy. Lung cancer is unlikely because of
more information than the CXR. Paired serology the duration of the cough.
would determine whether the patient had been
infected by legionella but would not be available 17.30. Answer: C.
in a timely fashion. Differential cell count would
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 exacerbations 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 CTPA
with recurrent pleuritic chest pain but more may determine the source of bleeding (e.g.
commonly is associated with progressive tumour or pulmonary arteriovenous
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. Smoking is a very strong risk
The likely cause of haemoptysis here is a factor for lung cancer.
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 useful for nodules > 1 cm 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
Respiratory medicine • 179
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.
17.39. Answer: B.
17.44. Answer: B.
Transudative effusions include organ failure: The scenario does not provide enough
cardiac, renal, liver and thyroid. Hypothyroidism information to advocate initiation of omalizumab
is therefore the correct answer, although it is (we do not know patient’s body mass
relatively rare. index (BMI), total IgE, sensitisation to
allergens). Montelukast and oral theophylline
17.40. Answer: B.
preparations are recommended as
Light’s criteria suggest an exudate additional therapy at this stage. Doubling the
where two of the three criteria are met. prednisolone would increase side-effects
It is nonetheless important to take a without increasing efficacy. There is no
holistic overview of the case as the criteria indication for an antibiotic here. Home
misclassify transudates as exudates 25% of nebulisers are not recommended in asthma
the time. because of the risk of late presentation with
significant exacerbation.
17.41. Answer: C.
17.47. Answer: B.
17.52. Answer: C.
The diagnosis is likely to be allergic The patient has recently returned from
bronchopulmonary aspergillosis. This is an the Middle East and has a serious
allergic reaction to Aspergillus, which can drive respiratory infection. Isolation and
excess sputum production, bronchiectasis and exclusion (or diagnosis) of MERS are priorities.
lobar collapse (this would explain the pleuritic Burkholderia pseudomallei is endemic to
chest pain and CXR findings). The key tests South-east Asia and Northern Australia. Local
would be Aspergillus serology, sputum antibiotic protocol is irrelevant here because of
mycology and HRCT. The management would the patient’s travel history. CPE testing is
include oral corticosteroids, an antifungal agent, important when patients have been hospitalised
nebulised bronchodilators and chest in countries with a high prevalence of this
physiotherapy. Bronchoscopy to remove thick organism.
secretions may be required to promote lung
re-inflation. 17.53. Answer: D.
17.50. Answer: D.
17.56. Answer: B.
The common cold is most frequently caused by The patient has developed haematogenous
the rhinovirus. Bordetella pertussis causes lung abscesses from an infected injection site.
whooping cough, which can be very prolonged It is likely that the right side of the heart
in adults. (pulmonary and tricuspid valves) is affected and
the patient has infective endocarditis.
17.51. Answer: E.
test relies on the release of interferon-gamma not associated with the usual features of the
from sensitised T cells. carcinoid syndrome.
17.59. Answer: E.
17.65. Answer: D.
This presentation is consistent with psoas Significant survival benefits are conferred by
abscess and, whilst there may be a treatment with tyrosine kinase inhibitor drugs in
bacteriological cause, this would be a typical patients with EGFR mutation, even in the
extrapulmonary presentation of TB. Malignancy presence of metastatic disease. The presence
is a major differential diagnosis. The type of of these mutations is more common in
imaging utilised above is not identified, but a non-smoking patients with adenocarcinoma.
CT/magnetic resonance imaging (MRI) would
be invaluable to assess for spinal disease and 17.66. Answer: B.
17.63. Answer: D.
17.70. Answer: D.
17.64. Answer: C.
17.71. Answer: E.
A young non-smoker with isolated haemoptysis The presence of extensive fibrosis even in the
and a localised, vascular tumour is likely to presence of enlarged lymph nodes is
have a bronchial carcinoid. These tumours are suggestive of sarcoidosis stage IV. The
rare but have an excellent outcome. They are patient’s breathlessness and abnormal lung
182 • Respiratory medicine
failure from a silent progression of pulmonary The answers above are a reasonable differential
sarcoidosis. The absence of inspiratory crackles diagnosis for the presentation. A progressive
on examination suggests the fibrotic change is pneumonitis is a side-effect of nitrofurantoin
due to sarcoidosis. taken long term for prevention of urinary tract
infections. The subacute onset with systemic
17.72. Answer: E.
symptoms mitigates against IPF or NSIP, whilst
Rheumatoid arthritis has many respiratory atypical pneumonia would be expected to be
complications including nodules, pleural more acute. A cryptogenic organising
effusion, bronchiectasis and interstitial lung pneumonia should not be assumed whilst a
disease. In addition, medications given for potential cause is evident.
rheumatoid arthritis also have respiratory
complications and leave patients prone to a 17.77. Answer: C.
the likely diagnosis. As the patient has become A patient who works with beryllium and
systemically unwell with an oxygen requirement presents with a sarcoid-like clinical picture and
it is reasonable to start prednisolone as well as imaging should have berylliosis excluded as a
stopping the causative agent. The high priority. Her husband’s work should not
eosinophil count makes HAP unlikely. TB influence her respiratory status unless she is
should be considered (it can also cause a spending significant amounts of time assisting
discitis) but does not cause a peripheral blood him. It is possible that where there is damp,
eosinophilia. Fluid overload is considered less mould is also present, but hilar adenopathy
likely because of the presence of fever and would be uncommon in hypersensitivity
atypical radiology. pneumonitis. Although she has some work
stress, dysfunctional breathing would not
17.75. Answer: E.
explain her arthralgia, cough or X-ray
The presentation here is of multisystem appearances.
granulomatous polyangiitis. The patient has
multiple nodules on CXR and the presentation 17.80. Answer: E.
with stridor suggests subglottic stenosis. It Finger clubbing and basal crackles are
seems likely the patient also has renal characteristic of idiopathic pulmonary fibrosis.
involvement. Sinusitis and conductive deafness Melanoptysis (black sputum) is associated.
are also suggestive of granulomatous Simple coal worker’s pneumoconiosis has no
polyangiitis. impact on lung function but PMF may lead to
Respiratory medicine • 183
the mediastinum, chest wall pain that keeps This is a clear case of pulmonary
him awake at night and significant asbestos thromboembolism (PTE) in a high-risk patient.
exposure. Although he has had benign D-dimer has been inappropriately checked as
asbestos pleurisy in the past, the presentation the patient is high risk and this test only safely
here is more sinister. Asbestosis is a fibrosing excludes VTE in low-to-moderate risk patients.
lung condition that would be picked up on CT. Echocardiogram may show right heart strain
Although the patient has pleural plaques, these but cannot diagnose PTE. Sputum microscopy,
should not affect his respiratory function or culture and sensitivity, and respiratory virus
clinical condition. throat swab would be appropriate if the history
and CXR were in keeping with respiratory
17.83. Answer: C.
infection. The elevated diaphragm here is likely
The patient has exposure to a parrot and to reflect pleuritic pain or potentially atelectasis
a CT in keeping with hypersensitivity in keeping with PTE. Diaphragmatic studies are
pneumonitis. It is very likely she has not indicated here.
bird fancier’s lung. Although the CT was
focused on the coronary arteries, the image 17.87. Answer: D.
quality is not likely to have created these
CT scan focused on the lungs was arranged to Pulmonary hypertension is defined as mean
ensure optimal imaging available at baseline. pulmonary artery pressure of at least 25 mmHg
Removal of the parrot and deep cleaning of the at rest, as measured at right heart
room it resided in are likely to lead to complete catheterisation.
resolution of the clinical and radiological
findings. 17.89. Answer: E.
actively during inspiration. Abnormal ventilatory This man has a past history of polio and he
drive is present in central sleep apnoea. Forty seems to have bilateral diaphragmatic
per cent of middle-aged men snore. During weakness that is significantly impairing his
sleep muscle tone decreases. respiratory function. A diaphragmatic defect or
eventration would be unlikely to cause
17.93. Answer: C.
respiratory failure. Bronchial carcinoma would
The patient’s presentation is typical of be more likely to cause unilateral diaphragmatic
obstructive sleep apnoea and 15 or more paralysis. A history of polio means that this is
apnoea/hypopnoeas per hour of sleep is unlikely to be idiopathic.
diagnostic.
17.97. Answer: E.
17.94. Answer: B.
Thoracic kyphoscoliosis is caused by vertebral
There is no vocal cord paralysis, so local disease, trauma, neuromuscular disease or can
trauma during intubation is the likely cause of be a congenital abnormality. Asthma is
the acute-onset hoarseness. associated with pectus carinatum.
AJ Anderson
18
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-α)
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
to have thickened pigmented skin at the back E. Posterior pituitary
of his neck and in the axillae. His body mass
index (BMI) is elevated at 38 kg/m2. 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
What is the underlying cause? 18.5. Where does arginine vasopressin (AVP)
A. Cranial diabetes insipidus exert its maximum effect in the kidney?
B. Diabetes mellitus A. Collecting ducts
C. Nephrogenic diabetes insipidus B. Distal convoluted tubule
D. Normal response to water deprivation C. Glomerulus
E. Psychogenic polydipsia D. Loop of Henle
E. Proximal tubule
186 • Endocrinology
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
(T3) 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 µg 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 pmol/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 pmol/L (0.39 ng/dL) 18.12. A 34 year old woman presents to her
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 pmol/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 6 mIU/L, and free pattern of uptake.
T4 of 12.4 pmol/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 2 × 3 cm 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
18.25. A 32 year old woman attends her family total testosterone 5.6 nmol/L (162 ng/dL),
physician with a 12-month history of inability to SHBG 42.1 nmol/L (4.00 µg/mL), FSH 2.1 IU/L
conceive. She has been having regular periods (0.5 µg/L) and LH 1.76 IU/L (0.2 µg/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 10 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
C. Day 14 surge in 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 C. 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 BMI of
underpinned by which process? 31 kg/m2 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
C. High circulating leptin from which of the following?
D. Hyperprolactinaemia A. Genetic mutation in 3β-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. C. Increased pulsatility of GnRH
She is noted to be of short stature. Blood D. Reduced aromatisation of androgens by
18
tests reveal FSH 26.2 IU/L (5.9 µg/L), LH theca cells
18.5 IU/L (2.0 µg/L) and oestradiol < 50 pmol/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.
C. 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 IQ
B. Increased risk of ovarian cancer
18.28. A 12 year old boy attends his family C. 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 noticed that he is
C. Occurs as young as 3–6 months of age taller than his classmates. On 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 nmol/L (216 ng/dL), FSH
endocrinology clinic with a history of poor libido 12 IU/L (2.8 μg/L), LH 11 IU/L (1.2 µg/L). What
and erectile dysfunction. Blood tests reveal is the most appropriate next test?
190 • Endocrinology
and body odour, and her voice has become A. Bilateral lesions
deeper. A diagnosis of congenital adrenal B. Hounsfield units < 10 HU
hyperplasia (CAH) is being considered. C. Retention of contrast
What is the commonest enzyme deficiency D. Size < 4 cm
in CAH? E. Smooth surface
A. 11β-hydroxysteroid dehydrogenase
B. 17α-hydroxylase 18.45. A 24 year old man is admitted to the
C. 17β-hydroxysteroid dehydrogenase emergency department having collapsed at the
D. 18-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 nmol/L (5.55 µg/dL). Which B. Dexamethasone
of the following would be an appropriate next C. Fludrocortisone
investigation? D. Ketoconazole
A. 24-hour urine free cortisol E. Phenoxybenzamine
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 mmol/L. He
has been commenced on antihypertensive
18.42. A 56 year old man with recently therapy and is referred in for investigation of 18
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-1
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
192 • Endocrinology
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
A. ACTH diabetes insipidus?
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 mmol/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
B. GH PTH level. He has recently been investigated
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 mmol/L (76 mg/dL). E. Phaeochromocytoma
Answers
18
18.1. Answer: D. 18.2. Answer: B.
Primary hypoadrenalism results in increased High concentrations of insulin
synthesis and secretion of adrenocorticotrophic (hyperinsulinaemia) exert proliferative effects
hormone (ACTH) from the pituitary gland. Due through the insulin-like growth factor-1 (IGF-1)
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
194 • Endocrinology
Stimulates all
Diiodotyrosine (DIT) MIT
steps 1 8 Iodide 7
NH2 DIT
+ hyperplasia
HO CH2 CH COOH
T4
8
4 T3
Thyroxine (T4)
NH2 Target tissues
HO O CH2 CH COOH rT3 Increased metabolic rate
Mimic β-adrenergic action,
Blood e.g. on heart rate, gut motility
Free T4,T3 T4
CNS activation
( < 1%) 8 Bone demineralisation
Reverse T3 (rT3) Negative
T3 Cellular differentiation
NH2 feedback
etc.
HO O CH2 CH COOH
Protein-bound
T4, T3 ( > 99%)
Fig. 18.6 Structure and function of the thyroid gland.
(1) Thyroglobulin (Tg) is synthesised and secreted into the colloid of the follicle. (2) Inorganic iodide (I–) is actively transported into the
follicular cell (‘trapping’). (3) Iodide is transported on to the colloidal surface by a transporter (pendrin, defective in Pendred’s syndrome)
and ‘organified’ by the thyroid peroxidase enzyme, which incorporates it into the amino acid tyrosine on the surface of Tg to form
monoiodotyrosine (MIT) and diiodotyrosine (DIT). (4) Iodinated tyrosines couple to form T3 and T4. (5) Tg is endocytosed. (6) Tg is cleaved
by proteolysis to free the iodinated tyrosine and thyroid hormones. (7) Iodinated tyrosine is dehalogenated to recycle the iodide. (8) T4 is
converted to T3 by 5′-monodeiodinase.
Endocrinology • 195
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: C.
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
doses for replacement. replacement with levothyroxine and close
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 µg
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, unless 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.
Endocrinology • 197
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’ XXY 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. 3β-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 no
Constitutional delay is observed more frequently increased risk of ovarian cancer. Excess
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 pregnancies.
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 hypergonadotrophic 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,
Endocrinology • 199
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 WCC 23 × 109/L, platelets
in clinic after recently emigrating to the UK. Her 340 × 109/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 ECG 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 µg 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 19
responsive, disorientated, anicteric, cachectic D. Pork
and has restricted horizontal eye movement E. Sunflower oil
bilaterally. His lab results are notable for mildly
elevated transaminases and low albumin. 19.13. A 32 year old woman gives birth to a
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 pyruvate to acetyl-co-
E. Thiamine is fat soluble enzyme A to initiate the Krebs cycle
C. Donating a methyl group 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 39°C 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
206 • Nutritional factors in disease
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 WHO recommended population
This is an obese patient being evaluated for i 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
calorie diets require the supervision of an Trans fatty acids 0 2
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
i 19.1 Potentially reversible causes of weight gain
Protein 10 15
19
Endocrine factors
Hypothyroidism
Cushing’s syndrome 19.3. Answer: D.
carbohydrates and 10–15% for proteins (Box This patient with a history of chronic alcoholism
19.2). High saturated fat consumption is is at risk for malnutrition and 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
208 • Nutritional factors in disease
Habit
Hedon c
response
Supplementation with vitamin D, or
cholecalciferol, is recommended for this woman
to food Sat ety Neuro endocrine responses Reproductive
growth hormone cortisol thyroxine) hormones
Autonomic nervous system
years for nutritional status to stabilise before This patient from Angola presents with
becoming pregnant. dementia, diarrhoea and dermatitis consistent
with pellagra, or niacin deficiency. The enlarged
19.6. Answer: B.
tongue is due to non-infective inflammation of
This patient is presenting with anaemia in the the gastrointestinal tract leading to glossitis.
setting of chronic blood loss, koilonychias, and Pellagra can develop in certain parts of Africa
pica, consistent with iron deficiency anaemia. In and South America where corn-based diets
a state of iron deficiency, hepcidin production predominate. Treatment is with oral or
decreases in order to promote the transport of parenteral nicotinamide and usually results in
iron from the enterocyte basolateral surface into rapid improvement of symptoms.
circulation. Absorption of iron is facilitated by
vitamin C and impaired by dietary calcium. 19.10. Answer: A.
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.
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 1000 mL of a
cellular division. glucose/electrolyte solution with a sodium
concentration of at least 90 mmol/L should be
19.14. Answer: D.
given (e.g. St Mark’s solution or Glucodrate,
The residual length of jejunum following Nestlé) 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 cm 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 mmol/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 cm 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 cm 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.
addition to the other treatments above. There are nine essential amino acids (Box
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.
19.19. Answer: E.
19.20. Answer: E.
The evidence that tube feeding in advanced Gastrostomy is known to be associated with
dementia improves any of these parameters is risks of insertion (pain, bleeding, aspiration
very weak and inconsistent. Patients and their pneumonia, infection of the insertion site,
families are often caught up in a vicious cycle inadvertent damage to an intra-abdominal
of dementia and malnourishment (Fig. 19.19). organ or viscus, tube displacement) and
It is important to screen patients with dementia longer-term risks (infection at insertion site,
for malnutrition, to monitor body weight, tube displacement, aspiration of feed). It does
encourage an adequate intake of food and not offer any advantage over nasogastric
provide a pleasant home-like environment for feeding in terms of aspiration risk. The decision
meals. Oral nutritional supplements have been to go ahead should be taken when patients or
shown to be of benefit. Cases should be their carers are fully aware of the risks and
assessed individually. However, unless there is benefits involved.
some acute, reversible event (e.g. further
stroke, treatable infection), which may be
bridged by a short period of tube feeding, there
is little benefit to artificial nutritional support in
advanced cases of dementia.
Dementia Age-related
Frailty Cognitive changes and
Sarcopenia impairment diseases
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?
Diabetes mellitus • 213
a day. Which of the following conditions has a 20.17. 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/m2 and undergoes an OGTT, the
C. NAFLD results of which are: fasting plasma glucose
D. Optic atrophy 4.8 mmol/L (86 mg/dL); 2-hour plasma glucose
E. Rheumatoid arthritis 7.0 mmol/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 mmol/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 coast 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 mmol/L (101 mg/dL); 120 minutes = B. Deep vein thrombosis (DVT)
9.2 mmol/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/m2); 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/mmol (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 mmol/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. HbA1c
E. No need to monitor blood glucose in view of D. Urinalysis
his age E. Weight
Diabetes mellitus • 215
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 m2 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 mmol/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
6.2 × 109/L negative plasma glucose after recovery from infection
Urea 5.2 mmol/L Antineutrophil B. Commence treatment with liraglutide
(31 mg/dL) cytoplasmic C. Commence treatment with metformin
Creatinine 62 µmol/L antibody D. No further assessment of glycaemic control
(0.70 mg/dL) (ANCA): negative E. Variable-rate intravenous insulin infusion
Glucose 11.4 mmol/L Ferritin 1137 µg/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 mmol/L (238 mg/dL), confirming a
diagnosis of diabetes. She takes a number of
A. Hereditary haemochromatosis
medications for hypertension, ischaemic heart
B. MODY
disease and polymyalgia rheumatica. Which of
C. Steroid-induced diabetes
the following medications can precipitate
D. Type 1 diabetes
hyperglycaemia?
E. Type 2 diabetes
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 β cells. These cells regulate blood D. Nitrate (e.g. isosorbide mononitrate) 20
glucose concentrations by coupling glucose E. Steroid (e.g. prednisolone)
with insulin secretion. Glucose enters the
pancreatic β cells by facilitated diffusion down 20.25. An 18 year old female with type 1
its concentration gradient through cell diabetes is admitted with suspected
membrane glucose transporters (GLUTs). pyelonephritis. She has not taken any insulin for
Through which GLUT does glucose enter 24 hours during her acute illness. Her initial
pancreatic β cells? blood tests include: plasma glucose 24 mmol/L
(432 mg/dL), bicarbonate 12 mmol/L and
A. GLUT1 ketones 5.5 mmol/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 amoxicillin by
B. Inhibition of insulin release his family physician for a suspected chest
C. Stimulation of glucagon release infection 2 weeks ago. He appears clinically
216 • Diabetes mellitus
dehydrated. His initial blood tests include: A. Advise him to avoid exercise
plasma glucose 55 mmol/L (991 mg/dL), B. Always omit the short-acting insulin dose
ketones 0.1 mmol/L, sodium 149 mmol/L and after exercise
serum osmolality 368 mmol/kg. Which of the C. Reduce his total daily insulin dose to relax
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/m2
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 1α
appropriate if he wishes a strategy that
(HNF1α) 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. PPARγ agonist/thiazolidinedione (e.g.
A. Activation of PPARγ
pioglitazone)
B. Activation of the GLP-1 receptor
E. Sulphonylurea (e.g. glipizide)
C. Closure of the transmembrane β-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 not
settled with topical antifungal treatment. She
20.28. A 21 year old female with type 1 had been started on a new oral hypoglycaemic
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. PPARγ agonist/thiazolidinedione (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. 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 be 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 transglutaminase (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
Diabetes mellitus • 217
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 GI 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 mmol/L (396 mg/dL), ketones 4.3 mmol/L,
bicarbonate 11 mmol/L, alkaline phosphatase 20.37. A 72 year old man is admitted to hospital
250 U/L, white cell count 19 × 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 mmol/L 20
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 (10.4%). 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 deteriorate significantly should
filtration (eGFR) rate is 54 mL/min/1.73 m2. her glycaemic control improve suddenly?
Which of the following drugs would be most A. Foot ulceration
beneficial? B. Gastroparesis
A. ACE inhibitor (e.g. lisinopril) C. Microalbuminuria
B. β-blocker (e.g. atenolol) D. Peripheral vascular disease
C. Calcium channel blocker (e.g. amlodipine) E. Retinopathy
218 • Diabetes mellitus
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 mmol/L
a suboptimal HbA1c of 68 mmol/mol (8.4%) and (360 mg/dL), ketones 2 mmol/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/m2 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. β-cell antibodies are
is constant checked and he is found to have a very high
C. 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 C. 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 ≥ 11.1 mmol/L (≥ 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.
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. Caution 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 DKA 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
Diabetes mellitus • 219
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 PPARγ. 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.
Thiazolidinediones enhance the action of The history here suggests vomiting to be the
endogenous insulin in the adipose cells but also most likely cause of ketonuria.
20
alter the release of adipokines, which adjust
insulin sensitivity in the liver. 20.12. Answer: B.
to swallow, GlucoGel or refined sugar drink can The most likely diagnosis is hyperemesis
be used. Blood glucose should be re-checked gravidarum, a complication of pregnancy
after 15 minutes and re-treated if needed. characterised by severe nausea, vomiting and
Once conscious, an oral complex-carbohydrate dehydration. The diagnosis is usually clinical but
snack should be given. Insulin should not be has been defined as three of more episodes
omitted. If a dosing error was made, then of vomiting in a day such that weight loss of
adjustment may be required. Fifty per cent 5% has occurred and there is evidence of
glucose is generally discouraged due to risk of ketones in the urine. Risk factors include first
infusion vein irritation. pregnancy, multiple pregnancy, obesity and a
family history. When vomiting is severe it can
20.15. Answer: A.
lead to dehydration and ketosis.
