CLINICAL SCIENCES MCQs

Q-1 A. Calcium ions

A 69-year-old female with a history of multiple myeloma is B. Tropomyosin
admitted with confusion. The following results are obtained: C. Actin
D. Myosin
Na+ 147 mmol/l E. Sarcoplasmic reticulum
K+ 4.7 mmol/l
Urea 14.2 mmol/l ANSWER:
Creatinine 102 µmol/l Tropomyosin
Adjusted calcium 3.9 mmol/l
EXPLANATION:
What is the most appropriate initial management? Troponin T binds to tropomyosin, forming a troponin-
tropomyosin complex
A. IV 0.45% saline The clinical and electrographic features raise concerns over
B. IV zoledronic acid an inferior myocardial infarction which is confirmed by the
C. Oral prednisolone raised troponin. Troponin T binds to tropomyosin, forming a
D. IV pamidronate troponin-tropomyosin complex. It is specific to myocardial
E. IV 0.9% saline damage.

ANSWER: Troponin C binds to calcium ions. It is released by damage to

IV 0.9% saline both skeletal and cardiac muscle making it an insensitive
marker for myocardial necrosis.
EXPLANATION:
IV fluid therapy is the first-line management in patients with Troponin I binds to actin to hold the troponin-tropomyosin
hypercalcaemia complex in place. It is specific to myocardial damage.
The raised sodium is a function of dehydration and will
correct once the patient is adequately rehydrated Myosin is the thick component of muscle fibres. Actin slides
along myosin to generate muscle contraction.
HYPERCALCAEMIA: MANAGEMENT The sarcoplasmic reticulum regulates the calcium ion
The initial management of hypercalcaemia is rehydration with concentration in the cytoplasm of striated muscle cells
normal saline, typically 3-4 litres/day. Following rehydration
bisphosphonates may be used. They typically take 2-3 days to TROPONIN
work with maximal effect being seen at 7 days Troponin is a complex of three proteins involved in skeletal
and cardiac muscle contraction
Other options include: Subunits of troponin
• calcitonin - quicker effect than bisphosphonates • troponin C: binds to calcium ions
• steroids in sarcoidosis • troponin T: binds to tropomyosin, forming a troponin-
tropomyosin complex
Loop diuretics such as furosemide are sometimes used in
• troponin I: binds to actin to hold the troponin-
hypercalcaemia, particularly in patients who cannot tolerate
tropomyosin complex in place
aggressive fluid rehydration. However, they should be used
with caution as they may worsen electrolyte derangement Q-3
and volume depletion. A 14-year-old girl presents with a swollen left knee. Her
parents state she suffers from haemophilia and has been
Q-2
treated for a right-sided haemarthrosis previously. What
A 68-year-old man is admitted with central chest pain which
other condition is she most likely to have?
is crushing in character. He has associated flushing.
A. Turner's syndrome
ECG results:
B. Down's syndrome
ECG T wave inversion in II,III and AVF
C. Ataxia telangiectasia
Blood results: D. Hunter's syndrome
Troponin T 0.9 ng/ml (normal <0.01) E. Coeliac disease

Which substance does troponin T bind to? ANSWER:

Turner's syndrome
 The following conditions are autosomal dominant:
EXPLANATION: • Achondroplasia
Haemophilia is a X-linked recessive disorder and would hence • Acute intermittent porphyria
be expected only to occur in males. As patients with Turner's
• Adult polycystic disease
syndrome only have one X chromosome however, they may
• Antithrombin III deficiency
develop X-linked recessive conditions
• Ehlers-Danlos syndrome
• Familial adenomatous polyposis
X-LINKED RECESSIVE
In X-linked recessive inheritance only males are affected. An • Hereditary haemorrhagic telangiectasia
exception to this seen in examinations are patients with • Hereditary spherocytosis
Turner's syndrome, who are affected due to only having one X • Hereditary non-polyposis colorectal carcinoma
chromosome. X-linked recessive disorders are transmitted by • Huntington's disease
heterozygote females (carriers) and male-to-male • Hyperlipidaemia type II
transmission is not seen. Affected males can only have • Hypokalaemic periodic paralysis
unaffected sons and carrier daughters. • Malignant hyperthermia
• Marfan's syndromes
Each male child of a heterozygous female carrier has a 50% • Myotonic dystrophy
chance of being affected whilst each female child of a • Neurofibromatosis
heterozygous female carrier has a 50% chance of being a • Noonan syndrome
carrier. • Osteogenesis imperfecta
• Peutz-Jeghers syndrome
The possibility of an affected father having children with a • Retinoblastoma
heterozygous female carrier is generally speaking extremely • Romano-Ward syndrome
rare. However, in certain Afro-Caribbean communities G6PD • tuberous sclerosis
deficiency is relatively common and homozygous females with • Von Hippel-Lindau syndrome
clinical manifestations of the enzyme defect are seen. • Von Willebrand's disease*

Q-4 *type 3 von Willebrand's disease (most severe form) is

Which one of the following conditions is NOT an autosomal inherited as an autosomal recessive trait. Around 80% of
dominant condition? patients have type 1 disease

A. Retinoblastoma Q-5
B. Tuberose sclerosis Which of the following conditions is inherited in an
C. Achondroplasia autosomal dominant fashion?
D. Myotonic dystrophy
E. Albinism A. Familial Mediterranean Fever
B. Homocystinuria
ANSWER: C. Tuberous sclerosis
Albinism D. Ataxia telangiectasia
E. Friedreich's ataxia
EXPLANATION:
Autosomal recessive conditions are 'metabolic' - exceptions: ANSWER:
inherited ataxias Tuberous sclerosis

Autosomal dominant conditions are 'structural' - exceptions: EXPLANATION:

Gilbert's, hyperlipidaemia type II
AUTOSOMAL DOMINANT CONDITIONS
Autosomal recessive conditions are often thought to be
'metabolic' as opposed to autosomal dominant conditions
being 'structural', notable exceptions:
• some 'metabolic' conditions such as Hunter's and G6PD
are X-linked recessive whilst others such as
hyperlipidaemia type II and hypokalaemic periodic
paralysis are autosomal dominant
• some 'structural' conditions such as ataxia telangiectasia
and Friedreich's ataxia are autosomal recessive
Autosomal recessive conditions are 'metabolic' - exceptions:
inherited ataxias
Autosomal dominant conditions are 'structural' - exceptions:
Gilbert's, hyperlipidaemia type II
Please see Q-4 for Autosomal Dominant Conditions
Q-6
A scientist is developing an assay whereby he heats up a
DNA specimen at 95ºC then cools it to 55ºC whilst adding
primers to specific sequences. Following each primer, heat-
stable DNA polymerase is added and the cycle is repeated.
Which molecular technique has been described? Q-7
You have been asked to investigate the potential benefit of
A. Southern blot setting up a service to help patients with multiple sclerosis in
B. Western blot the local area. What is the most important factor when
C. SDS-PAGE determining how many resources will be required?
D. Polymerase Chain Reaction (PCR)
E. Cloning A. Incidence
B. Bayesian factor
ANSWER: C. Prevalence
Polymerase Chain Reaction (PCR) D. Denominator data
E. P value
EXPLANATION:
Polymerase Chain Reaction (PCR) uses denaturation, ANSWER:
annealing and elongation to amplify a desired fragment of Prevalence
DNA
PCR is a common technique used to amplify a desired EXPLANATION:
fragment of DNA. INCIDENCE AND PREVALENCE
These two terms are used to describe the frequency of a
Other answers: condition in a population.
• Southern blot: detection of DNA.
• Western blot: detection of RNA The incidence is the number of new cases per population in a
• SDS-PAGE: protein separation by electrophoresis given time period.
• Cloning: recombinant DNA production using bacteria
For example, if condition X has caused 40 new cases over the
POLYMERASE CHAIN REACTION past 12 months per 1,000 of the population the annual
Polymerase chain reaction (PCR) is a molecular genetic incidence is 0.04 or 4%.
investigation technique. The main advantage of PCR is its
sensitivity: only one strand of sample DNA is needed to detect The prevalence is the total number of cases per population at
a particular DNA sequence. It now has many uses including a particular point in time.
prenatal diagnosis, detection of mutated oncogenes and
diagnosis of infections. PCR is also extensively used in For example, imagine a questionnaire is sent to 2,500 adults
forensics. Prior to the procedure it is necessary to have two asking them how much they weigh. If from this sample
DNA oligonucleotide primers. These are complimentary to population of 500 of the adults were obese then the
specific DNA sequences at either end of the target DNA prevalence of obesity would be 0.2 or 20%.

Initial prep Relationship

• sample of DNA is added to test tube along with two DNA
primers
• a thermostable DNA polymerase (Taq) is added
The following cycle then takes place
• mixture is heated to almost boiling point causing
denaturing (uncoiling) of DNA
• mixture is the allowed to cool: complimentary strands of
DNA pair up, as there is an excess of the primer
sequences they pair with DNA preferentially
The above cycle is then repeated, with the amount of DNA
doubling each time
Reverse transcriptase PCR
• used to amplify RNA
• RNA is converted to DNA by reverse transcriptase
• gene expression in the form of mRNA (rather than the
actually DNA sequence) can therefore be analyzed
• prevalence = incidence * duration of condition
• in chronic diseases the prevalence is much greater than
the incidence
• in acute diseases the prevalence and incidence are
similar. For conditions such as the common cold the
incidence may be greater than the prevalence
Q-8
A new biochemical marker has been found which is
increased in mothers who are carrying fetuses with Down's
syndrome. The new blood test is trialled in 1,000 women
over the age of 35 years. Of these women 20 were found to
be carrying a fetus with Down's syndrome as assessed using
standard measures. The new test was positive in 15 of the 20
cases but was also positive in 30 of the remaining 980
women. What is the positive predictive value of the test?
A. 0.66
B. 950/980
C. 0.33
D. 0.8
E. 0.5
ANSWER: Measure Formula Plain english
0.33 negative
test result
EXPLANATION:
Positive and negative predictive values are prevalence
A contingency table can be constructed from the above data,
dependent. Likelihood ratios are not prevalence dependent.
as shown below:
Precision
Down's Not Down's The precision quantifies a tests ability to produce the same
Test positive 15 30 measurements with repeated tests.
Test negative 5 950
Q-9
You are advising a patient who has recently been diagnosed
Positive predictive value = TP / (TP + FP) = 15 / (15 + 30) =
with chronic kidney disease stage 4 with regards to her diet.
0.33
Which one of the following foods should she eat in
moderation due to the high potassium content?
SCREENING TEST STATISTICS
Patients and doctors need to know if a disease or condition is A. Tomatoes
present or absent. Tests can be used to help us decide. Tests B. Plums
generally guide us by indicating how likely it is that the patient C. Cranberry juice
has the condition. D. Grapes
E. Green beans
In order to interpret test results we need to have a working
knowledge of the statistics used to describe them. ANSWER:
Tomatoes
Contingency tables (also known as 2 * 2 tables, see below) are
EXPLANATION:
used to illustrate and calculate test statistics such as
HYPERKALAEMIA
sensitivity. It would be unusual for a medical exam not to
Plasma potassium levels are regulated by a number of factors
feature a question based around screening test statistics.
including aldosterone, acid-base balance and insulin levels.
Commit the following table to memory and spend time
Metabolic acidosis is associated with hyperkalaemia as
practicing using it as you will be expected to make calculations
hydrogen and potassium ions compete with each other for
using it in your exam.
exchange with sodium ions across cell membranes and in the
distal tubule. ECG changes seen in hyperkalaemia include tall-
TP = true positive; FP = false positive; TN = true negative; FN =
tented T waves, small P waves, widened QRS leading to a
false negative
sinusoidal pattern and asystole
Disease present Disease absent
Causes of hyperkalaemia:
Test positive TP FP • acute kidney injury
Test negative FN TN • drugs*: potassium sparing diuretics, ACE inhibitors,
angiotensin 2 receptor blockers, spironolactone,
The table below lists the main statistical terms used in relation ciclosporin, heparin**
to screening tests: • metabolic acidosis
• Addison's
Measure Formula Plain english • rhabdomyolysis
Sensitivity TP / (TP + FN ) Proportion of patients with the condition • massive blood transfusion
who have a positive test result
Specificity TN / (TN + FP) Proportion of patients without the Foods that are high in potassium:
condition who have a negative test result • salt substitutes (i.e. Contain potassium rather than
Positive TP / (TP + FP) The chance that the patient has the sodium)
predictive condition if the diagnostic test is positive • bananas, oranges, kiwi fruit, avocado, spinach, tomatoes
value
*beta-blockers interfere with potassium transport into cells
Negative TN / (TN + FN) The chance that the patient does not have
predictive the condition if the diagnostic test is and can potentially cause hyperkalaemia in renal failure
value negative patients - remember beta-agonists, e.g. Salbutamol, are
Likelihood sensitivity / (1 - How much the odds of the disease sometimes used as emergency treatment
ratio for a specificity) increase when a test is positive
positive test **both unfractionated and low-molecular weight heparin can
result cause hyperkalaemia. This is thought to be caused by
Likelihood (1 - sensitivity) / How much the odds of the disease inhibition of aldosterone secretion
ratio for a specificity decrease when a test is negative
Q-10 • after entering a cell the enzyme reverse transcriptase
A scientist is investigating potential targets for anti-HIV creates dsDNA from the RNA for integration into the host
drugs. What is the role of reverse transcriptase in HIV cell's genome
infection?
A. Inhibits topoisomeras II (DNA gyrase) and
topoisomerase IV
B. Prevents supercoiling during replication
C. Unwinds the DNA double helix at the replication fork
D. Transcribes viral RNA to host DNA
E. Produces viral RNA in host cells from DNA template

ANSWER:
Transcribes viral RNA to host DNA

EXPLANATION:
HIV: THE VIRUS
Basics
• HIV is a RNA retrovirus of the lentivirus genus
(lentiviruses are characterized by a long incubation
period)
• two variants - HIV-1 and HIV-2
• HIV-2 is more common in west Africa, has a lower
transmission rate and is thought to be less pathogenic
with a slower progression to AIDS

An illustration model of the HIV Replication Cycle. Each step of the cycle is
numbered and concisely described. Credit: NIAID

Q-11
When establishing a screening programme, which one of the
following is not a key criteria as defined by Wilson and
Junger?

A. There should be a recognised latent or early

Basics structure
• spherical in shape with two copies of single-stranded RNA
enclosed by a capsid of the viral protein p24
• a matrix composed of viral protein p17 surrounds the
capsid
• envelope proteins: gp120 and gp41
• pol gene encodes for viral enzymes reverse transcriptase,
integrase and HIV protease
Cell entry
• HIV can infect CD4 T cells, macrophages and dendritic
cells
• gp120 binds to CD4 and CXCR4 on T cells and CD4 and
CCR5 on macrophages
• mutations in CCR5 can give immunity to HIV
Replication
symptomatic stage
B. The condition should be an important public health
problem
C. The test or examination should be acceptable to the
population
D. There should be agreed policy on whom to treat as
patients
E. The condition should be potentially curable
ANSWER:
The condition should be potentially curable
EXPLANATION:
SCREENING: WILSON AND JUNGER CRITERIA
1. The condition should be an important public health
problem
2. There should be an acceptable treatment for patients
with recognised disease
3. Facilities for diagnosis and treatment should be available
4. There should be a recognised latent or early symptomatic
stage
5. The natural history of the condition, including its A. Right 6th nerve palsy
development from latent to declared disease should be B. Right 4th nerve palsy
adequately understood C. Right 3rd nerve palsy
6. There should be a suitable test or examination D. Left 6th nerve palsy
7. The test or examination should be acceptable to the E. Left 3rd nerve palsy
population
8. There should be agreed policy on whom to treat ANSWER:
9. The cost of case-finding (including diagnosis and Left 6th nerve palsy
subsequent treatment of patients) should be EXPLANATION:
economically balanced in relation to the possible CRANIAL NERVES
expenditure as a whole The table below lists the major characteristics of the 12
10. Case-finding should be a continuous process and not a cranial nerves:
'once and for all' project
Nerve Functions Clinical Pathway/foramen
I (Olfactory) Smell Cribriform plate
Q-12
II (Optic) Sight Optic canal
Which of the following conditions is not caused by a
III (Oculomotor) Eye movement Palsy results in Superior orbital
trinucleotide repeat expansion? (MR, IO, SR, IR) fissure (SOF)
Pupil
A. Fragile X syndrome constriction
• ptosis
B. Huntington's Accomodation
Eyelid opening
• 'down
C. Ataxia telangiectasia and out'
D. Myotonic dystrophy eye
E. Friedreich's ataxia • dilated,
fixed
ANSWER: pupil
Ataxia telangiectasia
IV (Trochlear) Eye movement Palsy results in SOF
EXPLANATION:
(SO) defective
TRINUCLEOTIDE REPEAT DISORDERS downward gaze →
Trinucleotide repeat disorders are genetic conditions caused vertical diplopia
by an abnormal number of repeats (expansions) of a V (Trigeminal) Facial sensation Lesions may cause: V1: SOF, V2: Foramen
repetitive sequence of three nucleotides. These expansions Mastication rotundum,
are unstable and may enlarge which may lead to an earlier V3: Foramen ovale
age of onset in successive generations - a phenomenon known • trigeminal
as anticipation*. In most cases, an increase in the severity of neuralgia
symptoms is also noted • loss of
corneal reflex
Examples - note dominance of neurological disorders (afferent)
• Fragile X (CGG) • loss of facial
• Huntington's (CAG) sensation
• myotonic dystrophy (CTG) • paralysis of
• Friedreich's ataxia* (GAA) mastication
muscles
• spinocerebellar ataxia
• deviation of
• spinobulbar muscular atrophy jaw to weak
• dentatorubral pallidoluysian atrophy side

*Friedreich's ataxia is unusual in not demonstrating

VI (Abducens) Eye movement Palsy results in SOF
anticipation
(LR) defective
abduction →
Q-13 horizontal diplopia
You are examining a patient who complains of double vision. VII (Facial) Facial Lesions may result Internal auditory
Whilst looking forward the patient's left eye turns towards movement in: meatus
the nose. On looking to the patient's right there is no Taste (anterior
obvious squint. However, on looking to the left the patient is 2/3rds of
tongue)
unable to abduct the left eye and double vision worsens. • flaccid
Lacrimation
What is the most likely underlying problem? paralysis of
Salivation
upper +
lower face
 Nerve Functions Clinical Pathway/foramen
• loss of
corneal reflex
(efferent)
• loss of taste
• hyperacusis

VIII Hearing, Hearing loss Internal auditory

(Vestibulocochlear) balance Vertigo, nystagmus meatus
Acoustic neuromas
are Schwann cell
tumours of the
cochlear nerve
IX Taste (posterior Lesions may result Jugular foramen
(Glossopharyngeal) 1/3rd of in;
tongue)
Salivation
Swallowing
• hypersensitiv
Mediates input
e carotid
from carotid
sinus reflex
body & sinus
• loss of gag
reflex View from the inferior surface of the brain showing the emergence of the cranial
(afferent) nerves

X (Vagus) Phonation Lesions may result Jugular foramen

Swallowing in;
Innervates
viscera
• uvula
deviates
away from
site of lesion
• loss of gag
reflex
(efferent)

XI (Accessory) Head and Lesions may result Jugular foramen

shoulder in;
movement

• weakness
turning head
to
contralateral
side
Diagram showing the nuclei of the cranial nerves in the brainstem

XII (Hypoglossal) Tongue Tongue deviates Hypoglossal canal Cranial nerve reflexes
movement towards side of
Reflex Afferent limb Efferent limb
lesion
Corneal Ophthalmic nerve (V1) Facial nerve (VII)
Some cranial nerves are motor, some sensory and some are Jaw jerk Mandibular nerve (V3) Mandibular nerve (V3)
both. The most useful mnemonic is given below. Gag Glossopharyngeal nerve (IX) Vagal nerve (X)
Carotid sinus Glossopharyngeal nerve (IX) Vagal nerve (X)
CN I --------------------------------------------------------------------→XII Pupillary light Optic nerve (II) Oculomotor nerve (III)
Some Say Marry Money But My Brother Says Big Brains Matter Most Lacrimation Ophthalmic nerve (V1) Facial nerve (VII)
S = Sensory, M = Motor, B = Both
Q-14
The commonest chromosomal defect in Down's syndrome is: MOLECULAR BIOLOGY TECHNIQUES
The following table shows a very basic summary of molecular
A. Trinucleotide repeat disorder biology techniques
B. Autosomal dominant
C. Translocation Technique Description
D. Mosaicism Southern blotting Detects DNA
E. Non-dysjunction Northern blotting Detects RNA
Western blotting Detects proteins
ANSWER: Uses gel electrophoresis to separate native proteins by 3-D
Non-dysjunction structure
Examples include the confirmatory HIV test
EXPLANATION:
DOWN'S SYNDROME: EPIDEMIOLOGY AND GENETICS Molecular biology techniques
Risk of Down's syndrome with increasing maternal age • SNOW (South - NOrth - West)
Age (years) Risk • DROP (DNA - RNA - Protein)
20 1 in 1,500
30 1 in 800 Enzyme-linked immunosorbent assay (ELISA)
35 1 in 270 • a type of biochemical assay used to detect antigens and
40 1 in 100 antibodies
45 1 in 50 or greater • a colour changing enzyme is attached to the antibody if
looking for an antigen and to an antigen if looking for an
One way of remembering this is by starting at 1/1,000 at 30 antibody
years and then dividing the denominator by 3 (i.e. 3 times • the sample therefore changes colour if the antigen or
more common) for every extra 5 years of age antibody is detected
• an example includes the initial HIV test
Cytogenetics
Mode % of cases Risk of recurrence
Q-16
Non-disjunction 94% 1 in 100 if under mother < 35
years
Which one of the following features is not associated with
Turner's syndrome?
Robertsonian translocation 5% 10-15% if mother is
(usually onto 14) translocation carrier
2.5% if father is translocation A. Short stature
carrier B. High-arched palate
Mosaicism 1% C. Coarctation of the aorta
D. Webbed neck
The chance of a further child with Down's syndrome is E. Secondary amenorrhoea
approximately 1 in 100 if the mother is less than 35 years old.
If the trisomy 21 is a result of a translocation the risk is much ANSWER:
higher Secondary amenorrhoea

Q-15 EXPLANATION:
Southern blotting is used to: Primary, not secondary, amenorrhoea is seen in Turner's
syndrome
A. Amplify RNA
B. Detect DNA TURNER'S SYNDROME
C. Detect RNA Turner's syndrome is a chromosomal disorder affecting
D. Detect and quantify proteins around 1 in 2,500 females. It is caused by either the presence
E. Amplify DNA of only one sex chromosome (X) or a deletion of the short arm
of one of the X chromosomes. Turner's syndrome is denoted
ANSWER: as 45,XO or 45,X
Detect DNA
Features
EXPLANATION: • short stature
Molecular biology techniques • shield chest, widely spaced nipples
• SNOW (South - NOrth - West) • webbed neck
• DROP (DNA - RNA - Protein) • bicuspid aortic valve (15%), coarctation of the aorta (5-
10%)
• primary amenorrhoea
• cystic hygroma (often diagnosed prenatally)
• high-arched palate
• short fourth metacarpal
• multiple pigmented naevi
• lymphoedema in neonates (especially feet)
• gonadotrophin levels will be elevated

There is also an increased incidence of autoimmune disease

(especially autoimmune thyroiditis) and Crohn's disease

Q-17
A 24-year-old man presents with a three day history of
painful ulcers on the shaft of his penis and dysuria. He has
had no similar previous episodes. A clinical diagnosis of
primary genital herpes is made. What is the most Pap smear. Multinucleated giant cells representing infection by the herpes simplex
appropriate management? virus. Note the 3 M's; Multinucleation, Margination of the chromatin, Molding of
the nuclei
A. Topical famciclovir
B. No treatment is indicated
C. Topical podophyllotoxin
D. Topical valaciclovir
E. Oral aciclovir