The aim of managing gestational diabetes is to A diagnosis of gestational diabetes is based
normalise the maternal blood glucose and upon maternal blood glucose measures that
therefore reduce excessive fetal growth. The are associated with increased fetal growth.
first step is dietary modification, namely Women at high risk of developing gestational
reducing the amount of fast-acting refined diabetes include: BMI > 30 kg/m2; previous
carbohydrate. Regular blood glucose macrosomic baby; previous gestational
monitoring is required. If diet alone does not diabetes; a first-degree relative with gestational
achieve targets, then metformin should be diabetes; and high-risk ethnicity. These women
started. If not tolerated or additional treatment should all undergo screening. This woman has
is required, insulin should be commenced. a BMI of 36 kg/m2, so warrants screening;
Glibenclamide can be used if metformin and however, her results did not reach the NICE
insulin are not tolerated, because it does not criteria for gestational or any other type of
cross the placenta. In some countries, diabetes.
glibenclamide and metformin are not licensed
for use in pregnancy. There is no evidence for 20.18. Answer: A.
safety of any other hypoglycaemic agents in Acute Charcot arthropathy almost always
pregnancy. presents with signs of inflammation – a hot,
red, swollen foot. Initial X-ray may show bony
20.16. Answer: A.
destruction but can be normal. There is often a
The aims of treatment and target HbA1c history of peripheral neuropathy or previous
depends on the individual patient. Early in foot ulceration. As Charcot can be difficult to
diabetes a target HbA1c of 48 mmol/mol (6.5%) differentiate from osteomyelitis, MRI of the foot
or less may be appropriate to try to prevent can be helpful. The pathophysiology is not well
microvascular disease. An HbA1c of 58 mmol/ understood but may involve unperceived
mol (7.5%) or less may be more appropriate in trauma with underlying neuropathy leading to
some older patients with cardiovascular progressive destruction. In this case, minor
Diabetes mellitus • 221
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 β 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 β 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. Microalbuminuria is insulin and is responsible for insulin-regulated
present if ACR is 2.5–30 mg/mmol creatinine in glucose storage. GLUT5 is a fructose
men and 3.5–30 mg/mmol 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.
This patient has good glycaemic control The patient most likely has ‘stress
and has a healthy BMI with normal level of hyperglycaemia’ provoked by acute illness, in
cholesterol. Blood pressure may 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, hyperglycaemia 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 an increased risk
heart, skin, gonads, joints and pancreas. of developing diabetes while taking
Patients can present with cirrhosis, β-adrenoceptor antagonists (β-blockers) and
polyarthropathy, adrenal failure, heart failure or thiazide diuretics for blood pressure 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
222 • Diabetes mellitus
adipose tissue. GLP-1 analogues activate the Empagliflozin, an inhibitor of the sodium and
GLP-1 receptor. SGLT2 inhibitors have their glucose co-transporter 2 (SGLT2) in the kidney,
action in the kidney where they inhibit SGLT2, exerts its glycaemic effect by increasing the
thereby reducing re-uptake of glucose from amount of glucose in the urine. This can result
the urine. in fungal infection in approximately 5% of
Diabetes mellitus • 223
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 genital tract 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
99m
technetium 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.
20.34. Answer: D.
20.38. Answer: E.
The patient’s clinical status and biochemical It is well recognised that when glycaemic
findings are consistent with DKA. He requires control improves rapidly, there can be a
urgent treatment in hospital. His pH on venous transient deterioration in the degree of
or arterial blood gas would be < 7.30 (H+ > retinopathy. This is thought to be due to loss of
50.1 nmol/L) consistent with metabolic hyperglycaemia-induced hyperperfusion in the
acidosis. The white cell count and alkaline retinal circulation. The effect typically wears off
phosphatase levels are often elevated in DKA within 18 months. Therefore, in patients with
and subside with treatment. Due to significant established retinopathy, it is recommended that
volume depletion in this condition, haemoglobin improvement in glycaemic management should
concentrations are often elevated and will be effected gradually. Transient worsening of
reduce with expansion of the intravascular peripheral neuropathy symptoms can similarly
compartment following administration of be seen in this situation.
intravenous fluid.
20.39. Answer: D.
20.35. Answer: A.
Insulin pump therapy is becoming more widely
ACE inhibitors such as lisinopril or angiotensin used for glycaemic control in type 1 diabetes.
receptor blockers would be the most The pump delivers a constant infusion of
224 • Diabetes mellitus
additional long-acting insulin. CGMS is not It is estimated that 50% of cases of type 1
mandatory, although it is a useful adjunct for diabetes present in adulthood. The patient is
monitoring glucose levels while on pump best described as having LADA, an insidious
therapy. As the technology becomes more form of type 1 diabetes that develops in
sophisticated, there will be more ‘closed loop’ adulthood. This condition initially presents like
systems, whereby the glucose monitor and type 2 diabetes but is characterised by a
pump communicate with one another to relatively rapid progression to insulin treatment
optimise insulin delivery. DKA is still a and the presence of β-cell antibodies. MODY
possibility, for example in the case of pump and mitochondrial diabetes typically occur
failure. One of the attractions of pump therapy where there is a strong family history of
is the ability to alter the basal rate of insulin diabetes, sometimes with other clinical
depending on the time of day or level of manifestations such as sensorineural deafness
physical activity (i.e. lower basal rate at night in the case of mitochondrial disease. Pancreatic
or during exercise to reduce the risk of exocrine disease typically occurs in those
hypoglycaemia). The risk of microvascular with a history of conditions that affect
complications of diabetes depends on the pancreatic function such as pancreatitis,
HbA1c and glucose variability rather than the haemochromatosis, pancreatectomy and
mode of insulin delivery. pancreatic cancer.
E El-Omar, F Clegg,
MH McLean
21
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 10% 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/m2 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 physician prescribes a 1-month course of
routine blood tests, offers her advice and starts omeprazole, which cures his symptoms but
her on an oral medication. Which statement is they soon return after stopping the omeprazole.
correct? The family physician refers him for an upper
A. Asking about dysphagia is irrelevant because gastrointestinal (GI) endoscopy, which shows
this is not caused by fungal infections evidence of a small hiatus hernia and Barrett’s
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 (GORD)
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 GORD 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 Question 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
226 • Gastroenterology
endoscopy report, which his internet search settled on the highest dose of esomeprazole.
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 (5–10% 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 middle third of the
heartburn, severe regurgitation and retrosternal/ oesophagus
epigastric pain. An upper GI 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
Gastroenterology • 227
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 GI 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 GI endoscopy
C. Oesophageal adenocarcinoma is very
sensitive to radiotherapy 21.14. The above patient undergoes upper GI
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 GI 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
21.12. A 55 year old man presents with E. There is no strong indication to stop
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
21
anaemia and hypoalbuminaemia. Upper GI 21.15. The patient in Question 21.14 is found to
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. GI manifestations of thyrotoxicosis week
E. Ménétrier’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
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 population
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
228 • Gastroenterology
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 IgA 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
Lieberkühn B. Ingestion of gluten-containing foods in
E. They only bleed if patients also take genetically susceptible individuals leading to
NSAIDs a T-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-DQ2/DQ8 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 µg/L and to microbial dysbiosis and microbial
a folate of 1 µg/L and are otherwise normal. secretion 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 of Th17 immune cells that
B. Coeliac serology with serum immunoglobulin react with gluten in the proximal small bowel
A (IgA)
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 oral antibiotics for 1 year
21
weight loss and low-grade fever. Blood analysis B. Seven days of oral metronidazole
reveals alkaline phosphatase (ALP) of 235 U/L C. Intravenous immunoglobulin
and γ-glutamyl transferase (GGT) of 120 U/L. D. No treatment is re1quired – 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 IgA. B. Endoscopic argon plasma coagulation
What is the next best investigation? C. Loperamide
A. Check anti-endomysial antibody (anti-EMA) D. Predfoam enema
and immunoglobulin G (IgG) E. Sucralfate enema
230 • Gastroenterology
21.29. A 36 year old woman presents with an A. Intramuscular glucocorticoids for 10 days,
intermittent history of diarrhoea and increased low-molecular-weight heparin (LMWH),
bowel-opening frequency over a 2-year period. intravenous fluid and then reassess response
For the last 8 months, her symptoms have B. Intravenous glucocorticoids for 3 days,
worsened and become persistent. She is LMWH, intravenous fluid and then reassess
currently passing stool 8 times per day with response
urgency. The consistency of stool is watery and C. Intravenous vedolizumab infusion and
she reports that her stool is green in colour. smoking cessation
Her past medical history is mild asthma and D. Loperamide and metronidazole
cholecystectomy 12 months ago. She has no E. Surgery with subtotal colectomy and
family history of note. ileostomy
What investigation is most likely to lead to
the diagnosis? 21.33. A 54 year old man with ulcerative colitis
A. Colonoscopy is receiving hospital treatment for acute severe
B. Endoscopy and duodenal biopsy ulcerative colitis. He becomes acutely unwell
C. Hydrogen breath test with sweating and shortness of breath.
D. 75Se-homocholic acid taurine (SeHCAT) Pulse is 110 beats/min, blood pressure is
scan 120/68 mmHg, temperature is 37.7°C and
E. Thyroid function test respiratory rate is 28 breaths/min. Oxygen
saturation is 94% on air. What is the most
21.30. A 19 year old woman presents with appropriate investigation to lead to the
a 6-month history of diarrhoea, right iliac diagnosis?
fossa pain and weight loss. Blood tests A. Chest X-ray
show her platelet count is 721 × 109/L, B. CT pulmonary angiography
haemoglobin 100 g/L and C-reactive protein C. Echocardiogram
(CRP) 62 mg/L. Investigation reveals a D. Electrocardiogram
diagnosis of terminal ileal Crohn’s disease and E. Troponin I
her symptoms improve with a course of oral
prednisolone. What is the next most 21.34. A patient with inflammatory bowel
appropriate treatment? disease is commenced on azathioprine for
A. A 4-week course of ciprofloxacin maintenance immunosuppression. What is the
B. Anti-α4β7 integrin biologic therapy appropriate advice to give the patient?
C. Azathioprine A. The patient requires an annual chest X-ray
D. Immunoglobulin and hepatitis serology
E. Methotrexate B. The patient requires blood analysis within 1
week of starting this medication to test
21.31. Inflammatory bowel disease is associated amylase
with extra-intestinal manifestations of disease. C. The patient requires regular blood analysis to
Which of the following is most commonly test liver and bone marrow function
associated with ulcerative colitis? D. The patient should not conceive whilst on
A. Blepharitis this medication
B. Primary sclerosing cholangitis E. This medication reduces the risk of future
C. Psoriasis malignancy
D. Pyoderma gangrenosum
E. Renal calculi 21.35. Which of the following statements most
accurately describes a key pathophysiological
21.32. A 27 year old man with known ulcerative process underlying the development of Crohn’s
colitis is admitted to hospital for management disease?
of an acute severe flare in colitis. His stool A. Activation of colonic nicotinic receptors by
frequency is 10 times per day including smoking leads to altered host handling of
nocturnal bowel opening, and he has a mild adherent invasive Escherichia coli
fever. Blood pressure is 122/78 mmHg, pulse B. Cytokines secreted from innate lymphoid
is 88 beats/min; CRP is 82 mg/L. What is the cells cause mucosal inflammation
most appropriate initial management? throughout the colon
Gastroenterology • 231
morning and associated with bloating in the 21.46. A 40 year old male with a diagnosis of
evening. She describes left-sided crampy chronic pancreatitis complains of foul-smelling
abdominal pain, relieved by defaecation. She is pale stools, which are difficult to flush. A
a single mother to a 3 year old boy. The deficiency in which of the following hormones/
company she works for has declared that jobs enzymes is responsible?
may not be stable during a management A. Chymotrypsin
change. Thyroid function is normal and coeliac B. Glucagon
serology is normal. C. Lipase
What is the next best investigation? D. Maltase
A. C-reactive protein E. Somatostatin
B. Platelet count
C. Small bowel MRI 21.47. A 42 year old man has recurrent
D. Stool calprotectin duodenal ulceration with bleeding despite
E. Upper GI endoscopy and duodenal omeprazole therapy use. H. pylori serology has
biopsies been negative on three occasions. An
abnormality is noticed on imaging of his
21.43. A 30 year old woman has a diagnosis of pancreas. What other health problems might
diarrhoea-predominant IBS. Her symptoms are this man have?
negatively impacting her ability to work in the A. Marfan’s syndrome
local supermarket and she is avoiding social B. Medullary thyroid cancer
functions for fear of unpredictable onset of C. Phaeochromocytoma
symptoms. She has tried a variety of dietary D. Pituitary adenoma
manipulations including a wheat-exclusion diet, E. Type 1 diabetes mellitus
a dairy-free diet and avoidance of caffeinated
drinks, with no improvement of her symptoms. 21.48. A 56 year old man with a history of
What is the next most appropriate treatment to heavy alcohol use presents with abdominal
consider? bloating following a recent episode of severe
A. 5-HT4 agonist, prucalopride central abdominal pain radiating to the back.
B. Nocturnal small-dose diazepam Clinical examination reveals resolving
C. Peppermint capsule periumbilical bruising and abdominal distension
D. Probiotics with shifting dullness. Blood tests demonstrate
E. Referral to dietician for consideration of a bilirubin 18 µmol/L (1.05 mg/dL), alanine
low-FODMAP (fermentable oligo-, di- and aminotransferase (ALT) 50 U/L, ALP 200 U/L,
monosaccharides, and polyols) diet GGT 823 U/L, international normalised ratio
(INR) 1.1. What initial test is most likely to give
21.44. Which of the statements is true the correct diagnosis?
when considering the normal function of the A. Alpha-fetoprotein
colon? B. Ascitic fluid albumin
A. Absorption of folic acid occurs in the C. Ascitic fluid amylase
colon D. Ascitic fluid cell count
B. The colon absorbs 50% of ingested protein E. Serum albumin
and fats
C. The colon absorbs electrolytes and water 21.49. Pancreatic fluid is normally excreted via
D. The colonic microbiota is acquired at birth the main pancreatic duct into the duodenum.
and is static throughout life In pancreas divisum, during embryonic
E. The pH of the colonic lumen is 3 development the dorsal and ventral ducts fail to
fuse, leading to main excretion via the dorsal
21.45. The arterial blood supply to the pancreas duct. Which structure does pancreatic fluid
is shared with which other organ/tissue? bypass in pancreas divisum?
A. Left kidney A. Ampulla of Vater
B. Ovaries B. Duodenum
C. Psoas muscle C. Gallbladder
D. Sigmoid colon D. Hepatic portal vein
E. Terminal ileum E. Liver
Gastroenterology • 233
A. Basal cell carcinoma 21.63. A 24 year old man presents with fresh
B. Crohn’s disease haematemesis the day after a night of heavy
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 mmol/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 varices 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
Gastroenterology • 235
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.
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 started 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
236 • Gastroenterology
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 B12 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 on
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 GI 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–Ellison
lead to pneumonia and pleural effusion. syndrome and gastroduodenal Crohn’s
Gastroenterology • 237
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.
21.13. Answer: E.
She has a high urea but her creatinine level is
This patient clearly requires urgent upper GI within the upper range of normal for women. 21
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 GI 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 GI 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 GI 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 GI
21.14. Answer: A.
bleed. Lower GI 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 GI 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
238 • Gastroenterology
on resuscitation. Upper GI endoscopy The stomach is the most common site for
should not be carried out before extranodal non-Hodgkin lymphoma and 60% of
resuscitation. all primary gastrointestinal lymphomas occur at
this site. H. pylori infection is closely associated
21.18. Answer: C.
with the development of a low-grade lymphoma
The incidence of gastric cancer has, in fact, (classified as extranodal marginal-zone
been falling steadily across the world, although lymphomas of mucosa-associated lymphoid
it is still a global killer. H. pylori infection is the tissue (MALT) type). EUS plays an important
most important risk factor and this far role in staging these lesions by accurately
outweighs all the other traditional risk factors, defining the depth of invasion into the gastric
such as diet. H. pylori plays a key pathogenic wall. High-grade B-cell lymphomas should be
role and the infection has been classified by the treated by a combination of rituximab,
International Agency for Research on Cancer chemotherapy, surgery and radiotherapy. While
(IARC) as a definite human carcinogen. Despite initial treatment of low-grade lesions confined to
advances in treatment, the overall 5-year the superficial layers of the gastric wall consists
survival is still low (< 30%). Africa has a low of H. pylori eradication and close observation,
incidence of gastric cancer (the so-called 25% contain t(11 : 18) chromosomal
African enigma) despite having high rates of H. translocations. In these cases, additional
pylori infection. radiotherapy or chemotherapy is usually
necessary.
21.19. Answer: D.
arising from mucus-secreting cells in the base of GISTs arise from the interstitial cells of Cajal.
the gastric crypts. Gastric cancers are very They are differentiated from other mesenchymal
aggressive and usually present quite late tumours by expression of the c-kit
with large sizes and with distant spread. While proto-oncogene. They are usually benign
most gastric cancers are initiated by H. pylori tumours, particularly the smaller lesions < 2 cm,
infection, the organism often disappears in the and asymptomatic, but the larger ones may
latter stages with onset of gastric atrophy have malignant potential. Very large lesions
and achlorhydria. Krukenberg tumours are should be treated pre-operatively with imatinib
metastatic deposits on the ovaries. Sister to reduce their size and make surgery easier.
Joseph’s nodule is a metastatic deposit in the Imatinib can also be used for prolonged control
umbilicus usually from a cancer in the pelvis or of metastatic GISTs. They can bleed
abdomen. independently of NSAIDs.
21.20. Answer: D.
21.23. Answer: B.
Endoscopic management of gastric cancer is Given the duration of the symptoms, this is not
confined to very early mucosal or submucosal likely to be infection. X-ray is not likely to aid
disease with no spread elsewhere. For the diagnosis and exposes the patient to ionising
majority of patients with locally advanced radiation. Given the constellation of symptoms,
disease, total gastrectomy with mild anaemia and low folate in a patient of this
lymphadenectomy is the operation of choice. In age, coeliac disease should be considered
the surgical management of proximal gastric initially and therefore coeliac serology is the
cancers involving the oesophago-gastric next best investigation.
junction, distal oesophagectomy is also
required. The biological agent trastuzumab may 21.24. Answer: D.
21.25. Answer: A.
disease, as well as anti-tumour necrosis factor
Anti-tTG response is IgA mediated and (TNF) biological therapy. Methotrexate would
therefore can be false negative in IgA not be used here given toxicities that include
deficiency. Therefore, IgG-mediated antibodies teratogenicity in women of child-bearing age.
should be checked next. If positive, the patient Thiopurine immunosuppression with
should be offered an endoscopy for distal azathioprine is the next most appropriate
duodenal/duodenal bulb biopsies. HLA status is medication to prevent a further flare in
not exclusive and is not a reliable diagnostic disease.
test, although it can aid diagnosis in some
cases where serology/histology are equivocal. 21.31. Answer: B.
21.28. Answer: E.
inflammatory bowel disease bowel disease activity
Conjunctivitis
commonly occurs after radiotherapy for Primary scleros ng cho ang tis
and cho angiocarc noma
21
Sacroili tis/ankylosing spondyl tis
are ineffective. Endoscopic argon plasma (Crohn s with HLA B27)
coagulation (APC) can be used for acute Venous thrombosis Metabol c bone disease
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 review 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, non-response to
deficiency. Options B, C and E (all intravenous (IV) steroid therapy ± rescue
immunosuppressants) can be used in Crohn’s medical therapies require a surgical review for
240 • Gastroenterology
consideration of subtotal colectomy and from these cells. Crohn’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-α4β7 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.
pain and vomiting soon after starting this This patient’s symptoms are consistent with
medication. If a patient is stable on active small bowel Crohn’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 intestinal inflammation, but would
genetically susceptible individuals. not give additional information 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
Gastroenterology • 241
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 IBD. CRP and
patients require defunctioning colostomy. Botox platelet count may be elevated in the latter
injection and topical diltiazem 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 to 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 21
individuals with these mutations develop mildly acidic to neutral (5.5–7). The colonic
colorectal cancer and not all colorectal microbiota is acquired at birth, matures to that
tumours will contain all of these genetic of an adult by the age of 3 years and changes
mutations. Approximately 5% of colorectal over time as a natural part of ageing in the
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.
anaemic with a macrocytosis and low vitamin The pancreatic body and tail receive supply
B12 due to bacterial utilisation of the vitamin B12 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 superior 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 supplied 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
21.46. Answer C.
21.50. Answer: E.
This man gives a history of steatorrhoea, due to All the options listed are recognised
high lipid contents in his stools. Pancreatic complications of ERCP, but an extremely
lipase, in the presence of its co-factor, high amylase would point to pancreatitis.
colipase, cleaves long-chain triglycerides, The complication rate following ERCP is
yielding fatty acids and monoglycerides, which 5–10% with a 30-day mortality of 0.5–1%,
are small enough to diffuse across enterocyte depending on the procedure complexity,
cell membranes. In chronic pancreatitis, underlying condition and comorbidities.
inadequate pancreatic lipase production leads Acute pancreatitis is the most common
to high fat content in stools due to poor complication.
digestion. Chymotrypsin may be deficient as
well, but leads to protein deficiencies. Glucagon 21.51. Answer: B.
and somatostatin are endocrine hormones This man had alcohol-related acute pancreatitis
secreted by the pancreas and for unclear and has developed a pancreatic pseudocyst.
reasons tend not to be associated with Large pancreatic pseudocysts can cause
deficiency in chronic pancreatitis. Maltase compression of surrounding structures
is an enzyme found on small intestine brush and in this case gastric outlet obstruction.
border. Endoscopy, barium and water-soluble contrast
meals will all demonstrate dilatation of the
21.47. Answer: D.
stomach, but not the cause. Oesophageal
In recurrent duodenal ulceration in a young manometry would be expected to be normal in
patient, Zollinger–Ellison syndrome should be this case.
considered. Gastrinoma as part of multiple
endocrine neoplasia (MEN) type 1 is a 21.52. Answer: A.
21.48. Answer C.
Significant hypoxia, low serum calcium,
This man gives a history of acute pancreatitis, elevated serum glucose and very high CRP
probably secondary to alcohol, and now over 150 mg/L are associated with a poor
presents with ascites. His liver function tests prognosis in acute pancreatitis. Amylase level
show a normal liver synthetic function (bilirubin alone has not been proven to be prognostic.
and INR), which makes portal hypertension due Other adverse factors are given in Boxes
to chronic liver disease an unlikely cause of the 21.53A and 21.53B.
ascites. Ruptured pancreatic pseudocyst
is a recognised complication of acute
pancreatitis and leads to an elevated ascitic
fluid amylase.
21.56. Answer: E.
i
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
Body mass index > 30 kg/m2
or vomiting. This will dictate what further
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.
21.54. Answer: D.
21.59. Answer: A.
would be elevated in the main differential Rheumatoid arthritis may be associated with
diagnosis of carcinoma of head of pancreas. atlantoaxial subluxation due to flexion of the
Alpha-fetoprotein is elevated in hepatocellular neck during endoscopy. This can lead to high
carcinoma, germ cell tumours and pregnancy, spinal cord injury. Rheumatoid arthritis is the
none of which would be expected to respond most common cause of this complication in
to glucocorticoids. Hepatitis E IgM is elevated adults. 21
in acute infection and is not steroid responsive.
Serum IgM levels are not affected by 21.61. Answer: A.
polycythaemia vera and myeloproliferative The Blatchford scoring system (Box 21.63) risk
disorders. stratifies upper gastrointestinal bleeding
244 • Gastroenterology
and comorbidities, giving a score of 0 in this Band ligation is the endoscopic management of
case. This history is typical of a Mallory–Weiss choice for bleeding oesophageal varices.
tear. In the presence of a low Blatchford score, Options B–E are used in the management of
Mallory–Weiss tear can often be managed bleeding peptic ulcers or mucosal defects, but
without endoscopy. Whilst the majority of cases are likely to worsen bleeding secondary to
stop bleeding without intervention, those with varices.
elevated Blatchford scores and evidence of
ongoing bleeding require endoscopy and 21.65. Answer: D.
around 10% require endoscopic therapy due to Diarrhoea is one of the most common
life-threatening bleeding. symptoms associated with HIV and should be
considered in all individuals with unexplained
symptoms. A recent opportunistic herpes
zoster infection, alongside his other symptoms,
would support HIV as the unifying diagnosis.
21.63 Modified Blatchford score: risk
i stratification in acute upper gastrointestinal
bleeding
21.66. Answer: D.
C. In unexplained jaundice, recently started found to be over 10 000 U/L. What is the most
medications can be safely continued likely diagnosis?
provided there have been no reports of DILI A. Alcoholic hepatitis
associated with them B. Hepatitis B virus
D. It is seen with opiate use C. Hepatitis C virus
E. The risk of co-amoxiclav-induced liver injury D. Hepatitis E virus
goes down with each repeat exposure E. Wilson’s disease
22.7. A 35 year old man is being considered 22.11. A 25 year old woman 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
cirrhosis the following is a medical therapy appropriate
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. Tranexamic 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 (ALT) is investigation you should consider?
Hepatology • 247
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
C. Laparoscopy about diagnosis and treatment is correct?
D. Liver biopsy A. First-line imaging technique for the bile ducts
E. Positron emission tomography (PET) 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 C. 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
C. 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
C. Delayed graft function C. 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
C. Large liver size on ultrasound occupational health screening for entrance to
D. Older age at disease onset medical school. His results are as follows: 22
E. Presence of intercurrent autoimmune disease LFTs:
Bilirubin 12 µmol/L (0.70 mg/dL)
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) IgM negative
A. Acute viral hepatitis is a likely cause
Anti-HBc IgG positive
B. Fatty liver of pregnancy is the most likely
What is the next step in his management?
diagnosis
C. 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 C. 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
248 • Hepatology
had fluctuations in her LFTs with an abnormal 22.25. A 37 year old male prisoner is newly
ALT despite a low viral load. Her delta serology diagnosed with HCV. He has no significant past
is checked and is positive with a high titre. medical history or drug history. His results are
Which of the following statements is true about as follows:
the hepatitis D virus (HDV)? Full blood count:
A. All patients with HBV have HDV Haemoglobin 130 g/L
co-infection White cell count (WCC) 4.2 × 109/L
B. HBV–HDV co-infection has the same annual Platelets 98 × 109/L
rate of cirrhosis and HCC as HBV LFTs:
mono-infection Bilirubin 42 µmol/L (2.46 mg/dL)
C. HDV can infect individuals simultaneously ALT 60 U/L
with any acute hepatitis ALP 64 U/L
D. HDV contains a single antigen to which Ultrasound liver: irregular, shrunken liver with
infected individuals make an antibody no focal lesion and no free fluid. Splenomegaly.
(anti-HDV) HCV genotype 1a. HCV RNA 750 000 U/mL.
E. HDV is a DNA virus like HBV Elastography 25 kPa (2–7 kPa).
What is the next appropriate management
22.23. A 25 year old female who has chronic step?
hepatitis B and is under long-term follow-up in A. Genotype 1a is more difficult to treat
the hepatology clinic is 27 weeks pregnant, and therefore he should have interferon
about to enter her third trimester. She is therapy
worried she will give her baby hepatitis B and B. He does not have advanced fibrosis and
would like you to reassure her. You review her therefore can be discharged from the clinic
blood tests from this clinic appointment at 27 C. He needs a liver biopsy to accurately stage
weeks’ gestation. his liver disease
LFTs: D. He should be offered oral antiviral therapy
Bilirubin 18 µmol/L (1.05 mg/dL) E. No treatment; patient should be observed
ALT 14 U/L with continued outpatient follow-up
ALP 84 U/L
HBsAg positive 22.26. A 64 year old man has been admitted to
HBeAg negative hospital feeling tired and unwell, suffering from
HBV DNA 48 U/mL (low titre) nausea and itching. A careful history elicits that
What is the most appropriate next step in he recently celebrated his wedding anniversary
her management plan? on a cruise ship from which they returned a
A. Advise elective caesarean delivery few weeks ago. He has recently noted dark
B. Interferon-alfa in third trimester urine and pale stool. His wife is not unwell
C. Observe but she is vegetarian and he mentions he ate
D. Tenofovir in third trimester large amounts from the seafood buffet. He has
E. Vaccinate infant at birth no other risk factors for jaundice. His LFTs
confirm he is jaundiced with an acute hepatitis.
22.24. A 52 year old male ex-intravenous Which of the following is most likely to test
drug user with liver cirrhosis from hepatitis positive?
C virus has complications of diuretic-resistant A. Delta antibody
ascites and previous episodes of B. Hepatitis A virus (HAV) RNA in sweat
encephalopathy. He has been waiting for C. Hepatitis B surface antigen
treatment. Whilst he waits for treatment to be D. Hepatitis C antibody
initiated, what is the most appropriate E. Hepatitis E virus RNA in stool
management plan?
A. AFP and ultrasound in 12 months for HCC 22.27. There has been an outbreak of hepatitis
surveillance A virus (HAV) at a local nursery. The head
B. Assessment for liver transplantation teacher of a primary school in the same area
C. Liver biopsy would like some advice on prevention of
D. Tenofovir secondary cases of hepatitis A infection. Of
E. Trial of interferon for 4 weeks note, no one at the primary school (child or
Hepatology • 249
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 HCC
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. HAV is not highly infectious A. Carcinoembryonic 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 CT 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 vaccination body mass index (BMI) 33 kg/m2. He has mildly
D. Interferon-alfa 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
WCC 5.3 × 109/L
emergency department with rigors and
Platelets 89 × 109/L
abdominal pain. He has a past medical history
LFTs:
of hypertension with no history of travel abroad.
Bilirubin 33 µmol/L (1.93 mg/dL)
On examination he is febrile with a temperature
ALT 54 U/L
of 40°C 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
WCC 24 × 109/L and C-reactive protein (CRP) of
300 mg/L. He has deranged LFTs with bilirubin
requested. 22
What is the likely description of the lesion on
64 µmol/L (3.74 mg/dL), ALT 74 U/L, ALP
a CT scan?
320 U/L. A liver screen was sent. An
ultrasound 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 recommendations 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
250 • Hepatology
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 µmol/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 µg/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 Maddrey ‘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
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 γ-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 GI 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 transaminitis (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?
252 • Hepatology
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 µg/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 100 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–Blakemore tube immediately
upper quadrant pains. Blood tests show C. Repeat upper GI endoscopy in 6 months
bilirubin 120 µmol/L (7.02 mg/dL), ALT 65 U/L, D. Start non-selective β-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 GI 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. Isosorbide 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
Hepatology • 253
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). Paracetamol 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.
pre-hepatic jaundice through increased red DILI 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 history and drug
of bilirubin (other liver biochemistry is typically exposure) and other immunological features of
normal), particularly in times of physiological AIH (elevated IgG and autoantibodies) sought.
stress such as intercurrent illness, which would Opiates are not reported to cause DILI; in
254 • Hepatology
terms of drugs of abuse, the major risk is condition. The name was changed following a
ecstasy. When approaching a patient with patient campaign in 2015. Typically thought of
possible DILI, the precautionary principle should as a disease of middle-aged and older women
apply and any potential risk therapy should be (it is 10 times commoner in women than men),
stopped until the causality becomes clearer. recent large cohort studies have identified an
important group of younger patients (aged
22.7. Answer: C.
20–50) who are more symptomatic and less
Hepatorenal failure complicating chronic liver likely to respond to UDCA. Younger patients
disease is best regarded as a vascular should be monitored closely and treated
consequence of cirrhosis and it typically aggressively. UDCA is first line-therapy and
improves when liver function returns to normal. should be used at a dose of 13–15 mg/kg in all
HLA matching is unnecessary in liver patients, regardless of symptom status or
transplantation (ABO and weight matching, in disease severity. The most characteristic blood
contrast, are important). Immunosuppression test change is elevation of the alkaline
regimes differ between centres but most phosphatase value, which reflects the
centres continue life-long immunosuppression. cholestatic nature of the disease. Transaminase
Research into safe discontinuation of elevation can be a feature of aggressive
immunosuppression has not translated into disease and overlap with AIH. PT, as well as
clinical practice. MMF monotherapy can be bilirubin and albumin levels, tend to be normal
associated with very resistant cellular rejection. until late in the disease, as hepatocellular
The most common time window for acute function is typically well preserved in this
cellular rejection is days 7–10. cholestatic disease.
22.8. Answer: B.
22.10. Answer: D.
The Kupffer cells play a key role in innate The clinical scenario is strongly suggestive of
immunity, in particular acting as a barrier for an acute viral hepatitis infection and the timing
gut bacteria/bacterial products entering the of onset would be most compatible with
portal vein. Sepsis is one of the major causes hepatitis E virus (HEV). The prodrome and
of death in acute liver failure. Steroid hormone onset in hepatitis B virus (HBV) are much more
clearance is a liver function and loss of prolonged than those described here (although
clearance function contributes to fluid retention/ clearly infection prior to the holiday is possible).
ascites (aldosterone) and feminisation in men Hepatitis C virus (HCV) almost exclusively
(oestrogen) with chronic liver failure. There is no causes chronic liver injury with no recognised
impact in the acute setting. The liver plays a acute infection event. Wilson’s disease can
critical role in glucose homeostasis, buffering present with an acute hepatitis episode but is a
portal venous blood through glycogen rare condition and the acute presentation even
synthesis/breakdown. Hepatocytes are also key rarer. There is an almost automatic assumption
in gluconeogenesis. Acute liver failure is in some quarters that a hepatitis in a young
frequently characterised by hypoglycaemia but man returning from abroad will be
this is relatively easy to manage with alcohol-related. In this case this is very unlikely,
intravenous (IV) glucose in practice, and it is as an ALT of 10 000 U/L would be very atypical
only rarely so profound as to impact on (normal or even low ALT is characteristic of
outcomes. Breakdown of red cells at the end alcoholic hepatitis).
of their life span is a function of the spleen not
the liver. Hyperoxaluria is an inborn error of 22.11. Answer: A.
oxalic acid metabolism, expressed in the liver AIH typically improves in terms of disease
but manifest as renal failure. Transplantation of activity during pregnancy. It can, however, flare
the kidney without the liver simply results in up during the early post-partum period. If
rapid renal failure in the graft. Combined patients have cirrhosis, then portal hypertension
transplant, in contrast, is highly effective. Oxalic can worsen during the third trimester, so
acid plays no role in acute liver failure. consideration should be given to endoscopy
as they enter the third trimester. This only
22.9. Answer: D.
applies to cirrhosis patients. MMF is teratogenic
Primary biliary cholangitis is the new name for and is contraindicated in pregnancy, so
primary biliary cirrhosis, so it is the same azathioprine should be continued. The
Hepatology • 255
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.
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.
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
256 • Hepatology
pre-existing maternal liver disease. Cholestasis infection with normal transaminases and
pruritus can be very severe. The major clinical negative anti-HBc IgM. Further management of
concern is sudden intrauterine death due, it is the patient will depend on HBeAg status and
thought, to a toxic effect of bile acids on the HBV DNA to distinguish disease phase.
fetal cardiac conducting apparatus. The risk
rises exponentially from 36 weeks’ gestation 21.22. Answer: D.
onwards and there is a strong case for early HDV is an RNA-defective virus that requires the
delivery to avoid this risk. simultaneous presence of HBV for replication
and has the same sources and modes of
22.19. Answer: D.
spread. HBV replication is usually suppressed
PSC is a fibrotic cholestatic liver disease of by HDV. Liver damage is believed to be due to
presumed autoimmune aetiology, which has a HDV and persistent HDV replication in
male predominance. Although UDCA is widely co-infected patients leads to higher annual
used, and typically improves the cholestatic rates of cirrhosis and HCC. Interferon-alfa is the
liver function tests seen in PSC, there is no only effective drug against HDV but the optimal
evidence that it reduces mortality and there is duration of therapy is not well defined.
no evidence to support any drug therapy. HCC
can complicate cirrhosis PSC (as with cirrhosis 22.23. Answer: E.
of any cause) but the specific associated Pregnant women with chronic hepatitis B are
cancers are cholangiocarcinoma and colonic most infectious when markers of continuing
carcinoma, both of which should be screened viral replication, such as HBeAg, and high
for. Imaging of the bile ducts is a key part of levels of HBV-DNA are present in the blood.
the diagnostic workup but should be through Tenofovir can be given if there are high levels of
magnetic resonance cholangiopancreatography HBV-DNA in the last trimester of pregnancy;
(MRCP) in the first instance because of the however, in this clinical scenario, the patient
risks associated with ERCP. The latter should has very low titres. Interferon-alfa is
be reserved for therapeutic, rather than contraindicated in pregnancy. Neonates born to
diagnostic, procedures. hepatitis B-infected mothers should be
immunised at birth. In addition, to prevent
22.20. Answer: B.
vertical transmission, hepatitis B
Flucloxacillin-induced liver injury is one of the immunoglobulin (HBIg) is given to newborns of
commoner forms of drug-induced liver injury. It highly viraemic HBeAg-positive mothers.
is thought to have an immune pathogenesis Guidelines do not recommend elective
(there is a strong HLA association) and there is caesarean delivery for mothers with chronic
no crossover with other penicillins, which can hepatitis B infection.
be used safely. The immune element probably
underpins the characteristic pattern of 22.24. Answer: B.
HCC surveillance, and as he has only been AFP is produced by 60% of HCCs; therefore a
recently diagnosed with cirrhosis he should also negative AFP does not exclude HCC.
have an endoscopy to screen for varices. Carcinoembryonic antigen is a tumour marker
that can be raised in colorectal cancer.
22.26. Answer: E.
Combination of imaging modalities more
The clinical presentation of hepatitis E is similar accurately diagnoses and stages the extent of
to that of hepatitis A with the likely source as disease, and using at least two modalities
shellfish in this clinical scenario. However, this (typically, CT or MRI following initial screening
question focuses on detection methods. ultrasound identification of a mass lesion) is
Hepatitis A virus is excreted in faeces or recommended.
diagnosis is made by detection of HAV IgM
antibodies in the blood, which persists for up to 22.31. Answer: A.
14 weeks after initial infection. Alternative In this clinical scenario, the patient has cirrhosis
samples such as serum and saliva can be used as evidenced by thrombocytopenia and
but assays are expensive and sensitivities vary. ultrasound imaging of liver. In this case, the
Therefore, answer E is the correct option. likely aetiology is NAFLD with risk factors of
diabetes, hypertension and obesity. The high
22.27. Answer: B.
AFP is diagnostic for HCC. HCC are
HAV belongs to the picornavirus group of hypervascular in the arterial phase, followed by
enteroviruses. HAV is highly infectious and is washout in the portal venous phase. Option E
spread by the faecal–oral route, but a chronic is typical of a hydatid cyst and daughter cysts
carrier state does not occur. Infected may be present. Option C is the appearance of
individuals may be asymptomatic. Health a hepatic adenoma and focal nodular
departments will investigate outbreaks and hyperplasia can be differentiated from adenoma
advise regarding vaccination. In this scenario because of a focal central scar.
vaccinating everyone is not necessary, as no
one has been identified as the index case or 22.32. Answer: D.
close contact at the primary school. This patient has biliary colic. Gallstones are
conventionally classified into cholesterol or
22.28. Answer: B.
pigment stones, although the majority are of
The use of post-liver transplant prophylaxis with mixed composition. Patients are generally
direct-acting antiviral agents and hepatitis B advised a low-fat diet to help reduce symptoms
immunoglobulins has reduced the reinfection as fat releases cholecystokinin, which
rate to 10% and increased 5-year survival to precipitates gallbladder contraction and might
80%, making transplantation an acceptable result in biliary pain. Low-oxalate diet is 22
treatment option. Hepatitis B vaccination is associated with renal stones. A FODMAP diet
ineffective in those already infected by HBV. is a treatment option for patients with irritable
Ribavirin is a treatment used in hepatitis C bowel syndrome and gluten-free diets are for
infection. patients with coeliac disease.
22.29. Answer: E.
22.33. Answer: C.
Hepatic abscesses are rare and clinical features Primary sclerosing cholangitis carries a lifetime
of pyogenic and amoebic liver abscesses can risk of cholangiocarcinoma of approximately
be similar. However, pyogenic abscesses are 20%. It can arise from anywhere in the biliary
most common in older patients and usually tree. Often the diagnosis is made by a
result from ascending infection due to biliary combination of CT and MRI. A liver biopsy may
obstruction (cholangitis). They are often cause tumour seeding. The patient will need an
described as more aggressive. E. coli and ERCP due to biliary obstruction but is not
various streptococci, particularly Strep. milleri, currently septic and therefore the best next
are the most common organisms. Any investigation would be further imaging. Patients
associated biliary obstruction and cholangitis with ulcerative colitis and PSC should undergo
require biliary drainage. Hepatic hydatid disease yearly colonoscopy as they are at high risk of
is a parasitic zoonosis caused by the colorectal cancer, but this is not the focus of
Echinococcus tapeworm. this scenario.
258 • Hepatology
22.34. Answer: E.
to the virus in the past but has been immunised
The patient has SOD type I. The gold standard to the virus.
for diagnosis is sphincter of Oddi manometry.
All biliary SOD patients with type I disease are 22.40. Answer: C.
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 CA19-9 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
Hepatology • 259
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 1103 patients, no
significant benefit from pentoxifylline treatment 22.45. 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
250 × 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 22
organisms on culture should arouse suspicion more classically associated with a painless
of a perforated viscus. obstructive jaundice.
22.44. Answer: D.
22.47. Answer: D.
cent of individuals exposed to the virus become The patient carries two copies of the most
chronically infected and late spontaneous viral common HFE variant, C282Y, and has
clearance is rare. Unlike HBV, there is no active evidence of iron overload. Venesection would
260 • Hepatology
frequency adjusted according to fall in ferritin Increasingly sedentary lifestyles and changing
and transferrin saturation. Vitamin C dietary patterns mean that the prevalence of
supplementation increases absorption of iron obesity and insulin resistance has increased
from the diet and so should be avoided. worldwide; thus, fat accumulation in the liver is
a common finding during abdominal imaging
22.49. Answer: D.
studies and on liver biopsy. In the absence of
TIPSS is used in the management of refractory high alcohol consumption (typically a threshold
variceal bleeding that has not responded to of < 20 g/day for women and < 30 g/day for
other therapies. Placement of a Sengstaken– men is adopted), this is called non-alcoholic
Blakemore tube is an emergency holding fatty liver disease. Non-alcoholic fatty liver
measure used when there is an uncontrollable disease (NAFLD) is the most common cause
variceal haemorrhage – for example, while for abnormal LFTs worldwide, estimated to
plans are made for a TIPSS – and so is not affect 20–30% of the general population in
necessary in this situation. Western countries and 5–18% in Asia, with
If non-bleeding varices are identified at about 1 in 10 NAFLD cases exhibiting
endoscopy, β-blocker therapy with propranolol non-alcoholic steatohepatitis (NASH). NAFLD is
(80–160 mg/day) or nadolol is effective in the leading cause of liver dysfunction in the
reducing portal venous pressure. Administration non-alcoholic, viral hepatitis-negative population
of these drugs at doses that reduce the heart in Europe and North America and is predicted
rate by 25% has been shown to be effective to become the main aetiology in patients
in the primary prevention of variceal bleeding. undergoing liver transplantation during the next
In patients with cirrhosis, treatment with 5 years.
propranolol reduces variceal bleeding by 47%
(number needed to treat for benefit (NNTB) 10), 22.51. Answer: E.
death from bleeding by 45% (NNTB 25) and Although the virus has been successfully
overall mortality by 22% (NNTB 16). The efficacy cleared, the patient was found to have cirrhosis
of β-blockers in primary prevention is similar to and so remains at risk of developing
that of prophylactic banding, which may also hepatocellular carcinoma (HCC). He will require
be considered, particularly in patients unable to follow-up and management to check for risks
tolerate β-blocker therapy. Carvedilol, a associated with cirrhosis, including HCC and
non-cardioselective vasodilating β-blocker, is portal hypertension/varices.
also effective.
HG Watson, DJ Culligan,
LM Manson
23
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 immune-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 × 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. Ischaemic 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
262 • Haematology and transfusion medicine
alternative oral anticoagulant. You review her A. Haemophilia A carrier with low VIII levels
clinical case. In which of the following clinical B. Type 1 von Willebrand disease
circumstances would the answer be that she C. Type 2A von Willebrand disease
should stay on warfarin? D. Type 2N von Willebrand disease
A. Atrial fibrillation in a patient with a prosthetic E. Type 3 von Willebrand disease
mitral valve
B. Distal deep vein thrombosis (DVT) following 23.11. In the context of routine clerking of a
plaster cast immobilisation pre-surgical patient, which of the following is
C. Lone atrial fibrillation with a CHA2DS2-VASc the most informative question in detecting an
score of 2 underlying bleeding disorder in a patient who
D. Proximal DVT following total knee reports a ‘problem with bleeding’?
replacement A. Bleeding after shaving
E. Unprovoked pulmonary embolism B. Easy bruising
C. Epistaxis as a child
23.8. A patient who is admitted to the intensive D. Post-partum haemorrhage
care unit (ICU) with multi-organ failure and E. Previous post-surgical bleeding
sepsis is suspected of having heparin-induced
thrombocytopenia (HIT). Which of the following 23.12. A Dutch woman is referred following the
pieces of clinical information is most likely to development of a pulmonary embolism without
suggest an alternative diagnosis? obvious provoking factors. If she were
A. The heparin treatment commenced 16 days investigated further, which form of inherited
ago thrombophilia would you be most likely to find
B. The patient has been receiving treatment in this case?
with unfractionated heparin (UFH) A. Antithrombin deficiency
C. The patient has had complex cardiac surgery B. Factor V Leiden
with cardiopulmonary bypass C. Protein C deficiency
D. The patient has sustained a post-operative D. Protein S deficiency
pulmonary embolus E. Prothrombin gene mutation
E. The platelet count has dropped from normal
to a level of 53 × 109/L 23.13. A 65 year old man is admitted as a
medical emergency. A diagnosis of pulmonary
23.9. What is the most likely diagnosis in a 2 embolism is made. Which of the following
year old boy who presents with an apparently features in his clinical history is most likely to
unprovoked knee haemarthrosis? have contributed most to his thrombosis risk?