ANSWER:
Oral aciclovir

EXPLANATION:
Oral antiviral therapy is indicated for primary genital herpes
infections, even if the presentation is delayed for up to 5
days

HERPES SIMPLEX VIRUS

There are two strains of the herpes simplex virus (HSV) in
humans: HSV-1 and HSV-2. Whilst it was previously thought
HSV-1 accounted for oral lesions (cold sores) and HSV-2 for
genital herpes it is now known there is considerable overlap Further Pap smear showing the cytopathic effect of HSV (multi-nucleation, ground
glass & marginated chromatin)
Features
• primary infection: may present with a severe Q-18
gingivostomatitis A 59-year-old male patient presents to the gastroenterology
• cold sores clinic with a 6-months history of weight loss, frequent loose
• painful genital ulceration and greasy stool. He has a long-standing history of heavy
alcohol use and recurrent hospital admissions for acute
Management pancreatitis. On examination, the patient looks
• gingivostomatitis: oral aciclovir, chlorhexidine malnourished. There is mild tenderness elicited on palpation
mouthwash of the epigastric region.
• cold sores: topical aciclovir although the evidence base
for this is modest Which hormone will likely be relevant in the investigation of
• genital herpes: oral aciclovir. Some patients with frequent his symptoms?
exacerbations may benefit from longer term aciclovir
A. Gastrin
Pregnancy B. Secretin
• elective caesarean section at term is advised if a primary C. Incretin
attack of herpes occurs during pregnancy at greater than D. Insulin
28 weeks gestation E. Glucagon
• women with recurrent herpes who are pregnant should
be treated with suppressive therapy and be advised that ANSWER:
the risk of transmission to their baby is low Secretin
EXPLANATION: Source Stimulus Actions
Secretin increases secretion of bicarbonate-rich fluid from secretion
pancreas and hepatic duct cells inhibits trophic effects of
This patient has symptoms suggestive of pancreatic gastrin, stimulates
insufficiency likely secondary to chronic pancreatitis, given gastric mucous
production
the weight loss and steatorrhoea as well as the history of
alcohol misuse. Secretin increases the secretion of
bicarbonate-rich fluid from pancreas and hepatic duct cells Q-19
and it can be used as a test for pancreatic function (secretin A new anti-epileptic drug is trialled for children with absence
stimulation test). seizures. There are 250 children in the control group and 150
children assigned to take the new drug. After 4 months 100
Gastrin increases HCL production. children in the control group had had a seizure compared to
15 children in the group taking the new medication. What is
Incretin is released following food intake and stimulates the relative risk reduction?
insulin secretion.
A. 4
Insulin and glucagon are pancreatic hormones but they are B. 30%
not the main hormones that stimulate the secretion of C. 3.33
bicarbonate-rich fluid from pancreas and hepatic duct cells. D. 75%
They are mainly involved in glucose regulation. E. 40%

GASTROINTESTINAL HORMONES ANSWER:

Below is a brief summary of the major hormones involved in 75%
food digestion:
EXPLANATION:
Relative risk reduction = (EER - CER) / CER
Source Stimulus Actions
Experimental event rate, EER = 15 / 150 = 0.1
Gastrin G cells in Distension of Increase HCL,
antrum of stomach, vagus pepsinogen and IF
the nerves (mediated by secretion, increases
Control event rate, CER = 100 / 250 = 0.4
stomach gastrin-releasing gastric motility,
peptide), luminal stimulates parietal cell Relative risk reduction = (EER - CER) / CER = (0.1 - 0.4) / 0.4 =
peptides/amino acids maturation -0.75 or a 75% reduction
Inhibited by: low
antral pH, RELATIVE RISK
somatostatin
Relative risk (RR) is the ratio of risk in the experimental group
CCK I cells in Partially digested Increases secretion of
(experimental event rate, EER) to risk in the control group
upper small proteins and enzyme-rich fluid from
intestine triglycerides pancreas, contraction of
(control event rate, CER). The term relative risk ratio is
gallbladder and sometimes used instead of relative risk.
relaxation of sphincter of
Oddi, decreases gastric To recap
emptying, trophic effect • EER = rate at which events occur in the experimental
on pancreatic acinar
group
cells, induces satiety
• CER = rate at which events occur in the control group
Secretin S cells in Acidic chyme, fatty Increases secretion of
upper small acids bicarbonate-rich fluid
intestine from pancreas and For example, if we look at a trial comparing the use of
hepatic duct cells, paracetamol for dysmenorrhoea compared to placebo we
decreases gastric acid may get the following results
secretion, trophic effect
on pancreatic acinar cells
Total number of patients Experienced significant pain relief
VIP Small Neural Stimulates secretion by
Paracetamol 100 60
intestine, pancreas and intestines,
pancreas inhibits acid secretion Placebo 80 20

Somatostatin D cells in Fat, bile salts and Decreases acid and

the glucose in the pepsin secretion, Experimental event rate, EER = 60 / 100 = 0.6
pancreas & intestinal lumen decreases gastrin
stomach secretion, decreases Control event rate, CER = 20 / 80 = 0.25
pancreatic enzyme
secretion, decreases
Therefore the relative risk ratio = EER / CER = 0.6 / 0.25 = 2.4
insulin and glucagon

If the risk ratio is > 1 then the rate of an event (in this case
experiencing significant pain relief) is increased compared to
controls. It is therefore appropriate to calculate the relative
risk increase if necessary (see below).
A blood transfusion is clearly in the patient's best interests
and in the scenario described above may potentially be life-
saving. Whilst a child cannot refuse treatment they are able
to provide consent. Giving the blood transfusion is therefore
both clinically and ethically the right course of action.

If the risk ratio is < 1 then the rate of an event is decreased Not giving the blood transfusion not only fails to respect the
compared to controls. The relative risk reduction should patient's wishes but also causes potential harm.
therefore be calculated (see below).
Q-21
Relative risk reduction (RRR) or relative risk increase (RRI) is A 17-year-old male is diagnosed with alpha-thalassaemia.
calculated by dividing the absolute risk change by the control What chromosome is the alpha-globulin genes located on?
event rate
A. Chromosome 4
Using the above data, RRI = (EER - CER) / CER = (0.6 - 0.25) / B. Chromosome 8
0.25 = 1.4 = 140% C. Chromosome 12
D. Chromosome 16
Q-20 E. Chromosome 20
A 14-year-old girl is admitted to hospital following a
ruptured ectopic pregnancy. She comes from a family of ANSWER:
Jehovah's Witnesses. Her haemoglobin on admission is 6.9 Chromosome 16
g/dl. She consents to a blood transfusion but her mother
refuses. What is the most appropriate course of action? EXPLANATION:
ALPHA-THALASSAEMIA
A. Advise the parents she will have to get a High Court Alpha-thalassaemia is due to a deficiency of alpha chains in
injunction in order to stop the transfusion haemoglobin
B. Give the blood transfusion
C. Transfer the patient to a hospital run by Jehovah's Overview
Witnesses • 2 separate alpha-globulin genes are located on each
D. Respect parental wishes and withhold the blood chromosome 16
transfusion
E. Ask the hospital lawyer to come in and decide upon the Clinical severity depends on the number of alpha chains
correct course of action present

ANSWER: If 1 or 2 alpha chains are absent then the blood picture would
Give the blood transfusion be hypochromic and microcytic, but the Hb level would be
typically normal
EXPLANATION:
The GMC gives the following guidance: Loss of 3 alpha chains results in a hypochromic microcytic
'You should encourage young people to involve their parents anaemia with splenomegaly. This is known as Hb H disease
in making important decisions, but you should usually abide
by any decision they have the capacity to make themselves' If all 4 alpha chains absent (i.e. homozygote) then death in
utero (hydrops fetalis, Bart's hydrops)
With respect to Jehovah's witnesses:
'You should not make assumptions about the decisions that a Q-22
Jehovah's Witness patient might make about treatment with A 59-year-old man is investigated for exertional chest pain
blood or blood products. You should ask for and respect their and is found to have extensive coronary artery disease on
views and answer their questions honestly and to the best of angiogram. Which of the following cell types is most
your ability. You may also wish to contact the hospital liaison implicated in the development of coronary artery plaques?
committees established by the Watch Tower Society (the
governing body of Jehovah's Witnesses) to support Jehovah's A. Lymphocytes
Witnesses faced with treatment decisions involving blood. B. Platelets
These committees can advise on current Society policy C. Macrophages
regarding the acceptability or otherwise of particular blood D. Neutrophils
products. They also keep details of hospitals and doctors who E. Basophils
are experienced in 'bloodless' medical procedures.'
ANSWER: Complications of atherosclerosis
Macrophages Taking the coronary arteries as an example, once a plaque has
formed a number of complications can develop:
EXPLANATION: • the plaque forms a physical blockage in the lumen of the
Although platelets are clearly central to the thrombotic coronary artery. This may cause reduced blood flow and
cascade which develops following plaque rupture hence oxygen to the myocardium, particularly at times of
macrophages play a greater role in the initial development increased demand, resulting clinically in angina
of the plaque. • the plaque may rupture, potentially causing a complete
occlusion of the coronary artery. This may result in a
ATHEROSCLEROSIS myocardial infarction
Atherosclerosis is a complex process which develops over a
number of years. A number of changes can be seen:
• initial endothelial dysfunction is triggered by a number of
factors such as smoking, hypertension and
hyperglycaemia
• this results in a number of changes to the endothelium
including pro-inflammatory, pro-oxidant, proliferative and
reduced nitric oxide bioavailability
• fatty infiltration of the subendothelial space by low-
density lipoprotein (LDL) particles
• monocytes migrate from the blood and differentiate into
Ruptured coronary artery plaque resulting in thrombosis and associated
macrophages. These macrophages then phagocytose myocardial infarction.
oxidized LDL, slowly turning into large 'foam cells'. As
these macrophages die the result can further propagate
the inflammatory process.
• smooth muscle proliferation and migration from the
tunica media into the intima results in formation of a
fibrous capsule covering the fatty plaque.

Pathological specimen showing infarction of the anteroseptal and lateral wall of

the left ventricle. There is a background of biventricular myocardial hypertrophy.

Q-23
In a normal distribution what percentage of values lie within
3 standard deviations of the mean?
Diagram showing the progression of atherosclerosis in the coronary arteries with A. 68.3%
associated complications on the right.
B. 98.3%
C. 95.4%
D. 99.7%
E. 97.2%

ANSWER:
99.7%

Slide showing a markedly narrowed coronary artery secondary to atherosclerosis.
Stained with Masson's trichrome.
EXPLANATION:
NORMAL DISTRIBUTION
The normal distribution is also known as the Gaussian
distribution or 'bell-shaped' distribution. It describes the
spread of many biological and clinical measurements
Properties of the Normal distribution
• symmetrical i.e. Mean = mode = median
• 68.3% of values lie within 1 SD of the mean
• 95.4% of values lie within 2 SD of the mean
• 99.7% of values lie within 3 SD of the mean
• this is often reversed, so that within 1.96 SD of the mean
lie 95% of the sample values
• the range of the mean - (1.96 *SD) to the mean + (1.96 *
SD) is called the 95% confidence interval, i.e. If a repeat
sample of 100 observations are taken from the same
group 95 of them would be expected to lie in that range
Standard deviation
• the standard deviation (SD) is a measure of how much
dispersion exists from the mean
• SD = square root (variance)
Q-24
A 19-year-old man with a history of learning disabilities and
ectopia lentis is diagnosed as having homocystinuria.
Supplementation of which one of the following may help
improve his condition?
A. Folic acid
B. Niacin
C. Pyridoxine
D. Vitamin B7
E. Thiamine
ANSWER:
Pyridoxine
EXPLANATION:
Homocystinuria - give vitamin B6 (pyridoxine)
HOMOCYSTINURIA
Homocystinuria is a rare autosomal recessive disease caused
by deficiency of cystathionine beta synthase. This results in an
accumulation of homocysteine which is then oxidized to
homocystine.
Features
• often patients have fine, fair hair
• musculoskeletal: may be similar to Marfan's -
arachnodactyly etc
• neurological patients may have learning difficulties,
seizures
• ocular: downwards (inferonasal) dislocation of lens
• increased risk of arterial and venous thromboembolism
• also malar flush, livedo reticularis
Diagnosis is made by the cyanide-nitroprusside test, which is
also positive in cystinuria
Treatment is vitamin B6 (pyridoxine) supplements
Q-25
A 1-month old male baby presents to the paediatric
emergency department with an episode of tonic-clonic
seizure preceded by a 1-week history of poor feeding,
wheezing and general failure to thrive. The baby was born at
term with no complication. There is no significant past
medical history. On examination, the baby has a small jaw
and mouth, low set ears and long face. Chest X-ray shows
opacification in the right lower zone. An echocardiogram
confirms a large ventricular septal defect.
What other pathology is this patient likely to have?
A. B lymphocyte deficiency
B. T and B lymphocyte deficiency
C. T lymphocyte deficiency
D. Granulocyte deficiency
E. Complement deficiency
ANSWER:
T lymphocyte deficiency
EXPLANATION:
DiGeorge syndrome - a T-cell disorder
The baby's presentation suggests DiGeorge syndrome. The
seizure episode is likely caused by hypocalcaemia from
hypoparathyroidism. He also has syndromic features of
DiGeorge syndrome and congenital heart disease. There is
evidence of infection which indicates that immunodeficiency
is likely. T-lymphocyte deficiency in DiGeorge syndrome is
usually due to thymic hypoplasia.
The other options are not correct as they are not consistent
with DiGeorge syndrome.
DIGEORGE SYNDROME
DiGeorge syndrome is a primary immunodeficiency disorder
caused by T-cell deficiency and dysfunction. It is an example of
a microdeletion syndrome (deletion of a section of
chromosome 22).
It is also known as velocardiofacial syndrome and 22q11.2
deletion syndrome and is an autosomal dominant condition.
Features
• at risk of viral and fungal infections
• parathyroid gland hypoplasia → hypocalcaemic tetany
• thymus hypoplasia
• T-lymphocyte deficiency/dysfunction
It has a variable presentation however its features can be
remembered with the mnemonic CATCH22:
• C - Cardiac abnormalities
• A - Abnormal facies
• T - Thymic aplasia
• C - Cleft palate
• H - Hypocalcaemia/ hypoparathyroidism
• 22 - Caused by chromosome 22 deletion
Q-26 Q-27
In the Gell and Coombs classification of hypersensitivity Each one of the following is an acute phase protein, except:
reactions scabies is an example of a:
A. Haptoglobin
A. Type I reaction B. Alpha-1 antitrypsin
B. Type II reaction C. CRP
C. Type III reaction D. Ferritin
D. Type IV reaction E. ESR
E. Type V reaction ANSWER:
ESR
ANSWER:
Type IV reaction EXPLANATION:
ACUTE PHASE PROTEINS
EXPLANATION: Acute phase proteins
Type IV hypersensitivity reaction - scabies • CRP*
Scabies produces a delayed type IV hypersensitivity reaction • procalcitonin
approximately one month after infestation. This produces • ferritin
the characteristic intense itching • fibrinogen
• alpha-1 antitrypsin
HYPERSENSITIVITY • caeruloplasmin
The Gell and Coombs classification divides hypersensitivity • serum amyloid A
traditionally divides reactions into 4 types: • serum amyloid P component**
• haptoglobin
Type Mechanism Examples
• complement
Type I - Anaphylactic Antigen reacts with • Anaphylaxis
IgE bound to mast • Atopy (e.g. asthma, eczema During the acute phase response the liver decreases the
cells and hayfever)
production of other proteins (sometimes referred to as
Type II - Cell bound IgG or IgM binds to • Autoimmune haemolytic
negative acute phase proteins). Examples include:
antigen on cell surface anaemia
• ITP
• albumin
• Goodpasture's syndrome • transthyretin (formerly known as prealbumin)
• Pernicious anaemia • transferrin
• Acute haemolytic • retinol binding protein
transfusion reactions • cortisol binding protein
• Rheumatic fever
• Pemphigus vulgaris *Levels of CRP are commonly measured in acutely unwell
/ bullous pemphigoid patients. CRP is a protein synthesised in the liver and binds to
Type III - Immune Free antigen and • Serum sickness phosphocholine in bacterial cells and on those cells
complex antibody (IgG, IgA) • Systemic lupus
undergoing apoptosis. In binding to these cells it is then able
combine erythematosus
• Post-streptococcal
to activate the complement system. CRP levels are known to
glomerulonephritis rise in patients following surgery. However, levels of greater
• Extrinsic allergic alveolitis than 150 at 48 hours post operatively are suggestive of
(especially acute phase) evolving complications.
Type IV - Delayed T-cell mediated • Tuberculosis / tuberculin
hypersensitivity skin reaction **plays a more significant role in other mammals such as mice
• Graft versus host disease
• Allergic contact dermatitis
Q-28
• Scabies A 26-year-old gentleman has been recently diagnosed with
• Extrinsic allergic alveolitis an intracranial neoplasm. His family history includes that of
(especially chronic phase) multiple carcinomas. These include breast, bone and colon
• Multiple sclerosis cancer. A diagnosis of Li-Fraumeni is suspected.
• Guillain-Barre syndrome
What is the likely gene defect causing this condition?
In recent times a further category has been added:
Type Mechanism Examples A. APC
Type Antibodies that recognise and bind to the cell surface • Graves' B. NF1
V receptors. disease C. p53
• Myasthenia
D. WT1
This either stimulating them or blocking ligand gravis
binding
E. BRCA1
ANSWER: before longer flights. This is due to the fact that air may be
p53 trapped beneath the cast
EXPLANATION: FITNESS TO FLY
The answer is the p53 tumour suppressor gene. The Civil Aviation Authority (CAA) has issued guidelines on air
travel for people with medical conditions; please see the link
Li-Fraumeni is an autosomal dominant disorder provided.
characterised by multiple cancers such as leukaemias,
sarcomas, brain, breast and adrenal malignancies. Cardiovascular disease
• unstable angina, uncontrolled hypertension, uncontrolled
The other answers are all tumour suppressor genes. APC is
cardiac arrhythmia, decompensated heart failure, severe
associated with colorectal cancer, NF1 with
symptomatic valvular disease: should not fly
neurofibromatosis, WT1 with Wilms tumour, and BRCA1 with
• uncomplicated myocardial infarction: may fly after 7-10
breast and ovarian cancer.
days
TUMOUR SUPPRESSOR GENES • complicated myocardial infarction: after 4-6 weeks
Basics • coronary artery bypass graft: after 10-14 days
• genes which normally control the cell cycle • percutaneous coronary intervention: after 5 days
• loss of function results in an increased risk of cancer
Respiratory disease
• both alleles must be mutated before cancer occurs
• pneumonia: should be 'clinically improved with no
Examples residual infection'
Gene Associated cancers • pneumothorax: absolute contraindication, the CAA
p53 Common to many cancers, Li-Fraumeni suggest patients may travel 2 weeks after successful
syndrome drainage if there is no residual air. The British Thoracic
APC Colorectal cancer Society used to recommend not travelling by air for a
BRCA1 Breast and ovarian cancer period of 6 weeks but this has now been changed to 1
BRCA2 Breast and ovarian cancer week post check x-ray
NF1 Neurofibromatosis
Pregnancy
Rb Retinoblastoma
• most airlines do not allow travel after 36 weeks for a
WT1 Wilm's tumour
single pregnancy and after 32 weeks for a multiple
Multiple tumor suppressor 1 (MTS-1, Melanoma
pregnancy
p16)
• most airlines require a certificate after 28 weeks
Tumour suppressor genes - loss of function results in an confirming that the pregnancy is progressing normally
increased risk of cancer
Surgery
Oncogenes - gain of function results in an increased risk of • travel should be avoided for 10 days following abdominal
cancer surgery
• laparoscopic surgery: after 24 hours
Q-29 • colonoscopy: after 24 hours
Of the following scenarios, which one would indicate it was • following the application of a plaster cast, the majority of
inappropriate for the patient to take an airline flight? airlines restrict flying for 24 hours on flights of less than 2
hours or 48 hours for longer flights
A. A 54-year-old woman who had a laparoscopic Haematological disorders
cholecystectomy 5 days ago • patients with a haemoglobin of greater than 8 g/dl may
B. A 17-year-old flying back to the UK who broke his leg travel without problems (assuming there is no coexisting
whilst skiing in Canada. Had a plaster cast applied 24 condition such as cardiovascular or respiratory disease)
hours ago
C. A 59-year-old man who had a colonoscopy 2 days ago Q-30
D. A 62-year-old man who had an uncomplicated Which one of the following statements regarding
myocardial infarction 3 weeks ago significance tests is incorrect?
E. A woman who is 27-weeks pregnant with twins
A. Parametric data is usually normally distributed
ANSWER: B. Student's t-test may be paired or unpaired
A 17-year-old flying back to the UK who broke his leg whilst C. Pearson's product-moment coefficient is used to assess
skiing in Canada. Had a plaster cast applied 24 hours ago correlation between two variables
D. Chi-squared test is used to compare parametric data
EXPLANATION: E. Paired data refers to data obtained from a single group
Following the application of a plaster cast patients should of patients
wait 24 hours before short flights (< 2 hours) and 48 hours
ANSWER: Nerve
Chi-squared test is used to compare parametric data root Landmark Mnemonics
hand
EXPLANATION: C8 Ring + little finger
SIGNIFICANCE TESTS: TYPES T4 Nipples T4 at the Teat Pore
The type of significance test used depends on whether the
T5 Inframammary fold
data is parametric (something which can be measured, usually
T6 Xiphoid process
normally distributed) or non-parametric
T10 Umbilicus BellybuT-TEN
Parametric tests L1 Inguinal ligament L for ligament, 1 for 1nguinal
• Student's t-test - paired or unpaired* L4 Knee caps Down on aLL fours - L4
• Pearson's product-moment coefficient - correlation L5 Big toe, dorsum of foot L5 = Largest of the 5 toes
(except lateral aspect)
Non-parametric tests S1 Lateral foot, small toe S1 = the smallest one
• Mann-Whitney U test - unpaired data S2, S3 Genitalia
• Wilcoxon signed-rank test - compares two sets of
observations on a single sample
• chi-squared test - used to compare proportions or
percentages
• Spearman, Kendall rank - correlation
*paired data refers to data obtained from a single group of
patients, e.g. Measurement before and after an intervention.
Unpaired data comes from two different groups of patients,
e.g. Comparing response to different interventions in two
groups
Q-31
A 61-year-old man complains of a four month history of neck
and arm pain. The pain is described as being like 'electric
shocks' and is worse when he turns his head. There is no
history of trauma and no other obvious trigger. He is
otherwise fit and well and takes no other medication. On
examination he has decreased sensation on the dorsal
aspect of the thumb and index finger. What is the most likely
underlying diagnosis?
A. C4 radiculopathy
B. C5 radiculopathy
C. C6 radiculopathy
D. C7 radiculopathy
E. T1 radiculopathy
ANSWER:
C6 radiculopathy
EXPLANATION:
DERMATOMES
The table below lists the major dermatome landmarks:
Nerve
root Landmark Mnemonics
C2 Posterior half of the skull
(cap)
C3 High turtleneck shirt
C4 Low-collar shirt
C5 Ventral axial line of upper
limb
C6 Thumb + index finger Make a 6 with your left hand by
touching the tip of the thumb & index
finger together - C6
C7 Middle finger + palm of
 EXPLANATION:
Even after correction for the low albumin level this patient
has significant hypocalcaemia which should be corrected.
HYPOCALCAEMIA: CAUSES AND MANAGEMENT
The clinical history combined with parathyroid hormone levels
will reveal the cause of hypocalcaemia in the majority of cases