Initial investigations show that he has a A. He had a total knee replacement (TKR) 9
normal platelet count and a normal prothrombin months previously
time (PT). His activated partial thromboplastin B. He had just flown back to the UK from a
time (APTT) is prolonged at 76 seconds. weekend break in Paris
A. Lupus anticoagulant C. He has recently started quinine for night
B. Severe factor XI deficiency cramps
C. Severe factor XII deficiency D. He was discharged from hospital 4 weeks
D. Severe haemophilia A (factor VIII deficiency) ago following treatment for congestive
E. Severe haemophilia B (factor IX deficiency) cardiac failure (CCF)
E. His 64 year old cousin has recently suffered
23.10. A 13 year old girl with significant from a pulmonary embolism following bowel
menorrhagia is investigated to see if there is an surgery
underlying bleeding disorder. Her investigations
show a normal platelet count, PT and 23.14. You are asked to see a 59 year old man
fibrinogen. Her APTT is prolonged and her following 3 months of anticoagulation for an
factor VIII level is 0.2 U/mL, her von Willebrand episode of proximal DVT that occurred without
factor ristocetin co-factor (vWF : RiCO) level is any identifiable risk factor. You are trying to
0.05 U/mL and her von Willebrand factor decide whether you think he would benefit from
antigen (vWF : Ag) is 0.14 U/mL. What is the long-term anticoagulation or not. Of the
most likely diagnosis? following, which is the strongest risk factor for
Haematology and transfusion medicine • 263
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 therapy 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 therapy 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 5 × 109/L and G-CSF
266 • Haematology and transfusion medicine
23.35. A 68 year old woman has been found to Investigations show: haemoglobin 61 g/L;
have a low haemoglobin in the context of white cell count (WCC) 5.2 × 109/L; platelet
long-term rheumatoid arthritis and chronic count 84 × 109/L.
kidney disease. What does the mechanism of You request 4 units of packed red cells
the anaemia of chronic disease include? urgently. Group and screen 2 years previously
A. Chronic gastrointestinal (GI) tract bleeding showed group B Rhesus D (RhD)-positive with
B. High hepcidin levels inhibiting iron export a negative antibody screen.
from macrophages There is insufficient time to do compatibility
C. Iron toxicity to the bone marrow testing. What is the most appropriate blood to
D. Poor iron absorption because of transfuse?
achlorhydria A. AB RhD-negative
E. Red cell sequestration in a chronically B. B RhD-negative
enlarged spleen C. B RhD-positive
D. O RhD-negative
23.36. A 4 year old girl is brought to her doctor E. O RhD-positive
with fever and is found to have acute
leukaemia. Which of the following is considered 23.39. A 28 year old female, para 1 + 0, presents
the most important prognostic feature for to obstetric triage at 27 weeks. All was well at
childhood acute lymphoblastic leukaemia? booking. She reports intermittent vaginal
A. T-cell rather than B-cell phenotype bleeding for the past 2 weeks. Other than
B. The age and sex of the child requiring a 3-unit red cell transfusion following
C. The chromosomal abnormalities acquired by a road traffic accident 3 years ago she has
the leukaemic cells been well.
D. The height of the white cell count at Investigations show: haemoglobin 121 g/L;
presentation WCC 8.4 × 109/L; platelet count 238 × 109/L.
E. The presence of minimal residual disease Group and screen: group A RhD-negative
(MRD) post induction therapy with a positive antibody screen.
Antibodies: anti-D (titre 1/32)
23.37. A 6 year old patient has had severe What is the most likely reason for the
neutropenia (< 0.2 × 109/L) lasting for more than development of the antibody?
7 days following initial treatment for AML. A. Fetal maternal haemorrhage during this
Which of the following is true? pregnancy
A. Azole prophylaxis against fungal infection B. Physiological increase in naturally occurring
with posaconazole is not recommended antibody
B. Gram-negative sepsis is more common than C. Previous pregnancy
Gram-positive sepsis D. Routine antenatal anti-D prophylaxis
C. Indwelling Hickman lines are more commonly E. Transfusion
infected with Gram-negative organisms than
Gram-positive ones 23.40. A patient receives a blood transfusion
D. Neutropenic fever should be treated and has developed complications. Which of the
empirically prior to receiving the results of following combinations will result in least insult
blood cultures to the patient?
E. Quinolone prophylaxis is not recommended A. Group AB red cells into a group O adult
to prevent sepsis B. Group B red cells into a group A adult
C. Group B red cells into a group A neonate
23.38. A 42 year old woman with alcoholic liver D. Group O fresh frozen plasma (FFP) into a
disease presents as an emergency to hospital group A adult
with massive haematemesis. Her temperature is E. Group O FFP into a group B adult
37°C, pulse rate 130 beats/min and blood
pressure is 70/40 mmHg. She is cool 23.41. A 28 year old female, para 1 + 1, presents
peripherally. She has stigmata of chronic liver to obstetric triage at 22 weeks. She reports
disease with a palpable spleen at 3 cm below intermittent vaginal bleeding for the past 24
the left costal margin. She is initially hours and thinks it is likely implantation
resuscitated with intravenous fluids. bleeding. There has been no preceding trauma.
Haematology and transfusion medicine • 267
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. CHA2DS2-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.
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 APTT. 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 APTT 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
Haematology and transfusion medicine • 271
are very non-specific indicators of a bleeding Eosinophilia is often seen in association with
disorder. Post-partum haemorrhage is usually atopic and allergic conditions. It can also be
associated with other pregnancy-associated seen in pulmonary vasculitis. Other causes of
illness, uterine atony or vaginal trauma. reactive eosinophilia include drug reactions and
parasitic infections.
23.12. Answer: B.
first-degree relative and the event suffered by The described appearances are all part of a
this man’s cousin was provoked. CCF, or hyposplenic picture. Irrespective of the cause of
indeed any significant hospitalisation, is a the hyposplenism or splenectomy. Liver disease
strong risk factor for subsequent VTE – The is associated with target cells but not with a
Million Women Study suggests the period of hyposplenic picture. Myelofibrosis is associated
attributable risk is about 12 weeks. with target cells, teardrop poikilocytes,
polychromasia and a leucoerythroblastic
23.14. Answer: E.
appearance but not with the features of
The background to the event is the strongest hyposplenism.
predicting factor for recurrence. Unprovoked
events have a far higher rate of recurrence than 23.20. Answer: E.
provoked events where the provoking factor The oxygen dissociation curve shifts to the right
has been removed. In predicting recurrence – i.e. improves the release of oxygen to tissues
after an unprovoked event, male sex and – in conditions where the pH is decreased
elevated D-dimer are predictive of recurrence. (Fig. 23.20). The other changes would tend to 23
move the dissociation curve to the left, making
23.15. Answer: D.
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 SF3B1 (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. IgM 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
1000-fold by mobilisation procedures following usually with an increase in bone marrow
chemotherapy, G-CSF or plerixafor. In this way, monoclonal plasma cells. Option D 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
Haematology and transfusion medicine • 273
phase the blast count is low and platelets The donor-derived T cells provide a new
tend to be high (sometimes very high: cell-mediated immune system that attacks
> 2000 × 109/L). First-choice therapy for all residual leukaemic cells – GvL. Maintaining
patients in chronic phase is tyrosine kinase full (100%) donor chimerism in the T-cell
inhibition (TKI), e.g. imatinib, nilotinib or population promotes long-term remission of
dasatinib, with allogeneic stem cell AML and other haematological malignancies.
transplantation reserved for TKI failure. The The T cells also cause acute and chronic
translocation t(15;17) occurs in acute GVHD, which for similar reasons is associated
promyelocytic leukaemia (APL). with lower relapse rates. Older females are
more likely to have been pregnant and to be
23.29. Answer: B.
sensitised to human leucocyte antigens (HLAs)
HL most commonly starts in the cervical region and therefore younger male donors are
and spreads contiguously along the lymphatic preferable, all other criteria such as HLA
channels. Young women with the nodular matching and cytomegalovirus (CMV) status
sclerosing subtype of HL typically present with being equal. RIC is less tissue damaging and
cervical and mediastinal lymphadenopathy. The safer for older patients; however, younger and
nodes are typically painless and rubbery or fitter patients benefit from full conditioning. The
sometimes firm or hard if there is lots of TRM for allogeneic transplants after 2 years is
sclerosis. All the other answers are more in about 20%, mainly from infection and GVHD.
keeping with forms of NHL: option C, primary The figure of 1–5% would apply to autologous
mediastinal large B-cell lymphoma; option E, stem cell transplantation.
follicular lymphoma; option D, primary central
nervous system lymphoma; option A, 23.33. Answer: E.
have blast cells, not mature lymphocytes, and The treatment of choice is immunosuppression
DLBL is also a high-grade lymphoma with with horse ATG, which is safer than currently 23
centroblasts. available rabbit ATG. Horse ATG should be
followed by ciclosporin as longer-term
23.31. Answer: D.
immunosuppression. Allogeneic stem cell
This is a requirement for CLL diagnosis. transplantation is reserved as first-line treatment
Patients with lower CLL lymphocyte counts are for young patients (< 30 years), ideally with a
termed monoclonal B-cell lymphocytosis of fully matched sibling donor. Supportive care is
uncertain significance. Some patients present important but not as sole therapy and there is
with lymphadenopathy and lymphocyte counts no proven useful role for G-CSF. Long-term
< 5 × 109/L and are called small cell lymphocytic glucocorticoids dramatically increase the risk of
lymphoma. Most patients are asymptomatic at fatal fungal infection in neutropenic patients.
presentation and undergo watch and wait.
Mutated immunoglobulin genes carry a good 23.35. Answer: B.
prognosis and TP53 mutations carry a poor The anaemia of chronic disease largely results
prognosis and a tendency to chemotherapy from induced hepcidin production from the
resistance. Targeting the BCR complex with liver. This occurs secondary to increased
drugs such as ibrutinib (Bruton’s tyrosine interleukin-6 (IL-6) levels in inflammation. Iron is
kinase inhibitor) is a successful new form of trapped in iron-exporting cells, including
therapy. duodenal enterocytes and macrophages. Iron
274 • Haematology and transfusion medicine
does not cause direct marrow toxicity. Chronic RhD-negative can safely be given to any patient
GI tract bleeding leads to iron deficiency as it lacks isohaemoglutinins that can react
anaemia, as does achlorhydria, e.g. against the patient’s red cell surface antigens.
post-gastrectomy. Option E describes
hypersplenism. 23.39. Answer: A.
identified Gram-positive infections than Group O 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 O 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 O red cells can be this sensitising event. Implantation bleeds occur
given safely to any patient as the group O 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 RhD sensitisation
23.38). There is a historic ABO and Rhesus D 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 RhD-negative. Plasma of group AB
23.42. Answer: A.
23.43. Answer: C.
23.48. Answer: B.
All symptoms and signs of a possible Investigations are in keeping with haemolysis. A
transfusion reaction require rapid clinical positive direct antiglobulin (Coombs) test would
assessment of the patient after the transfusion support an autoimmune aetiology, the most
has been stopped (Fig. 23.43). His symptoms likely cause of this woman’s haemolysis.
are consistent with a febrile non-haemolytic A bone marrow aspirate is not indicated.
transfusion reaction. Spherocytes are not associated with
hepatitis, vitamin B12 or folate deficiency, or
23.44. Answer: B.
hypothyroidism.
His PT and APTT are significantly prolonged;
therefore, FFP is indicated at a dose of 15 mL/ 23.49. Answer: E.
kg. He will likely require platelets; however, This patient is experiencing a vaso-occlusive
at present, they are greater than the crisis with compromised blood flow to the small
recommended threshold of 50 × 109/L. vessels. A red cell transfusion will facilitate
Cryoprecipitate is primarily used to replace oxygenation and reverse the sickling process.
fibrinogen when below 1.5 g/L. Prothrombin Exchange is reserved for life-threatening crises.
complex concentrate is used to reverse Folic acid and LMWH are indicated but not the
warfarin. Vitamin K has a 4- to 6-hour onset of most important next step. Sickle-cell disease is
action. associated with small cells and normal iron
metabolism.
23.45. Answer: E.
23.46. Answer: C.
23.51. Answer: C.
Vitamin B12 deficiency results in ineffective Patients with sickle-cell disease have
haematopoiesis with nucleocytoplasmic compromised splenic function resulting from
asynchrony. Iron deficiency results in anaemia microvascular occlusion. This puts them at risk 23
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
and poor diet, usually leading to folate suggest a vaso-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.
ABO incompatibility No
• Take down unit and giving set; return
intact to blood bank
• Commence IV saline infusion
• Monitor urine output/catheterise Severe allergic reaction?
Maintain urine output at > 100 mL/hr • Bronchospasm, angioedema, Yes
Give furosemide if urine output falls* abdominal pain, hypotension
• Treat DIC with appropriate blood
components
• Inform hospital transfusion department No
immediately
Bacterial contamination?
• Blood pack discoloured or damaged
Yes • Rapid onset of hyper- or hypotension, rigors or collapse
• Temperature ≥ 39°C or rise of ≥ 2°C
If acute dyspnoea/hypotension
• Monitor blood gases
Raised • Perform chest X-ray Normal
CVP • 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; DIC = disseminated intravascular coagulation; FBC
= full blood count; IV = intravenous)
Haematology and transfusion medicine • 277
23.53. Answer: E.
chronic disease. Anaemia of chronic disease
Neonatal alloimmune thrombocytopenia occurs results from impaired iron handling. In iron
when maternal alloantibodies form against deficiency anaemia, the patient is iron depleted,
fetal platelet antigens inherited from the father. leading to a raised iron-binding capacity in the
This can result in severe life-threatening context of low iron and transferrin saturation.
thrombocytopenia in utero or at delivery, and in Folate deficiency, myelodysplasia and
first pregnancy. Immune thrombocytopenic autoimmune haemolysis are associated with an
purpura is unlikely given the absence of a elevated MCV.
history of maternal immune thrombocytopenia.
The coagulation is normal. Aside from the 23.56. Answer: D.
petechial rash, there are no concerns regarding Non-specific allergic reactions can occur during
the baby. The platelet count will recover a transfusion. Iron overload is associated with
spontaneously. repeated red cell transfusion. Massive
transfusion is associated with hyperkalaemia,
23.54. Answer: A.
hypothermia and thrombocytopenia.
Hepatitis A is transmitted through the
faeco-oral route. All the other infective agents 23.57. Answer: A.
are transmitted through direct contact with Bacterial contamination of platelets can result in
infected blood or bodily fluids. The rate of rapid onset of acute circulatory compromise.
transfusion-transmitted infection is monitored It is thought to occur secondary to exposure
through national haemovigilance schemes. The to significant bacterial toxin within the
UK Serious Hazards of Transfusion (SHOT) contaminated platelet unit rather than the
scheme has reported on proven or suspected bacterial load itself. Transfusion-associated
cases of infection transmission arising from circulatory overload is associated with
blood and component use in the UK since transfusion of large volumes relative to the
1996. patient. Whilst transfusion can cause
hyperkalaemia, this is in the context of massive
23.55. Answer: A.
transfusion. Pulmonary emboli are not generally
She has a normochromic, normocytic anaemia associated with fever. ABO incompatibility
with low iron, iron-binding capacity and resulting in catastrophic circulatory collapse is
transferrin saturation in keeping with anaemia of most often associated with red cell transfusion.
23
SH Ralston, GPR Clunie
24
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
A. Gout peptide antibodies (ACPAs) and rheumatoid
B. Osteoarthritis factor are negative, but that she has an elevated
C. Psoriatic arthritis ESR (25 mm/hr) and a raised CRP (65 mg/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 rheumatica (PMR)
tests reveal a neutrophilia (white cell count E. The presentation is typical of seronegative
12.5 × 109/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
A. Calcium pyrophosphate deposition disease rheumatoid factor negative) rheumatoid
B. Gout arthritis?
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-α) 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 mm/hr and a CRP 24
effusion. What would be the most appropriate of 84 mg/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 mg 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 mg weekly, folic acid 5 mg
E. Increase the dose of methotrexate to 25 mg weekly and prednisolone 30 mg daily
weekly D. Prednisolone 30 mg daily, ibuprofen 400 mg
3 times daily and omeprazole 30 mg daily
24.9. A 66 year old woman presents with pain E. Rituximab 1000 mg on two occasions a
and stiffness affecting the wrists, proximal fortnight apart combined with prednisolone
interphalangeal (PIP) and metacarpophalangeal 5 mg daily
280 • Rheumatology and bone disease
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 cm, 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
foot. Investigations show an elevated ESR haemoglobin of 118 g/L, white cell count
(35 mm/hr), CRP of 56 mg/L, a mild 6.3 × 109/L, platelets 355 × 109/L and ESR
neutrophilia (12.1 × 109/L), serum creatinine 20 mm/hr. An X-ray of the hands and wrists is
75 µmol/L (0.85 mg/dL), estimated glomerular performed.
filtration rate (eGFR) > 60 mL/min/1.73 m2 and Which radiological features are typical of
a serum uric acid level of 450 µmol/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? C. 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 µmol/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
C. 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 µmol/L
has been avoiding dairy products since he
(6.1 mg/dL)
thinks they cause gastrointestinal upset.
24.18. A 35 year old woman with well-controlled Which of the following risk factors predispose
RA states that she wishes to become pregnant. to the development of osteoarthritis?
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 C. Immobilisation
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
B. She should stop the ibuprofen for at least 3
weight-bearing. Examination reveals limitation 24
and pain on internal rotation of the right hip.
months before trying to conceive but can
Her height is 154 cm and weight is 82 kg
continue the methotrexate
(body mass index (BMI) 34.6 kg/m2). A pelvic
C. 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
least 3 months before trying to conceive but A. A cyclo-oxygenase 2 (COX-2) selective
can continue the ibuprofen NSAID is more likely to be effective than a
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 C. Long-term prophylactic NSAID therapy has a
joints (PIPJs) and distal interphalangeal joints disease-modifying effect
282 • Rheumatology and bone disease
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 mmol/L (9.0 mg/dL), phosphate 24.29. Which of the following clinical or
0.60 mmol/L (1.86 mg/dL), PTH 12.5 pmol/L radiographic features is consistent with a
(118 pg/mL), ALP 160 U/L and serum 25(OH)D diagnosis of Scheuermann’s disease?
54 nmol/L (22 ng/mL).
A. At least two wedge deformities in the
What is the most likely diagnosis?
thoracic spine with a T-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 (OI) and has a history of low trauma
antigen (HLA) locus on chromosome 6
fractures dating back to childhood.
24.28. A 68 year old man presents with gradually Which of the following statements is true with
worsening pain in the right hip region, which is regard to this condition?
present at rest and worsens slightly on A. Bisphosphonates are highly effective at
weight-bearing. Investigations reveal a creatinine preventing fractures in adults with OI
of 140 µmol/L (1.58 mg/dL) and an eGFR of B. Fractures of the vertebrae are an uncommon
35 mL/min/1.73 m2 but otherwise normal urea complication 24
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 6.5 × 109/L, platelets 456 × 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
8.2 × 109/L, platelets 345 × 109/L, ESR 20 mm/ C. Mutations in the FBN1 gene are the most
hr, serum iron 100 µmol/L (558 µg/dL), AST common cause
35 U/L, bilirubin 15 µmol/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?
A. The arthritis is an incidental finding unrelated 24.35. A 67 year old woman with a 15-year
to the diagnosis of haemochromatosis history of type 2 diabetes treated with diet,
B. The clinical picture is consistent with metformin and sitagliptin presents with gradual
rheumatoid arthritis onset of pain and deformity affecting the right
C. The most likely cause for his joint symptoms 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 cm 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 µmol/L (1.87 mg/dL) and eGFR of 25 mL/
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 µmol/L (0.70 mg/dL) and
and anterior aspects of the index and second serum uric acid 400 µmol/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 110 g/L and an ESR of
active synovitis but there is altered perception 25 mm/hr.
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(OH)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(OH)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-B27 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-B27 24
A. Cigarette smoking E. Pelvis radiograph, whole-spine and SIJs MRI,
B. Excessive alcohol intake (> 21 units per and HLA-B27
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 polymyalgia rheumatica
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
286 • Rheumatology and bone disease
24.43. A woman, aged 51 years, has never had mild weight loss and some altered cognitive
a fracture but has been on intermittent steroids function.
(5 × 4-week courses) for her Crohn’s disease Which one of the following diagnoses is least
over the last 2 years. Her DXA scan results are: likely?
lumbar spine bone mineral density (BMD) A. Autoimmune connective tissue disease
T-score −2.0; femoral neck BMD T-score −1.5; B. Fibromyalgia
and total hip BMD T-score −2.2. C. Inflammatory bowel disease
Which is the correct statement? D. Malignancy
A. Calcium and vitamin D should be the only E. Sarcoidosis
therapy considered
B. FRAX assessment will be useful in this case 24.47. A 65 year old man presents with low
C. Lateral spinal X-rays should NOT be thoracic back pain for the first time. It has been
obtained present for about 3 months, starting initially
D. Nothing should be done as T-scores are over the course of a week and now at a
> −2.5, except DXA to be arranged in 5 years constant level (no worsening, but no
time improvement). His sleep is disturbed. There are
E. Steroids should NOT be used to treat her no systemic symptoms and no leg pains.
Crohn’s disease Of the following, which is the most likely
diagnosis?
24.44. Blood is taken from a pre-menopausal A. Axial spondyloarthritis
woman with joint pains, xerostomia and fatigue. B. Intervertebral disc prolapse
Antinuclear antibody (ANA) is positive; anti-DNA C. Osteoporotic fracture
antibody titre 1 U/L, anti-Ro(SSA) positive, D. Septic discitis
anti-La(SSB) positive, complement C3 and C4 E. Spondylolisthesis
normal, rheumatoid factor positive, ACPA
negative. Based on the following immunology 24.48. A 13 year old girl presents with limp and
results, which is the most likely diagnosis? examination evidence of left knee swelling.
A. Primary Sjögren’s syndrome (PSS) There are no systemic symptoms, sore throat
B. RA or rash. Blood tests show normal full blood
C. RA and systemic lupus erythematosus (SLE) count, CRP of 10 mg/L, ESR of 10 mm/hr,
together negative rheumatoid factor, ACPA and ANA
D. SLE autoantibodies.
E. Systemic sclerosis (SScl) Which is most likely to be correct?
A. As there is no psoriasis, the condition is
24.45. In discriminating causes of inflammatory unlikely to be PsA
polyarthritis, which statement is most likely to B. Methotrexate should be started immediately
be true? C. Screening for uveitis is not necessary
A. An absence of joint synovitis on examination D. The condition is best classified as
rules out RA oligoarticular juvenile idiopathic arthritis (JIA)
B. Enthesitis occurring in PsA always causes E. The girl has juvenile RA
pain or local tenderness
C. Polyarticular joint involvement may be a 24.49. Which of the following statements about
typical presentation of gout in an older JIA is most likely to be correct?
woman A. Oligoarthritis in the presence of high acute
D. Pseudogout/calcium pyrophosphate phase response measures is not a
deposition disease affects only peripheral presenting feature of leukaemia or
joints inflammatory bowel disease (IBD)
E. Synovitis in PIP and some MCP joints rules B. Only ANA-positive JIA patients need an
out OA ophthalmological examination
C. Systemic JIA is associated with
24.46. A woman aged 34 years presents with haemophagocytic syndrome
a 24-month fluctuating history of fatigue, D. Systemic JIA is usually associated with a
widespread pains, poor appetite, non-specific positive ANA
bowel symptoms, non-specific skin rashes, E. The prevalence of JIA is about 1 in 10 000
Rheumatology and bone disease • 287
24.50. Which of the following treatments has C. 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-17A monoclonal (secukinumab) are HLA-B27
B. Anti-IL-23/12 monoclonal (ustekinumab) E. Enthesitis only occurs in lower limbs
C. Anti-TNF-α
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. C. 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
C. 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 C. 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-B27
24.57. Which of the following is thought to
C. ANK-H
be a consequence of, or associated with,
D. IL-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?
C. Hypertension
A. Achilles tendon enthesitis, anterior uveitis D. Plantar fasciitis
and pubic symphysitis E. Uterine fibroids
B. An aunt who has psoriasis, rheumatoid 24
factor and fatigue 24.58. The autoantibody profile: ANA positive,
C. 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
C. Primary Sjögren’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) presents 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
288 • Rheumatology and bone 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.
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 TNF-α 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.
24.10. Answer: B.
24.16. Answer: C.
with prednisolone therapy at first presentation Acute gout can be managed with either NSAID
to gain disease control. Option B would be therapy or colchicine, but urate-lowering
inappropriate in view of the very active disease therapy with allopurinol is indicated to control
given that hydroxychloroquine has relatively hyperuricaemia in the long term, to reduce the
weak immunosuppressive effects. Options A risk of recurrence and prevent long-term joint
and E would not be indicated as first-line damage. Allopurinol alone would not be
treatments. Option D would not give adequate appropriate since it may cause a further flare in
disease control. acute gout due to the change in uric acid
levels.
24.12. Answer: E.
and osteoporosis does not cause bone pain Methotrexate is teratogenic and must be
unless a fracture has occurred. Calcium and stopped completely at least 3 months before
vitamin D supplements are used in the attempting to become pregnant. It is not
treatment of osteoporosis, mainly as an necessary to stop ibuprofen before becoming
adjunct to other treatments, but alone pregnant but NSAIDs are contraindicated after
they are ineffective in the prevention of 20 weeks.
osteoporosis. Osteoporosis is a common
complication of PMR, not a rare 24.19. Answer: B.
There is no indication at present to start Previous joint injury is a strong risk factor for
treatment with either alendronate or calcium osteoarthritis due to destabilisation of the joint.
and vitamin D supplements, nor is there a None of the other factors significantly influences
reason to advise her to stop alcohol since she the development of osteoarthritis.
has a moderate intake.
24.21. Answer: E.
24.15. Answer: E.
Systemic NSAIDs are more effective that
Options A, B and D are rare adverse effects. paracetamol in controlling pain in OA. There
Leucopenia is not a recognised adverse effect is no evidence that COX-2 selective and
of oral bisphosphonates. non-selective NSAIDs differ in efficacy. There is
292 • Rheumatology and bone disease
some evidence that glucosamine has a weak recessive disorders, which would be
beneficial effect in knee OA but it has not been inconsistent with the family history of an
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.
24.23. Answer: D.
The radiograph shows changes typical of
The inactive metabolite 25(OH) vitamin D Paget’s disease with alternating areas of
(25(OH)D) is hydroxylated in the kidney at the osteosclerosis and osteolysis and expansion of
1α position by the enzyme CYP27B1 to give the femur. There is also a pseudofracture on
the active metabolite 1,25(OH)2D. Although the lateral femoral cortex. The site of Paget’s
25(OH)D is hydroxylated at the 1 and 24 corresponds with the location of the pain, and
positions, the 24,25(OH)2D 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(OH)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(OH)D levels impairment.
of 25–50 nmol/L (10–20 ng/mL). Polymyalgia is
unlikely in view of the normal ESR, and 24.29. 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 unknown whether
bisphosphonates reduce fracture risk in adults
24.26. Answer: E.
with OI. Option B is incorrect: vertebral
Option A is unlikely in view of the positive family fractures occur commonly. Option C is
history. Vitamin D-deficiency rickets is unlikely incorrect: blue sclerae are typical of type I OI
in view of the positive family history and the but normal sclerae do not exclude other
normal 25(OH)D level. Options C and D are subtypes.
Rheumatology and bone disease • 293
24.31. Answer: B.
Ehlers–Danlos syndrome type III, which is a
The presentation is typical of fibrous dysplasia, polygenic disorder. Option B is incorrect since
which is caused by a somatic mutation in hypermobility is common in osteogenesis
GNAS1, which activates signalling through the imperfecta. Option D is incorrect. Hypermobility
PTH receptor causing a focal increase in bone is diagnosed with a Beighton score of 4 or
turnover and osteolytic lesions. It is also above in the presence of arthralgia. Joint
associated with café-au-lait pigmentation due dislocations are not a prerequisite to make the
to activation of signalling through the diagnosis.
melanocyte-stimulating hormone receptor and
endocrine abnormalities. Paget’s disease can 24.35. Answer: B.
also present with focal bone deformity but The presentation is typical of a Charcot
would be extremely unusual in a patient of this joint secondary to peripheral neuropathy
age. Osteomyelitis is unlikely in the absence of associated with the diabetes. Although the
a previous history of infection. Camurati– patient has hyperuricaemia, the history does
Engelmann disease can present similarly but is not suggest gout. The history is also
bilateral rather than unilateral. The diagnosis is inconsistent with calcium pyrophosphate
not consistent with osteopetrosis, which is a deposition disease. Diabetic cheiroarthropathy
systemic rather than local disorder affects the hands, not the ankle. The clinical
characterised by high bone mass. picture is not consistent with OA, which in
the lower limbs typically affects the hips
24.32. Answer: D.
and knees.
Calcium pyrophosphate deposition disease
(CPPD) is a common feature of the arthropathy 24.36. Answer: D.
24.33. Answer: B.
The main mechanism is inhibition of bone
The symptoms are typical of median nerve formation due to osteoblast and osteocyte 24
compression syndrome, which is a recognised apoptosis. Osteoclastic bone resorption
complication of RA. Mononeuritis can occur can be increased due to secondary
secondary to vasculitis in RA but this is unlikely hyperparathyroidism but this is not the main
since the disease is under good control. mechanism of bone loss. Options A, C and
Osteoarthritis of the CMC joint presents with E are all incorrect; glucocorticoids do not
local pain rather than neurological symptoms. affect vitamin D metabolism or cause
Bone erosions are a cause of pain in RA but hypoparathyroidism.
not neurological symptoms.
24.38. Answer: A.
24.34. Answer: A.
Smoking has been associated with severity and
Postural orthostatic hypotension syndrome susceptibility to RA as well as response to
(POTS) is a recognised complication of treatment. There is no evidence that alcohol,
hypermobility. Option C is incorrect. Although body weight or HIV infection predispose to RA.
FBN1 mutations cause hypermobility as part of Although vitamin D insufficiency is common in
Marfan’s syndrome, this is a rare cause of RA, there is no evidence that it plays a causal
hypermobility – the most common cause is role or influences disease activity.
294 • Rheumatology and bone disease
24.39. Answer: D.
spinal fractures can be relatively clinically silent
The available results are consistent with acute – causing few symptoms – so often need
gout (urate crystals are negatively birefringent) pro-action ‘ruling out’ with imaging. If present,
but do not exclude the possibility that infection a fragility spine fracture will elevate her further
may also be present. In sepsis, often bacterial fracture risk considerably.
identification is not possible until culture is FRAX (www.shef.ac.uk/FRAX) allows an
available. A negative Gram stain suggests there overall quantification of fracture risk using the
might not be infection but does not rule it out. main BMD-independent risk factors for fracture.
The cause of pseudogout is calcium-containing It is well established that the level of BMD at
crystals (usually pyrophosphate) and these which fragility fractures are likely is higher than
crystals are positively birefringent. Reactive would otherwise be expected if steroids were
arthritis is certainly possible but intervention not being taken.
should be delayed until it is clear it is not Patients with Crohn’s disease, and patients
septic arthritis. on steroids, can be calcium and/or vitamin D
deficient and supplements should be
24.40. Answer: B.
considered but antiresorptive therapies should
Calcification of peri-odontoid ligaments is a also be considered if overall risk warrants.
feature of crowned dens syndrome, which is a Whilst steroids should be minimised, there may
lesion seen in CPPD. Syndesmophytes are the be no other option for treatment of her acute
hallmark radiographic sign in advanced Crohn’s flare-ups.
ankylosing spondylitis. Bone sclerosis is a
recognised feature of PsA; juxta-articular new 24.44. Answer: A.
bone formation is very common in PsA and Autoimmune serology results interpreted alone
is included in the diagnostic (CASPAR) out of clinical context are rarely, if ever,
classification. Sacroiliac disease is a common diagnostic. The serology is typical of PSS.
feature in all spondyloarthritides (SpA). Positive anti-DNA antibodies are typically
associated with SLE. Anti-Ro can be present in
24.41. Answer: E.
both SLE and PSS but if both Ro and La are
The history suggests inflammatory back pain positive, PSS is more likely. Although patients
and hence either axSpA or ankylosing with SScl can be ANA positive, antibodies more
spondylitis (AS) is possible. AS and axSpA can specific for SScl are anti-centromere or
be associated with normal ESR. Diagnosis of anti-topoisomerase (Scl-70). Rheumatoid factor
AS requires an abnormality of SIJs on x-ray to is not specific for RA and in the context of
be present but a diagnosis of axSpA can be these other serology results and negative
made before SIJ X-ray changes are present ACPA, the rheumatoid factor is far more likely
using axial skeletal MRI. Although HLA-B27 to represent PSS.
does not diagnose either disease, its presence
increases the likelihood of either axSpA or AS 24.45. Answer: C.
in the appropriate clinical context. The presentation of gout in men and women
is typically different; particularly in post-
24.42. Answer: B.
menopausal women, the first presentation may
Ultrasound has poor ability to detect soft tissue be polyarticular. Synovitis in RA can be subtle
abnormalities if there is extensive bone (which and is not always clinically obvious – MRI and
appears as an interface linear high signal with a ultrasound (US) are useful in confirming early
reflectance void beyond it, i.e. black!). There synovial disease. Axial skeletal forms of CPPD
are no characteristic features of PMR-related include crowned dens syndrome, intervertebral
lesions on ultrasound. With Doppler, ultrasound disc inflammation and ligament flavum
is useful for gauging the vascularity of joint and inflammation/thickening. Studies using US
tendon synovitis. have shown subclinical inflammation at
entheses in PsA.
24.43. Answer: B.
Generalised OA can present as an
Her osteoporosis risk may be quite high given inflammatory ‘storm’ of symptoms in small
her age (likely peri-menopausal), steroids and joints with synovial inflammation. Involvement of
systemic inflammatory disease, and despite just PIPJs and DIPJs is more common than
an osteopenia-level BMD. Mild but definite MCPJs, but often the index and sometimes
Rheumatology and bone disease • 295
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 IBD 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.
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 24
transporting inorganic pyrophosphate.
24.48. Answer: D.
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-α inhibitors ustekinumab
anaesthetic). (anti-IL-12/23 monoclonal) and secukinumab
296 • Rheumatology and bone disease
(anti-IL-17) treat enthesitis successfully, although – of MCTD. Patients with MCTD have some
evidence that non-biologic immunotherapies do features of SScl, SLE and myositis but the
is scant. Ultrasound studies have shown sclerodactyly differs in appearance to the
inflammation at painful and at symptomless sclerodactyly of SScl. Antibodies to DNA and
entheses in PsA. MRI and US can detect Sm (‘Smith’) are characteristic of SLE and
enthesitis. Enthesitis can occur at any site of positivity to Ro(SSA) and La(SSB) together
entheseal tissue – which includes any soft tissue suggests PSS.
structure attachment to bone and at the nail
bed–distal interphalangeal joint tissue complex. 24.59. Answer: D.
Enthesitis occurs in both HLA-B27 positive and The patient may well have SLE and an
negative individuals with spondyloarthritis. associated glomerulonephritis needs to be
promptly identified/ruled out. Steroids may be
24.55. Answer: B.
indicated but more initial information is needed
Apremilast inhibits PDE4, which then – and that may include kidney biopsy to grade
secondarily reduces pro-inflammatory cytokine glomerulonephritis and guide therapy choices.
production including IL-17 and TNF-α but also Any delay in obtaining information in a potential
increases production of the anti-inflammatory case of lupus nephritis can be dangerous.
cytokine IL-10. Inhibition of RANK ligand is
achieved by denosumab monoclonal antibody, 24.60. Answer: E.
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 vasculopathy 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-B51 is associated
24.63. Answer: D.
with Behçet’s disease – the main manifestation
In theory, all the features can conceivably occur of which is a vasculitis. IgA 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–Schönlein 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 24
(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 Behçet’s cancer (SIR 1.64). Relapsing polychondritis can
disease (BD). A history of genital lesions may be associated with coincident hematological
not be volunteered. Various 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
298 • Rheumatology and bone disease
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 Behçet’s disease. Local glucocorticoid
i 24.69 The CASPAR criteria for psoriatic arthritis
injection is useful for treating a number of
Inflammatory articular disease (joint, 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 IgM rheumatoid factor*
improve salivary and other glandular secretion
Current dactylitis
History of dactylitis in all but late PSS. A trial of therapy 5–10 mg 3
Juxta-articular new bone† times daily can be attempted over a month.
*Established by any method except latex. †Ill-defined
ossification near joint margins (excluding osteophytes) on 24.72. Answer: D.
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–Barré 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, coming 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-month 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-Barré 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
A. Metastatic lesion in the upper spinal cord coughing, sometimes accompanied by transient
B. Motor neuron disease flashing lights lasting seconds at a time. 25
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
302 • Neurology
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 haematoma D. Spontaneous intracranial hypotension
C. Post-traumatic tonic–clonic seizure E. Subarachnoid haemorrhage
D. Subdural haematoma
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 ischaemic attacks and is on aspirin shin. He has slight tenderness over the lower
and ramipril. 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 having
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 haematoma C. Prolonged post-ictal dysphasia
C. Ischaemic stroke D. Prolonged seizure (lasting 2–3 hours)
D. Metabolic encephalopathy E. Seizures on awakening
E. Subdural haematoma
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 abnormality 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
Neurology • 303
25.31. A 35 year old female presents with a Which feature would suggest a lesion within
6-day history of delirium and disorientation. the spinal cord as the cause of his problems?
She is pyrexial but aside from being unable to A. Bilateral lower limb hypertonicity,
answer questions or follow direction, exhibits hyper-reflexia, and upgoing plantar reflexes
no neurological deficit. B. Circumduction of the left foot
After normal imaging has been carried out, a C. Difficulty with heel-toe waking
lumbar puncture is done, which shows the D. High-stepping gait
following results: white cell count 35 × 109/L; E. Slapping of the feet against the ground
blood film – 90% lymphocytes; CSF protein
0.65 g/L; CSF glucose 4.2 mmol/L (76 mg/dL); 25.35. A 35 year old patient presents with
serum glucose 6.0 mmol/L (108 mg/dL) (normal weeks of progressively worsening left-sided
CSF glucose is > 60% of contemporary serum facial pain. Which of the following would
glucose). suggest that the cause is outside the superior
Which process would be a likely cause of orbital fissure?
this picture?
A. Diplopia on gaze to the left
A. Brainstem encephalitis B. Diplopia on gaze to the right
B. Meningococcal meningitis C. Left proptosis
C. Subarachnoid haemorrhage D. Reduced visual acuity in the left eye
D. Tuberculous meningitis E. Sensory alteration over the left eye
E. Viral encephalitis
25.36. A 43 year old woman presents with a
25.32. A 76 year old man presents with history of vertigo and vomiting.
a left-sided facial weakness of rapid Which of the following features would be
onset. He has no past medical history most in keeping with a diagnosis of acute
of note. labyrinthitis?
Which feature would suggest that the
A. Evolving symptoms over weeks
deficit is caused by an upper motor neuron
B. Improvement in symptoms following an Epley
lesion?
manoeuvre
A. Deviation of the tongue to the left on C. Ipsilateral sensorineural hearing loss
protrusion D. Nystagmus worsened by change in position
B. Hyperacusis on the left E. Precipitation by minor head injury
C. Loss of taste in the anterior two-thirds of the
tongue on the left 25.37. A 28 year old right-handed man
D. Preservation of eyebrow elevation on the complains of visual disturbance after sustaining
affected side a significant head injury in a road traffic
E. Weakness of eyebrow elevation on the accident. CT scan shows a fracture in the left
opposite side parietal region with an underlying cerebral
contusion and extradural haematoma.
25.33. A 64 year old woman presents with a left What visual symptoms would you expect to
foot drop of gradual onset. result from this injury?
Which of the following would suggest that
A. Diplopia on looking to the right
the responsible lesion is in the common
B. Left-sided neglect
peroneal nerve rather than a more proximal
C. Left superior quadrantanopia
lesion?
D. Reduced visual acuity on the left
A. Reduced left ankle jerk E. Right inferior quadrantanopia
B. Reduced pin-prick in lateral shin
C. Reduced pin-prick sensation in the medial 25.38. A 54 year old female presents with a
shin 6-month history of recurrent headaches. They
D. Tinel’s sign over the fibular neck affect the right periorbital region, with a
E. Weakness of ankle inversion throbbing quality, and make her feel sick.
Sometimes the right eyelid appears droopy with
25.34. A 57 year old man is referred to the clinic the pain, and she prefers to go to bed and
because of some difficulty with unsteadiness on sleep it off. It usually lasts a few hours. When
walking. younger, she recalled headaches with her
Neurology • 305
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
B. Muscle-specific kinase (MuSK) D. Tremor improves with small amounts of
C. N-methyl-D-aspartate (NMDA) receptor alcohol 25
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
sixth month of her first pregnancy with with Parkinson’s disease. He is reluctant to
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
306 • Neurology
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 10 00 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 ischaemic 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
Neurology • 307
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 medication, does not What is the likely diagnosis?
smoke and drinks only occasionally. He A. Brainstem 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
C. Left parietal lobe (angular gyrus) 12 months. A post-micturition ultrasound scan 25
D. Right motor strip reveals a residual volume of 182 mL of urine.
E. Right subthalamic nucleus What is the most appropriate treatment?
A. Bladder-stabilising (anticholinergic) drug
25.51. An 82 year old female was seen in the B. In-dwelling catheter
neurology clinic with a progressive history of C. Intermittent self-catheterisation
speech and swallowing problems over the D. Long-term antibiotic prophylaxis
previous 9 months. Initially she had some E. Pelvic floor exercises
slurring of speech, and was seen in an ear,
nose and throat (ENT) clinic; no vocal cord 25.54. A 36 year old male presents with a
pathology was found. 3-week history of headaches, typically
Her speech deteriorated, and is now difficult awakening him in the early hours. They are
to understand, with a rather squeaky severe, affecting the right periorbital region, last
characteristic. Her swallowing has also about an hour and are very distressing; he is
deteriorated with frequent choking, and she has unable to find a comfortable position. He has
308 • Neurology
noticed that his right eye waters and goes red A. Aquaporin-4 antibody
with the pain. Occasionally he gets an attack B. Lumbar puncture for oligoclonal bands
during the day. He thinks he had something C. Paraneoplastic antibodies
similar about 2 years ago but it disappeared D. Repeat imaging with contrast
after a week or so. He is otherwise well, but E. Visual evoked potentials
terrified that he has a brain tumour such is the
severity of the pain. 25.57. A 21 year old female was diagnosed with
What is the likely diagnosis? MS 2 years ago after presenting with ataxia,
A. Cluster headache from which she recovered fully; she declined
B. Hypnic headache further treatment at the time as she was
C. Migraine considering starting a family. She has now
D. Paroxysmal hemicrania developed numbness of her left arm, which has
E. Temporal arteritis alarmed her but is not compromising her
function. She has no other symptoms.
What is the most appropriate immediate
25.55. A 50 year old male describes a 3-week
management?
history of dizziness, often occurring in bed.
Shortly before the dizziness started, he had A. Broad-spectrum antibiotic
walked into a glass door, ‘seen stars’ but not B. Conservative
lost consciousness. On closer questioning, he C. High-dose oral glucocorticoids
has noted that getting into or out of bed and D. Physiotherapy
rolling over to the left can trigger his symptoms, E. Start a disease-modifying drug of high
which is brief vertigo lasting a few seconds. He efficacy such as natalizumab
has fallen on two occasions as he got out of
bed as a result. He occasionally gets it during 25.58. A 30 year old female presents to
the day, usually when getting into his sports her family physician. Her identical twin
car, but otherwise he is generally well. He is sister was diagnosed with MS last year, and
on no medication, but drinks about 60 units of she has read that her own risk of MS is
alcohol per week. therefore increased, and she is enquiring
What is the appropriate management? about this.
Approximately what is her risk of developing
A. Alcohol abstention
MS?
B. Betahistine
C. Low-salt diet A. 5%
D. Short course of glucocorticoids B. 20%
E. Vestibular repositioning (e.g. Epley C. 35%
manoeuvre) D. 50%
E. 85%
25.56. A 36 year old female presents with
progressive difficulty walking over the previous 25.59. Which of the following scenarios would
week, and now has difficulty passing urine. represent a reasonable case for requesting an
One year previously she had an episode of electroencephalogram (EEG)?
monocular visual loss which lasted about 2 A. A 15 year old female with a single
weeks. She was abroad at the time, and by the unwitnessed blackout thought to be
time she returned, her vision was recovering so syncope but with associated urinary
she did not seek attention. On examination she incontinence
has an upper motor neuron pattern weakness B. A 24 year old male in a psychiatric unit on
in both legs, with brisk reflexes and upgoing multiple antipsychotics and consistently
plantar responses, and a palpable bladder; drowsy in the mornings
her right optic disc is pale. Her non-contrast C. A 64 year old female having had a single
MRI head is normal, but there is a long lesion generalised tonic–clonic seizure
seen in the thoracic spine, stretching over D. A 68 year old female with two witnessed
several spinal segments, thought to be generalised tonic–clonic seizures
inflammatory. E. A 68 year old male with a previous left
Which investigation is most likely to make hemisphere stroke and recent episodes of
confirm a diagnosis? unwitnessed collapse
Neurology • 309
Examination shows her to have a small right with loss of vibration sensation to the knees
pupil with mild degree of right ptosis. Eye and reduced proprioception in toes and ankles.
movements are full and fundal examination is Initial investigation shows: random glucose
normal. Cranial nerve examination is otherwise 6.8 mmol/L (123 mg/dL); full blood count
normal. normal; erythrocyte sedimentation rate (ESR)
What is the most likely cause of her 78 mm/hr.
symptoms? What is the likely cause of his symptoms?
A. Extradural haematoma A. Alcoholic neuropathy
B. Subarachnoid haemorrhage B. Diabetic neuropathy
C. Subdural haematoma C. Motor neuron disease
D. Traumatic brachial plexopathy D. Myelopathy secondary to lymphomatous
E. Traumatic dissection of the extracranial deposits
carotid artery E. Neuropathy secondary to myeloma
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?
C. Ménière’s disease A. Bell’s palsy
D. Migraine without aura B. Lyme disease
E. Multiple sclerosis C. 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 C. 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,
Neurology • 313
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.
and any drugs with an uncertain safety profile necessary, a lumbar puncture can be carried
in pregnancy. While topiramate can be useful in out in due course, but only once the serious
GGE, the safety in pregnancy is uncertain and underlying sepsis has been addressed.
it is therefore best avoided in the first instance.