Causes
• vitamin D deficiency (osteomalacia)
• chronic kidney disease
• hypoparathyroidism (e.g. post thyroid/parathyroid
surgery)
• pseudohypoparathyroidism (target cells insensitive to
PTH)
• rhabdomyolysis (initial stages)
• magnesium deficiency (due to end organ PTH resistance)
• massive blood transfusion
Acute pancreatitis may also cause hypocalcaemia.
Contamination of blood samples with EDTA may also give
falsely low calcium levels
Management
• acute management of severe hypocalcaemia is with
intravenous replacement. The preferred method is with
intravenous calcium gluconate, 10ml of 10% solution over
10 minutes
• intravenous calcium chloride is more likely to cause local
irritation
• ECG monitoring is recommended
• further management depends on the underlying cause
Q-33
A 32-year-old man with familial hypercholesterolaemia
comes to the lipid clinic for review. Despite 80mg of
atorvastatin, his LDL cholesterol is still 3.8 and he suffered an
inferior myocardial infarction some 3 months earlier. You
elect to commence evolocumab.
Q-32 Which of the following reflects the mode of action of
A 54-year-old man is brought to the Emergency Department evolocumab?
after being found collapsed in the street. He is known to
have a history of alcoholic liver disease. Blood tests reveal A. Activates lipoprotein lipase
the following: B. Blocks absorption of cholesterol in the GI tract
C. Inhibits PPAR-alpha
Calcium 1.62 mmol/l D. Inhibits SGLT-1
Albumin 33 g/l E. Prevents PCSK9-mediated LDL receptor degradation

Which one of the following is the most appropriate ANSWER:

management of the calcium result? Prevents PCSK9-mediated LDL receptor degradation

A. 10ml of 10% calcium chloride over 10 minutes EXPLANATION:

B. 20% albumin infusion Evolocumab prevents PCSK9-mediated LDL receptor
C. 10ml of 10% calcium gluconate over 10 minutes degradation. Evolocumab binds selectively to PCSK9 and
D. No action prevents circulating PCSK9 from binding to the low-density
E. 10ml of 10% calcium chloride over 4 hours lipoprotein receptor (LDLR) on the liver cell surface, thus
preventing PCSK9-mediated LDLR degradation. Increasing
ANSWER: liver LDLR levels results in associated reductions in serum
10ml of 10% calcium gluconate over 10 minutes LDL-cholesterol. Use of evolocumab is associated with a
reduction in levels of free PCSK9 and this is taken as a
measure of target engagement. it lowers LDL cholesterol by EXPLANATION:
more than 50% in 85% of patients who are treated. Please see Q-8 for Screening Test Statistics
Fibrates increase lipoprotein lipase activity via PPAR-alpha Q-35
agonism, and ezetimibe reduces intestinal absorption of A 55-year-old man with a history of type 2 diabetes mellitus,
cholesterol. SGLT-1 inhibitors reduce intestinal absorption of bipolar disorder and chronic obstructive pulmonary disease
glucose. has bloods taken as part of his annual diabetic review:
Use of evolocumab is endorsed by NICE under certain Na+ 129 mmol/l
conditions only, namely that the dosage is 140mg every 2 K+ 3.8 mmol/l
weeks and LDL cholesterol is persistently above 3.5 mmol/l. Bicarbonate 24 mmol/l
FAMILIAL HYPERCHOLESTEROLAEMIA Urea 3.7 mmol/l
Familial hypercholesterolaemia (FH) is an autosomal dominant Creatinine 92 µmol/l
condition that is thought to affect around 1 in 500 people. It
results in high levels of LDL-cholesterol which, if untreated, Due to his smoking history a chest x-ray is ordered which is
may cause early cardiovascular disease (CVD). FH is caused by reported as normal. Which one of the following medications
mutations in the gene which encodes the LDL-receptor is most likely to be responsible?
protein.
A. Metformin
Clinical diagnosis is now based on the Simon Broome criteria: B. Lithium
• in adults total cholesterol (TC) > 7.5 mmol/l and LDL-C > C. Carbamazepine
4.9 mmol/l or children TC > 6.7 mmol/l and LDL-C > 4.0 D. Sodium valproate
mmol/l, plus: E. Exenatide
• for definite FH: tendon xanthoma in patients or 1st or 2nd
degree relatives or DNA-based evidence of FH ANSWER:
• for possible FH: family history of myocardial infarction Carbamazepine
below age 50 years in 2nd degree relative, below age 60
in 1st degree relative, or a family history of raised EXPLANATION:
cholesterol levels SIADH - drug causes: carbamazepine, sulfonylureas, SSRIs,
tricyclics
Management
Lithium can cause diabetes insipidus but this is generally
• the use of CVD risk estimation using standard tables is not
associated with a high sodium. Lithium only tends to cause
appropriate in FH as they do not accurately reflect the
raised antidiuretic hormone levels following a severe
risk of CVD
overdosage. Please see the BNF for more details.
• referral to a specialist lipid clinic is usually required
• the maximum dose of potent statins are usually required SIADH: CAUSES
• first-degree relatives have a 50% chance of having the The syndrome of inappropriate ADH secretion (SIADH) is
disorder and should therefore be offered screening. This characterised by hyponatraemia secondary to the dilutional
includes children who should be screened by the age of effects of excessive water retention.
10 years if there is one affected parent
• statins should be discontinued in women 3 months Causes of SIADH
before conception due to the risk of congenital defects Category Examples

Q-34 Malignancy • small cell lung cancer

What is the correct formula to calculate the negative • also: pancreas, prostate
predictive value of a screening test?
Neurological • stroke
TP = true positive; FP = false positive; TN = true negative; FN
• subarachnoid haemorrhage
= false negative
• subdural haemorrhage
A. TN / (TN + FN) • meningitis/encephalitis/abscess
B. TP / (TP + FP)
C. TN / (TN + FP) Infections • tuberculosis
D. Sensitivity / (1 - specificity) • pneumonia
E. TP / (TP + FN )
Drugs • sulfonylureas*
ANSWER:
TN / (TN + FN) • SSRIs, tricyclics
 Category Examples Please see Q-13 for Cranial Nerves
• carbamazepine
• vincristine Q-37
• cyclophosphamide Which of the following statements is true regarding the
standard polymerase chain reaction (PCR)?
Other causes • positive end-expiratory pressure (PEEP)
A. Restriction endonuclease enzymes are applied to DNA
• porphyrias
fragments prior to electrophoresis
B. PCR use is limited by its relatively low sensitivity
Management C. A thermostable DNA polymerase is required
• correction must be done slowly to avoid precipitating D. PCR is currently limited to prenatal diagnosis and
central pontine myelinolysis forensics
• fluid restriction E. A single DNA oligonucleotide primer is necessary
• demeclocycline: reduces the responsiveness of the
collecting tubule cells to ADH ANSWER:
A thermostable DNA polymerase is required
• ADH (vasopressin) receptor antagonists have been
developed
EXPLANATION:
*the BNF states this has been reported with glimepiride and Please see Q-6 for Polymerase Chain Reaction
glipizide.
Q-38
Q-36 A 17-year-old girl with Turner's syndrome is reviewed in the
A 78-year-old man presented to the eye casualty with cardiology clinic. Other than coarctation of the aorta, what is
diplopia. He has been noticing this double vision for the past the most common cardiac abnormality found in patients
two weeks. On examination, there was horizontal diplopia with Turner's syndrome?
and minimal restriction of one of the extraocular muscles in
the left eye. His past medical history includes longstanding A. Ventricular septal defect
prostate cancer and hypertension. Imaging of the brain B. Bicuspid aortic valve
revealed metastatic lesion in the clivus encasing the C. Aortic stenosis
cavernous sinus and carotid artery. D. Pulmonary stenosis
E. Partial anomalous venous drainage
Which one of the following cranial nerve palsy leads to
diplopia in this patient? ANSWER:
Bicuspid aortic valve
A. Right third cranial nerve (CN3) palsy
EXPLANATION:
B. Left sixth cranial nerve (CN6) palsy
Turner's syndrome - most common cardiac defect is bicuspid
C. Right sixth cranial nerve (CN6) palsy
aortic valve
D. Left fourth cranial nerve (CN4) palsy
Up to 15% of adults with Turner's syndrome have bicuspid
E. Left third cranial nerve (CN3) palsy
aortic valves
ANSWER: Please see Q-16 for Turner’s Syndrome
Left sixth cranial nerve (CN6) palsy
Q-39
A 37-year-old female patient presents to the GP surgery with
EXPLANATION:
a 6-months history of joint pains. She reports the joint pains
CN6 palsy manifesting as diplopia could be the first sign of
mainly involve the elbows, knees, joints in the fingers and
brain metastasis
toes. She has an erythematous rash covering the cheeks,
The sixth cranial nerve (CN6) innervates the lateral rectus
sparing the nasolabial folds. She reports the rash was worse
muscle which is responsible for moving the eye laterally. CN6
when she went to Spain on holiday.
arises from the pons which sits on the clivus. Hence, a
tumour involving the clivus would compress the CN6 causing What is the most common complement deficiency
its palsy. This leads to restricted lateral gaze which results in associated with this condition?
horizontal diplopia as seen in this patient. Right cranial nerve
palsies are irrelevant as the question clearly states the A. C5-9 deficiency
involvement of left extraocular muscle. CN4 palsy causes B. C5 deficiency
vertical diplopia. CN3 palsy causes ptosis and involves four C. C1 inhibitor (C1-INH) protein deficiency
extraocular muscles rather than one that is mentioned in the D. C3 deficiency
question. E. C1q, C1rs, C2 and C4 deficiency
ANSWER: What is the most likely underlying diagnosis?
C1q, C1rs, C2 and C4 deficiency
A. CADASIL
EXPLANATION: B. Fabry disease
Deficiency in C1q, C1rs, C2 and C4 predisposes to immune C. MELAS
complex disease such as SLE D. Primary CNS angiitis
This lady has signs of systemic lupus (SLE). Deficiency in C1q, E. Cholesterol embolism
C1rs, C2 and C4 predisposes to immune complex disease such
as SLE. ANSWER:
Fabry disease
C5-9 predisposes to Neisseria meningitidis infections.
EXPLANATION:
C3 deficiency causes recurrent bacterial infections. The answer is Fabry disease. This condition typically presents
with proteinuria and is associated with early onset strokes or
C5 deficiency predisposes to Leiner disease myocardial infarctions with a typical rash known as
angiokeratomas.
C1 inhibitor (C1-INH) protein deficiency causes hereditary
angioedema. CADASIL or cerebral autosomal dominant arteriopathy with
subcortical infarcts and leukoencephalopathy is an inherited
COMPLEMENT DEFICIENCIES condition which presents with a history of migraines and
Complement is a series of proteins that circulate in plasma multiple strokes. It is not associated with angiokeratomas or
and are involved in the inflammatory and immune reaction of corneal whirls. MELAS or mitochondrial encephalopathy with
the body. Complement proteins are involved in chemotaxis, lactic acidosis and stroke symptoms is weakened by the
cell lysis and opsonisation absence of lactic acidosis in the stem. There is no evidence of
connective tissue disease in the stem to suggest primary CNS
C1 inhibitor (C1-INH) protein deficiency angiitis and cholesterol embolism is typically associated with
• causes hereditary angioedema eosinophilia, livedo reticularis and a precipitant such as
• C1-INH is a multifunctional serine protease inhibitor preceding angiography.
• probable mechanism is uncontrolled release of bradykinin
resulting in oedema of tissues ANDERSON-FABRY DISEASE
Overview
C1q, C1rs, C2, C4 deficiency (classical pathway components) • X-linked recessive
• predisposes to immune complex disease • deficiency of alpha-galactosidase A
• e.g. SLE, Henoch-Schonlein Purpura
Features
C3 deficiency • burning pain/paraesthesia in childhood
• causes recurrent bacterial infections • angiokeratomas
• lens opacities
C5 deficiency • proteinuria
• predisposes to Leiner disease • early cardiovascular disease
• recurrent diarrhoea, wasting and seborrhoeic dermatitis
Q-41
C5-9 deficiency You are performing a study of blood pressure readings in
• encodes the membrane attack complex (MAC) patients with chronic kidney disease. Assuming that the
• particularly prone to Neisseria meningitidis infection results are normally distributed, what percentage of values
lie within two standard deviations of the mean blood
Q-40 pressure reading?
A 42-year-old gentleman is admitted to the Emergency
Department as a potential stroke. A later CT scan of his head A. 95.4%
confirms an established infarct and is unfortunately outside B. 5.3%
the thrombolysis window. During his time in the Emergency C. 98.3%
Department, you notice a rash in a bathing-suit distribution D. 10%
consistent with angiokeratomas. E. 97.5%

Testing your hypothesis, you use a slit-lamp to confirm the ANSWER:

presence of corneal whirls. 95.4%
EXPLANATION: normally paired osmolalities exclude SIADH and diabetes
Please see Q-23 for Normal Distribution insipidus, whilst the absence of glucosuria makes diabetes an
unlikely cause.
Q-42
A contingency table is constructed for a new blood protein HYPONATRAEMIA
marker to screen for prostate cancer in men aged between Hyponatraemia may be caused by water excess or sodium
50 and 70 years: depletion. Causes of pseudohyponatraemia include
hyperlipidaemia (increase in serum volume) or a taking blood
Prostate cancer present Prostate cancer absent from a drip arm. Urinary sodium and osmolarity levels aid
New test positive 19 20 making a diagnosis
New test negative 14 723
Urinary sodium > 20 mmol/l
What is the positive predictive value of the new test?
Sodium depletion, renal loss (patient often hypovolaemic)
A. 19/20 • diuretics: thiazides, loop diuretics
B. 723/743 • Addison's disease
C. 19/39 • diuretic stage of renal failure
D. 19/33
E. 723/737 Patient often euvolaemic
• SIADH (urine osmolality > 500 mmol/kg)
ANSWER: • hypothyroidism
19/39
Urinary sodium < 20 mmol/l
EXPLANATION:
Positive predictive value = true positives / (true positives + Sodium depletion, extra-renal loss
false positives) • diarrhoea, vomiting, sweating
• burns, adenoma of rectum
= 19 / (19 + 20)
Water excess (patient often hypervolaemic and oedematous)
Please see Q-8 for Screening Test Statistics • secondary hyperaldosteronism: heart failure, liver
cirrhosis
Q-43 • reduced GFR: renal failure
A 25-year-old man presents to endocrinology clinic for
• IV dextrose, psychogenic polydipsia
review. He has been referred with a sodium of 130mmol/L.
He feels well in himself and denies any systemic symptoms
Q-44
and specifically has no headaches or neurological symptoms.
Which one of the following causes of primary
He has been passing normal volumes of urine. He has a past
immunodeficiency is a T-cell disorder?
medical history of familial hypercholesterolemia and is
under review by a metabolic team as he still has a total
A. Chediak-Higashi syndrome
cholesterol of 9.1mmol/L. Paired osmolalities are normal.
B. Chronic granulomatous disease
Urine dipstick test is normal. His examination is largely
C. Common variable immunodeficiency
normal apart from evidence of xanthomas. U&E, FBC, LFTs
D. DiGeorge syndrome
are normal. What is the most likely diagnosis?
E. Wiskott-Aldrich syndrome
A. Pseudohyponatraemia
ANSWER:
B. Nephrogenic SIADH
DiGeorge syndrome
C. Cranial SIADH
D. Diabetes insipidus
EXPLANATION:
E. Type two diabetes mellitus
DiGeorge syndrome - a T-cell disorder
DiGeorge syndrome is a primary immunodeficiency disorder
ANSWER:
caused by T-cell deficiency and dysfunction. It is an example
Pseudohyponatraemia
of a microdeletion syndrome. Patients are consequently at
increased risk of viral and fungal infections.
EXPLANATION:
The correct answer is pseudo hyponatraemia. This is a
Please see Q-25 for DiGeorge Syndrome
patient with clinical and biochemical evidence of very high
cholesterol levels in addition to his mild hyponatraemia. The
Q-45
A 43-year-old man has a routine medical for insurance ANSWER:
purposes. The following result is obtained: Rubella

Uric acid622 µmol/l (210 - 480) EXPLANATION:

Congenital rubella
He is well with no significant past medical history. What is • sensorineural deafness
the most appropriate test to perform next? • congenital cataracts

A. Lipid profile CONGENITAL INFECTIONS

B. Thyroid function test The major congenital infections encountered in examinations
C. Calcium are rubella, toxoplasmosis and cytomegalovirus
D. Parathyroid hormone
E. Pyrophosphate levels Cytomegalovirus is the most common congenital infection in
the UK. Maternal infection is usually asymptomatic
ANSWER:
Lipid profile Rubella Toxoplasmosis Cytomegalovirus
Characteristic Sensorineural Cerebral calcification Growth retardation
EXPLANATION: features deafness Chorioretinitis Purpuric skin lesions
Hyperuricaemia may be associated with both Congenital cataracts Hydrocephalus
Congenital heart
hyperlipidaemia and hypertension. It may also be seen in
disease (e.g. patent
conjunction with the metabolic syndrome ductus arteriosus)
Glaucoma
HYPERURICAEMIA Other features Growth retardation Anaemia Sensorineural
Increased levels of uric acid may be seen secondary to either Hepatosplenomegaly Hepatosplenomegaly deafness
increased cell turnover or reduced renal excretion of uric acid. Purpuric skin lesions Cerebral palsy Encephalitis/seizures
'Salt and pepper' Pneumonitis
Hyperuricaemia may be found in asymptomatic patients who chorioretinitis Hepatosplenomegaly
have not experienced attacks of gout Microphthalmia Anaemia
Cerebral palsy Jaundice
Hyperuricaemia may be associated with hyperlipidaemia and Cerebral palsy
hypertension. It may also be seen in conjunction with the
metabolic syndrome Q-47
Which one of the following is true regarding bacterial
Increased synthesis exotoxins?
• Lesch-Nyhan disease
• myeloproliferative disorders A. They are mainly produced by Gram positive bacteria
• diet rich in purines B. Cholera toxin inhibits cAMP release in intestinal cells
• exercise C. Diphtheria toxin necrosis is limited to the pharynx,
• psoriasis nasopharynx and tonsils
D. Staph. sureus exotoxins are not known to cause
• cytotoxics
gastroenteritis
E. 'Lockjaw' seen in tetanus is secondary to blockade of the
Decreased excretion
neuromuscular junction by Botulinus toxin
• drugs: low-dose aspirin, diuretics, pyrazinamide
• pre-eclampsia
ANSWER:
• alcohol
They are mainly produced by Gram positive bacteria
• renal failure
• lead EXPLANATION:
EXOTOXINS AND ENDOTOXINS
Q-46 Exotoxins are secreted by bacteria where as endotoxins are
Which one of the following congenital infections is most only released following lysis of the cell. Exotoxins are
characteristically associated with sensorineural deafness? generally released by Gram positive bacteria with the notable
exceptions of Vibrio cholerae and some strains of E. coli
A. Toxoplasma gondii
B. Parvovirus B19 It is possible to classify exotoxins by their primary effects:
C. Rubella • pyrogenic toxins
D. Treponema pallidum
• enterotoxins
E. Group B streptococcus
• neurotoxins Organism Toxin Notes
• tissue invasive toxins Staphylococcus Exfoliatin Staphylococcal scalded skin
aureus syndrome
• miscellaneous toxins

Pyrogenic toxins Miscellaneous toxins

Pyrogenic toxins stimulate the release of endogenous
Organism Toxin Notes
cytokines resulting in fever, rash etc. They are superantigens
Corynebacterium Diphtheria ADP ribosylates elogation factor (EF-2), resulting
which bridge the MHC class II protein on antigen-presenting
diphtheriae toxin in inhibition, causing a 'diphtheric membrane'
cells with the T cell receptor on the surface of T cells resulting on tonsils caused by necrotic mucosal cells.
in massive cytokine release. Systemic distribution may produce necrosis of
myocardial, neural and renal tissue
Organism Toxin Notes Pseudomonas Exotoxin A Also inhibits EF-2 by the same mechanism as
Staphylococcus Toxic shock syndrome Results in high fever, aeruginosa above
aureus (TSST-1 superantigen) toxin hypotension, exfoliative rash Bacillus anthracis Oedema Forms a calmodulin-dependent adenylate
Streptococcus Streptococcal pyrogenic Results in scarlet fever factor (EF) cyclase which increases cAMP, impairing the
pyogenes exotoxin A & C function of neutrophils/macrophages →
reduced phagocytosis
Bordetella Pertussis Inhibits Gi leading to increases in cAMP levels,
Enterotoxins pertussis exotoxin impairing the function of
neutrophils/macrophages → reduced
• Enterotoxins act on the gastrointestinal tract causing one phagocytosis
of two patterns of illness:
diarrhoeal illness Endotoxins
• vomiting illness ('food poisoning') Endotoxins are lipopolysaccharides that are released from
Gram-negative bacteria such as Neisseria meningitidis.
Organism Toxin Notes
Vibrio cholerae Cholera toxin Causes activation of adenylate cyclase Q-48
(via Gs) leading to increases in cAMP A 52-year-old has a fasting lipid profile checked as part of an
levels, which in turn leads to increased annual occupational health check. Combined with his blood
chloride secretion and reduced sodium
pressure and current smoking status his 10-year risk of
absorption
cardiovascular disease is calculated to be 23% percent.
Shigella Shiga toxin Inactivates 60S ribosome → epithelial
dysenteriae cell death Following appropriate counselling he chooses to start
Escherichia coli 1. Heat labile toxin 1. Activates adenylate cyclase (via Gs), atorvastatin 20mg. He is followed up 3 months later when a
increasing cAMP → watery diarrhoea full lipid profile is repeated. What should his target be?
2. Heat stabile toxin
2. Activates guanylate cyclase, increasing
A. A greater than 40% reduction in non-HDL cholesterol
cGMP → watery diarrhoea
B. Total cholesterol < 5 mmol/l
Staphylococcus Staphylococcus Vomiting and diarrhoeal illness lasting <
aureus aureusenterotoxin 24 hours C. Target cholesterol is inappropriate in this situation
Bacillus cereus Cereulide Potent cytotoxin that destroys D. Total cholesterol < 4 mmol/l
mitochondria. Causes a vomiting illness E. Total cholesterol:HDL ratio < 4
which may present within 4 hours of
ingestion ANSWER:
A greater than 40% reduction in non-HDL cholesterol
Neurotoxins
Neurotoxins act on the nerves (tetanus) or the neuromuscular EXPLANATION:
junction (botulism) causing paralysis. In the primary prevention of CVD using statins aim for a
reduction in non-HDL cholesterol of > 40%
Organism Toxin Notes
Clostridium Tetanospasmin Blocks the release of the inhibitory neurotransmitters HYPERLIPIDAEMIA: MANAGEMENT
tetani GABA and glycine resulting in continuous motor neuron
activity → continuous muscle contraction → lockjaw and
In 2014 NICE updated their guidelines on lipid modification.
respiratory paralysis This proved highly controversial as it meant that we should be
Clostridium Botulinum Blocks acetylcholine (ACh) release leading to flaccid recommending statins to a significant proportion of the
botulinum toxin paralysis population over the age of 60 years. Anyway, the key points of
the new guidelines are summarised below.
Tissue invasive toxins

Organism Toxin Notes

Clostridium α-toxin, a Causes gas gangrene (myonecrosis)
perfringens lecithinase and haemolysis