25.13. Answer: E.
25.9. Answer: D.
Acute bacterial meningitis (unless already
The main reason to carry out cervical spine treated with antibiotics) will cause a rise in
imaging is to provide information on any lesion neutrophils in CSF. Bacterial infection will
that might be operable. It is in such cases that usually raise protein and lower glucose. Viral
a good history and neurological examination encephalitis will cause a rise in CSF
are most important. Where clinical features of lymphocytes and often have little effect on
motor radiculopathy are found (as here) and are protein and glucose. A raised CSF protein and
persistent, then imaging may be considered. no effect on white cells is characteristic of
Signs or symptoms of spinal cord compression inflammatory processes such as Guillain–Barré
(upper motor neuron signs in the legs, or syndrome.
sphincter dysfunction) would make imaging
more important. ‘Clunking’ sensations in the 25.14. Answer: E.
neck are common and unrelated to specific Syringomyelia is a slowly progressive problem
pathologies. Nocturnal hand symptoms are with expansion of the central canal causing
more likely with carpal tunnel syndrome, while destruction of the cells and tracts in the
prolonged duration of symptoms is common anterior spinal cord. The occurrence of
with benign non-progressive spinal disease. selective spinothalamic loss and anterior horn
cell loss localises this process to the anterior
25.10. Answer: E.
spinal cord. The lack of leg symptoms makes
Assessment of lower back pain is another this a process in the cervical and thoracic cord.
occasion when a good history and neurological The slow evolution would not be in keeping
examination are required. New onset of urinary with a vascular origin. The sensory findings (as
symptoms or focal radiculopathy may suggest well as the limitation to the arms) makes motor
a structural cause. Localised tenderness is neuron disease much less likely.
common in muscular back pain, while costal
hyperaesthesia would suggest a thoracic 25.15. Answer: B.
localisation. Neurological examination in old age The concurrence of leg symptoms and
is likely to elicit some ‘deficits’ such as distal sphincter dysfunction with or without pain in
reflex loss and sensory disturbance, even in such a patient is highly suggestive of a
asymptomatic patients. malignant spinal cord compression. Urgent
imaging is needed to allow intervention to
25.11. Answer: B.
prevent progression to destruction of the spinal
The pyrexia and evolving neurological deficit cord. Note that this should include the thoracic
makes it likely that there is an encephalitic and spinal cord as there may be a ‘dropped’
process rather than just a meningitis. It should spinal level.
be noted that the patient is not ‘confused’; she
is dysphasic. Herpes simplex is the most 25.16. Answer: A.
common cause of a viral encephalitis. Bacterial The scenario of severe pain followed by some
meningitis can cause some isolated cranial minor neurological deficit is typical of brachial
nerve deficits, but the cortical nature of her neuralgia (neuralgic amyotrophy). Cervical
expressive dysphasia would not be expected in radiculopathies can cause pain, but any
a pure meningitis. neurological deficit will coincide with this rather
than follow its remission. There is no rash to
25.12. Answer: A.
suggest a herpes zoster infection (which would
This is a classic scenario with rapidly evolving usually also cause a persisting rather than an
clinical disease where it is important to treat early-then-remitting neuralgic pain). Transverse
first and think later! The rapid development of myelitis may cause back and neck pain but
meningococcal sepsis is a severe threat to life would usually have more marked sensory
and limb and requires immediate treatment. deficit, perhaps with long tract signs in the
Investigation with imaging, bloods and, if lower limbs.
Neurology • 315
25.17. Answer: B.
Cerebral venous sinus thrombosis can cause
The gradual onset of headache with features of severe postural headache but, like other causes
high pressure (papilloedema, worsening with of headache in the list, will usually cause
moves that increase intracranial pressure), and headache precipitated by manoeuvres that
no focal neurological deficit make IIH the most raise intracranial pressure.
likely diagnosis. This is more likely when
patients are obese and where there has been 25.21. Answer: C.
exposure to steroids, oral contraceptives or The singular loss of ankle dorsiflexion makes
tetracyclines. sciatic nerve or radicular involvement unlikely. If
While serious conditions like intracranial ankle inversion is intact (usually tibialis posterior
tumour and cerebral venous sinus thrombosis – supplied by L5 and tibial nerve), then the
should be excluded, the lack of other features likely cause is common peroneal weakness
in someone of this age and gender make IIH selectively affecting tibialis anterior. Alcohol
most likely. There is no episodicity to her excess may make nerves more susceptible to
headaches and no clear features to suggest localised damage, but the focal nature of the
migraine with aura. Optic neuritis can cause deficit would make a generalised process an
optic disc changes and some ocular pain, unlikely cause. It would be unlikely that a
but the pressure features will mitigate cortical lesion would cause such a focal
against this. combined lower motor neuron and sensory
deficit.
25.18. Answer: B.
followed by deterioration, after a head injury, is Prolonged post-ictal dysphasia would suggest
classically that of an arterial bleed into the a focus of onset in the dominant hemisphere
extradural space following head injury. This (either Broca’s or Wernicke’s areas).
requires urgent imaging and probably acute Generalised epilepsies are thought to be
drainage/decompression. genetic in origin, and will often be accompanied
There is nothing to suggest any extra alcohol by other seizure types such as myoclonus or
intake and the presence of focal signs would absences. Very prolonged episodes lasting
be against this. There is no suggestion of an hours or more are rare with epilepsy and
infective process and there are no markers to (especially where awareness is retained)
suggest a seizure – this would be a diagnosis may result from non-epileptic attack
of exclusion in a case like this. disorder.
25.19. Answer: E.
25.23. Answer: B.
The effect of minor head injury, especially in the In right-handed patients, the dominant
presence of cerebral atrophy and aspirin hemisphere for both limb movement and
treatment, is a risk factor for chronic speech is usually the left. Speech
development of a subdural haematoma, which comprehension is usually sited in Heschl’s
is impairing consciousness. Alzheimer’s disease gyrus in superior temporal lobe, while
itself would not usually cause such a rapid Broca’s area in the frontal lobe is devoted to
25
decline, and it is unusual for ischaemic strokes formation of speech. Damage to the former will
to impair consciousness. The presence of focal result in so-called receptive or fluent dysphasia
neurological signs would go against her (inability to understand auditory input from
drowsiness having an encephalopathic speech) and the latter with expressive
cause. dysphasia.
25.20. Answer: D.
25.24. Answer: D.
The history is key here – providing evidence Dysarthria can be caused by many
that the headache is related to low intracranial things (Box 25.24) but cerebellar deficits
pressure. A dural tear is likely to have will cause consistently poor articulation
happened while vomiting, caused by the with impaired cadence (scanning) as this
original migraine, and the clear postural worsens. Poor coordination of limb
association of the subsequent headache makes movement would also usually be noted at
this the prime diagnostic consideration. these times.
316 • Neurology
reduction in colour vision on the affected A metabolic muscular problem means that
side(s). Peripheral retinal problems will cause prolonged exercise is liable to cause muscle
Neurology • 317
damage resulting in myoglobinuria: presence of Bilateral facial weakness should raise the
myoglobin causing the black urine. suspicion of either myasthenia or Guillain-Barré
Diabetes mellitus can occur in mitochondrial syndrome, while ipsilateral protrusion of the
conditions, but it is common and unlikely to be tongue occurs often with a facial palsy and
directly relevant unless there are other clues without other signs would not imply
(accompanying systemic disease, maternal involvement of any other cranial nerves.
transmission and deafness). Nocturnal leg
cramps are common and history of dropping 25.33. Answer: D.
things is non-specific for muscular problems. The common peroneal nerve supplies tibialis
anterior, the toe extensors and sensation
25.30. Answer: E.
to the lateral aspect of the shin. The nerve runs
The occurrence of daytime sleepiness in round the fibular neck and irritation at that
narcolepsy is usually accompanied by some of point can produce a Tinel’s sign (localised
the other three components of the narcolepsy tenderness of dysaesthesia over a site of nerve
tetrad: namely, cataplexy (collapses with fright damage) in a nerve that is affected early. The
or laughter), hypnagogic hallucinations (visual common peroneal nerve is mostly derived from
hallucinations often with an emotional content) L5 roots, so clinical differentiation can be
and sleep paralysis (loss of voluntary movement difficult.
on awakening). The genetic basis for this An L5 lesion will cause a foot drop alongside
condition means that a family history of reduced pin-prick in the lateral shin, as well as
excessive sleepiness may help diagnosis. Of weakness of ankle inversion (as it supplies
the tetrad components, sleep paralysis is the tibialis posterior).
one that is most likely to be physiological, and The ankle jerk depends on contraction of
isolated sleep paralysis should not in itself soleus and gastrocnemius, which are supplied
trigger invasive or prolonged testing. by tibial nerve and S1 root.
Hypnic jerks on falling asleep are a normal
phenomenon. The important treatable cause of 25.34. Answer: A.
daytime sleepiness is lack of night-time sleep A lesion of the spinal cord is likely to affect
– exclusion of obstructive sleep apnoea may be both legs equally in provoking upper motor
required. neuron signs, leading to a spastic paraparesis
with increased tone, increased reflexes and
25.31. Answer: E.
extensor plantar reflexes.
A raised neutrophil count in CSF is strongly Selective or particular difficulty with heel-toe
associated with a bacterial infection, although walking results from cerebellar dysfunction,
the very earliest stages of a viral encephalitis while a high-stepping gait and slapping gait will,
may cause neutrophils to rise. respectively, compensate for or result from
Infections by mycobacteria, viruses, or impaired ankle dorsiflexion (i.e. a foot drop),
partially treated bacterial meningitis may be which results most usually from a common
associated with lymphocytic CSF. Where there peroneal or radicular lesion.
has been a large subarachnoid haemorrhage, Unilateral circumduction is a sign of a
the irritant effect of blood on the meninges may unilateral upper motor neuron lesion, where the
25
cause a lymphocytic CSF, but would more leg has to drift sideways while walking to
likely have an abrupt onset and mild (or no) compensate for the partial plantar flexion
pyrexia. caused by increased tone in soleus and
gastrocnemius.
25.32. Answer: D.
cerebral cortices), so a unilateral facial The superior orbital fissure is formed by the
weakness caused by an upper motor lesion will cleft between the lesser and greater wings of
be modified by the residual supply from the the sphenoid bone. Lesions in this will affect
ipsilateral cortex. the structures that pass through, including
Hyperacusis and dysguesia (altered taste) cranial nerves III, IV and VI, which, if affected,
originate from lesion of the facial nerve and will cause diplopia on gaze to either side or on
would not be prominent with an upper motor downgaze. Compression of the orbital vein
neuron facial weakness. would lead to proptosis, and any effect on the
318 • Neurology
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 much 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
Ménière’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 mouth 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 from 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 may return (potentiate) with
function and may 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.
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.
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
Neurology • 319
suggests essential tremor (ET; usual bilateral), This is a very typical Essential tremor (ET)
and whilst PD can be familial, the family history history – both arms involved, postural and
of a tremor would also fit ET better. Family kinetic components, autosomal dominant
history of learning disabilities suggests possible pattern of inheritance and an alcohol response
fragile X tremor ataxia syndromes, which can in some members (only about 50% note such a
manifest sometimes in women. response). Parkinson’s tremor is more typically
asymmetrical, and at rest. It can be difficult to
25.44. Answer: B.
distinguish an enhanced physiological tremor
There remains some controversy about when from a mild ET, as they look similar, although
best to start treatment in PD, although there is the other features help (family history, alcohol
consensus that presently we have no proven responsiveness). Whilst sensible to check his
disease-modifying therapies. Anticholinergics thyroid status, it is unlikely to explain a 10-year
are no longer favoured due to their adverse history.
effect profile and poor efficacy. Whilst the
response to dopaminergic therapies becomes 25.48. Answer: D.
both attenuated and complicated as PD This is a typical story for TGA, with a profound
progresses, people do not become ‘immune’ anterograde amnesia lasting several hours
to it. Whilst DBS is a very effective treatment leading to repetitive (and irritating) questions,
for tremor (where drugs often fail), few would and retrograde amnesia stretching back at least
advocate this approach prior to a trial of 2 years, but not so long that she had forgotten
medication. Most would recommend her friends or husband. Psychogenic amnesia
dopaminergic therapy sooner or later, and in often involves loss of self-identity (functional
the UK we would be inclined to wait until his fugue state); the post-ictal state is usually
symptoms trouble him, although there is confusion, rather than this very specific isolated
greater enthusiasm for earlier treatment amnestic syndrome. Isolated amnesia is almost
elsewhere. never due to a TIA, and Alzheimer’s presents in
a much more insidious way.
25.45. Answer: C.
tests are rarely helpful. This is unlikely to be In general, people who worry about their
Wilson’s disease (caeruloplasmin) with this age memory, which no one else has noticed, rarely
at presentation, and the scenario is not have an underlying disease; clinicians should
suggestive of a genetic cause (in any case, one worry much more about the family who bring a
would need to undertake genetic counselling patient who seems blithely unaware of any
first before any genetic testing). Structural problem. Minimal cognitive impairment (MCI) is
imaging is rarely indicated in a typical story a controversial entity, although some will
such as this, and, similarly, functional imaging progress to dementia. Depression can present
25
with either SPECT or positron emission with a pseudo-dementia, but there are no
tomography (PET) is unnecessary when the specific features of depression here. Sleep
diagnosis is clear clinically. apnoea can disturb memory but is usually
associated with excessive daytime sleepiness,
25.46. Answer: A.
and a sleep history of snoring and apnoeic
This is likely to be secondary to long-term spells.
metoclopramide use, even though many
doctors and patients think of it as an innocuous 25.50. Answer: E.
drug. Chorea can occur with stroke, but is He has developed acute hemiballism, which
usually unilateral and acute. Such dyskinesias usually localises to the contralateral subthalamic
may complicate Parkinson’s disease when nucleus in the basal ganglia. In this case, it is
treated with levodopa, but are not a presenting almost certainly due to a stroke, but is often
feature in patients not on treatment. not recognised as such as the symptoms are
Huntington’s disease can present this late, unusual and may be missed by inexperienced
320 • Neurology
clinicians. Lesions in the motor strip would (TACs). The pain is always severe, lasting
cause weakness, and lesions affecting the between 30 and 180 minutes, associated with
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 TAC, 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.
symptomatic infection. Physiotherapy will not An acute onset of vertigo that begins to resolve
help sensory symptoms. over days is likely to be related to an acute
vestibular syndrome.
25.58. Answer: C.
BPPV is a chronic condition precipitated
The risk of developing MS is increased by usually by a specific movement in each
10- to 25-fold in first-degree relatives of people individual, and would merit treatment with the
with MS, but varies depending upon the Epley manoeuvre. A brainstem stroke would
kinship. The highest risk is in female usually cause more widespread neurological
monozygotic (MZ) twins (in male MZ twins it is changes, while Ménière’s disease is a chronic
about a 6% risk of occurring). condition causing vertigo with associated
deafness and tinnitus.
25.59. Answer: C.
Vertigo associated with migraine is a
Of course in an adult with new onset seizures recurring condition of relatively short-lived
imaging is the important investigation, but EEG vertigo most usually associated with headache
can have a role in some cases. In someone and/or other migrainous symptoms.
with a single seizure, a timely EEG (within 4
weeks) can help inform the risk of recurrence, 25.62. Answer: C.
and so will be worthwhile after a single The coexistence of headache and papilloedema
generalised tonic–clonic seizure at any age. will always merit imaging to exclude an
In patients under the age of about 30 years intracranial lesion, but the patient’s age and
with new-onset epilepsy (either multiple morphology, intermittent nature of the
seizures or single seizure with high risk of symptoms and lack of other findings would
recurrence), the EEG can help with make IIH most likely. Transient loss of vision on
classification of epilepsy and so will carry bending (or other manoeuvres that transiently
therapeutic implications. raise intracranial pressure; ICP) are
In elderly patients with multiple seizures, characteristic, and called visual obscurations.
epilepsy is almost certainly going to have a Optic neuropathy would cause disc pallor and
focal origin and the EEG is unlikely to be useful. reduced colour vision, while retinopathy would
In anyone of any age with unwitnessed or cause field defects or, if affecting the maculae,
indeterminate transient loss of consciousness, reduced visual acuity. Neuromyelitis optica is an
the inter-ictal EEG may not only fail to show inflammatory condition causing neurological
abnormalities but also any resultant deficit but not headache.
‘abnormalities’ may be red herrings; this applies
especially to patients with focal injury or to 25.63. Answer: E.
younger females who have a higher chance of The aqueduct of Sylvius is the small channel
displaying epileptiform features on EEG such as that allows CSF to travel from the third to the
photosensitivity. fourth ventricle. Stenosis can become apparent
in adult life and lead to symptoms of raised ICP.
25.60. Answer: B. Imaging will show that the ventricles ‘upstream’
CIDP is a condition that causes loss of myelin (lateral and third ventricles) will be dilated, but
25
in peripheral nerves. Nerve conduction studies the fourth will be small or of normal size.
can demonstrate demyelination of peripheral IIH is associated with normal or small
nerves (via slowed conduction) or axonal ventricular size, while space-occupying lesions
damage to sensory or motor nerves (with will be apparent on imaging, and if severe
reduced numbers of functioning axons leading enough to cause raised intracranial pressure
to reduced amplitude of response). EMG will often cause other neurological deficits.
shows spontaneous activity in muscle Venous sinus thrombosis will usually be
(fasciculation or positive sharp waves) when apparent on imaging (often resulting in
nerve supply to muscle is lost due to axonal haemorrhage). Normal pressure hydrocephalus
damage, but not as a consequence of usually occurs in older patients, and will have
demyelination. The peripheral demyelination no features of acutely raised ICP, but rather a
therefore would be expected to cause only triad of reduced cognition, urinary incontinence
abnormal nerve conduction velocities and not and gait abnormalities, resulting in dilation of all
EMG changes. ventricles apparent on imaging.
322 • Neurology
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.org/). 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.
athetosis but not usually ataxia; β2-agonists will The only localising features here are the
cause tremor in acute stage. symptoms of left sensory change and the
quadrantanopia, which 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
Neurology • 323
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.
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 ESR 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.
324 • Neurology
myelopathy (no upper motor neuron symptoms Spinal cord problems will often cause motor,
or sphincter deficit) and the presence of sensory and sphincter problems. Any sensory
sensory symptoms and signs would not be problems caused by spinal cord lesions may
suggestive of motor neuron disease. relate to dissociated sensory loss, which may
be asymmetrical if only half of the cord is
25.77. Answer: B.
affected. Motor deficit caused by spinal cord
The symptoms and signs suggest a lower problems are upper motor neuron lesion in
motor neuron facial palsy on the affected side. character below the lesion and may be lower
Recurrent facial palsy in someone at high risk motor neuron character at the level of the
of Borrelia burgdorferi infection makes Lyme lesion, rather than a widespread mixture of
disease the likely cause here. The onset and upper motor neuron and lower motor neuron
relapse would be unusual for a vascular cause, signs.
and multiple sclerosis causes upper motor Distal sensory loss is usually caused by a
neuron problems, being unlikely to cause an peripheral neuropathy, and cranial nerve deficits
isolated facial palsy. Syphilis can cause some (e.g. diplopia) will require involvement superior
vasculitic central nervous system problems, but to the spinal cord.
the typical pattern would involve a myelopathy Timing of the evolution of the symptoms
and some brainstem signs. Even with the tends to give information on the nature rather
recent rise in incidence, it remains rarer than than the site of the lesion.
that other spirochete, Borrelia.
P Langhorne
26
Stroke medicine
26.6. The ROSIER (Rule Out Stroke In the A. It can be offered to most stroke patients
Emergency Room) clinical stroke tool can be B. It is effective in intracerebral haemorrhage
used to triage patients with clinical suspicion of C. It is effective in large-vessel occlusion
stroke. Which of the following features are D. It requires less technological support than
given a negative score on the ROSIER scale intravenous thrombolysis
(i.e. are not thought to be consistent with a E. It is a treatment that is widely available
clinical diagnosis of stroke)?
A. Leg weakness 26.11. A 38 year old man is brought to the
B. Loss of speech emergency department with a suspected
C. Seizure intracerebral haemorrhage. Which of the
D. Unilateral arm weakness following are recognised risk factors for
E. Visual field defect intracerebral haemorrhage?
A. Antiphospholipid abnormality
26.7. A patient is admitted with a clinical picture B. Cardiac embolism
of acute stroke. You request a plain CT scan C. Carotid artery stenosis
as initial emergency brain imaging. What D. Cocaine use
information can you get from plain E. Raised cholesterol
(non-contrast) CT brain scanning in acute
stroke patients? 26.12. A 70 year old man with recent minor
stroke is found to be in atrial fibrillation. When
A. Distinguishes acute stroke from TIA
advising him on anticoagulant therapy, which of
B. Reliably detects intracerebral blood
the following features would make you favour
C. Reliably detects subtle acute ischaemic
warfarin over a direct oral anticoagulant
changes
(DOAC)?
D. Shows brain function (functional imaging)
E. Shows blood flow in vessels A. Fewer drug interactions
B. Lower drug costs
C. Lower risk of intracerebral haemorrhage
26.8. A 65 year old woman with a previous
D. More effective at preventing embolism
history of diabetes and breast carcinoma is
E. Simpler dosing regimes
found collapsed at home with drowsiness and
a left hemiparesis. Which of the following
26.13. A 45 year old woman is admitted to
should be carried out first?
hospital with symptoms of raised intracranial
A. Check blood glucose level pressure, seizures and focal neurological
B. Check temperature symptoms. Which of the following is correct
C. Clarify breast carcinoma history about the suspected diagnosis of cerebral vein
D. Examine for peripheral neuropathy thrombosis?
E. Examine for symmetrical plantar responses
A. CT brain scanning is the definitive
imaging
26.9. An 83 year old woman is brought to the B. It can include an associated haemorrhage
emergency department after becoming unwell C. It is never caused by infection
at home. Which of the following is true of total D. It is rarely treated with anticoagulation
anterior circulation stroke? E. It usually presents like arterial stroke
A. It is caused by occlusion of small perforating
arteries 26.14. A 62 year old man with a stroke is being
B. It includes higher cerebral dysfunction and considered for thrombolysis therapy. Which of
motor loss the following is true of intravenous thrombolysis
C. It involves isolated homonymous hemianopia with recombinant tissue plasminogen activator
D. It is not caused by cerebral embolism (rt-PA)?
E. It is a pure motor stroke A. It can be given up to 12 hours after
symptom onset
26.10. A patient with an acute stroke is B. It can be offered to most stroke
admitted to the specialist stroke unit. Which of patients
the following currently apply to mechanical clot C. It improves the chance of recovery of
retrieval (thrombectomy)? independence
Stroke medicine • 327
D. 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, C. 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 her
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: C.
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 simvastatin 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; ECG = electrocardiogram; INR = international
normalised ratio; MRI = magnetic resonance imaging; TIA = transient ischaemic attack; U&Es = urea and electrolytes)
26.5. Answer: E.
mimic of stroke. For that reason, it scores −1
In addition to lifestyle modifications, antiplatelet, 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.
26.6. Answer: C.
26.8. Answer: A.
Although seizure does occur in < 5% of acute Hypoglycaemia can mimic stroke, is a medical
stroke patients, seizure (with post-seizure emergency and is easily corrected. Although
paresis) is more commonly recognised as a we do not know what drugs this patient takes,
Stroke medicine • 329
26.11. Answer: D.
i
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
a stroke in acute presentations:
pressure, smoking, excess alcohol intake,
structural abnormalities, coagulopathies and
Unilateral facial weakness +1
drugs such as cocaine and amphetamines.
Unilateral grip weakness +1
Unilateral arm weakness +1
Raised cholesterol, antiphospholipid
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
Check comprehension (‘lift your arms, close your eyes’) to
simpler dosing regimes with fewer drug
identify 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.
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 patient 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.
R Darbyshire, J Olson
27
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
Medical ophthalmology • 331
A. Control of hypertension
B. Intravitreal anti-vascular endothelial growth
factor (anti-VEGF) therapy
C. 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. Intraretinal microvascular anomalies
27.13. A 69 year old male presents with a 2-day
C. 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. Ipratropium is an antimuscarinic
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.
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 of endophthalmitis until proven otherwise and
or MR angiography in the first instance. requires specialist review. The worrying features
are the initial subjectively good vision, followed
27.5. Answer: D.
by rapid deterioration, new floaters, which may
Nebulised salbutamol and ipratropium are suggest infection in the vitreous, and increasing
involved in the management of a life-threatening pain.
334 • Medical ophthalmology
27.9. Answer: A.
• stage 2: the temporal disc head becomes
Optic neuritis is an acute inflammatory process involved, creating a 360° circumferential
affecting the optic nerve. It usually presents swelling
with sudden monocular visual loss over hours • stage 3: vessel obscuration occurs at the
to days and eye pain in young adults, more disc margin
commonly in women. The Optic Neuritis • stage 4: vessel obscuration occurs at the
Treatment Trial (ONTT) elucidated the typical disc head
features of a demyelinating optic neuritis as
In established papilloedema, circumferential
follows:
retinal folds or Paton lines may form.
• Age 20–50 years Haemorrhage and cotton wool spots represent
• Unilateral ischaemic damage. In this setting, optic nerve
• Worsens over hours/days function will be reduced on examination and
• Recovery starts within 2 weeks may not recover. Severe hypertension causes
• Retrobulbar pain bilateral optic disc swelling in the absence of
raised intracranial pressure.
• Reduced colour vision
• Relative afferent pupillary defect
27.12. Answer: C.
In two-thirds of cases, the optic disc itself
27
RM Steel, SM Lawrie
28
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 perception 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
Medical psychiatry • 337
28.6. When on-call over the weekend in a large 28.10. 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 this 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. Kinaesthetic hallucination feels anxious and jumpy all of the time and
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 28
he has recently separated. She is concerned terrifies him. Which is the most likely diagnosis?
that he is confused and ‘talking nonsense’. A. Acute stress reaction
He has an unsteady gait yet his breath B. Adjustment disorder
alcohol level is zero. On examination he has C. Delirium
ophthalmoplegia and is disorientated in time. D. Depression
His liver function tests are deranged. 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
338 • Medical psychiatry
he suffered an acute myocardial infarct 28.16. A 45 year old man presents with dry,
requiring thrombolysis and subsequent broken skin on both hands. He reports a
coronary artery stenting. He appears to be 10-month history of distressing repetitive
making a good physical recovery but he tells thoughts with a theme of hygiene. He
you that for the past few weeks he has been recognises that these are his own thoughts.
unable to experience pleasure from activities He describes a short-lived reduction in distress
that he would ordinarily enjoy (such as following hand washing and says that in recent
watching his favourite football team score a weeks he has been washing his hands more
goal). Which of the following terms most and more. What are the man’s thoughts most
accurately describes this symptom? likely to be?
A. Anhedonia A. Auditory hallucinations
B. Depression B. Catastrophisations
C. Dysphoria C. Compulsions
D. Euthymia D. Obsessions
E. Hypomania E. Ruminations
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/m2)
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
that over the past 25 years she has had management?
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 mirtazapine 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
Medical psychiatry • 339
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
A. Post-partum blues with cellulitis in her foot. When the nurse gives
B. Post-partum depression her lunch, she comments that this is the first
C. Post-traumatic stress disorder meal she has had for weeks as she has been
D. Puerperal psychosis spending all of her money on cider. On
E. Schizophrenia examination she is fully orientated and does not
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. Acamprosate 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
abnormality on neuroimaging emergency department. He is agitated, difficult
D. Schizophrenia is associated with increased to converse with, smells of alcohol and says
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
imaging (MRI) is the technique of choice for following is the most likely diagnosis?
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 28
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 lithium 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
340 • Medical psychiatry
C. They have a wide therapeutic range statements relating to depression is true and
D. They should be reserved for might guide diagnosis and management?
treatment-resistant cases of bipolar A. Antidepressants do not work if patients have
disorder ongoing medical problems
E. Toxic effects include nausea, vomiting, B. CBT and other psychotherapies are less
tremor and convulsions effective for depression than antidepressants
C. Electroconvulsive therapy (ECT) is the
28.26. A 55 year old man with a history of treatment of choice for severe depression
ischaemic heart disease complains of low D. Depression has a similar prevalence in
mood and an inability to derive pleasure from people with chronic medical complaints as in
activities he used to enjoy, as well as fatigue, the general population
disturbed sleep, poor concentration and E. Tricyclic antidepressants and SSRIs can
reduced appetite. Which of the following cause QTc interval prolongation
Answers
28.1. Answer: D.
i
28.1 How to structure a psychiatric interview
‘Drug history’ 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
childhood, education, occupational history,
The mental state examination (MSE) is a
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%.
Medical psychiatry • 341
28.4. Answer: C.
Most cases of SH that come to medical
A delusion is a false belief, out of keeping with attention involve overdose, but other methods
a patient’s cultural background, which is held include asphyxiation, drowning, hanging,
with conviction despite evidence to the jumping from a height or in front of a moving
contrary. It is common to classify delusions on vehicle, and firearms. Methods that carry a high
the basis of their content. They may be: chance of being fatal are more likely to be
• persecutory – such as a conviction that associated with serious psychiatric disorder.
others are out to harm one Self-cutting is common and often repetitive, but
• hypochondriacal – such as an unfounded rarely leads to contact with medical services.
conviction that one has cancer SH is more common in women than men, in
young adults than the elderly, and in lower
• grandiose – such as a belief that one has
socioeconomic groups. In contrast, completed
special powers or status
suicide is more common in men and the elderly
• nihilistic – such as ‘My head is missing’,
(Box 28.6).
‘I have no body’ or ‘I am dead’
Option A describes an obsessional thought,
B describes an over-valued idea, D describes
i 28.6 Risk factors for suicide
Psychiatric illness (depressive illness, schizophrenia)
thought insertion and E describes loosening of Older age
associations. Male sex
Living alone
Unemployment
28.5. Answer: E.
Recent bereavement, divorce or separation
A sensory perception arising without an Chronic physical ill health
external stimulus is an hallucination. Meanwhile, Drug or alcohol misuse
an external stimulus that is misperceived is an Suicide note written
History of previous attempts (especially if a violent method
illusion. A false perception that does not have
was used)
the characteristics of a normal sensory
perception (such as a voice heard in one’s 28.7. Answer: A.
head rather than in external space) is called a The main differentials in a man of this age with
pseudo-hallucination. A belief that has no no previous psychiatric history are delirium and
rational basis is simply a false belief. ‘A fixed, dementia. The acute onset, disrupted sleep–
false belief out of keeping with a patient’s
cultural background’ is the conventional
wake cycle and visual hallucinations are all 28
suggestive of delirium.
definition of a delusion. Personality disorders, bipolar affective disorder
and schizophrenia typically emerge during
28.6. Answer: D.
adolescence or early adult life; they are unlikely
Self-harm (SH) is a common reason for to present for the first time at the age of 80.
presentation to medical services. ‘Self-harm’
and ‘attempted suicide’ are not synonymous. 28.8. Answer: D.
Whilst some patients who self-harm are An autoscopic hallucination is the experience of
motivated by a desire to end their life, many seeing an image of oneself in external space. A
have other motivations. functional hallucination is a false perception that
342 • Medical psychiatry
arousal can lead to agitation and to psychotic ‘Anhedonia’ is classically described as the
symptoms such as auditory hallucinations and inability to feel pleasure in normally pleasurable
formication (the sensation of ants crawling activities. The term ‘depression’ is often used in
under one’s skin). Cocaine can also cause a non-medical context to mean ‘low mood’ but
hyperthermia (rather than hypothermia). in a medical context it is a diagnosis rather
than a symptom. This man is not reporting low
28.11. Answer: E.
mood per se but rather an inability to feel
The clinical presentation is highly suggestive of pleasure. ‘Dysphoria’ is a feeling of being ill at
a panic attack. Anxiety leads to hyperventilation ease. ‘Euthymia’ describes mood that is neither
and a respiratory alkalosis that triggers the high nor low. ‘Hypomania’ is a milder form of
physical symptoms described. These physical mania.
symptoms are catastrophically interpreted,
thereby generating more anxiety and a vicious 28.14. Answer: D.
serotonin re-uptake inhibitors; SSRIs) 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.
Disulfiram and acamprosate are both used to Lithium is the treatment of choice for bipolar
support long-term abstinence in alcohol disorder, as it has proven efficacy in both
dependence syndrome. They have no role in phases of the disorder. Lithium salts are
acute presentations. associated with hyperparathyroidism and have
a narrow therapeutic range. They may be
28.23. Answer: E.
teratogenic, although this has probably been
Alcohol addiction sufficient to cause a exaggerated over the years and the risk (if
withdrawal syndrome is rare in the young and anything) is with Ebstein’s anomaly; thus,
the patient smells of alcohol, suggesting he still pregnant mothers with bipolar disorder may be
has some in his system. Cannabis, stimulant or better treated than untreated, although this is a
hallucinatory drug intoxication or induced clinical decision that should be made in
psychosis could cause such a presentation, but consultation with a specialist following
would usually also be associated with some exploration of the risks and benefits for the
degree of cognitive impairment and/or patient and her unborn child. Neural tube
disorientation. Bipolar disorder is possible but defects are associated with valproate and
the content of any delusions present is usually carbamazepine, which are therefore
mood-congruent, for example, a patient with contraindicated in pregnancy.
mania might report being persecuted because
of some special talents or identity. 28.26. Answer: E.
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.
found out through the internet that vitamin D B. Non-sedating antihistamines are usually
deficiency can lead to impaired 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 vitamin D intake is effective for D. She is advised that this is unlikely to be a
vitamin D deficiency problem in subsequent pregnancies
B. Skin fibroblasts are the main source of E. Topical glucocorticoids should be avoided
vitamin D synthesis due to potential adverse fetal effects
C. UVA exposure is required for cutaneous
vitamin D synthesis 29.23. A 63 year old woman presents with a
D. UVB exposure is required for cutaneous pigmented lesion on the anterior chest noted
vitamin D synthesis by her family physician during Well Woman
E. Vitamin D toxicity is a risk for patients with screening. She had been aware of the lesion
increased photosensitivity for 10 years and did not think it had
significantly changed, although on closer
29.21. A 54 year old woman with chronic questioning, she said it had enlarged over the
urticaria, without obvious history of trigger, last year. Excisional surgery confirms a
is referred to dermatology for investigation diagnosis of invasive superficial spreading
and management (see below). With the malignant melanoma (Breslow thickness
exception of hay fever and long-standing 0.8 mm).
vitiligo, she is otherwise well and is taking no
medications.
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. Subcorneal blister on histology during PDT
29
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?
A. Pityriasis rosea
B. Pityriasis versicolor
C. Polymorphic light eruption
D. Psoriasis
E. Secondary syphilis
Dermatology • 355
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 DLQI 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
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
29
Answers
29.1. Answer: D.
sun exposure and lasting a few days before
This immunological photodermatosis occurs in resolving. In contrast, solar urticaria will almost
18% of the population in Northern Europe. It invariably occur within 15 minutes of sun
presents as a delayed-onset papulovesicular exposure and will last only a few hours before
eruption, typically occurring a few hours after resolving. Chronic actinic dermatitis can occur
358 • Dermatology
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 possibility 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.
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.
be readily excised. Curettage would also not be In the first instance, as a trial, lymecycline
recommended if melanoma was suspected. would be an appropriate next step.
Erythromycin would be an alternative but the
29.8. Answer: B.
dose of 250 mg daily is sub-therapeutic and
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. 29
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
does commonly occur during a course of would usually only be considered or added in if
phototherapy and, if this is the case, there there was an inadequate response to a trial of
is concern that Köbnerisation of psoriasis systemic antibiotics. Isotretinoin would not be
360 • Dermatology
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 SCC,
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 arising as part of field change carcinogenesis.
contagious, treatment is only recommended for Imiquimod 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: C.
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: C.
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: C.
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: C.
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
Dermatology • 361
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 IgE and specific IgE 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.
29.18. Answer: C.
29.23. Answer: A.
Langerhans’ cells have the primary function of Breslow thickness is the most important
antigen presentation to lymphocytes. prognostic factor. For a tumour less than 1 mm
in histological thickness, routine CT scanning
29.19. Answer: E.
and sentinel node biopsy would not be
The tonofilaments mainly consist of keratins 5 indicated. Prognosis should be around 95%
and 14. The lamina lucida lies immediately below disease-free survival at 5 years. Wide local
the basal cell membrane. The lamina densa is excision with a 1-cm margin is advised. For a
made up mainly of type IV collagen. The main good prognosis in melanoma such as this,
hemi-desmosomal collagen is type XVII. The long-term follow-up is not required.
anchoring fibrils consist of type VII collagen.
29.24. Answer: C.
29.20. Answer: D.
This history is very suggestive of a diagnosis of
The main cell type involved in vitamin D porphyria cutanea tarda, and this would be an
photosynthesis in skin is the keratinocyte. UVB easy screening test. If this proved positive, then
is required for this. UVA exposure does not more detailed investigations would be required
result in adequate cutaneous vitamin D including urine porphyrins and investigating for
production. Dietary absorption of vitamin D is an underlying cause of iron overload and liver
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 29
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.
autoimmune hypo- or hyperthyroidism. Patch
testing is the investigation of choice for delayed 29.25. Answer: D.
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
362 • Dermatology
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-α)
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
psychological support and discussion of As people get older there 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
Dermatology • 363
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 SCC, 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
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 29
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
immunosuppressed patient population is most 29.42. Answer: B.
at risk of SCC, with only a slight increased risk The description of the rash and its distribution
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.
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-α 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, β-adrenoceptor
avoidance does not suffice then patch testing antagonists (β-blockers), ACE inhibitors, proton
should be considered. Late-onset atopic pump inhibitors, non-steroidal anti-
Dermatology • 365
underlying malignancy but not in most cases. Erythema multiforme may have multiple
Investigations should be with this in mind. triggers, which include infections and drugs.
Penicillamine may actually trigger pemphigus However, in many cases, a trigger is not
and a positive Nikolsky sign indicates that there identified. Where there is an evident provoking
is superficial intra-epidermal blistering but does factor, this is most usually herpes simplex virus
not necessarily indicate a drug-induced cause. infection.
29.51. Answer: D.
29.54. Answer: A.
The presence of a trichrome pattern, where The description of her presentation is very
normal skin colour, hypopigmentation and much consistent with drug reaction and
depigmentation are present, is a good eosinophilia with systemic symptoms (DRESS).
prognostic factor. All of the others are poorer This diagnosis is often confused with an
prognostic factors. infectious cause and patients are not
uncommonly admitted to infectious diseases
29.52. Answer: C.
units for investigation. High fever can occur due
The description of tense blistering, scarring and to drug hypersensitivity and can be misleading.
milia on photo-exposed sites of back of hands Facial oedema and lymphadenopathy, with
in a patient with underlying liver disease should eosinophilia and systemic involvement such as
strongly raise the suspicion of a diagnosis of hepatitis, are classical features of DRESS.
porphyria cutanea tarda, which is almost Carbamazepine is one of the most common
invariably associated with chronic liver disease culprits for DRESS. Co-codamol is not a typical
and iron overload. Examination findings are culprit. Patients are usually investigated for
often not striking if the disease is relatively underlying infection, including meningococcal
quiescent but the presence of scarring and infection given the purpura, and other causes 29
milia should raise suspicions. The screening of hepatitis. Overseas travel should always raise
investigation of choice would be porphyrin the possibility of an infectious cause. However,
plasma scan as a first step. The abnormal these patients are often extensively investigated
porphyrins in porphyria cutanea tarda are water for underlying infection because of high fever.
soluble and thus biochemical analysis of urine The diagnosis of DRESS is often not reached
will also show raised porphyrins in urine. until a dermatological consultation is requested
Hepatitis C, per se, does not cause blistering or infection screening is negative, so this is a
and most patients with hepatitis C will not have diagnosis to be aware of.
porphyria cutanea tarda. Skin biopsy to exclude
L Mackillop, F Neuberger
30
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
Which of the following factors is LEAST likely to C. Lactate > 2 mmol/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 (ECG) and a
Maternal medicine • 367
30.9. A 17 year old woman who is 30 weeks 30.13. A 25 year old woman with ulcerative colitis 30
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-pregnancy counselling. Which of the
following statements is TRUE? following pieces of advice is 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
368 • Maternal medicine
C. 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 C. 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: C.
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: C.
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.
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 ECGs 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.
Maternal medicine • 369
30.7. Answer: A.
30.11. Answer: C.
Many women with chronic kidney disease Spider naevi and palmar erythema (not
(CKD) have successful pregnancies. However, pigmentation) can be part of normal pregnancy,
there are increased risks of pre-eclampsia, fetal and are also signs of chronic liver disease. The
growth restriction, miscarriage, pre-term other physical signs are not seen in normal
delivery and fetal death for these women. pregnancy. Ascites is observed in chronic liver
Women with CKD are more likely to require disease, and yellow sclerae indicate raised
antihypertensives, but they do not need to be bilirubin, which is not part of normal
started routinely. Women who are already pregnancy.
taking angiotensin-converting enzyme inhibitors
should stop this drug at conception and switch 30.12. Answer: A.
pneumonia, and both are safe in pregnancy. Some women with complex ulcerative colitis
will require a caesarean section, but this mode
30.9. Answer: D.
of delivery is usually reserved for obstetric
Chest X-ray should be carried out for the same indications. Methotrexate is teratogenic and
reasons as outside of pregnancy, and is safe. should be stopped 3 months prior to
Nebulised salbutamol and ipratropium, steroids, conception. Most women with well-controlled
magnesium sulphate and aminophylline can all ulcerative colitis will have uneventful
be given safely in pregnancy. Peak flow pregnancies. Sulfasalazine can be taken safely
measurement is valid in pregnancy, and should throughout pregnancy. Infliximab can be taken
be carried out. Women should be advised to safely in the first and second trimesters.
continue their inhalers in pregnancy, and aim
for freedom from symptoms. 30.14. Answer: E.
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?
Adolescent and transition medicine • 371
31.11. You are taking over the care of a 18 year transmembrane conductance regulator
old male with severe spastic quadriplegic (CFTR) protein
cerebral palsy. Which of the following D. She is likely to be infertile, and the chances
statements is true? of pregnancy are low
A. A common cause of mortality is renal failure E. The OCP seems to be safe and effective for
related to recurrent urinary tract infections most patients with CF
B. Formal assessment of respiratory function
such as spirometery and peak flows will help 31.14. An 18 year old female has been referred
assess respiratory risks to your late-effects clinic, after treatment for
C. Gastro-oesophageal reflux is an important acute lymphoblastic leukaemia (ALL) in
comorbidity that needs to be assessed and childhood, ultimately requiring treatment with
treated if necessary total body irradiation and bone marrow
D. Now that he is 18 years old he automatically transplantation at 15 years of age. She is
assumes the capacity to consent to currently treated with thyroxine but her general
treatment and decisions about his care health seems good. Which of the following
E. Nutritional support is unlikely to be necessary statements is true?
now growth has been completed A. As her periods are regular she can be
reassured of normal fertility in the future
31.12. An 18 year old male with Duchenne B. Her risk of future malignancy is no higher
muscular dystrophy is admitted in end-stage than the normal population
respiratory failure. After treatment with C. She has previously been treated with
antibiotics and stabilisation on non-invasive high-dose doxorubicin and therefore is at
respiratory support, he is ready for discharge risk of cardiomyopathy
with ongoing respiratory support and careful D. She needs 7 years more follow-up before
long-term follow-up. At his next clinic discharge, as 10-year disease-free survival
appointment, he asks for a discussion about equates to cure in ALL
the genetics of his condition and how it might E. When plotted on a centile chart, her growth
involve his wider family – his younger brother is is 50th centile for height and weight,
also a Duchenne sufferer. He has a 10 year old suggesting she has normal growth hormone
sister. levels
Which of the following statements are true?
A. He will be infertile 31.15. A 16 year old girl has undergone liver
B. His father must be a carrier of the Duchenne transplant following a Kasai procedure for biliary
gene atresia in the newborn period. She has been
C. His sister could be affected well for 8 years post-transplant. She had a viral
D. His sister should be referred for genetic illness characterised by lymphadenopathy,
testing for carrier status malaise and hepatosplenomegaly 6 months
E. There are no genetic implications for ago and now has persistent palpable cervical
second-generation family members lymphadenopathy. Which of these statements
is most correct?
31.13. A 17 year old female with cystic fibrosis A. If her lymphadenopathy persists you need to
(CF) is referred to your adolescent respiratory consider blood tests, including a full blood
clinic. She has good nutritional status and is count, liver function tests, Epstein–Barr virus
generally well, attending full-time school. Which (EBV) and cytomegalovirus (CMV) PCR and
of the following are true regarding her current serology
status? B. She is at increased risk of chronic fatigue
A. As she has good nutritional status and syndrome
growth, her bone mineral density is likely to C. T-cell activation and proliferation is the likely
be normal and treatment with vitamin D is underlying pathological process in
not necessary post-transplant lymphoproliferative disorder
B. Clarithromycin will affect oral contraceptive (PTLD), often triggered by EBV infection
pill (OCP) effectiveness D. The most likely cause of her infection was
C. Most patients gain benefit from newer hepatitis B infection
treatments that rectify defects in the CF E. There is a 10% chance of this being a PTLD
Adolescent and transition medicine • 373
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 Crohn’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%.
31.2. Answer: E.
31.3. Answer: D.
31
Adolescent females have a increase in Complex medicine and treatment regimes
testosterone and androgen production make it harder for young people to adhere
(manifest as the development of pubic hair, strictly to their treatment. The other factors are
increased sweating, acne) from the ovaries and all associated with better patient adherence
the adrenal glands. The earliest pubertal with medication and treatment regimes, and in
374 • Adolescent and transition medicine
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.
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 5–10% 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.
palsy are also intellectually impaired, and many PTLD is a well-recognised complication
do not have the capacity to give informed occurring in more than 10% of solid organ
consent. They are unlikely to be able to comply recipients – particularly those who receive a
with formal lung function tests, although solid organ in childhood when they are
respiratory disease, often complicated by commonly EBV seronegative. It is often
recurrent chest infections or aspiration and triggered by EBV infection leading to
scoliois, is a common cause of death. Many do uncontrolled B-cell proliferation and tumour
not manage to ingest their full nutritional proliferation, including development of
requirements and need additional/supportive lymphoma. Blood tests need to be undertaken
feeding, often by gastrostomy. immediately in this high-risk patient and further
investigation for possible lymphoma is
31.12. Answer: C.
necessary.
Female carriers of Duchenne muscular
dystrophy are at risk of cardiomyopathy and 31.16. Answer: E.
around 10% also experience muscle weakness Smoking is a particular risk factor for
and fatigue. They should be referred for genetic exacerbation and reduces effectiveness of
testing when they are able to understand the many immunosuppressant therapies, as well as
implications of the diagnosis, possibly in the increasing the risk of steroid and other therapy.
mid-teens. This patient’s mother must be a Adolescents/teenagers do have more
carrier of the Duchenne muscular dystrophy aggressive disease than older patients, and
gene, not his father, and his sister has a 50% about 20% will require surgery or treatment
risk of also being a carrier. Fertility is normal in with biological agents. First-line therapy is a
males. There are potentially risks for the wider 6- to 8-week trial of elemental diet;
family, with his mother’s sisters having a 50% methotrexate is used as maintenance therapy
chance of being carriers of the Duchenne but is not a first-line agent.
genetic mutation.
31.17. Answer: C.
31.13. Answer: E.
A few adolescents present with repeated
The OCP is contraindicated in patients with episodes of DKA because of non-adherence
pulmonary hypertension but is safe and with insulin therapy. In females it is thought that
effective in most patients with CF. There is motivating factors might include weight loss/
increasing evidence of effectiveness of CFTR concerns about body image. The extent of
modification in patients with specified (G551D) non-adherence amongst adolescents is high,
CFTR gene mutations, but these affect a very with 25% not taking their insulin as prescribed,
small proportion of CF sufferers. Females with 80% not following their diet and around 30%
CF usually have normal fertility if their general not checking blood glucose and/or submitting
nutrition and health are good; males have fabricated results. Microvascular complications
obstructive azoospermia. All patients are at can develop within 10 years of diagnosis, so
significant risk of osteoporosis. may already be present in later teenage years.