Primary prevention - who and how to assess risk
A systematic strategy should be used to identify people aged
over 40 years who are likely to be at high risk of
cardiovascular disease (CVD), defined as a 10-year risk of 10%
or greater.
NICE recommend we use the QRISK2 CVD risk assessment tool
for patients aged <= 84 years. Patients >= 85 years are at high
risk of CVD due to their age. QRISK2 should not be used in the
following situations as there are more specific guidelines for
these patient groups:
• type 1 diabetics
• patients with an estimated glomerular filtration rate
(eGFR) less than 60 ml/min and/or albuminuria
• patients with a history of familial hyperlipidaemia
NICE suggest QRISK2 may underestimate CVD risk in the
following population groups:
• people treated for HIV
• people with serious mental health problems
• people taking medicines that can cause dyslipidaemia
such as antipsychotics, corticosteroids or
immunosuppressant drugs
• people with autoimmune disorders/systemic
inflammatory disorders such as systemic lupus
erythematosus
Measuring lipid levels
When measuring lipids both the total cholesterol and HDL
should be checking to provide the most accurate risk of CVD.
A full lipid profile should also be checked (i.e. including
triglycerides) before starting a statin. The samples does not
need to be fasting.
In the vast majority of patient the cholesterol measurements
will be fed into the QRISK2 tool. If however the patient's
cholesterol is very high we should consider familial
hyperlipidaemia. NICE recommend the following that we
should consider the possibility of familial
hypercholesterolaemia and investigate further if the total
cholesterol concentration is > 7.5 mmol/l and there is a family
history of premature coronary heart disease. They also
recommend referring people with a total cholesterol > 9.0
mmol/l or a non-HDL cholesterol (i.e. LDL) of > 7.5 mmol/l
even in the absence of a first-degree family history of
premature coronary heart disease.
Interpreting the QRISK2 result
Probably the headline changes in the 2014 guidelines was the
new, lower cut-off of 10-year CVD risk cut-off of 10%.
NICE now recommend we offer a statin to people with a
QRISK2 10-year risk of >= 10%
Lifestyle factors are of course important and NICE recommend
that we give patients the option of having their CVD risk
reassessed after a period of time before starting a statin.
Atorvastatin 20mg should be offered first-line.
Special situations
Type 1 diabetes mellitus
• NICE recommend that we 'consider statin treatment for
the primary prevention of CVD in all adults with type 1
diabetes'
• atorvastatin 20 mg should be offered if type 1 diabetics
who are:
→ older than 40 years, or
→ have had diabetes for more than 10 years or
→ have established nephropathy or
→ have other CVD risk factors
Chronic kidney disease (CKD)
• atorvastatin 20mg should be offered to patients with CKD
• increase the dose if a greater than 40% reduction in non-
HDL cholesterol is not achieved and the eGFR > 30
ml/min. If the eGFR is < 30 ml/min a renal specialist
should be consulted before increasing the dose
Secondary prevention
All patients with CVD should be taking a statin in the absence
of any contraindication.
Atorvastatin 80mg should be offered first-line.
Follow-up of people started on statins
NICE recommend we follow-up patients at 3 months
• repeat a full lipid profile
• if the non-HDL cholesterol has not fallen by at least 40%
concordance and lifestyle changes should be discussed
with the patient
• NICE recommend we consider increasing the dose of
atorvastatin up to 80mg
Lifestyle modifications
These are in many ways predictable but NICE make a number
of specific points:
Cardioprotective diet
• total fat intake should be <= 30% of total energy intake
• saturated fats should be <= 7% of total energy intake
• intake of dietary cholesterol should be < 300 mg/day
• saturated fats should be replaced by monounsaturated
and polyunsaturated fats where possible
• replace saturated and monounsaturated fat intake with
olive oil, rapeseed oil or spreads based on these oils
• choose wholegrain varieties of starchy food
• reduce their intake of sugar and food products containing
refined sugars including fructose
• eat at least 5 portions of fruit and vegetables per day
• eat at least 2 portions of fish per week, including a
portion of oily fish
• eat at least 4 to 5 portions of unsalted nuts, seeds and
legumes per week
Physical activity
• each week aim for at least 150 minutes of moderate
intensity aerobic activity or 75 minutes of vigorous
intensity aerobic activity or a mix of moderate and
vigorous aerobic activity
• do musclestrengthening activities on 2 or more days a
week that work all major muscle groups (legs, hips, back,
abdomen, chest, shoulders and arms) in line with national
guidance for the general population
Weight management
• no specific advice is given, overweight patients should be
managed in keeping with relevant NICE guidance
Alcohol intake
• again no specific advice, other than the general
recommendation that males drink no more than 3-4
units/day and females no more than 2-3 units/day
Smoking cessation
• smokers should be encouraged to quit
Q-49
A 62-year-old man presents to the cardiology clinic for
review some 6 weeks after suffering an anterior myocardial
infarction. His medication has been optimised, his blood
pressure is 122/82 mmHg, pulse is 67 beats per minute and
regular. LDL cholesterol is 1.4 mmol/l, hsCRP is 15mg/l.
Which of the following medications has been shown to
impact on future risk of myocardial infarction in patients like
this?
A. Canakinumab
B. Prednisolone
C. Infliximab
D. Rituximab
E. Methotrexate
ANSWER:
Canakinumab
EXPLANATION:
Modulating inflammation can reduce ischaemic
cardiovascular events
Canakinumab is an anti-IL1 monoclonal antibody, which has
been shown to reduce systemic inflammation. In patients
who have an elevated CRP of >2mg/l, (as here), patients in
the CANTOS trial who had suffered a previous MI were
treated with canakinumab. Those patients treated with
canakinumab in addition to standard of care had a 15%
reduction in major adverse cardiovascular events versus
those treated with standard of care alone. This trial has
established 'proof of concept' for modulating inflammation
in those patients at increased risk of cardiovascular disease.
https://www.nejm.org/doi/full/10.1056/NEJMoa1707914?q
uery=OF
There is some evidence that use of anti-TNF agents used in
the treatment of rheumatic disease may be associated with
reduced incidence of cardiovascular events, although this is
from post-hoc statistical analyses. Infliximab is therefore not
the correct answer here. There is no evidence of
cardiovascular benefit from any of the other agents listed,
(prednisolone, rituximab or methotrexate).
Please see Q-22 for Atherosclerosis
Q-50
A 27-year-old female presents to her General Practitioner
with severe morning headaches associated with nausea. She
is referred for an MRI head scan that reveals a large tumour
arising from the falx cerebri and pushing on the brain. There
is a well-defined border between the tumour and the brain
parenchyma.
What is the most likely diagnosis?
A. Glioblastoma
B. Metastasis
C. Low-grade glioma
D. Meningioma
E. Craniopharyngioma
ANSWER:
Meningioma
EXPLANATION:
Meningiomas are typically benign tumours that develop
from the dura mater of the meninges
Meningiomas are typically benign tumours that arise from
the cap cells of the dura mater of the meninges. They are
extra-axial lesions, meaning they do not arise from the brain
parenchyma. They do not invade the brain substance, but
rather cause symptoms by compression.
Q-51 Type of tumour Features
A 27-year-old female presents to her General Practitioner adults
with severe morning headaches associated with nausea. She
• Meningiomas are typically benign, extrinsic tumours of
is referred for an MRI head scan that reveals a large tumour
the central nervous system. They arise from the dura
arising from the falx cerebri and pushing on the brain. There mater of the meninges and cause symptoms by
is a well-defined border between the tumour and the brain compression rather than invasion.
parenchyma.
• They typically are located at the falx cerebri, superior
sagittal sinus, convexity or skull base.
What is the most likely diagnosis?
• Histology: Spindle cells in concentric whorls and calcified
A. Glioblastoma psammoma bodies
B. Metastasis
• Investigation is with CT and MRI, and treatment will
C. Low-grade glioma involve either observation, radiotherapy or surgical
D. Meningioma resection.
E. Craniopharyngioma Vestibular • A vestibular schwannoma (previously termed acoustic
schwannoma neuroma) is a benign tumour arising from the eighth
ANSWER: cranial nerve (vestibulocochlear nerve). Often seen in the
cerebellopontine angle. It presents with hearing loss, facial
Meningioma
nerve palsy (due to compression of the nearby facial
nerve) and tinnitus.
EXPLANATION:
Meningiomas are typically benign tumours that develop • Neurofibromatosis type 2 is associated with bilateral
from the dura mater of the meninges vestibular schwannomas.

Meningiomas are typically benign tumours that arise from
the cap cells of the dura mater of the meninges. They are
extra-axial lesions, meaning they do not arise from the brain
parenchyma. They do not invade the brain substance, but
rather cause symptoms by compression.
BRAIN TUMOURS
The majority of adult tumours are supratentorial, where as
the majority of childhood tumours are infratentorial.
Type of tumour Features
• Histology: Antoni A or B patterns are seen. Verocay
bodies (acellular areas surrounded by nuclear palisades)
• Treatment may involve observation, radiotherapy or
surgery.
Pilocytic astrocytoma • The most common primary brain tumour in children
• Histology: Rosenthal fibres (corkscrew eosinophilic
bundle)
Medulloblastoma • A medulloblastoma is an aggressive paediatric brain
tumour that arises within the infratentorial compartment.
It spreads through the CSF system. Treatment is surgical
with and chemotherapy.

Metastases Metastatic brain cancer is the most common form of brain

• Histology: Small, blue cells. Rosette pattern of cells with
tumours. They are often multiple and not treatable with
many mitotic figures
surgical intervention.
Ependymoma • Commonly seen in the 4th ventricle
Tumours that most commonly spread to the brain include: • May cause hydrocephalus
• Histology: perivascular pseudorosettes
Oligodendroma • Benign, slow-growing tumour common in the frontal
lobes
• breast • Histology: Calcifications with 'fried-egg' appearance
• lung Haemangioblastoma • Vascular tumour of the cerebellum
• bowel • Associated with von Hippel-Lindau syndrome
• skin (namely melanoma) • Histology: foam cells and high vascularity
• kidney Pituitary adenoma • Pituitary adenomas are benign tumours of the pituitary
gland. They are either secretory (producing a hormone in
excess) or non-secretory. They may be divided into
Gliolastoma • Glioblastoma is the most common primary tumour in microadenomas (smaller than 1cm) or macroadenoma
multiforme adults and is associated with a poor prognosis (~ 1yr). (larger than 1cm).

• On imaging they are solid tumours with central necrosis
and a rim that enhances with contrast. Disruption of the
blood-brain barrier and therefore are associated with
vasogenic oedema.
• Histology: Pleomorphic tumour cells border necrotic
areas
• Treatment is surgical with postoperative chemotherapy
and/or radiotherapy. Dexamethasone is used to treat the
Craniopharyngioma • Most common paediatric supratentorial tumour
oedema.
Meningioma • The second most common primary brain tumour in
• Patients will present with the consequences of hormone
excess (e.g. Cushing’s due to ACTH, or acromegaly due to
GH) or depletion. Compression of the optic chiasm will
cause a bitemporal hemianopia due to the crossing nasal
fibers.
• Investigation requires a pituitary blood profile and MRI.
Treatment can either be hormonal or surgical (e.g.
transphenoidal resection).
 Type of tumour Features
• A craniopharyngioma is a solid/cystic tumour of the
sellar region that is derived from the remnants of Rathke’s
pouch. It is common in children, but can present in adults
also. It may present with hormonal disturbance,
symptoms of hydrocephalus or bitemporal hemianopia.
• Histology: Derived from remnants of Rathke pouch
• Investigation requires pituitary blood profile and MRI.
Treatment is typically surgical with or without
postoperative radiotherapy.
A. Demonstrate the heterogeneity of a meta-analysis
B. Demonstrate the existence of publication bias in meta-
analyses
C. Provide a graphical representation of the relative risk
results in a case-control study
D. Provide a graphical representation of the relative risk
results in a cohort study
E. Provide a graphical representation of the probability of
a patient experiencing a particular adverse effect
ANSWER:
Demonstrate the existence of publication bias in meta-
analyses

EXPLANATION:
Funnel plots - show publication bias in meta-analyses

Funnel plot
A funnel plot is primarily used to demonstrate the existence of
publication bias in meta-analyses. Funnel plots are usually
drawn with treatment effects on the horizontal axis and study
size on the vertical axis.

Meningioma - MRI showing the typical well-circumscribed appearance. A dural tail can
be where the tumour 'connects' to the dura. It is seen in around 65% of meningiomas.
Interpretation
• a symmetrical, inverted funnel shape indicates that
publication bias is unlikely
• conversely, an asymmetrical funnel indicates a
relationship between treatment effect and study size.
This indicates either publication bias or a systematic
difference between smaller and larger studies ('small
study effects')
Q-53
As part of a research project you are trying to ascertain
whether the use of dummies in infants is linked to sudden
infant death syndrome. What is the most appropriate form
of study design?

A. Randomised controlled trial

B. Cross-over trial
C. Cross-sectional survey
D. Case-control study
E. Cohort study

ANSWER:
Case-control study

EXPLANATION:
As sudden infant death syndrome is relatively rare a case-
control design is more appropriate than a cohort study.
Glioblastoma multiforme - CT showing a peripherally enhancing lesion within the left
frontal lobe. Note the contrast to the more homogenous meningioma above. STUDY DESIGN
The following table highlights the main features of the main
Q-52 types of study:
What are funnel plots primarily used for?
 • Congenital adrenal hyperplasia
Study type Key features • Cystic fibrosis
Randomised Participants randomly allocated to intervention or control • Cystinuria
controlled trial group (e.g. standard treatment or placebo) • Familial Mediterranean Fever
Practical or ethical problems may limit use
• Fanconi anaemia
Cohort study Observational and prospective. Two (or more) are selected • Friedreich's ataxia
according to their exposure to a particular agent (e.g. • Gilbert's syndrome*
medicine, toxin) and followed up to see how many develop a • Glycogen storage disease
disease or other outcome.
• Haemochromatosis
The usual outcome measure is the relative risk. • Homocystinuria
• Lipid storage disease: Tay-Sach's, Gaucher, Niemann-Pick
Examples include Framingham Heart Study • Mucopolysaccharidoses: Hurler's
Case-control Observational and retrospective. Patients with a particular
• PKU
study condition (cases) are identified and matched with controls.
Data is then collected on past exposure to a possible causal • Sickle cell anaemia
agent for the condition. • Thalassaemias
• Wilson's disease
The usual outcome measure is the odds ratio.

Inexpensive, produce quick results *this is still a matter of debate and many textbooks will list
Useful for studying rare conditions Gilbert's as autosomal dominant
Prone to confounding
Cross-sectional Provide a 'snapshot', sometimes called prevalence studies Q-55
survey
An 18-year-old female is admitted with a headache,
Provide weak evidence of cause and effect
photophobia, fever and confusion. She is managed with
empirical antibiotics. What is the mechanism of action of the
Q-54
most commonly used first line antibiotic class?
Which of the following conditions is inherited in an
autosomal recessive fashion?
A. Inhibition of RNA polymerase
B. Inhibition of cell wall synthesis
A. Hypokalaemic periodic paralysis
C. Inhibition of DNA gyrase
B. Adult polycystic disease
D. Inhibition of the ribosome
C. Huntington's disease
E. Inhibition of folate synthesis
D. Friedreich's ataxia
E. Ehlers-Danlos syndrome
ANSWER:
Inhibition of cell wall synthesis
ANSWER:
Friedreich's ataxia
EXPLANATION:
Cephalosporins act by inhibiting cell wall formation
EXPLANATION:
The correct answer is inhibition of cell wall synthesis. The
Autosomal recessive conditions are 'metabolic' - exceptions:
first line antibiotics for possible bacterial meningitis are
inherited ataxias
cephalosporins. Penicillins, cephalosporins, carbapenems and
monobactams all act via inhibition of cell wall synthesis.
Autosomal dominant conditions are 'structural' - exceptions:
Gilbert's, hyperlipidaemia type II
ANTIBIOTICS: MECHANISM OF ACTION
The lists below summarise the site of action of the commonly
AUTOSOMAL RECESSIVE CONDITIONS
used antibiotics
Autosomal recessive conditions are often thought to be
'metabolic' as opposed to autosomal dominant conditions
Inhibit cell wall formation
being 'structural', notable exceptions:
• penicillins
some 'metabolic' conditions such as Hunter's and G6PD are X-
• cephalosporins
linked recessive whilst others such as hyperlipidemia type II
and hypokalemic periodic paralysis are autosomal dominant
Inhibit protein synthesis
some 'structural' conditions such as ataxia telangiectasia and
• aminoglycosides (cause misreading of mRNA)
Friedreich's ataxia are autosomal recessive
• chloramphenicol
The following conditions are autosomal recessive: • macrolides (e.g. erythromycin)
• Albinism • tetracyclines
• Ataxic telangiectasia • fusidic acid
 • Ecchymosis
Inhibit DNA synthesis • Poor wound healing
• quinolones (e.g. ciprofloxacin) • Gingivitis with bleeding and receding gums
• metronidazole • Sjogren's syndrome
• sulphonamides • Arthralgia
• trimethoprim • Oedema
• Impaired wound healing
Inhibit RNA synthesis • Generalised symptoms such as weakness, malaise,
• rifampicin anorexia and depression

Q-56 Q-57
A 43-year-old homeless lady has been referred to Which one of the following conditions is usually inherited in
gastroenterology as the GP was concerned of a possible a X-linked dominant fashion?
malabsorption syndrome. She complains of weakness and
longstanding diarrhoea. On examination you note enlarged A. Albinism
and bleeding gums. She takes no medications. B. Hurler's syndrome
C. Ataxia telangiectasia
Which of the following deficiency syndromes can lead to D. Homocystinuria
gum hypertrophy? E. Alport's syndrome

A. Pellagra ANSWER:
B. Beri-Beri Alport's syndrome
C. Menkes Disease
D. Scurvy EXPLANATION:
E. Osteomalacia Alport's syndrome is inherited in a X-linked dominant fashion
in around 85% of cases
ANSWER:
Scurvy X-LINKED DOMINANT
The following conditions are inherited in a X-linked dominant
EXPLANATION: fashion*:
Scurvy causes gum hypertrophy
The answer is scurvy - caused by vitamin C deficiency. Alport's syndrome (in around 85% of cases - 10-15% of cases
Patients classically can present with gingivitis, non-healing are inherited in an autosomal recessive fashion with rare
ulcers, myalgia and even convulsions. autosomal dominant variants existing)
Rett syndrome
Other important causes of gingivitis include pregnancy, Vitamin D resistant rickets
acute promyelocytic leukaemia and drugs such as phenytoin,
ciclosporin and nifedipine. *pseudohypoparathyroidism was previously classified as an X-
linked dominant condition but has now been shown to be
Pellagra is niacin (B3) deficiency, classically causing inherited in an autosomal dominant fashion in the majority of
dermatitis, diarrhoea and dementia. Beri-Beri is caused by cases.
thiamine deficiency (B1) and is further categorised into wet
(predominantly high output heart failure) and dry Q-58
(predominantly neuropathic). Menkes Disease is a rare Which one of the following is not associated with
congenital disorder of copper metabolism leading to copper hypocalcaemia combined with a raised phosphate level?
deficiency and osteomalacia is vitamin D deficiency.
A. Chronic renal failure
VITAMIN C DEFICIENCY (SCURVY) B. Pseudohypoparathyroidism
Vitamin C is found in citrus fruits, tomatoes, potatoes, Brussel C. Hypoparathyroidism
sprouts, cauliflower, broccoli, cabbage and spinach. Deficiency D. Osteomalacia
leads to impaired collagen synthesis and disordered E. Acute rhabdomyolysis
connective tissue. It is associated with severe malnutrition as
well as drug and alcohol abuse, and those living in poverty ANSWER:
with limited access to fruits and vegetables. Osteomalacia

Symptoms and signs include: EXPLANATION:

• Follicular hyperkeratosis and perifollicular haemorrhage Osteomalacia causes hypocalcaemia associated with a low
serum phosphate, rather than a raised phosphate level.
 • generally classed as 'acyanotic'. However, uncorrected
Please see Q-32 for Hypocalcaemia: Causes and can eventually result in late cyanosis in the lower
Management extremities, termed differential cynaosis.
• connection between the pulmonary trunk and descending
Q-59 aorta
Which one of the following cell types secretes the majority • more common in premature babies, born at high altitude
of pulmonary surfactant? or maternal rubella infection in the first trimester

A. Type II pneumoncytes
B. Kupffer cells
C. Type I pneumoncytes
D. Macrophages
E. Elastocytes

ANSWER:
Type II pneumoncytes

EXPLANATION:
PULMONARY SURFACTANT
Surfactant is a mixture of phospholipids, carbohydrates and
proteins released by type 2 pneumocytes. The main
functioning component is dipalmitoyl phosphatidylcholine
(DPPC) which reduces alveolar surface tension.

Basics Features
• first detectable around 28 weeks • left subclavicular thrill
• as alveoli decrease in size, surfactant concentration is • continuous 'machinery' murmur
increased, helping prevent the alveoli from collapsing • large volume, bounding, collapsing pulse
• reduces the muscular force needed to expand the lungs • wide pulse pressure
(i.e. decreases the work of breathing) • heaving apex beat
• lowers the elastic recoil at low lung volumes and thus
helps to prevent the alveoli from collapsing at the end of Management
each expiration • indomethacin closes the connection in the majority of
cases
Q-60 • if associated with another congenital heart defect
A 1-year-old girl is noted to have a continuous murmur, amenable to surgery then prostaglandin E1 is useful to
loudest at the left sternal edge. She is not cyanosed. A keep the duct open until after surgical repair
diagnosis of patent ductus arteriosus is suspected. What
pulse abnormality is most associated with this condition? Q-61
Which of the following statements is true regarding
A. Collapsing pulse autosomal dominant inheritance?
B. Bisferiens pulse
C. Pulsus parodoxus A. Individuals who are symptomatic of the disease always
D. 'Jerky' pulse have parents who are symptomatic of the disease
E. Pulsus alternans B. Only heterozygotes manifest disease
C. 50% of children will be carriers
ANSWER: D. Responsible for the majority of enzyme deficiency
Collapsing pulse disorders
E. The risk remains the same for each successive pregnancy
EXPLANATION:
Patent ductus arteriosus - large volume, bounding, collapsing ANSWER:
pulse The risk remains the same for each successive pregnancy

PATENT DUCTUS ARTERIOSUS EXPLANATION:

Due to non-penetrance affected individuals do not always
Overview have affected parents
• a form of congenital heart defect
AUTOSOMAL DOMINANT Phase Description Mechanism
In autosomal dominant diseases: 4 Restoration of ionic Resting potential is restored by Na+/K+ ATPase
• both homozygotes and heterozygotes manifest disease concentrations There is slow entry of Na+ into the cell decreasing the
potential difference until the threshold potential is
(there is no carrier state) reached, triggering a new action potential
• both males and females affected
• only affected individuals can pass on disease NB cardiac muscle remains contracted 10-15 times longer
• disease is passed on to 50% of children than skeletal muscle
• normally appears in every generation (although see
below) Conduction velocity
• risk remains same for each successive pregnancy Site Speed
Atrial Spreads along ordinary atrial myocardial fibres at 1 m/sec
Complicating factors: conduction
• non-penetrance: lack of clinical signs and symptoms AV node 0.05 m/sec
(normal phenotype) despite abnormal gene. E.g. 40% conduction

otosclerosis Ventricular Purkinje fibres are of large diameter and achieve velocities of 2-4
conduction m/sec (this allows a rapid and coordinated contraction of the
• spontaneous mutation: new mutation in one of gametes ventricles
e.g. 80% of individuals with achondroplasia have
unaffected parents Q-63
You are discussing conception with two parents who both
Q-62 have achondroplasia. They ask you what the chances are
Which of the following is responsible for the rapid that a child of theirs would be of normal height. What is the
depolarisation phase of the myocardial action potential? correct response?

A. Rapid sodium influx A. 0%

B. Slow sodium efflux B. 25%
C. Slow efflux of calcium C. 50% independent of gender
D. Efflux of potassium D. 50% if male
E. Rapid calcium influx E. 75%

ANSWER: ANSWER:
Rapid sodium influx 25%

EXPLANATION: EXPLANATION:
CARDIAC ACTION POTENTIAL Many questions relating to autosomal dominant conditions
are based around one of the parents being affected. With
achondroplasia both parents are often affected which can
make the interpretation slightly trickier.

As an autosomal dominant condition, two affected parents

can expect:
• 1 in 4 chance of an unaffected child
• 1 in 2 chance of an affected heterozygous child
• 1 in 4 chance of an affected homozygous child. With
achondroplasia children unfortunately don't live past the
first few months of life

The answer of having a child of normal height is therefore 1

in 4 or 25%.

Phase Description
0 Rapid depolarisation
1 Early repolarisation
2 Plateau
3 Final repolarisation
ACHONDROPLASIA
Achondroplasia is an autosomal dominant disorder associated
Mechanism with short stature. It is caused by a mutation in the fibroblast
Rapid sodium influx growth factor receptor 3 (FGFR-3) gene. This results in
These channels automatically deactivate after a few msabnormal cartilage giving rise to:
Efflux of potassium • short limbs (rhizomelia) with shortened fingers
Slow influx of calcium (brachydactyly)
Efflux of potassium
• large head with frontal bossing and narrow foramen organ rejection. Which cells are primarily responsible for
magnum this?
• midface hypoplasia with a flattened nasal bridge
• 'trident' hands A. Helper T Cells
• lumbar lordosis B. Neutrophils
C. Eosinophils
In most cases (approximately 70%) it occurs as a sporadic D. Macrophages
mutation. The main risk factor is advancing parental age at the E. B Cells
time of conception. Once present it is typically inherited in an
autosomal dominant fashion. ANSWER:
B Cells
Treatment
There is no specific therapy. However, some individuals EXPLANATION:
benefit from limb lengthening procedures. These usually B cells mediate hyperacute organ rejection
involve application of Ilizarov frames and targeted bone B Cells mediate hyperacute organ rejection. Helper T cells
fractures. A clearly defined need and end point is the mediate both acute and chronic rejection. Macrophages and
cornerstone of achieving success with such procedures. neutrophils may be seen due to local inflammation but are
not chiefly responsible for mediating hyperacute organ
Q-64 rejection. Eosinophils do not play a role in transplant
Which one of the following statements regarding leptin is rejection
incorrect?
IMMUNE SYSTEM CELLS: ADAPTIVE IMMUNE RESPONSE
A. Is produced mainly by the hypothalamus
B. Stimulates the release of melanocyte-stimulating The following cells are mostly involved in the adaptive
hormone immune response:
C. Obese patients have higher leptin levels
D. Plays a key role in the regulation of body weight Cell type Functions and properties
E. High levels decrease appetite Helper T cells Involved in the cell-mediated immune response
Recognises antigens presented by MHC class II molecules
Expresses CD4
ANSWER: Also expresses CD3, TCR & CD28
Is produced mainly by the hypothalamus Major source of IL-2
Mediates acute and chronic organ rejection
EXPLANATION: Cytotoxic T cells Involved in the cell-mediated immune response
Recognises antigens presented by MHC class I molecules
Leptin is secreted by adipose tissue
Induce apoptosis in virally infected and tumour cells
Expresses CD8
OBESITY: PHYSIOLOGY Also expresses CD3, TCR
Leptin Mediates acute and chronic organ rejection
Leptin is thought to play a key role in the regulation of body B cells Major cell of the humoral immune response
weight. It is produced by adipose tissue and acts on satiety Acts as an antigen presenting cell
Mediates hyperacute organ rejection
centres in the hypothalamus and decreases appetite. More
Plasma cells Differentiated from B cells
adipose tissue (e.g. in obesity) results in high leptin levels. Produces large amounts of antibody specific to a particular
antigen
Leptin stimulates the release of melanocyte-stimulating
hormone (MSH) and corticotrophin-releasing hormone (CRH). Q-66
Low levels of leptin stimulates the release of neuropeptide Y Which one of the following is only secreted by the adrenal
(NPY) medulla?

Ghrelin A. Noradrenaline
Where as leptin induces satiety, ghrelin stimulates hunger. It B. Aldosterone
is produced mainly by the P/D1 cells lining the fundus of the C. Metadrenaline
stomach and epsilon cells of the pancreas. Ghrelin levels D. Cortisol
increase before meals and decrease after meals E. Adrenaline

Q-65 ANSWER:
A female with severe renal failure undergoes a kidney Adrenaline
transplant. After a few hours, the patient develops a fever
and stops passing urine. It is suspected she has hyperacute EXPLANATION:
ADRENAL MEDULLA PE diagnosed No PE
The adrenal medulla secretes virtually all the adrenaline in the Test negative 10 55
body as well as secreting small amounts of noradrenaline. It
essentially represents an enlarged and specialised The sensitivity is therefore 30 / (30 + 10) = 75%
sympathetic ganglion
Please see Q-8 for Screening Test Statistics
Q-67
Which one of the following is associated with increased lung Q-69
compliance? Which part of the renal tubule is impermeable to water?

A. Kyphosis A. Distal convoluted tubule

B. Pulmonary oedema B. Connecting tubule
C. Emphysema C. Descending limb of loop of Henle
D. Pulmonary fibrosis D. Thin ascending limb of loop of Henle
E. Pneumonectomy E. Thick ascending limb of loop of Henle

ANSWER: ANSWER:
Emphysema Thin ascending limb of loop of Henle

EXPLANATION: EXPLANATION:
RESPIRATORY PHYSIOLOGY: LUNG COMPLIANCE The thin ascending limb of the loop of Henle is impermeable
Lung compliance is defined as change in lung volume per unit to water
change in airway pressure The thin ascending limb is impermeable to water, but highly
permeable to sodium and chloride ions.
Causes of increased compliance
• age RENAL PHYSIOLOGY
• emphysema - this is due to loss alveolar walls and
associated elastic tissue Overview
• each nephron is supplied with blood from an afferent
Causes of decreased compliance arteriole that opens onto the glomerular capillary bed
• pulmonary oedema • blood then flows to an efferent arteriole, supplying the
• pulmonary fibrosis peritubular capillaries and medullary vasa recta
• pneumonectomy • the kidney receives up to 25% of resting cardiac output
• kyphosis

Q-68
A new test to screen for pulmonary embolism (PE) is used in Control of blood flow
100 patients who present to the Emergency Department. • the kidney is able to autoregulate its blood flow between
The test is positive in 30 of the 40 patients who are proven systolic pressures of 80-180mmHg so there is little
to have a PE. Of the remaining 60 patients, only 5 have a variation in renal blood flow
positive test. What is the sensitivity of the new test? • this is achieved by myogenic control of arteriolar tone,
both sympathetic input and hormonal signals (e.g. renin)
A. 8.33% are responsible
B. 30% • renal cortical blood flow > medullary blood flow (i.e.
C. 40% tubular cells more prone to ischaemia)
D. 66.66%
E. 75% Glomerular structure and function
• blood inside the glomerulus has considerable hydrostatic
ANSWER: pressure
75% • the basement membrane has pores that will allow free
diffusion of smaller solutes, larger negatively charged
EXPLANATION: molecules such as albumin are unable to cross
A contingency table can be constructed from the above data,
• the glomerular filtration rate (GFR) is equal to the
as shown below:
concentration of a solute in the urine, times the volume
of urine produced per minute, divided by the plasma
PE diagnosed No PE
concentration (assuming that the solute is freely diffused
Test positive 30 5
e.g. inulin)
• in clinical practice creatinine is used because it is
subjected to very little proximal tubular secretion
• although subject to variability, the typical GFR is 125ml
per minute
• glomerular filtration rate = Total volume of plasma per
unit time leaving the capillaries and entering the
Bowman's capsule
• renal clearance = volume plasma from which a substance
is removed per minute by the kidneys
Substances used to measure GFR have the following features:
1. Inert
2. Free filtration from the plasma at the glomerulus (not
protein bound)
3. Not absorbed or secreted at the tubules
4. Plasma concentration constant during urine collection
examples: inulin, creatinine
GFR = ( urine concentration (mmol/l) x urine volume (ml/min)
) / plasma concentration (mmol/l)
• the clearance of a substance is dependent not only on its
diffusivity across the basement membrane but also
subsequent tubular secretion and / or reabsorption
• so glucose which is freely filtered across the basement
membrane is usually reabsorbed from tubules giving a
clearance of zero
Tubular function
• reabsorption and secretion of substances occurs in the
tubules
• in the proximal tubule substrates such as glucose, amino
acids and phosphate are co-transported with sodium
across the semi permeable membrane
• up to two thirds of filtered water is reabsorbed in the
proximal tubules
• this will lead to increase in urea concentration in the
distal tubule allowing for its increased diffusion
• substances to be secreted into the tubules are taken up
from the peritubular blood by tubular cells
• solutes such as para-aminohippuric acid are cleared with
a single passage through the kidneys and this is why it is
used to measure renal plasma flow. Ions such as calcium
and phosphate will have a tubular reabsorption that is
influenced by plasma PTH levels
• potassium may be both secreted and reabsorbed and is
co-exchanged with sodium
Loop of Henle
• approximately 60 litres of water containing 9000mmol
sodium enters the descending limb of the loop of Henle in
24 hours
• loops from the juxtamedullary nephrons run deep into
the medulla
• the osmolarity of fluid changes and is greatest at the tip
of the papilla
• the thin ascending limb is impermeable to water, but
highly permeable to sodium and chloride ions
• this loss means that at the beginning of the thick
ascending limb the fluid is hypo osmotic compared with
adjacent interstitial fluid
• in the thick ascending limb the reabsorption of sodium
and chloride ions occurs by both facilitated and passive
diffusion pathways
• the loops of Henle are co-located with vasa recta, these
will have similar solute compositions to the surrounding
extracellular fluid so preventing the diffusion and
subsequent removal of this hypertonic fluid
• the energy dependent reabsorption of sodium and
chloride in the thick ascending limb helps to maintain this
osmotic gradient
Q-70
During a newborn physical examination, a paediatrician
notes cleft palate, low-set ears and a holo-systolic murmur
along the left lower sternal border. Blood tests show
hypocalcaemia and chest x-ray reveals an absent thymic
shadow and a 'boot-shaped' heart. Further investigations
confirm a ventricular septal defect, right ventricular
hypertrophy and an overriding aorta.
Which of the following congenital heart diseases is most
likely present in this newborn?
A. Total anomalous pulmonary venous return
B. Transposition of great vessels
C. Aortic coarctation
D. Tetralogy of Fallot
E. Tricuspid atresia
ANSWER:
Tetralogy of Fallot
EXPLANATION:
Cardiac abnormalities of DiGeorge syndrome include truncus
arteriosus and tetralogy of Fallot
This patient has a primary immunodeficiency disorder,
DiGeorge syndrome, which is also known as 22q11.2 deletion
syndrome. It is highly associated with Tetralogy of Fallot and
truncus arteriosus.
'CATCH22' is a mnemonic used to describe some of the key
features of this condition:
C - Cardiac abnormalities
A - Abnormal facies
T - Thymic aplasia
C - Cleft palate
H - Hypocalcaemia/ hypoparathyroidism
22 - Caused by chromosome 22 deletion
Please see Q-25 for DiGeorge Syndrome
Q-71
A new oral-hypoglycaemic is being developed. A number of
different study types are considered to demonstrate efficacy
in reducing the HbA1c. Which one of the following study C. RNA translation to protein
designs would require the most patients to produce a D. RNA amplification
significant result? E. DNA to RNA conversion

A. Equivalence trial ANSWER:

B. Non-inferiority trial DNA amplification
C. Superiority trial
D. Placebo-controlled trial EXPLANATION:
E. Study design would not affect the number of patients Please see Q-6 for Polymerase Chain Reaction
required
Q-73
ANSWER: What level of evidence does a study offer which is obtained
Superiority trial from a meta-analysis of randomised controlled trials?

EXPLANATION: A. Ia
As a superiority trial compares the new drug with an existing B. Ib
treatment, which would also lower HbA1c, a large sample C. IIa
size is required to demonstrate a significant difference. D. IIb
E. IV
STUDY DESIGN: NEW DRUGS
When a new drug is launched there are a number of options ANSWER:
available in terms of study design. One option is a placebo Ia
controlled trial. Whilst this may provide robust evidence it
may be considered unethical if established treatments are EXPLANATION:
available and it also does not provide a comparison with STUDY DESIGN: EVIDENCE AND RECOMMENDATIONS
standard treatments. Levels of evidence
• Ia - evidence from meta-analysis of randomised
If a drug is therefore to be compared to an existing treatment controlled trials
a statistician will need to decide whether the trial is intended • Ib - evidence from at least one randomised controlled
to show superiority, equivalence or non-inferiority: trial
• superiority: whilst this may seem the natural aim of a trial • IIa - evidence from at least one well designed controlled
one problem is the large sample size needed to show a trial which is not randomised
significant benefit over an existing treatment • IIb - evidence from at least one well designed
• equivalence: an equivalence margin is defined (-delta to experimental trial
+delta) on a specified outcome. If the confidence interval • III - evidence from case, correlation and comparative
of the difference between the two drugs lies within the studies
equivalence margin then the drugs may be assumed to • IV - evidence from a panel of experts
have a similar effect
• non-inferiority: similar to equivalence trials, but only the Grading of recommendation
lower confidence interval needs to lie within the • Grade A - based on evidence from at least one
equivalence margin (i.e. -delta). Small sample sizes are randomised controlled trial (i.e. Ia or Ib)
needed for these trials. Once a drug has been shown to • Grade B - based on evidence from non-randomised
be non-inferior large studies may be performed to show controlled trials (i.e. IIa, IIb or III)
superiority • Grade C - based on evidence from a panel of experts (i.e.
IV)
It should be remembered that drug companies may not
necessarily want to show superiority over an existing product. Q-74
If it can be demonstrated that their product is equivalent or A 28-year-old female with a history of primary amenorrhoea
even non-inferior then they may compete on price or and short stature is reviewed in clinic. On examination blood
convenience. pressure in her right arm is 175/84 mmHg and 170/82 mmHg
in her left. What is the most likely cause for her elevated
Q-72 blood pressure?
Which one of the following best describes the main action of
A. Coarctation of the aorta
the polymerase chain reaction?
B. Conn's syndrome
C. Essential hypertension
A. DNA identification using RNA
D. Renal aplasia
B. DNA amplification
E. Renal artery stenosis
 the corneal findings are characteristic of cornea verticillata,
ANSWER: both of which are suggestive fabry's disease. None of the
Coarctation of the aorta other 4 options presents with such characteristic clinical
EXPLANATION: signs.
Turner's syndrome is associated with aortic coarctation
This patient has Turner's syndrome which is associated with Fabry's disease is an X-linked recessive disorder
coarctation of the aorta. The site of the coarctation, for characterised by abnormal deposits of a particular fatty
example if it involves the origin of the left subclavian artery, substance called globotriaosylceramide in blood vessel walls
determines whether there is a difference between the right throughout the body. The primary defect which allows this to
and left arm blood pressure readings. There is no significant occur is the inherited deficiency of the enzyme, alpha-
difference in this case. galactosidase A, which is normally responsible for the
breakdown of globotriaosylceramide.
Another cause worth considering in a young hypertensive
patient with primary amenorrhoea would be congenital This abnormal accumulation of fatty substance results in the
adrenal hyperplasia narrowing of blood vessels and a whole range of symptoms
and signs which include:
Essential hypertension would be unusual in a 28-year-old
• Limb pain
Please see Q-16 for Turner’s Syndrome • Sensory neuropathy
• Raynaud's disease
Q-75 • Cardiac arrhythmias, cardiomyopathy
A 35-year-old male presents to the clinic with bilateral • Nephrotic syndrome
pitting oedema, lower limb pain and tingling in both arms. • Dermatological manifestation; angiokeratomas,
On examination, tiny, painless papules were noticed on his anhidrosis, cornea verticillata
abdomen and a whorl-like corneal pattern of cream-
coloured lines in the patient's cornea. He has no significant Please see Q-40 for Anderson-Fabry Disease
past medical history.
Q-76
Hb 131 g/l Na+ 137 mmol/l A 24-year-old man is investigated for visual loss and is
Platelets 330 * 109/l K+ 4.7 mmol/l diagnosed as having Leber's optic atrophy. Given the
WBC 7.2 * 109/l Urea 12.9 mmol/l mitochondrial inheritance of this condition, which one of the
Neuts 3.7 * 109/l Creatinine 150 µmol/l following relatives is most likely to be also affected?
Lymphs 1.9 * 109/l CRP 12 mg/l

C3 1.49 g/l A. Daughter

C4 0.3 g/l B. Sister
Anti-nuclear antibodies negative C. Son
Anti-neutrophil cytoplasmic antibodies negative D. Paternal uncle
E. Father
His urine dip showed proteinuria and the 24 hour protein
urine collection was quantified at 1.8 gram/day. What is the ANSWER:
most likely diagnosis? Sister

A. Gaucher's disease EXPLANATION:

B. Hypercholesterolaemia Mitochondrial diseases follow a maternal inheritance
C. Fabry's disease pattern
D. Amyloidosis All the children of an affected mother will inherit a
E. IgA nephropathy mitochondrial condition. His sister will therefore also be
affected.
ANSWER:
Fabry's disease MITOCHONDRIAL DISEASES
Whilst most DNA is found in the cell nucleus, a small amount
EXPLANATION: of double-stranded DNA is present in the mitochondria. It
The patient presented with nephrotic syndrome and sensory encodes protein components of the respiratory chain and
neuropathy bilaterally in the arms. Of the above options, some special types of RNA
Fabry's disease and amyloidosis can present as such. The
painless papules on the abdomen are angiokeratomas and Mitochondrial inheritance has the following characteristics:
• inheritance is only via the maternal line as the sperm
contributes no cytoplasm to the zygote
• all children of affected males will not inherit the disease
• all children of affected females will inherit it
• generally encode rare neurological diseases
• poor genotype:phenotype correlation - within a tissue or
cell there can be different mitochondrial populations -
this is known as heteroplasmy)

Histology
• muscle biopsy classically shows 'red, ragged fibres' due to
increased number of mitochondria

Examples include:
• Leber's optic atrophy
• MELAS syndrome: mitochondrial encephalomyopathy
lactic acidosis and stroke-like episodes
• MERRF syndrome: myoclonus epilepsy with ragged-red
fibres
• Kearns-Sayre syndrome: onset in patients < 20 years old,
external ophthalmoplegia, retinitis pigmentosa. Ptosis
may be seen
• sensorineural hearing loss

Q-77 An illustration model of the HIV Replication Cycle. Each step of the cycle is numbered
and concisely described. Credit: NIAID
Which one of the following immunological changes is seen in
progressive HIV infection?
Q-78
Haematuria is suspected by the presence of red or brown
A. Increase in IL-2 production
urine. It may be visible macroscopically (gross haematuria)
B. Increase in B2-microglobulin levels
or detectable in the urine sediment by microscopy. It is often
C. Increased type IV hypersensitivity responses
a symptom of an underlying disease, most of them treatable,
D. Increased natural killer (NK) cell function
so that is extremely important to do a clinical approach in
E. A rise in the CD4/CD8 ratio
order to identify its cause. Which of the following data
enhances the possibility that haematuria is of glomerular
ANSWER:
origin?
Increase in B2-microglobulin levels
A. Initial haematuria
EXPLANATION:
B. Dysmorphic red blood cells found on urine microscopy
HIV: IMMUNOLOGY
C. Haematuria plus pyuria
The following immunological changes are seen in progressive
D. Mono-symptomatic haematuria
HIV:
E. Fresh blood in urine with presence of clots
• reduction in CD4 count
• increase B2-microglobulin
ANSWER:
• decreased IL-2 production
Dysmorphic red blood cells found on urine microscopy
• polyclonal B-cell activation
• decrease NK cell function EXPLANATION:
• reduced delayed hypersensitivity responses Dysmorphic red blood cells if found in urine sediment
indicates a glomerular origin of hematuria
Abnormalities in the shape of red cells in the urine
(dysmorphism) indicates a glomerular origin of hematuria.

Initial haematuria and presence of fresh blood usually

indicates lower urinary bleeding, such as urethral bleeding.