31.14. Answer: C.
31.18. Answer: C.
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 C. Goal setting
B. Lumbar nerve root entrapment D. Medical leadership
C. Orthostatic hypotension E. The Barthel Index
378 • Ageing and disease
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 110/50 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 32
D. Spinal cord compression D. Parkinson’s disease
E. Subdural haematoma E. Peripheral neuropathy
380 • Ageing and disease
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.
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. α-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.
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
Ageing and disease • 381
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
range would be unsurprising after recent hip
i 32.13 How to assess a Fried Frailty score
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.
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 diseases, including 32
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
382 • Ageing and disease
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.
32.17. Answer: B.
32.19. Answer: B.
Onset of falls, particularly several falls in quick The ECG is suggestive of myocardial infarction
succession, should suggest intercurrent illness. – perhaps 2–3 days ago; this would also
Acute illness in older people may present explain her gallop rhythm. Myocardial infarction
atypically, as here – but there are still clues that may present without chest pain in older people
this is pneumonia. He has a low temperature – especially older women – and atypical
(equivalent to a fever of 38.8°C), a raised pulse symptoms such as tiredness and delirium are
rate and low oxygen saturations. The other common, as in this case, where she suffers
options do not explain all of these features; in from hypoactive delirium. The problem is acute,
particular, they do not explain his hypoxia. making depression or Parkinson’s disease
unlikely; the normal oxygen saturations make
32.18. Answer: C.
pneumonia and pulmonary embolism less likely
It is unlikely that performing any of the listed diagnoses.
investigations will improve the quality of this
woman’s life. She is asymptomatic: therefore 32.20. Answer: D
even if anaemia was discovered on a full blood The gait described is festinant (slow start, then
count, it is debatable as to whether transfusion accelerating), and shuffling (not lifting the feet).
would improve her quality of life. Clearly if she The lack of arm swing and difficulty turning are
were to become symptomatic, this would also consistent with a Parkinsonian gait.
change. Endoscopy would, in addition, be Cerebellar lesions cause ataxia; bilateral parietal
burdensome given her frailty, and you have lobe stroke disease may cause apraxia (e.g.
some indication from her last illness that she difficulties starting to walk) or marche à petits
might not want further medical intervention. pas and peripheral neuropathy can cause a
Even if you did decide to investigate anaemia, stamping gait, which may be high stepping if
ultrasonography is unlikely to find the cause. In foot drop is present. Hip osteoarthritis would
real life, the decision-making process would, of typically cause an antalgic gait, where the
course, need to be informed by the wishes of weight-bearing phase is shortened for the
the patient, and of those deputed to make affected leg (a ‘limp’).
GG Dark
33
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
A. Large exposure is required to develop the
tender to palpation over two well-circumscribed
most serious malignancies
areas in the thoracic and lumbar spine. There is
B. Leukaemia has the shortest latency period of
no neurological deficit.
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. Ultrasound 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 What is the most likely histological type of
33
(see figure). malignancy?
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
C. 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 C. 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?
C. 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 C. 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?
C. 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 C. Renal angiogram
E. An irregularly shaped mass at the apex of D. Transrectal prostatic biopsy
33
the right lung E. Trimethoprim–sulfamethoxazole
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/m2. Her blood pressure is
He has many questions about his disease 135/88 mmHg, 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 BRCA1 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. BRCA1 and BRCA2 screening is not rate is 450 L/min. Abdominal examination is
recommended normal.
B. BRCA1 and BRCA2 screening should be What is the most likely diagnosis?
performed after age 50 A. Collapse of the right lung
C. BRCA1 and BRCA2 screening should be B. Consolidation of the right lung
performed if breast pain recurs C. Interstitial fibrosis throughout right lung field
D. BRCA1 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
Oncology • 389
sit in the bladder for hours. After more than 10 aspiration, usually under echocardiogram
years, the risk of bladder cancer is significantly guidance.
elevated. The same is 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 B 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 D is 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. cause 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 B 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.
describes a pericardial 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.
33
developing cardiac tamponade. This requires After more than 10 years, this increases the
390 • Oncology
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.
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 most commonly 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 cancer, 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.
Oncology • 391
33.17. Answer: B.
may slightly increase the risk of hepatocellular
This patient has clinical signs that suggest carcinoma.
lower motor neuron weakness and as the
spinal cord ends at L1–L2, this abnormality is 33.22. Answer: E.
at a lower level than L2. Lung cancer will The clinical features are that of Horner’s
commonly metastasise to bone and although it syndrome and the clinical signs will be
can cause spinal cord compression, the ipsilateral, therefore suggesting an invasive
neurology in this presentation infers that this is lesion in the apex of the right lung (option E).
at a level where it results in compression of the The remaining options are non-invasive or in
cauda equina. the wrong location and therefore should not
cause impairment of the sympathetic
33.18. Answer: C.
innervation on the right side. The presence of
This patient is presenting with hypercalcaemia Horner’s syndrome in a patient with a chest
and the immediate management should infection is suggestive of an underlying cancer.
be to rehydrate the patient (option C).
Bisphosphonate therapy (option E) is indicated 33.23. Answer: B.
once his hydration state improves. Loop The past history of breast cancer should raise
diuretics can be used if fully rehydrated but not an index of suspicion for metastasis and the
a thiazide diuretic (option B) as it could increase new headache is different to her previous
the serum calcium. In patients with lung cancer, episodes. This should be investigated as brain
hypercalcaemia is most commonly associated metastasis and the best initial investigation of
with squamous cell carcinoma. those listed is CT scan (option B). The other
options would not enable this diagnosis to be
33.19. Answer: C.
made.
Patients with ulcerative colitis have an
increased risk of developing a colonic 33.24. Answer: A.
carcinoma due to the chronic inflammation. It The first step is to look for other lesions and to
often will have a lead time of 10 years and is examine for calcification and spiculation (option
more likely in those with more significant A). There is no need to wait for the menstrual
inflammation. In order to assess the whole cycle as the patient has not presented with
colon and biopsy for histology, option C is the cyclical changes in the breast. A fine needle
best investigation. Option E will not assess the aspiration will be required but a negative result
whole colon and the remaining options (without does not exclude malignancy. A biopsy will be
biopsy) do not allow histological assessment. required, whether a mammogram is performed
or not. In practice, patients attending a
33.20. Answer: C.
one-stop specialist breast clinic will have a
Epithelial ovarian cancer is most likely to cause mammogram or ultrasound, clinical examination
a rise in CA-125 and although this tumour and a fine needle biopsy at the same visit.
marker is rarely diagnostic it can assist in
disease activity monitoring. The remaining 33.25. Answer: B.
tumours do not normally cause a rise in A single episode of frank haematuria requires
CA-125 unless it is a false positive due to investigation and is unlikely to be a simple
inflammatory changes arising from the tumour. urinary infection (option E). CT imaging may not
Choriocarcinoma would cause a rise in serum detect small mucosal lesions (option A) and
hCG. without stream impairment it is unlikely that this
is related to prostatic enlargement (option D).
33.21. Answer: D.
The most likely diagnosis is a bladder lesion or
The risk of breast cancer and bone sarcoma cancer and that requires cystoscopy for
remains the same in patients taking the OCP. inspection and biopsy.
The risk of cervical cancer is slightly increased,
not by the medication but due to the increased 33.26. Answer: B.
sexual activity of this population of patients. Non-small cell cancer is the most likely
The risk of endometrial cancer is reduced due malignancy that occurs in patients with
to the reduced stimulation of this tissue. The asbestosis. Although asbestosis is due to
33
use of a steroid-based drug such as oestrogen previous asbestos exposure, only a small
392 • Oncology
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
L Colvin
34
Pain and palliative care
Multiple Choice Questions
34.1. Which of the following is normally involved into his legs. On examination, light touch is
in peripheral pain processing? painful, and he has reduced sensation to
A. Aβ fibres pin-prick testing in a stocking distribution,
B. Calcitonin gene-related peptide (CGRP)- typical of peripheral diabetic neuropathy. His
containing C fibres blood glucose control is not good, his renal
C. Interneurons function is impaired and he is overweight. He is
D. Meissner’s corpuscles reluctant to walk because of the pain, and lives
E. Pacinian corpuscles alone, becoming increasingly socially isolated.
What factor may make pharmacological
34.2. The pain system can change in response management more difficult?
to tissue injury. Which of the following A. Impaired renal function
neurotransmitters plays a key role in the B. Obesity
process of central sensitisation? C. Pin-prick hypoalgesia
A. Galanin D. Reduced mobility
B. Glutamate E. Social isolation
C. Glycine
D. β-Endorphin 34.5. A range of patient-reported outcome
E. γ-Aminobutyric acid (GABA) measures have been validated for use in
patients with chronic pain. Which one of the
34.3. A previously fit 72 year old man presents following assessment tools is likely to be most
with severe pain affecting his right chest wall, helpful in making the diagnosis of neuropathic
such that he is struggling to remain living pain?
independently. From his history you discover A. Beck Depression Inventory
that his clothes touching his skin is B. Brief Pain Inventory
excruciatingly painful. His family physician has C. Pain Catastrophising Scale
started him on tramadol 50 mg twice daily, D. Pain Detect
without significant benefit. What symptom is he E. Tampa Scale of Kinesiophobia
describing?
A. Breakthrough pain 34.6. A 79 year old woman has osteoporosis
B. Formication with vertebral collapse at T10, demonstrated on
C. Hyperalgesia plain X-ray. She is now struggling with washing
D. Mechanical allodynia and dressing herself because of severe pain.
E. Spontaneous pain She lives alone, although she has a daughter
who visits her every day, who has been giving
34.4. A 64 year old man with type 2 diabetes her two co-codamol 30/500 (30 mg codeine
mellitus is complaining of numbness, and 500 mg of paracetamol), morning and
paraesthesia and pain in both feet, spreading evening. Her daughter is concerned that her
394 • Pain and palliative care
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, further
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.
butylbromide Her initial blood results are as follows:
D. Gabapentin haemoglobin 79 g/L, white cell count
E. Oral morphine solution 6.7 × 109/L, platelets 314 × 109/L; urea
18.3 mmol/L (110 mg/dL), sodium 143 mmol/L,
34.14. A 52 year old woman has metastatic potassium 4.2 mmol/L, creatinine 213 µmol/L
cancer with bony metastases throughout her (2.4 mg/dL), calcium 2.94 mmol/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 mmol/L (13.1 mg/dL). 34
396 • Pain and palliative care
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 Aβ 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-D-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
NR1 NR2
Amino acids
Glycine Glutamate Amplified (and other
signal neurotransmitters)
Mg++ Dorsal root
ganglia
Kinase
Regulation of
pain response
Pain
signal
Neurotransmitter
changes
Fig. 34.2 Mechanisms of central sensitisation. Post-synaptic activation of the N-methyl-D-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.
Pain and palliative care • 397
i 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 Ca2+, Na+ or
K+, depending on subunit structure
NMDA Ion channel Excitatory; blocked by Mg2+ at resting state; block can
be altered if membrane potential changes; permeable
to Ca2+, Na+ and K+
Kainate Ion 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
Gp III GPCR Probably inhibitory; can decrease cAMP production;
pre-synaptic; decreases glutamate release
Glycine GlyR Ion channel Mainly inhibitory; permeable to Cl− blocked by
caffeine
γ-aminobutyric acid GABAA Ion 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
GABAB 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
β-endorphin OP3 (mu) GPCR Inhibitory
Nociceptin ORL-1 GPCR Inhibitory; also expressed by immune cells
*Excitatory = increased pain; inhibitory = reduced pain.
(AMPA = α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid; CALCRL = calcitonin receptor-like receptor; cAMP = cyclic
adenosine monophosphate; GABA = γ-aminobutyric acid; Gp = group; GPCR = G-protein-coupled receptor; NMDA = N-methyl-D-
aspartate; OP = opioid; ORL-1 = opioid receptor-like 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 β-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 the 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 34
398 • Pain and palliative care
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).
34.5. Answer: D.
34.7. Answer: B.
The Brief Pain Inventory was originally designed The diagnosis of CRPS type 1 requires a
for use in cancer patients and measures pain combination of sensory, vasomotor, sudomotor
intensity and its interference with different and motor changes to be present. It can occur
aspects of life. It does not assess the character after an injury such as a fracture, without
of the pain, which is necessary to make a definite peripheral nerve lesion. CRPS type 2
diagnosis of neuropathic pain. Pain Detect occurs if there is a defined peripheral nerve
does do this, and has been validated in a range lesion. CRPS is commoner in females between
of neuropathic pain types. The other measures the ages of 35 and 50, occurring in about 20
with early physiotherapy is important in Palliative care is the active total care for
management. patients with incurable disease. A palliative care
approach is likely to be suitable where
34.8. Answer: B.
symptom management becomes more
This is a challenging pain syndrome to manage, important than aggressive treatment of the
with very limited evidence for efficacy of underlying disease, although the two goals of
long-term opioids, and growing evidence of treatment can exist side by side. Although
possible harms. While opioids may be required initially targeted at patients with malignant
for short-term use, regular use of short-acting disease, patients with other life-limiting
strong opioids should be avoided if possible. conditions such as COPD are now often
Support in developing pain management suitable for palliative care input. There are
strategies, maintaining function, ensuring usually no stringent guidelines regarding
adequate nutrition and reducing opioids should physiological parameters. Prognosis is often
be the goal. Strong opioids should not be difficult to judge, but key events such as an
stopped abruptly unless the patient is at risk of admission to higher-level care are good
overdose. opportunities to consider the future and
make anticipatory care plans for the next
34.9. Answer: A.
exacerbation. Opiate medication is a possibility,
The pain has responded to a weak opioid, but but in the first instance he may benefit from
either some tolerance has developed or there is non-pharmacological treatments and an
disease progression. He is, therefore, likely to assessment as to whether his inhaled
get better analgesia from a strong opioid. medication is optimised.
Diazepam is not an analgesic, although it can
be used for short-term anxiolysis. While there 34.13. Answer: A.
may be neuropathic features, a strong opioid It is likely that this patient has liver capsule pain
should be started first. Non-steroidal as a result of metastases from his previous
anti-inflammatory drugs (NSAIDs) should be colonic carcinoma. This type of pain responds
avoided if there is a history of peptic ulcer poorly to opiates and is best treated by
disease. Adding in paracetamol is unlikely to be glucocorticoids. An antispasmodic will not
effective, as he is already taking paracetamol in relieve the stretch of the liver capsule. An
the compound preparation (co-codamol) and NSAID is better suited to ischaemic or bone
may result in exceeding safe dosing limits. pain and gabapentin to neuropathic pain
(Box 34.13).
34.10. Answer: A.
the management of breathlessness, it is Nausea and vomiting can occur initially with
important to assess for treatable causes first, opiate therapy but usually settle after a few
such as pleural effusion, cardiac failure or days. Dry mouth and constipation are
bronchospasm, even though the patient is long-term effects, however, and will need
being managed palliatively. Options B–E ongoing treatment. Tolerance usually develops
can all be useful in the management of to drowsiness, so this problem is often
breathlessness, but it is important to diagnose transient after an increase in dose. Opiate
and start to treat any potentially reversible toxicity is an ongoing concern for any patient
underlying cause first. on this medication and so follow-up review
is advisable. This patient may need
34.11. Answer: A.
adjustments to her medication over time
There are many potential causes for confusion depending on increasing pain, changes in
and nausea, including raised intracranial renal function or development of toxicity,
pressure and hypoxaemia due to a if it arises.
cardiovascular problem. While many of these Patients who develop renal failure are at
tests may be appropriate, rapid checking of particular risk of opiate toxicity and
blood results allows exclusion of correctable consideration should be given to swapping
causes such as electrolyte imbalance and, from morphine to an alternative opiate such as
particularly, hypercalcaemia. alfentanil. 34
400 • Pain and palliative care
34.15. Answer: E.
oxygen therapy reduces the sensation of
Breathlessness is one of the most common breathlessness in advanced cancer any better
symptoms in palliative care and is distressing than cool air flow, and oxygen is indicated only
for both patients and carers. Patients with if there is significant hypoxia. In this case,
breathlessness should be fully assessed to oxygen is also likely to be precluded by both
determine whether there is a reversible cause, the husband and wife continuing to smoke in
such as a pleural effusion, heart failure or the house.
bronchospasm; if so, this should be managed Opioids, through both their central and their
in the normal way. There is no suggestion in peripheral action, can palliate breathlessness
the scenario here of fluid overload or and might be an alternative in this scenario. If
new infection to justify antibiotics or anxiety is considered to be playing a significant
diuretics. role, a quick-acting benzodiazepine, such as
There are many potential causes of lorazepam (used sublingually for rapid
dyspnoea in cancer patients and in other absorption), may also be useful. Citalopram
chronic diseases; apart from direct involvement would be useful for longer-term treatment of
of the lungs, muscle loss secondary to established anxiety or depression, but would
cachexia, anxiety and fear can all contribute. not give instant relief in the short term in the
A cycle of panic and breathlessness, often way that lorazepam would.
associated with fear of dying, can be dominant.
Exploration of precipitating factors is important 34.16. Answer: D.
and patient education about breathlessness Although this patient is very unwell, her
and effective breathing has been shown to be hypercalcaemia may be amenable to treatment.
effective. Non-pharmacological approaches that Even if it is not life saving, it will make her feel
include using a hand-held fan, pacing, and more comfortable and reducing her calcium
following a tailored exercise programme can level will be the most effective way to help her
help. There is no evidence to suggest that vomiting. The other treatments may have a role
Pain and palliative care • 401
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 unnecessarily 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.
34
S. Jenks
35
Laboratory reference ranges
Notes on the International System of Units (SI Units)
Système International (SI) d’Unités are a Exceptions to the use of SI units
specific subset of the metre–kilogram–second By convention, blood pressure is excluded from
system of units and were agreed on as the the SI unit system and is measured in mmHg
everyday currency for commercial and scientific (millimetres of mercury) rather than pascals.
work in 1960, following a series of international Mass concentrations such as g/L and µg/L
conferences organised by the International are used in preference to molar concentrations
Bureau of Weights and Measures. SI units have for all protein measurements and for
been adopted widely in clinical laboratories but substances that do not have a sufficiently
non-SI units are still used in many countries. well-defined composition.
For that reason, values in both units are given Some enzymes and hormones are measured
for common measurements throughout this by ‘bioassay’, in which the activity in the
textbook and commonly used non-SI units are sample is compared with the activity (rather
shown in this chapter. The SI unit system is, than the mass) of a standard sample that is
however, recommended. provided from a central source. For these
Examples of basic SI units assays, results are given in standardised ‘units’
Length metre (m) (U/L), or ‘international units’ (IU/L), which
Mass kilogram (kg) depend on the activity in the standard sample
Amount of substance mole (mol)
and may not be readily converted to mass
Energy joule (J)
Pressure pascal (Pa) units.
Volume The basic SI unit of volume is the
cubic metre (1000 litres). For
convenience, however, the litre (L) is
used as the unit of volume in
laboratory work.
Stage of chronic
eGFR (mL/min/1.73 m2) 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 3B Moderately reduced function
15–29 CKD stage 4 Severely reduced function
<15 CKD stage 5 Very severely reduced function/end-stage
kidney failure
Laboratory reference ranges • 407
Non-diabetic men 35
Non-smoker Smoker
Age under 50 years
180 180
160 160
120 120
100 100
3 4 5 6 7 8 9 10 3 4 5 6 7 8 9 10
TC:HDL TC:HDL
Age 50–59 years
180 180
160 160
120 120
100 100
3 4 5 6 7 8 9 10 3 4 5 6 7 8 9 10
TC:HDL TC:HDL
Age 60 years and over
180 180
160 160
100 100
3 4 5 6 7 8 9 10 3 4 5 6 7 8 9 10
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.
i 35.13 Analytes that may be significantly affected by growth and puberty* – cont’d
Analyte Age/pubertal stage Gender Reference range
15–18 years M 39–92 µmol/L
(0.44–1.04 mg/dL)
F 34–72 µmol/L
(0.38–0.81 mg/dL)
Follicle-stimulating hormone Prepubertal M < 3.0 IU/L
(< 0.6 ng/mL)
F < 3.2 IU/L
(< 0.64 ng/mL)
Pubertal stage 2 M < 6.6 IU/L
(< 1.32 ng/mL)
F < 4.1 IU/L
(< 0.82 ng/mL)
Pubertal stage 3 M 0.7–5.0 IU/L
(0.14–1 ng/mL)
Pubertal stages 4–5 M 1.5–6.0 IU/L
(0.3–1.2 ng/mL)
Pubertal stages 3–5 F 2.5–13.5 IU/L
(0.5–2.7 ng/mL)
Insulin-like growth factor 1 < 7 years M 15–349 µg/L
F 17–272 µg/L
8–16 years M 67–510 µg/L
F 59–502 µg/L
Luteinising hormone Prepubertal M < 1.0 IU/L
(< 0.1 µg/L)
Pubertal stage 2 M < 3.0 IU/L
(< 0.3 µg/L)
Prepubertal and pubertal stage 2 F < 1.0 IU/L
(< 0.1 µg/L)
Pubertal stage 3 M 1.0–4.0 IU/L
(0.1–0.4 µg/L)
Pubertal stages 4–5 M 1.0–5.0 IU/L
(0.1–0.6 µg/L)
Pubertal stages 3–5 F 1.0–8.0 IU/L
(0.1–0.9 µg/L)
17β-Oestradiol Prepubertal and pubertal stages 2–3 M < 75 pmol/L
(< 20 pg/mL)
Prepubertal and pubertal stage 2 F < 100 pmol/L
(< 27 pg/mL)
Pubertal stages 4–5 M < 130 pmol/L
(< 35 pg/mL)
Pubertal stages 3–5 F < 150 pmol/L
(< 41 pg/mL)
Testosterone Prepubertal M < 0.5 nmol/L
(< 0.1 ng/mL)
F < 0.6 nmol/L
(< 0.2 ng/mL)
Pubertal stage 2 M < 10.6 nmol/L
(< 3.1 ng/mL)
F < 1.4 nmol/L
(< 0.4 ng/mL)
Pubertal stage 3 M 0.4–30 nmol/L
(0.1–8.7 ng/mL)
Pubertal stage 4 M 5.6–30 nmol/L
(1.6–8.7 ng/mL)
Pubertal stage 5 M 10–30 nmol/L
(2.9–8.7 ng/mL)
Pubertal stages 3–5 F 0.4–1.9 nmol/L
(0.1–0.5 ng/mL)
*Non-SI equivalents are given in brackets where appropriate.
Laboratory reference ranges • 413
Tanner
stage
I II III IV V 35
Female
Mature stage.
Elevation of breast Further enlargement Projection of Projection of papilla
Breast Pre-adolescent and papilla as a of breast and areola areola and papilla with recession of
small mound with no separation to form mound areola to contour
of contours above breast of breast
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
Fig. 13.5
Fig. 16.25
416 • Colour illustrations
38.40 38.40
L L
2 2
5 5
0 0
0.00 0.00
50 % PET 50 % PET
3.3 3.3
Fig. 27.13
418 • Colour illustrations
Fig. 29.7
Fig. 29.1
Fig. 29.5
Fig. 29.9
Fig. 29.48
Fig. 29.42
Fig. 29.53
Fig. 29.46
Colour illustrations • 421
Fig. 34.7
This page intentionally left blank
442 • INDEX