Pyuria indicates infection or inflammatory disease but not

necessary of a glomerular origin.
 EXPLANATION:
If a mono-symptomatic haematuria is noted in a middle age HLA ASSOCIATIONS
patient, in the absence of infection, a bladder tumour should HLA antigens are encoded for by genes on chromosome 6.
be ruled out. HLA A, B and C are class I antigens whilst DP, DQ, DR are class
II antigens. Questions are often based around which diseases
URINARY CASTS have strong HLA associations. The most important
The table below lists the most common causes of the different associations are listed below:
types of urinary cast:
HLA-A3
Type of cast Associated conditions • haemochromatosis
Red blood cell casts Glomerulonephritis
Renal ischaemia and infarction HLA-B5
White blood cell casts Acute pyelonephritis • Behcet's disease
Interstitial nephritis
Granular ('muddy-brown') casts Acute tubular necrosis
HLA-B27
Hyaline casts Common and non-specific
May be seen following exercise or
• ankylosing spondylitis
dehydration • Reiter's syndrome
Epithelial casts Acute tubular necrosis • acute anterior uveitis
Waxy casts Advanced chronic kidney disease
Fatty casts Nephrotic syndrome HLA-DQ2/DQ8
• coeliac disease
Q-79
A 31-year-old woman is diagnosed with familial HLA-DR2
hypercholesterolaemia. Genetic testing shows that she is • narcolepsy
heterozygous for the condition. You discuss the possibility of • Goodpasture's
screening her relatives. What is the chance her brother will
also be affected? HLA-DR3
• dermatitis herpetiformis
A. 50% • Sjogren's syndrome
B. 66% • primary biliary cirrhosis
C. 25%
D. 100% HLA-DR4
E. 0% • type 1 diabetes mellitus*
• rheumatoid arthritis
ANSWER:
50% *type 1 diabetes mellitus is associated with HLA-DR3 but is
more strongly associated with HLA-DR4.
EXPLANATION:
As familial hypercholesterolaemia is an autosomal dominant
Q-81
condition 50% of the first-degree relatives of heterozygotes
Which of the following conditions is NOT inherited in a X-
will be affected. Please see the PLoS link for more details.
linked recessive fashion:
Please see Q-33 for Familial Hypercholesterolaemia
A. Myotonic dystrophy
Q-80 B. G6PD deficiency
Which one of the following diseases is most strongly C. Haemophilia B
associated with HLA antigen DR2? D. Colour blindness
E. Fabry's disease
A. Behcet's disease
B. Type 1 diabetes mellitus ANSWER:
C. Coeliac disease Myotonic dystrophy
D. Haemochromatosis EXPLANATION:
E. Narcolepsy X-linked conditions: Duchenne/Becker, haemophilia, G6PD
ANSWER: X-LINKED RECESSIVE CONDITIONS
Narcolepsy The following conditions are inherited in a X-linked recessive
fashion:
Androgen insensitivity syndrome confidence interval at the 95% confidence level means that
Becker muscular dystrophy the confidence interval should contain the true effect of
Colour blindness intervention 95% of the time.
Duchenne muscular dystrophy
Fabry's disease How is the confidence interval calculated?
G6PD deficiency
Haemophilia A,B The standard error of the mean (SEM) is a measure of the
Hunter's disease spread expected for the mean of the observations - i.e. how
Lesch-Nyhan syndrome 'accurate' the calculated sample mean is from the true
Nephrogenic diabetes insipidus population mean
Ocular albinism
Retinitis pigmentosa Key point
Wiskott-Aldrich syndrome • SEM = SD / square root (n)
• where SD = standard deviation and n = sample size
The following diseases have varying patterns of inheritance, • therefore the SEM gets smaller as the sample size (n)
with the majority being in an X-linked recessive fashion: increases

Chronic granulomatous disease (in > 70%) A 95% confidence interval:

Q-82
A small study looks at the weight of patients diagnosed with
type 2 diabetes mellitus. Overall 64 patients were reviewed.
The average weight was 81 kg, with a standard deviation of
12 kg. What is the standard error of the mean?
A. Square root (64 / 12)
B. Square root (81 / 12)
C. 12 / 9
D. 9 / 12
E. 1.5
ANSWER:
1.5
EXPLANATION:
Standard error of the mean = standard deviation / square
root (number of patients)
The standard error of the mean is calculated by the standard
deviation / square root (number of patients)
= 12 / square root (64) = 12 / 8 = 1.5
CONFIDENCE INTERVAL AND STANDARD ERROR OF THE
MEAN
The confidence interval is a common and sometimes
misunderstood principle in medical statistics.
a formal definition may be: a range of values for a variable of
interest constructed so that this range has a specified
probability of including the true value of the variable. The
specified probability is called the confidence level, and the
end points of the confidence interval are called the
confidence limits*
in simpler terms: a range of values within which the true
effect of intervention is likely to lie
• lower limit = mean - (1.96 * SEM)
• upper limit = mean + (1.96 * SEM)
The above formula is a slight simplification:
• if a small sample size is used (e.g. n < 100) then it is
important to use a 'Student's T critical value' look-up
table to replace 1.96 with a different value
• if a different confidence level is required, e.g. 90% then
1.96 is replaced by a different value. For 90% this would
1.645
Results such as mean value are often presented along with a
confidence interval. For example, in a study the mean height
in a sample taken from a population is 183cm. You know that
the standard error (SE) (the standard deviation of the mean) is
2cm. This gives a 95% confidence interval of 179-187cm (+/- 2
SE).
Q-83
Whilst reviewing a patient's drug card you notice that you
prescribed the wrong dose of atenolol when the patient was
initially clerked. Instead of 25mg atenolol od you prescribed
50mg atenolol od. She has received the incorrect dose on
two occasions. On examining Mrs Smith you note her blood
pressure and pulse are normal. Mrs Smith has a past history
of anxiety and describes herself as a 'worrier'. What is the
most appropriate action?
A. Complete an entry in your e-portfolio
B. Apologise to the patient + complete a clinical incident
form
C. Complete a clinical incident form + avoid telling patient
to prevent unnecessary anxiety
D. Fill out a 'yellow card'
E. Keep her on the higher dose as she is suffering no ill
effects

The likelihood of the true effect lying within the confidence ANSWER:
interval is determined by the confidence level. For example a Apologise to the patient + complete a clinical incident form
 also recommend antibiotics if severe symptoms (high
EXPLANATION: fever, bloody diarrhoea, or more than eight stools per
In this scenario the patient appears to have come to no harm day) or symptoms have last more than one week
following the error. This should not however change your • the first-line antibiotic is clarithromycin
approach to the situation. The patient should be informed of
what has happened, an apology should be made and Complications
reassurance give that there appears to be no ill effects. By • Guillain-Barre syndrome may follow Campylobacter jejuni
completing a clinical incident form you add to a body of data infections
which may in the long term change to practice. • Reiter's syndrome
• septicaemia, endocarditis, arthritis
An entry to your e-portfolio at least shows that you both
acknowledge and are willing to learn from the error. The Q-85
yellow card system is intended to report side-effects from Each of the following organisms commonly cause respiratory
drugs rather than prescription errors and hence is fairly tract infections in patients with cystic fibrosis, except:
pointless.
A. Aspergillus
The dose of a drug a patient takes should be based on clinical B. Pseudomonas aeruginosa
need rather than a reluctance to acknowledge an error. C. Burkholderia cepacia
D. Staphylococcal aureus
Q-84 E. Strongyloides stercoralis
A 54-year-old woman with a history of rheumatoid arthritis
presents with a one week history of bloody diarrhoea. This ANSWER:
has been associated with fever and abdominal pain. Her Strongyloides stercoralis
rheumatoid is normally well controlled with methotrexate. A
stool sample is sent which shows Campylobacter jejuni. EXPLANATION:
What is the most appropriate management? CYSTIC FIBROSIS
Cystic fibrosis (CF) is an autosomal recessive disorder causing
A. Fluids alone increased viscosity of secretions (e.g. lungs and pancreas). It is
B. Fluids + metronidazole due to a defect in the cystic fibrosis transmembrane
C. Fluids + ciprofloxacin conductance regulator gene (CFTR), which codes a cAMP-
D. Fluids + clarithromycin regulated chloride channel
E. Fluids + mebendazole
In the UK 80% of CF cases are due to delta F508 on the long
ANSWER: arm of chromosome 7. Cystic fibrosis affects 1 per 2500 births,
Fluids + clarithromycin and the carrier rate is c. 1 in 25

EXPLANATION: Organisms which may colonise CF patients

This lady is immunocompromised on methotrexate and a • Staphylococcus aureus
severe infection (fever, bloody diarrhoea and prolonged • Pseudomonas aeruginosa
history). She should therefore be given an antibiotic. The BNF • Burkholderia cepacia*
advise clarithromycin first-line. • Aspergillus

CAMPYLOBACTER *previously known as Pseudomonas cepacia

Campylobacter is the commonest bacterial cause of infectious
intestinal disease in the UK. The majority of cases are caused Q-86
by the Gram-negative bacillus Campylobacter jejuni. It is A 74-year-old female is admitted with central chest pain. She
spread by the faecal-oral route and has an incubation period states that the pain comes on with exertion and is relived by
of 1-6 days. rest. She has a past medical history of hypertension.
Features
ECG results:
• prodrome: headache malaise
ECG T wave inversion in V4-V6
• diarrhoea: often bloody
• abdominal pain: may mimic appendicitis
Blood results:
Management Troponin I 0.02 ng/ml (normal <0.07)
• usually self-limiting
Which molecule does troponin I bind to?
• the BNF advises treatment if severe or the patient is
immunocompromised. Clinical Knowledge summaries
A. Neuromuscular junction A. IL-1
B. Calcium ions B. IL-3
C. Actin C. IL-4
D. Myosin D. Tumour necrosis factor-α
E. Sarcoplasmic reticulum E. Interferon-γ

ANSWER: ANSWER:
Actin Interferon-γ

EXPLANATION: EXPLANATION:
Troponin I binds to actin to hold the troponin-tropomyosin Interferon-γ is responsible for activating macrophages
complex in place Interferon-γ is a cytokine released from Th1 cells and is
Troponin I binds to actin to hold the troponin-tropomyosin responsible for activating macrophages. Tuberculosis elicits
complex in place. the release of Interferon-γ from T-cells and this is the reason
macrophages are tied to its pathology.
The clinical features are suggestive of stable angina. The T
wave inversion in the lateral leads gives further evidence to IL-2 is secreted from macrophages. IL-3 stimulates the
ischaemic heart disease. The normal troponin I rules out a proliferation and differentiation of myeloid progenitor cells.
myocardial infarction. IL-4 is responsible for the proliferation of B cells. Tumour
necrosis factor-α is responsible for acute fevers and
Cardiac myocytes do not have a neuromuscular junction. neutrophil chemotaxis.
They communicate with each other via gap junctions.
CYTOKINES
Troponin C binds to calcium ions. Interleukins
Cytokine Main sources Functions
Myosin is the thick component of muscle fibres. Actin slides IL-1 Macrophages Acute inflammation
along myosin to generate muscle contraction. Induces fever
IL-2 Th1 cells Stimulates growth and
differentiation of T cell response
The sarcoplasmic reticulum regulates the calcium ion
IL-3 Activated T helper cells Stimulates differentiation and
concentration in the cytoplasm of striated muscle cells proliferation of myeloid
progenitor cells
Please see Q-2 for Troponin IL-4 Th2 cells Stimulates proliferation and
differentiation of B cells
Q-87 IL-5 Th2 cells Stimulate production of
Where is somatostatin secreted from? eosinophils
IL-6 Macrophages, Th2 cells Stimulates differentiation of B
cells
A. D cells in the pancreas Induces fever
B. I cells in upper small intestine IL-8 Macrophages Neutrophil chemotaxis
C. K cells in upper small intestine IL-10 Th2 Inhibits Th1 cytokine production
D. S cells in upper small intestine cells Also known as human cytokine
E. G cells in stomach synthesis inhibitory factor and is an
'anti-inflammatory' cytokine
ANSWER: IL-12 Dendritic cells, macrophages, B Activates NK cells and stimulates
D cells in the pancreas cells differentiation of naive T cells
into Th1 cells
EXPLANATION:
D cells are also found in the stomach and intestine Other cytokines
Cytokine Main sources Functions
Please see Q-18 for Gastrointestinal Hormones Tumour necrosis factor-α Macrophages Induces fever
Neutrophil chemotaxis
Q-88
Interferon-γ Th1 cells Activates macrophages
A 34-year-old male comes into the GP complaining of
haemoptysis. He notes that he wakes up at night due to
Q-89
waking up in a pool of sweat and mentions he recently
Which of the following conditions is inherited in a X-linked
returned from a holiday in Pakistan. The GP suspects
recessive fashion?
tuberculosis and refers him to a respiratory physician. Which
of the following cytokines is primarily responsible for
A. Androgen insensitivity syndrome
activating macrophages?
B. Myotonic dystrophy
C. von Willebrand's disease Features
D. Ehlers-Danlos syndrome • failure to thrive
E. Huntington's disease • normal serum calcium, low phosphate, elevated alkaline
phosphotase
ANSWER: • x-ray changes: cupped metaphyses with widening of the
Androgen insensitivity syndrome epiphyses

EXPLANATION: Diagnosis is made by demonstrating increased urinary

X-linked conditions: Duchenne/Becker, haemophilia, G6PD phosphate

Please see Q-81 for X-Linked Recessive Conditions Management

• high-dose vitamin D supplements
Q-90 • oral phosphate supplements
A follow-up study is performed looking at the height of 100
adults who were given steroids during childhood. The Q-92
average height of the adults is 169cm, with a standard A new drug which may reduce the chance of patients with
deviation of 16cm. What is the standard error of the mean? chronic kidney disease developing gout is introduced. In one
study of 2,000 patients 1,200 received the new drug of which
A. Cannot be calculated 120 patients develop gout. The remaining 800 patients
B. 1.69 received a placebo of which 200 developed gout. What is the
C. 0.16 absolute risk reduction of developing gout?
D. 1.6
E. 1.3 A. 0.1
B. 15%
ANSWER: C. 120
1.6 D. 25%
E. 6.66
EXPLANATION:
Standard error of the mean = standard deviation / square ANSWER:
root (number of patients) 15%
The standard error of the mean is calculated by the standard
deviation / square root (number of patients) EXPLANATION:
Absolute risk reduction = (Control event rate) - (Experimental
= 16 / square root (100) = 16 / 10 = 1.6 event rate)
Absolute risk reduction = (Experimental event rate) - (Control
Please see Q-82 for Confidence Interval and Standard Error of event rate)
the Mean
Control event rate = 200 / 800 = 0.25
Q-91
Experimental event rate = 120 / 1,200 = 0.1
Which one of the following statements regarding vitamin D-
resistant rickets is false?
Absolute risk reduction = 0.25 - 0.1 = 0.15 = 15% reduction
A. Management includes the use of high-dose vitamin D
NUMBERS NEEDED TO TREAT AND ABSOLUTE RISK
supplements
REDUCTION
B. Is a X-linked dominant condition
Numbers needed to treat (NNT) is a measure that indicates
C. X-ray changes include cupped metaphyses
how many patients would require an intervention to reduce
D. Failure to thrive may be seen
the expected number of outcomes by one
E. Decreased urinary phosphate is characteristic
It is calculated by 1/(Absolute risk reduction) and is rounded
ANSWER:
to the next highest whole number
Decreased urinary phosphate is characteristic
Experimental event rate (EER) = (Number who had particular
EXPLANATION:
outcome with the intervention) / (Total number who had the
VITAMIN D-RESISTANT RICKETS
intervention)
Vitamin D-resistant rickets is a X-linked dominant condition
which usually presents in infancy with failure to thrive. It is Control event rate (CER) = (Number who had particular
caused by impaired phosphate reabsorption in the renal outcome with the control/ (Total number who had the
tubules control)
Absolute risk reduction = CER-EER or EER-CER?
The absolute risk reduction (ARR) may be calculated by finding
the absolute difference between the control event rate (CER)
and the experimental event rate (EER). You will often find
both versions of the above listed in different sources. In some
ways in doesn't matter which you use as you will end up with
the same answer but from a technical point of view:
• if the outcome of the study is undesirable then ARR = CER
- EER
• if the outcome of the study is desirable then ARR* = EER -
CER
*this may be more accurately termed absolute benefit
increase, rather than absolute risk reduction
Q-93
A study looks at whether golf actually increases the risk of
medial epicondylitis. Sixty people who regularly play golf are
matched to sixty people who do not play golf. Thirty of the
golfers had developed medial epicondylitis at some point
compared to ten of the non-golfers.
What is the odds ratio of developing medial epicondylitis for
people who play golf?
A. 0.3
B. 3 Huntington's disease. Which one of the following best
C. 5 describes the concept of anticipation?
D. 2.5
E. 3.33
ANSWER:
5 C. More severe disease in successive generations
EXPLANATION:
Remember to calculate the odds, rather than risk, initially:
Odds of a golfer developing medial epicondylitis = 30 / 30 =
1. If we were calculating the risk, rather than the odds that is
asked for, it would be 30 / 60 = 0.5.
Odds a non-golfer developing medial epicondylitis = 10 / 50 =
0.2. Again, the risk would be 10/60 = 0.16.
The odds ratio is therefore = 1 / 0.2 = 5
ODDS AND ODDS RATIO
Odds are a ratio of the number of people who incur a
particular outcome to the number of people who do not incur
the outcome. The odds ratio may be defined as the ratio of
the odds of a particular outcome with experimental treatment
and that of control.
Odds vs. probability
In contrast, probability is the fraction of times you'd expect to
see an event in many trials. When expressed as a single
number probability is always between 0 and 1. So, if we take
the example of rolling a dice:
the probability of rolling a six is 1/6 or 0.166666
the odds of rolling a six is 1/5 or 0.2
Odds ratios are the usual reported measure in case-control
studies. It approximates to relative risk if the outcome of
interest is rare.
For example, if we look at a trial comparing the use of
paracetamol for dysmenorrhoea compared to placebo we
may get the following results
Total number of patients Achieved = 50% pain relief
Paracetamol 60 40
Placebo 90 30
The odds of achieving significant pain relief with paracetamol
= 40 / 20 = 2
The odds of achieving significant pain relief with placebo = 30
/ 60 = 0.5
Therefore the odds ratio = 2 / 0.5 = 4
Q-94
A 25-year-old man is counselled regarding the genetics of
A. The psychological effect of a patient knowing they will
develop an incurable condition
B. Earlier age of onset in successive generations
D. Where there is a known history of inherited conditions,
patients may attribute symptoms to the onset of the
disease
E. Screening at risk families to allow early intervention and
improve outcomes
ANSWER:
Earlier age of onset in successive generations
EXPLANATION:
Anticipation in trinucleotide repeat disorders = earlier onset
in successive generations
Difficult question. In the exam both B and C were given as
choices. The 'classic' definition of anticipation is earlier onset
in successive generations. However, in most cases, an
increase in the severity of symptoms is also noted. If both
options are presented then B should be chosen, as this
represents the more accepted definition of anticipation.
What do you think?
Please see Q-12 for Trinucleotide Repeat Disorders
Q-95 • Mental Capacity Act: (MCA) used in patients who require
A 77-year-old woman who lives alone is assessed. She has a treatment physical disorders that affect brain function.
history of Alzheimer's disease. Her neighbours are Remember this may be delirium secondary to sepsis or a
increasingly concerned about her behaviour - they often see primary brain disorder such as dementia
her wandering around outside in an apparently confused • Mental Health Act (MHA): used in patients who require
state. You feel she may need a care package or residential treatment for mental disorders. For patients already
care but she refuses to countenance such a proposal. What is admitted to hospital, a section 5(2) is used if there is not
the most appropriate legal framework to use to approach the time for a more formal section 2 or 3. A typical
this issue? scenario would be a patient who has a mental health
disorder attempting to discharge themselves, when it is
A. Mental Health Act thought this may result in harm
B. Mental Capacity Act
C. Health and Social Care Act An excellent, more in-depth review can be found in the BMJ
D. Common law 'When and how to treat patients who refuse treatment'. BMJ
E. Professional Performance Act 2014;348;g2043

ANSWER: Q-96
Mental Capacity Act A 86-year-old gentleman on a care of the elderly ward he is
awaiting social care and is feeling well. The nurses have
EXPLANATION: asked you to review him as he is becoming increasingly
As this is not a mental health disorder the most appropriate confused. His clinical examination is normal. You order some
legal framework to use is the Mental Capacity Act. bloods:

The Mental Capacity Act of 2005 came into force in 2007. It Na+ 123 mmol/l
applies to adults over the age of 16 and sets out who can K+ 4.5 mmol/l
take decisions if a patient becomes incapacitated (e.g. Urea 3.6 mmol/l
following a stroke). Mental capacity includes the ability to Creatinine 91 µmol/l
make decisions affecting daily life, healthcare and financial
issues. In light of the low sodium, serum and urine osmolalities are
ordered. They are as follows:
The Act contains 5 key principles:
• A person must be assumed to have capacity unless it is Plasma osmolality 182 mOsmol/kg 285-295
established that he lacks capacity mOsmol/kg
• A person is not to be treated as unable to make a Urine osmolality 195 mOsmol/kg 500 - 800 mOsmol/kg
decision unless all practicable steps to help him to do so Urinary sodium concentration 51 mmol/l
have been taken without success
• A person is not to be treated as unable to make a
decision merely because he makes an unwise decision What is the most appropriate initial treatment?
• An act done, or decision made, under this Act for or on
behalf of a person who lacks capacity must be done, or A. Oral sodium tablets
made, in his best interests B. Fluid restrict
• Before the act is done, or the decision is made, regard C. IV saline
must be had to whether the purpose for which it is D. Increased dietary salt
needed can be as effectively achieved in a way that is E. Encourage oral fluids
less restrictive of the person's rights and freedom of
ANSWER:
action
Fluid restrict
PATIENTS WHO REFUSE TREATMENT
EXPLANATION:
Many patients who are admitted to hospital, or treated in the
SIADH is treated with fluid restriction
community, lack capacity. In the vast majority of cases, these
This patient has SIADH, the initial treatment is fluid
patients do not refuse treatment that is given that is deemed
restriction.
to be in their best interest. The problem arises when patients
who lack (or are suspected of lacking) capacity refuse Giving oral or IV salt would not treat his hyponatraemia as it
treatment. is caused by the dilutionary affect of increased ADH.
There are 3 main frameworks that are used in this scenario: Increasing his fluid intake would worsen his hyponatraemia
• common law: used to treat patients in emergency as you would dilute the sodium in his serum even further.
scenarios
 Q-98
Please see Q-35 for SIADH: Causes A 16-year-old girl attends your GP surgery due to concerns
about delayed menarche. On history, you note that there
Q-97 have been no developmental concerns. She is at the 65th
Which one of the following molecules acts as the co-receptor percentile for weight and 5th percentile for height. On
for cells expressing antigens combined with MHC class I examination, you note that she has a short webbed neck and
molecules? a broad chest. You perform karyotype analysis, which is
abnormal. What is the most common cardiac condition
A. CD4 associated with this presentation?
B. CD2b
C. CD1 A. Bicuspid aortic valve
D. CD8 B. Patent ductus arteriosus
E. CD2 C. Atrioventricular septal defect
D. Mitral valve prolapse
ANSWER: E. Tricuspid regurgitation
CD8
ANSWER:
EXPLANATION: Bicuspid aortic valve
CELL SURFACE PROTEINS
EXPLANATION:
The table below shows the most common cell surface proteins Turner's syndrome - most common cardiac defect is bicuspid
associated with particular cell types: aortic valve
Type of cell Cell surface markers Turner syndrome (45 XO) is associated with:
Haematopoietic stem cells CD34 • Bicuspid aortic valve
Helper T cell CD4, TCR, CD3, CD28 • Aortic root dilatation
Cytotoxic T cell CD8, TCR, CD3, CD28 • Coarctation of the aorta
Regulatory T cell CD4, CD25, TCR, CD3, CD28
B cell CD19, CD20, CD40, MHC II, B7 Please see Q-16 for Turner’s Syndrome
Macrophage CD14, CD40, MHC II, B7
Natural killer cell CD16, CD56 Q-99
Which of the following is not a tumour suppressor gene?
The table below lists the major clusters of differentiation (CD)
molecules and describes their function. A. p53
Cluster of B. APC
differentiation Function
C. NF-1
CD1 MHC molecule that presents lipid molecules
D. Rb
CD2 Found on thymocytes, T cells, and some natural killer
cells that acts as a ligand for CD58 and CD59 and is
E. myc
involved in signal transduction and cell adhesion
CD3 The signalling component of the T cell receptor (TCR) ANSWER:
complex myc
CD4 Found on helper T cells.
Co-receptor for MHC class II EXPLANATION:
Used by HIV to enter T cells
myc is an oncogene which encodes a transcription factor
CD5 Found in the majority of mantle cell lymphomas
CD8 Found on cytotoxic T cells.
Co-receptor for MHC class I
Please see Q-28 for Tumour Suppressor Genes
Found on a subset of myeloid dendritic cells
CD14 Cell surface marker for macrophages Q-100
CD15 Expressed on Reed-Sternberg cells (along with CD30) A 68-year-old man presents with headaches at the sides of
CD16 Bind to the Fc portion of IgG antibodies his head, worse on chewing and yawning. Which of the
CD21 Receptor for Epstein-Barr virus following findings would exclude giant cell arteritis?
CD28 Interacts with B7 on antigen presenting cell as
costimulation signal A. Presence of non-pulsatile temporal artery
CD45 Protein tyrosine phosphatase present on all leucocytes B. Normal plasma viscosity
CD56 Unique marker for natural killer cells C. No past medical history of polymyalgia rheumatica
CD95 Acts as the FAS receptor, involved in apoptosis D. Normal temporal artery biopsy
E. Normal temperature
 Q-101
ANSWER: Which one of the following diseases is most strongly
Normal plasma viscosity associated with HLA antigen DR4?

EXPLANATION: A. Ankylosing spondylitis

A normal temporal artery biopsy in a patient with suspected B. Behcet's disease
giant cell arteritis does not exclude the disease because of C. Reiter's syndrome
the potential for skip lesions D. Rheumatoid arthritis
The correct answer is normal plasma viscosity. Viscosity, ESR E. Coeliac disease
and CRP are almost invariably raised in patients with active
giant cell arteritis. A normal temporal artery biopsy would ANSWER:
make it less likely that he has GCA but is less reassuring than Rheumatoid arthritis
a normal viscosity because GCA can present in the temporal
artery with skip lesions. EXPLANATION:
Rheumatoid arthritis - HLA DR4
GCA is more common in patients with polymyalgia Around 70% of patients with rheumatoid arthritis are HLA-
rheumatica but can present alone. The temporal artery is DR4. Patients with Felty's syndrome (a triad of rheumatoid
likely to be thickened and non-pulsatile in GCA. arthritis, splenomegaly and neutropaenia) are even more
strongly associated with 90% being HLA-DR4
TEMPORAL ARTERY BIOPSY
• Superficial temporal artery is a terminal branch of the Please see Q-80 for HLA Associations
external carotid artery
Q-102
Main indication Which one of the following congenital infections is most
• Temporal arteritis characteristically associated with chorioretinitis?

American College of Rheumatology guidelines recommend a A. Cytomegalovirus

temporal artery biopsy if: B. Treponema pallidum
• Age of onset older than 50 years C. Rubella
• New-onset headache or localized head pain D. Toxoplasma gondii
• Temporal artery tenderness to palpation or reduced E. Parvovirus B19
pulsation
• ESR > 50 mm/h ANSWER:
Toxoplasma gondii
Histopathology
• Vessel wall granulomatous arteritis with mononuclear cell EXPLANATION:
infiltrates and giant cell formation Congenital toxoplasmosis
• cerebral calcification
Procedure • chorioretinitis
• Position: supine, head 45 degrees • A form of 'salt and pepper' chorioretinitis is also seen in
• USS doppler to locate the superficial temporal artery or congenital rubella but this is not a common feature.
palpate
• Local anaesthetic Chorioretinitis is found in around 75% of patients with
• Artery within temporoparietal fascia congenital toxoplasmosis.
• Clamp and ligate the vessel
Please see Q-46 for Congenital Infections
• Cut 3-5cm
• Ligate the remaining ends with absorbable suture
Q-103
• Close the skin
Which one of the following best describes the Bohr effect?
Contraindication A. Increase in pO2 means CO2 binds less well to Hb
• Glucocorticoid therapy > 30 days B. Decreasing acidity (or pCO2) means oxygen binds less
well to Hb
Risks C. Decrease in pO2 means CO2 binds less well to Hb
• Injury to facial or auriculotemporal nerve D. Raised 2,3-DPG enhances oxygen delivery to the tissues
E. Increasing acidity (or pCO2) means oxygen binds less
well to Hb
ANSWER: Q-105
Increasing acidity (or pCO2) means oxygen binds less well to Aldosterone is secreted by the:
Hb
A. Juxtaglomerular apparatus
EXPLANATION: B. Zona glomerulosa
RESPIRATORY PHYSIOLOGY C. Posterior pituitary
Chloride shift D. Zona reticularis
• CO2 diffuses into RBCs E. Zona fasciculata
• CO2 + H20 ---- carbonic anhydrase -→ HCO3- + H+
• H+ combines with Hb ANSWER:
• HCO3- diffuses out of cell,- Cl- replaces it Zona glomerulosa
Bohr effect
EXPLANATION:
• increasing acidity (or pCO2) means O2 binds less well to Adrenal cortex mnemonic: GFR - ACD
Hb

Haldane effect RENIN-ANGIOTENSIN-ALDOSTERONE SYSTEM

• increase pO2 means CO2 binds less well to Hb
Q-104
A 59-year-old male patient presents to the gastroenterology
clinic with a 6-month history of abdominal pain, diarrhoea
and weight loss. Gastroscopy reveals a gastrinoma in the
antrum of the stomach.
Adrenal cortex (mnemonic GFR - ACD)
• zona glomerulosa (on outside): mineralocorticoids, mainly
aldosterone
• zona fasciculata (middle): glucocorticoids, mainly cortisol
• zona reticularis (on inside): androgens, mainly
dehydroepiandrosterone (DHEA)

What is the function of the hormone secreted by this

tumour?

A. It increases HCL production and reduces gastric motility

B. It increases the secretion of pancreatic fluid
C. It inhibits HCL production and reduces gastric motility
D. It increases HCL production and increases gastric
motility
E. It inhibits HCL production and increases gastric motility

ANSWER:
It increases HCL production and increases gastric motility

EXPLANATION:
Gastrin increases HCL production and gastrointestinal
motility
Gastrinoma is a gastrin-secreting tumour. Gastrin increase
HCL production and gastrointestinal motility.
Renin
Options 1 is incorrect because gastrin actually decreases
gastric motility. • an enzyme that is released by the renal juxtaglomerular
cells in response to reduced renal perfusion
Option 2 is incorrect because gastrin doesn't increase the • other factors that stimulate renin secretion include
secretion of pancreatic fluid. VIP, CCK and secretin increases hyponatraemia, sympathetic nerve stimulation
the secretion of pancreatic fluid. • hydrolyses angiotensinogen to form angiotensin I

Option 3 is incorrect because gastrin increases HCL Angiotensin II

production and increases gastric motility.
Option 5 is incorrect because gastrin increases HCL
production.
Please see Q-18 for Gastrointestinal Hormones
• angiotensin-converting enzyme (ACE) in the lungs
converts angiotensin I → angiotensin II
• angiotensin II has a wide variety of actions:
o causes vasoconstriction of vascular smooth muscle
leading to raised blood pressure and vasoconstriction
of efferent arteriole of the glomerulus → increased
 filtration fraction (FF) to preserve GFR. Remember
that FF = GFR / renal plasma flow
o stimulates thirst (via the hypothalamus)
o stimulates aldosterone and ADH release
o increases proximal tubule Na+/H+ activity
Aldosterone
• released by the zona glomerulosa in response to raised
angiotensin II, potassium, and ACTH levels
• causes retention of Na+ in exchange for K+/H+ in distal
tubule
EXPLANATION:
The condition described is achondroplasia. This is due to a
gain of function mutation in the FGFR3 (fibroblast growth
factor receptor) gene. It is an autosomal dominant condition.
The vascular endothelial growth factor receptor is inhibited
by certain monoclonal antibodies in some cancers and in wet
macular degeneration by bevacizumab injections. The
epidermal growth factor receptor and tyrosine kinase
receptor are again inhibited by certain anti-cancer drugs. The
mesodermal growth factor receptor is made up.

Q-106 Please see Q-63 for Achondroplasia

T-Helper cells of the Th2 subset typically secrete:
Q-108
A. IL-4, IL-5, IL-6, IL-10, IL-13 During which of the following stages of mitosis does
B. IFN-gamma, IL-2, IL-3 chromatin condense to form chromosomes?
C. IL-1, IL-6, TNF-alpha
D. IFN-beta, IL-4, IL-8 A. Telophase
E. IL-1 B. Metaphase
C. Prophase
ANSWER: D. Interphase
IL-4, IL-5, IL-6, IL-10, IL-13 E. Anaphase

EXPLANATION: ANSWER:
T-HELPER CELLS Prophase
There are two major subsets of T-Helper cells:
EXPLANATION:
Th1 CELL DIVISION
• involved in the cell mediated response and delayed (type There are two types of cell division; mitosis and meiosis.
IV) hypersensitivity
• secrete IFN-gamma, IL-2, IL-3 The table below demonstrates the key differences:
Mitosis Meiosis
Th2 Occurs in somatic cells Occurs in gametes

• involved in mediating humoral (antibody) immunity
• e.g. stimulating production of IgE in asthma
• secrete IL-4, IL-5, IL-6, IL-10, IL-13
Q-107
You are working in general medicine. You are on the ward
round and see a 40-year-old patient who has been admitted
with a very swollen and painful right knee. He was unable to
walk on it so came into hospital. It is currently being treated
as gout with non steroidal anti-inflammatory drugs. You
notice he is of short stature, has shortened arms and legs
and a flat nasal bridge. A mutation in which gene is
responsible for this condition?
A. Fibroblast growth factor receptor
B. Vascular endothelial growth factor receptor
C. Mesodermal growth factor receptor
D. Epidermal growth factor receptor
E. Tyrosine kinase receptor
ANSWER:
Fibroblast growth factor receptor
Results in 2 diploid daughter Results in 4 haploid daughter cells
cells
Daughter cells are genetically Daughter cells contain one homologue of each
identical to parent cell chromosome pair and are therefore genetically
different
Remember:
• somatic cells have 22 pairs of autosomes and 1 pair of sex
chromosomes, i.e. 46XY or 46XX
• cells with a normal chromosome complement are known
as diploid cells
• gametes (ova or spermatozoa) have a single copy of each
chromosome and are known as haploid cells
Mitosis
Mitosis occurs during the M phase of the cell cycle. It
describes the process in which somatic cells divide and
replicate producing genetically identical diploid daughter cells.
This allows tissue to grow and renew itself.
During the S phase of the cell cycle the cell prepares itself for
division by duplicating the chromosomes. The table below
shows the phases of mitosis itself:
 Q-110
Prophase Chromatin in the nucleus condenses A scientist is developing a new test for Bovine spongiform
Prometaphase Nuclear membrane breaks down allowing the microtubules to encephalopathy that uses gel electrophoresis to separate
attach to the chromosomes native proteins by 3-D structure. This is an example of:
Metaphase Chromosomes aligned at middle of cell
Anaphase The paired chromosomes separate at the kinetochores and A. A microarray
move to opposite sides of the cell
B. Polymerase chain reaction
Telophase Chromatids arrive at opposite poles of cell
C. Northern blotting
Cytokinesis Actin-myosin complex in the centre of the cell contacts
D. Southern blotting
resulting in it being 'pinched' into two daughter cells
E. Western blotting

ANSWER:
Western blotting

EXPLANATION:
Molecular biology techniques
• SNOW (South - NOrth - West)
• DROP (DNA - RNA - Protein)

Please see Q-15 for Molecular Biology Techniques

Q-111
Which layer of the epidermis are melanocytes found in?

A. Stratum lucidum
B. Stratum germinativum
C. Stratum spinosum
D. Stratum corneum
E. Stratum granulosum

ANSWER:
Stratum germinativum
Q-109
One of your colleagues confides in you that he has just been EXPLANATION:
diagnosed with hepatitis B. He has not told anyone else as he Epidermis - 5 layers - bottom layer = stratum germinativum
is worried he may lose his job. He is currently working as a which gives rise to keratinocytes and contains melanocytes
general surgeon in the local hospital. You try to persuade
him to inform occupational health but he refuses. What is EPIDERMIS
the most appropriate action? The epidermis is the outermost layer of the skin and is
composed of a stratified squamous epithelium with an
A. Keep confidentiality but ask him to stop taking blood underlying basal lamina
B. Send an anonymous letter to his employer
C. Keep confidentiality It may be divided in to five layers:
D. Inform your colleague's employing body
E. Contact the police Layer Description
Stratum corneum Flat, dead, scale-like cells filled with keratin
ANSWER: Continually shed
Inform your colleague's employing body Stratum lucidum Clear layer - present in thick skin only
Stratum granulosum Cells form links with neighbours
EXPLANATION:
Stratum spinosum Squamous cells begin keratin synthesis
Whilst this may seem harsh patient safety has to be Thickest layer of epidermis
paramount. Please see the updated GMC guidelines for Stratum germinativum The basement membrane - single layer of columnar
further details. epithelial cells
Gives rise to keratinocytes
GMC GUIDANCE: CONFIDENTIALITY Contains melanocytes
We will not try to replicate the extensive guidance given by
the General Medical Council here. There is a link available for
more detailed information.
Q-112 Q-114
A small study is designed to look at the link between What level of evidence does a randomised control trial
drinking alcohol and liver cirrhosis. One hundred patients offer?
with liver cirrhosis were questioned and it was found that 80
of them drank excessive alcohol. As a control, one hundred A. Ia
patients without liver cirrhosis were questioned and only 20 B. Ib
of these patients drank excessively. What is the odds ratio of C. IIa
developing liver cirrhosis for people who drink excessively D. IIb
compared to those who do not? E. IV

A. 2 ANSWER:
B. 4 Ib
C. 0.25
D. 16 EXPLANATION:
E. 3 Please see Q-73 for Study Design: Evidence and
Recommendations
ANSWER:
16 Q-115
A 34-year-old man is referred to ophthalmology following a
EXPLANATION: deterioration in his vision. He is noted to be tall with thin,
Odds - remember a ratio of the number of people who incur long fingers and a degree of learning disabilities. Following
a particular outcome to the number of people who do not review he is suspected as having a displacement of his lens
incur the outcome on the right side. What is the most likely underlying
diagnosis?
NOT a ratio of the number of people who incur a particular
outcome to the total number of people A. Ehlers-Danlos syndrome
The odds of a patient with liver cirrhosis having a history of B. Homocystinuria
excessive drinking is 80/20 = 4. C. Rapadilino syndrome
D. Marfan's syndrome
The odds of a patient without liver cirrhosis having a history E. Crouzon disease
of excessive drinking is 20/80 = 0.25.
ANSWER:
Therefore the odds ratio = 4 / 0.25 = 16 Homocystinuria

Please see Q-93 for Odds and Odds Ratio EXPLANATION:

The presence of learning difficulties points to a diagnosis of
Q-113 homocystinuria rather than Marfan's syndrome.
A 64-year-old man collapses and dies shortly after
complaining of chest pain. During the post-mortem Please see Q-24 for Homycystinuria
extensive coronary artery disease is found. Examination of
the atherosclerotic plaques reveals multiple foam cells. Q-116
What is the origin of foam cells? A new test to screen for ovarian cancer in patients with a
positive family history is tested on 920 patients. The test is
A. Neutrophils positive in 16 of the 20 patients who are proven to have
B. Cardiac myocytes ovarian cancer. Of the remaining patients, only 10 have a
C. Macrophages positive test. What is the negative predictive value of the
D. Endothelial cells new test?
E. Lymphocytes
A. 900/920 = 97.8%
ANSWER: B. 890/900 = 98.9%
Macrophages C. 10/900 = 1.1%
D. 890/894 = 99.6%
EXPLANATION: E. 890/920 = 96.7%
Foam cells are fat-laden macrophages
ANSWER:
Please see Q-65 for Immune system cells: adaptive immune 890/894 = 99.6%
response
EXPLANATION: MUSCLE CONTRACTION
A contingency table can be constructed from the above data,
as shown below: Skeletal muscle contraction
Major steps:
Ovarian cancer No ovarian cancer • action potential reaches the neuromuscular junction,
Test positive 16 10 causing a calcium ion influx through voltage-gated
Test negative 4 890 calcium channels
• the calcium influx causes the release of acetylcholine into
The negative predictive value = TN / (TN + FN) = 890 / (890 + the extracellular space
4) = 890/894 • the acetylcholine activates nicotinic acetylcholine
receptors causing an influx of sodium, triggering an action
Please see Q-8 for Screening Test Statistics potential
• the action potential spreads through the T-tubules
Q-117 • the depolarization activates L-type voltage-dependent
A 45-year-old female presents with ptosis and muscle calcium channels (dihydropyridine receptors) in the T-
weakness which worsens towards the end of the day. She tubule membrane, which are close to calcium-release
has a past medical history of hypothyroidism. On channels (ryanodine receptors) in the adjacent
examination you note fatigable ptosis and proximal limb sarcoplasmic reticulum
weakness. You suspect a diagnosis of myasthenia gravis. • this causes the sarcoplasmic reticulum to release calcium
• calcium binds to troponin C (found on actin-containing
Which receptor is involved in the pathophysiology? thin filaments) causing a conformational change, allowing
tropomyosin to move, unblocking the binding sites
A. Muscarinic acetylcholine receptors • myosin binds to the newly released binding site releasing
B. Nicotinic acetylcholine receptors ADP, pulling the Z bands towards each other
C. Beta 1 adrenoceptor • ATP binds to myosin, releasing actin
D. Beta 2 adrenoceptor
E. Alpha 1 adrenoceptor

ANSWER:
Nicotinic acetylcholine receptors

EXPLANATION:
Skeletal muscle contraction is dependent on acetylcholine
which activates nicotinic acetylcholine receptors
Skeletal muscle contraction is dependent on acetylcholine
which activates nicotinic acetylcholine receptors.

Stimulation of the muscarinic acetylcholine receptor results

in a variety of different effects dependent upon the subclass
of receptor. For example stimulation of M2 receptors would
result in a decreased heart rate which could worsen the
compensation.

Stimulation of beta 1 adrenergic receptors result in increased Component Notes

heart rate and cardiac contractility. Sarcomere Basic unit of muscles that gives skeletal and cardiac
muscles their striated appearance. Segment between two
Stimulation of beta 2 adrenergic receptors result in smooth adjacent Z-lines
muscle dilation e.g. bronchodilation. I-band Zone of thin filaments that is not superimposed by thick
filaments
Stimulation of alpha 1 adrenergic receptors result in A-band Contains the entire length of a single thick filament

vasoconstriction of the skin, gut and kidney arterioles. This H-zone Zone of the thick filaments that is not superimposed by
the thin filaments
helps increases total peripheral resistance and mean arterial
M-line Middle of the sarcomere, cross-linking myosin
pressure, as well as facilitate perfusion of the brain, heart
Sarcoplasmic Releases calcium ion in response to depolarization
and lungs which are key organs of use in the flight or fright reticulum
response. Actin Thin filaments that transmit the forces generated by
myosin to the ends of the muscle
Myosin Thick filaments
 Component Notes • organic nitrates (metabolism produces NO) is widely used
Binds to thin filament to treat cardiovascular disease (e.g. angina, heart failure)
Titin Connects the Z-line to the thick filament, altering the • sildenafil is thought to potentiate the action of NO on
structure of tropomyosin
penile smooth muscle and is used in the treatment of
Tropomyosin Covers the myosin-binding sites on actin
erectile dysfunctions
Troponin-C Binds with calcium ions
T-tubule Is an invagination of the sarcoplasmic reticulum
Q-119
Helps co-ordinate muscular contraction
Which one of the following conditions is NOT an autosomal
recessive condition?
The table below shows the types of skeletal muscle fibres
(type II fibres are simplified into one category):
A. Haemochromatosis
Type I Type II
B. PKU
Contraction time Slow Fast
C. Hereditary spherocytosis
Colour Red (due to presence of White (due to absence
myoglobin) of myoglobin) D. Tay-Sach's
Main use Sustained force Sudden movement E. Friedreich's ataxia
Major fuel Triglycerides ATP
Mitochondrial High Low ANSWER:
density Hereditary spherocytosis

Mnemonic for type I fibres - 'One Slow, Fat, Red Ox' EXPLANATION:
Autosomal recessive conditions are 'metabolic' - exceptions:
Q-118 inherited ataxias
The nitric oxide receptor is an example of a:
Autosomal dominant conditions are 'structural' - exceptions:
A. Ligand-gated ion channel Gilbert's, hyperlipidaemia type II
B. MAPK/ERK receptor Hereditary spherocytosis is inherited in an autosomal
C. Guanylate cyclase receptor dominant fashion.
D. G protein-coupled receptor
E. Tyrosine kinase receptor Please see Q-54 for Autosomal Recessive Conditions

ANSWER: Q-120
Guanylate cyclase receptor Which one of the following statements regarding the
standard error of the mean is correct?
EXPLANATION:
The nitric oxide receptor is a soluble, intracellular guanylate A. Is the square root of standard deviation
cyclase B. It is independent of sample size
C. Is a measure of correlation between two variables
NITRIC OXIDE D. Confidence intervals cannot be applied to the standard
Previously known as endothelium derived relaxation factor, error of the mean
nitric oxide (NO) has emerged as a molecule which is integral E. Gets smaller as the sample size increases
to many physiological and pathological processes. It is formed
from L-arginine and oxygen by nitric oxide synthetase (NOS). ANSWER:
An inducible form of NOS has been shown to be present in Gets smaller as the sample size increases
macrophages. Nitric oxide has a very short half-life (seconds),
being inactivated by oxygen free radicals EXPLANATION:
Please see Q-82 for Confidence Interval and Standard Error of
Effects the Mean
• acts on guanylate cyclase leading to raised intracellular
cGMP levels and therefore decreasing Ca2+ levels Q-121
• vasodilation, mainly venodilation A 32-year-old female patient presents to the GP with a 2-day
• inhibits platelet aggregation history of abdominal pain and bloody diarrhoea. She reports
that she has been completely well until one week ago when
Clinical relevance she started having a headache and general tiredness. On
• underproduction of NO is implicated in hypertrophic further questioning, she admitted to eating at a dodgy
pyloric stenosis takeaway 3 days before the start of the symptoms.
• lack of NO is thought to promote atherosclerosis
• in sepsis increased levels of NO contribute to septic shock What is the most likely diagnosis?
 of the C8 myotome (flexion of the distal interphalangeal and
A. Diverticulitis metacarpophalangeal joints). The other options available
B. E. coli correspond to the C6 or C7 roots and these are unaffected as
C. Cholera evidenced by normal elbow flexion and thumb sensation (C6)
D. Giardiasis and normal sensation over the middle finger (C7). Elbow
E. Campylobacter extension is weak as it has roots from both C7 and C8 and so
cannot be used alone to decide between the two levels
ANSWER: clinically.
Campylobacter
The C8 nerve root exits the spine below the C7 vertebra,
EXPLANATION: being the only cervical nerve root which exits below a
Campylobacter infection is characterised by a prodrome, vertebra. The rest of the cervical nerve roots derive their
abdominal pain and bloody diarrhoea name from the vertebra below them. The most common
Campylobacter infection is characterised by a prodrome, acute pathology causing a radiculopathy is a disc herniation
abdominal pain and bloody diarrhoea. and therefore this is the correct answer.

Diverticulitis can cause bloody stool but the history here BRACHIAL PLEXUS
suggests an infectious cause.
Origin Anterior rami of C5 to T1
Most strains of E. coli, in general, do not cause bloody Sections of the • Roots, trunks, divisions, cords, branches
diarrhoea. plexus
• Mnemonic:Real Teenagers Drink Cold Beer

Cholera does not cause bloody diarrhoea. Roots • Located in the posterior triangle
• Pass between scalenus anterior and medius
Giardiasis has a longer incubation period and does not cause
bloody diarrhoea.
Trunks • Located posterior to middle third of clavicle
Please see Q-84 for Campylobacter • Upper and middle trunks related superiorly to the
subclavian artery
• Lower trunk passes over 1st rib posterior to the subclavian
Q-122 artery
A 61-year-old man is seen in clinic due to numbness and
tingling in his left hand. On examination he has weakness of
Divisions Apex of axilla
elbow extension, metacarpophalangeal joint flexion and
Cords Related to axillary artery
extension and distal interphalangeal joint flexion with all
other movements preserved, all reflexes are normal and
Diagram illustrating the branches of the brachial plexus
sensation is normal apart from reduced pin-prick sensation
over the medial aspect of the hand. An MRI scan of the
cervical spine is performed as a nerve lesion is suspected.

Which of the following pathologies is most likely to be found

on the scan based on the clinical findings?

A. Disc herniation between C5 and C6

B. Disc herniation between C6 and C7
C. Disc herniation between C7 and T1
D. Facet joint hypertrophy between C6 and C7
E. Facet joint hypertrophy between C7 and T1

ANSWER:
Disc herniation between C7 and T1

EXPLANATION:
C8 is the ONLY cervical nerve root that comes out BELOW the
vertebra
The scenario describes someone with a C8 radiculopathy
evidenced by reduced sensation in the C8 dermatome (the
medial side of the hand over the little finger) and weakness
Cutaneous sensation of the upper limb Further
Notes detail
dopamine

Increases secretion

• thyrotropin releasing hormone

• pregnancy
• oestrogen
• breastfeeding
• sleep
• stress
• drugs e.g. metoclopramide, antipsychotics

Decreases secretion

• dopamine
• dopaminergic agonists

Q-123 Q-124
A 33-year-old female is referred to the endocrine clinic. She Which one of the following is the most important stimulator
has missed her last two periods and has been lactating. She of the central chemoreceptors?
has gained weight and complains of vaginal dryness. The
endocrinologist chooses to measure her prolactin levels. A. Decrease in pO2
Which hormone is responsible for inhibiting prolactin release B. Decrease in pH
from the pituitary gland? C. Decrease in pCO2
D. Increase in nitric oxide
A. Thyrotropin releasing hormone E. Increase in K+
B. Oestrogen
C. Gonadotropin releasing hormone ANSWER:
D. Luteinising hormone Decrease in pH
E. Dopamine
EXPLANATION:
ANSWER: RESPIRATORY PHYSIOLOGY: CONTROL
Dopamine
Control of respiration
EXPLANATION: • central regulatory centres
Prolactin release is persistently inhibited by dopamine • central and peripheral chemoreceptors
Dopamine persistently inhibits prolactin. Prolactin release is • pulmonary receptors
upregulated by thyrotropin-releasing hormone and
oestrogen. Prolactin has an inhibitory effect on Central regulatory centres
gonadotropin-releasing hormone and luteinising hormone.
• medullary respiratory centre
• apneustic centre (lower pons)
PROLACTIN
• pneumotaxic centre (upper pons)
Further
Notes detail
Source Anterior pituitary Central and peripheral chemoreceptors
Function Stimulates breast development (both initially and • central: raised [H+] in ECF stimulates respiration
further hyperplasia during pregnancy) • peripheral: carotid + aortic bodies, respond to raised
Stimulates milk productio pCO2 & [H+], lesser extent low pO2
It decreases GnRH pulsatility at the hypothalamic level
and to a lesser extent, blocks the action of LH on the Pulmonary receptors
ovary or testis. • stretch receptors, lung distension causes slowing of
Regulation Prolactin secretion is under constant inhibition by respiratory rate (Hering-Bruer reflex)
• irritant receptor, leading to bronchoconstriction Na+ 140 mmol/l
• juxtacapillary receptors, stimulated by stretching of the K+ 3.8 mmol/l
microvasculature Urea 3.4 mmol/l
Creatinine 72 mol/l
Q-125
Each one of the following causes of hyponatraemia is Total cholesterol 5.1 mmol/l
associated with a urinary sodium of less than 20 mmol/L, HDL cholesterol 1.0 mmol/l
except: LDL cholesterol 2.9 mmol/l
Triglyceride 1.7 mmol/l
A. Diarrhoea
B. Psychogenic polydipsia Urine dip: No protein or blood
C. Burns
D. Secondary hyperaldosteronism She has no family history of note and her body mass index is
E. Syndrome of inappropriate ADH 20.5 kg/m. What is the most appropriate management with
regards to lipid modification?
ANSWER:
Syndrome of inappropriate ADH A. Start atorvastatin 10mg on
EXPLANATION: B. Start atorvastatin 20mg on
Syndrome of inappropriate ADH is associated with urinary C. Start atorvastatin 40mg on
sodium > 20 mmol/l D. Perform a QRISK2 assessment
E. Reassure her that lipid modification therapy is not
Please see Q-43 for Hyponatraemia required at this stage
Q-126
A rapid urine screening test is developed to detect ANSWER:
Chlamydia. A trial involving 200 men and women is Reassure her that lipid modification therapy is not required at
performed comparing the new test to the existing NAAT this stage
techniques:
EXPLANATION:
Chlamydia present Chlamydia absent NICE specifically state that we should not use QRISK2 for
New test positive 20 3 type 1 diabetics. Instead, the following criteria are used:
New test negative 5 172 • older than 40 years, or
• have had diabetes for more than 10 years or
What is the negative predictive value of the new test? • have established nephropathy or
• have other CVD risk factors
A. 172/177
B. 20/23 None of these apply in this case.
C. 172/192
D. 172/175 Please see Q-48 for Hyperlipidaemia: Management
E. 20/25
Q-128
ANSWER: A 35-year-old male has recently had a splenectomy following
172/177 damage to his spleen in a motorcycle accident. He is up to
date with all vaccinations which were offered as part of his
EXPLANATION: childhood vaccination scheme. It is July. Which of the
Negative predictive value = TN / (TN + FN) following vaccinations does he require in the first instance?

= 172 / (172 + 5) A. Influenza, pneumococcus, Haemophilus type B, pertussis

B. Pneumococcus, meningitis ACWY, pertussis
Please see Q-8 for Screening Test Statistics C. Meningococcus type B and C, Haemophilus type B, BCG
D. Pneumococcus, meningococcus type B and C,
Q-127 Haemophilus type B
You review a 21-year-old woman who has recently been E. Haemophilus type B, pneumococcus, BCG, meningitis
diagnosed with type 1 diabetes mellitus. She was admitted ACWY
three months ago with vomiting, abdominal pain and weight
loss and was found to hyperglycaemic. A diagnosis of type 1 ANSWER:
diabetes mellitus was made. She was started on insulin. Pneumococcus, meningococcus type B and C, Haemophilus
Recent bloods show the following: type B
 High-risk individuals should be counselled to take
EXPLANATION: penicillin or macrolide prophylaxis. Those at low risk may
Patients with hyposplenism should be vaccinated against choose to discontinue therapy. All patients should be
pneumococcal, Haemophilus type B and meningococcus type advised about taking antibiotics early in the case of
C intercurrent infections.
Adults who have had an unplanned splenectomy should be • Asplenic individuals travelling to malaria endemic areas
vaccinated against Pneumococcus, meningococcus type B are at high risk and should have both pharmacological
and C, and Haemophilus type B initially. These vaccines and mechanical protection.
should be given at least 14 days post-splenectomy for
maximal efficacy. They should also receive the influenza Dosing
vaccine if during the autumn or winter months. They should Penicillin V 500mg BD or amoxicillin 250mg BD
also have meningitis ACWY and a further dose of meningitis
B after 2 months. Q-129
Where is the majority of iron found in the body?
NICE Evidence search: post-splenectomy antibiotics
A. Bone
POST-SPLENECTOMY SEPSIS B. Haemoglobin
Hyposplenism may complicate certain medical conditions C. Ferritin and haemosiderin
where splenic atrophy occurs or may be the result of medical D. Myoglobin
intervention such as splenic artery embolization and E. Plasma iron
splenectomy for trauma. Diagnosis of hyposplenism is difficult
and whilst there may be peripheral markers of the ANSWER:
splenectomised state (e.g. Howell-Jolly bodies) these are Haemoglobin
neither 100% sensitive or specific. The most sensitive test is a
radionucleotide labelled red cell scan. EXPLANATION:
IRON METABOLISM
Hyposplenism, by whatever mechanism it occurs dramatically
increases the risk of post-splenectomy sepsis, particularly with Absorption
encapsulated organisms. Since these organisms may be • upper small intestine
opsonised, but this then goes undetected at an immunological • about 10% of dietary iron absorbed
level due to loss of the spleen. For this reason, individuals are • Fe2+ (ferrous iron) much better absorbed than Fe3+
recommended to be vaccinated and have antibiotic (ferric iron)
prophylaxis. • absorption is regulated according to body's need
• increased by vitamin C, gastric acid
Key recommendations • decreased by proton pump inhibitors, tetracycline, gastric
• All those with hyposplenism or may become so (such as achlorhydria, tannin (found in tea)
prior to an elective splenectomy) should receive
pneumococcal, Haemophilus type b and meningococcal Distribution in body
type C vaccines. These should be administered 2 weeks • total body iron = 4g
prior to splenectomy or two weeks following • haemoglobin = 70%
splenectomy. The vaccine schedule for meningococcal • ferritin and haemosiderin = 25%
disease essentially consists of a dose of Men C and Hib at
• myoglobin = 4%
2 weeks and then a dose of the MenACWY vaccine one
• plasma iron = 0.1%
month later. Those aged under 2 may require a booster at
2 years. A dose of pneumococcal polyvalent
Transport
polysaccharide vaccine (PPV) is given at two weeks. A
• carried in plasma as Fe3+ bound to transferrin
conjugated vaccine (PCV) is offered to young children.
The PCV is more immunogenic but covers fewer
Storage
serotypes. Boosting PPV is either guided by serological
• stored as ferritin in tissues
measurements (where available) or by routine boosting
doses at 5 yearly intervals.
Excretion
• Annual influenza vaccination is recommended in all cases
• lost via intestinal tract following desquamation
• Antibiotic prophylaxis is offered to all. The risk of post-
splenectomy sepsis is greatest immediately following
splenectomy and in those aged less than 16 years or
greater than 50 years. Individuals with a poor response to
pneumococcal vaccination are another high-risk group.
Q-130
A 70-year-old patient is brought to the emergency His ECG was normal and he was given calcium gluconate
department. She has a GCS of 11. Her relatives tell you that along with an insulin/dextrose infusion. Following this his
she has been drinking large amounts of water in order to potassium improved to 6.1, however over the next few days
remain well hydrated during the hot weather. You find that he remained persistently hyperkalaemic.
she has a sodium level of 108 mmol/l. Her most recent
sodium was 131 mmol/l when last checked 3 weeks ago. What would you suspect is the cause of his high potassium
What is the underlying pathology by which acute given his high cell counts?
hyponatraemia is causing her reduced GCS?
A. Pseudohyperkalaemia
A. Central pontine myelinolysis B. Tumour lysis syndrome
B. Concurrent hypoglycaemia C. Hypomagnasaemia
C. Intracranial haemorrhage D. Conn's syndrome
D. Cerebral oedema E. Chronic kidney disease
E. Cerebral vasospasm
ANSWER:
ANSWER: Pseudohyperkalaemia
Cerebral oedema
EXPLANATION:
EXPLANATION: High cell counts and high potassium: consider
Acute severe hyponatraemia can cause cerebral oedema pseudohyperkalaemia
The correct answer is cerebral oedema. The patient has
acute hyponatraemia, most likely as a result of water PSEUDOHYPERKALAEMIA
intoxication in this scenario. Acute hyponatraemia causes Pseudohyperkalaemia is a rise in serum potassium that occurs
cerebral oedema by reducing plasma osmolality, which due to excessive leakage of potassium from cells, during or
causes water to move out of the plasma into the brain cells after blood is taken. It is a laboratory artefact and does not
down the osmotic gradient. Cerebral oedema causes represent the true serum potassium concentration. The
drowsiness and seizures. majority of potassium is intracellular and thus leakage from
cells can significantly impact serum levels. In this case the
Central pontine myelinolysis can occur if hyponatraemia is potassium is released as the large numbers of platelets
corrected too rapidly. The other mechanisms are not aggregate and degranulate.
classically involved in hyponatraemia.
Causes include:
Effects of hyponatraemia on the brain • haemolysis during venepuncture (excessive vacuum of
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4470176/ blood drawing or too fine a needle gauge)
• delay in the processing of the blood specimen
HYPONATRAEMIA: CORRECTION • abnormally high numbers of platelets, leukocytes, or
Central pontine myelinolysis erythrocytes (such as myeloproliferative disorders)
• demyelination syndrome caused by rapid correction of • familial causes
chronic hyponatraemia
• may lead to quadriparesis and bulbar palsy Measuring an arterial blood gas will give a quick and accurate
• diagnosis: MRI brain measure of true serum potassium. For obtaining a lab sample,
using a lithium heparin tube, requesting a slow spin (on the
Q-131 lab centrifuge) and walking the sample to the lab should
A 74-year-old male is admitted to the Emergency ensure an accurate result.
Department after routine blood tests by his GP showed the
following results. The patient has a background of stable Q-132
essential thrombocytosis. Which one of the following is the most common genetic
cause of Prader-Willi syndrome?
Na+ 139 mmol/l
K+ 6.6 mmol/l A. Microdeletion of the paternal 15q11-13
Urea 4.2 mmol/l B. Maternal uniparental disomy of chromosome 15
Creatinine 68 umol/l C. Paternal uniparental disomy of chromosome 15
D. Microdeletion of the maternal 15q11-13
Hb 13.5 g/dl E. Trisomy 18
Plt 800 *109/l
WBC 6.6 *109/l
ANSWER: Please see Q-53 for Study Design
Microdeletion of the paternal 15q11-13
Q-135
EXPLANATION: Which cell organelle is involved in the breakdown of
Deletion of chromosome 15 oligopeptides?
Prader-Willi - paternal
Angelman syndrome - maternal A. Golgi apparatus
B. Rough endoplasmic reticulum
PRADER-WILLI SYNDROME C. Peroxisome
Prader-Willi syndrome is an example of genetic imprinting D. Lysosome
where the phenotype depends on whether the deletion E. Smooth endoplasmic reticulum
occurs on a gene inherited from the mother or father:
Prader-Willi syndrome if gene deleted from father ANSWER:
Angelman syndrome if gene deleted from mother Lysosome

Prader-Willi syndrome is associated with the absence of the EXPLANATION:

active Prader-Willi gene on the long arm of chromosome 15. Protein degradation in eukaryotes is also carried out by
This may be due to: protein complexes called proteasomes.
• microdeletion of paternal 15q11-13 (70% of cases)
• maternal uniparental disomy of chromosome 15 CELL ORGANELLES
The table below summarises the main functions of the major
Features cell organelles:
• hypotonia during infancy Organelle/macromolecule Main function
• dysmorphic features Endoplasmic reticulum Rough endoplasmic reticulum
• short stature
• hypogonadism and infertility
• learning difficulties • translation and folding of new proteins
• childhood obesity • manufacture of lysosomal enzymes

• behavioural problems in adolescence • site of N-linked glycosylation

• examples of cells with extensive RER
Q-133 include pancreatic cells, goblet cells,
Which one of the following karyotypes is associated with plasma cells

short stature?
Smooth endoplasmic reticulum
A. 45,XO
B. 46,YO
C. 46,XO
• steroid, lipid synthesis
D. 47,XYY
• examples of cells with extensive SER
E. 47,XXY
include those of the adrenal cortex,
hepatocytes, testes, ovaries
ANSWER:
45,XO
Golgi apparatus Modifies, sorts, and packages these molecules
EXPLANATION: that are destined for cell secretion
Site of O-linked glycosylation
Please see Q-16 for Turner’s Syndrome
Mitochondrion Aerobic respiration. Contains mitochondrial
Q-134 genome as circular DNA
The Framingham Heart Study is an example of a: Nucleus DNA maintenance and RNA transcription
Lysosome Breakdown of large molecules such as proteins
A. Cross-sectional survey and polysaccharides
B. Cohort study Nucleolus Ribosome production
C. Case-control study Ribosome Translation of RNA into proteins
D. Randomised controlled trial Peroxisome Catabolism of very long chain fatty acids and
E. Meta-analysis amino acids
Results in the formation of hydrogen peroxide
ANSWER: Proteasome Along with the lysosome pathway involved in
Cohort study degradation of protein molecules that have been
tagged with ubiquitin
EXPLANATION:
Q-136 for SIADH and mannitol is more likely to be used in the
In the Gell and Coombs classification of hypersensitivity context of traumatic brain injury.
reactions Grave's disease is an example of a:
A small, quick increase in the serum sodium is required in
A. Type I reaction order to decrease intracranial pressure. Hypertonic saline
B. Type II reaction (3%) boluses (after seeking senior advice) are the most
C. Type III reaction appropriate treatment to improve neurological status in such
D. Type IV reaction patients.
E. Type V reaction
Please see Q-130 for Hyponatraemia: Correction
ANSWER:
Type V reaction Q-138
A 64-year-old female patient is referred to the upper GI clinic
EXPLANATION: under the two-week rule. Her son first noticed that her skin
Please see Q-26 for Hypersensitivity and eyes are becoming yellow. Her past medical history
includes neurofibromatosis type 1. She was recently
Q-137 diagnosed with Type 2 diabetes mellitus however the blood
A 38-year-old male is admitted to the Emergency glucose has been very poorly controlled despite maximum
Department following a collapse while running a marathon. therapy of metformin and gliclazide. On examination, she is
His blood results are as follows: jaundiced. There is mild discomfort in the epigastric region
and the right upper quadrant. An urgent abdominal CT scan
Na+ 121 mmol/l shows a mass arising from the head of the pancreas and
K+ 3.4 mmol/l dilated common bile duct. A subsequent endoscopic
Urea 3.2 mmol/l retrograde cholangiopancreatography (ERCP) and biopsy
Creatinine 68 umol/l confirms a pancreatic somatostatinoma.

During assessment he becomes increasingly obtunded and Which cells in the pancreas is this tumour originating from?
goes on to have multiple tonic clonic seizures. What is the
most appropriate treatment from the list below to improve A. H cells
his neurological status? B. S cells
C. G cells
A. Decompressive craniotomy D. I cells
B. Demeclocycline E. D cells
C. Intravenous normal saline
D. Hypertonic saline ANSWER:
E. Mannitol D cells

ANSWER:
Hypertonic saline
EXPLANATION:
Acute hyponatraemia is that which occurs within a duration
of 48 hours.
Over consumption of fluids, prolonged race duration and
inadequate training all can predispose to acute
hyponatraemia in this setting. When hyponatraemia
develops over a short duration the ability of the brain to
adapt is exceeded and cerebral oedema can result which
may lead to confusion, seizures and coma. As a result
patients may die from brain herniation.
EXPLANATION:
Somatostatin is produced by D cells in the pancreas &
stomach
The question is essentially asking for the cells that produce
somatostatin. Somatostatinoma is a somatostatin-producing
tumour arising from the D cells in the pancreas and stomach.
Somatostatin is produced by D cells in the pancreas &
stomach. The newly-diagnosed diabetes is likely due to the
excessive secretion of somatostatin, as somatostatin inhibits
the release of insulin and glucagon.
There's no H cells in the gastrointestinal system.
S cells produce secretin.

The correct treatment to give is hypertonic saline. G cells produce gastrin.

Decompressive craniotomy would help alleviate raised
intracranial pressure due to cerebral oedema however is not I cells produce CCK.
an appropriate first line treatment. Demeclocycline is used
Please see Q-18 for Gastrointestinal Hormones
Q-139 A. 95% of values lie between 4.5 and 4.75 mmol/l
A young boy is diagnosed as having DiGeorge syndrome. B. 95.4% of values lie between 4.3 and 4.9 mmol/l
Which one of the following infections is he most at risk from, C. 99.7% of values lie between 4.0 and 5.2 mmol/l
secondary to his immune system dysfunction? D. 68.3% of values lie between 4.5 and 4.75 mmol/l
E. 68.3% of values lie between 4.3 and 4.9 mmol/l
A. Klebsiella pneumoniae
B. Haemophilus influenzae type b ANSWER:
C. Cryptococcus neoformans 68.3% of values lie between 4.3 and 4.9 mmol/l
D. Neisseria meningitidis
E. Salmonella typhi EXPLANATION:
We know that 68.3% of values of a normally distributed
ANSWER: variable lie within 1 standard deviation of the mean. This
Cryptococcus neoformans means the range is 4.3 to 4.9 mmol/l.

EXPLANATION: Please see Q-23 for Normal Distribution

Patients who have T-cell dysfunction are most at risk from Q-142
recurrent viral and fungal infections. You review a 30-year-old man shortly after he is discharged
from the Intensive Care Unit after being admitted with
Please see Q-25 for DiGeorge Syndrome pneumococcal pneumonia. This is his second admission in 18
months with a severe pneumonia. During his first admission
Q-140 Haemophilus influenzae was grown from his sputum. He also
A study looks at adding a new antiplatelet drug in addition to describes having frequent episodes of sinusitis and recurrent
aspirin to patients who've had a stroke. One hundred and skin abscesses. Which one of the following complement
seventy patients are enrolled for the study with 120 deficiencies is he most likely to be suffering from?
receiving the new drug in addition to aspirin and the
remainder receiving just aspirin. After 5 years 18 people who A. C1
received the new drug had a further stroke compared to 10 B. C2
people who just received aspirin. What is the number C. C3
needed to treat? D. C4
E. C5
A. 8
B. 15 ANSWER:
C. 1.8 C3
D. 20 EXPLANATION:
E. 10 Please see Q-39 for Complement Deficiencies

ANSWER: Q-143
20 Each one of the following is associated with Noonan's
syndrome, except:
EXPLANATION:
NNT = 1 / Absolute Risk Reduction A. Webbed neck
Control event rate = 10 / 50 = 0.2 B. Short stature
Experimental event rate = 18 / 120 = 0.15 C. Factor XI deficiency
D. Pulmonary valve stenosis
Absolute risk reduction = 0.2 - 0.15 = 0.05 E. Abnormal karyotype
Number needed to treat = 1 / 0.05 = 20
ANSWER:
Please see Q-92 for Numbers Needed to Treat and Absolute Abnormal karyotype
Risk Reduction EXPLANATION:
In contrast to Turner's syndrome, the karyotype is normal
Q-141
The serum potassium is measured in a 1,000 patients taking NOONAN SYNDROME
an ACE inhibitors. The mean potassium is 4.6 mmol/l with a Often thought of as the 'male Turner's', Noonan syndrome is
standard deviation of 0.3 mmol/l. Which one of the an autosomal dominant condition associated with a normal
following statements is correct? karyotype. It is thought to be caused by a defect in a gene on
chromosome 12
As well as features similar to Turner's syndrome (webbed A. Square root (Standard deviation / number of patients)
neck, widely-spaced nipples, short stature, pectus carinatum B. Number of patients / square root (mean)
and excavatum), a number of characteristic clinical signs may C. Number of patients / square root (standard deviation)
also be seen: D. Standard deviation / square root (number of patients)
• cardiac: pulmonary valve stenosis E. Standard deviation / square root (mean)
• ptosis
• triangular-shaped face ANSWER:
• low-set ears Standard deviation / square root (number of patients)
• coagulation problems: factor XI deficiency
EXPLANATION:
Q-144 Standard error of the mean = standard deviation / square
A 55-year-old woman complains of neck and right arm pain root (number of patients)
for the past two months. The pain is often triggered by
flexing her neck. Her past medical history includes Please see Q-82 for Confidence Interval and Standard Error of
osteoarthritis of her knee, obesity and depression. On the Mean
examination there is no obvious muscle atrophy or weakness
of the right arm. There is however some sensory loss over Q-147
the middle finger and palm of the hand. Which nerve root is You are a ST1 doctor working on a medical ward. You are
most likely to be affected by the impingement? struggling to cope with the workload and often leave the
ward late. Who is the most appropriate action to take?
A. C4
B. C5 A. Take time off-sick until the situation is sorted to protect
C. C6 patient care
D. C7 B. Speak to the medical director
E. C8 C. Arrive one-hour early every morning to give yourself
extra time
ANSWER: D. Speak to your consultant
C7 E. Speak to the postgraduate dean

EXPLANATION: ANSWER:
Please see Q-31 for Dermatomes Speak to your consultant

Q-145 EXPLANATION:
Which one of the following would invalidate the use of the Speaking to your consultant is the first action to take in this
Student's t-test when performing a significance test? scenario. They are best placed to be able to take action to try
and amend the situation. As the consultant is ultimately
A. Using it with unpaired data responsible for patient care they also have a right to know if
B. Using it with data that is not normally distributed you are struggling to cope as this may affect patient care.
C. Using it with data that has a small sample size
D. Using it to test whether the slope of a regression line The medical director may also be able to assist but would
differs significantly from 0 end up speaking to the consultant and hence is not the first
E. Using it to test a null hypothesis choice.

ANSWER: Arriving early may seem an option but does not ultimately
Using it with data that is not normally distributed address the cause of the problem. Taking time off sick is the
worst option - it doesn't address the problem and is
EXPLANATION: unprofessional.
Data must be parametric, i.e. follows a normal distribution
Q-148
Please see Q-30 for Significance Tests: Types Which of the following is responsible for the early
repolarisation phase of the myocardial action potential?
Q-146
A. Rapid sodium influx
Which one of the following defines the standard error of the
B. Rapid calcium influx
mean?
C. Slow sodium efflux
D. Slow efflux of calcium
E. Efflux of potassium
ANSWER: A. M
Efflux of potassium B. M0
C. G1
EXPLANATION: D. S
Please see Q-62 for Cardiac Action Potential E. G2

Q-149 ANSWER:
A 25-year-old woman presents with a symmetrical M
arthropathy affecting her hands. On examination she has
synovitis of the 2nd and 3rd metacarpophalangeal joints. EXPLANATION:
What type of HLA allele is most associated with this CELL CYCLE
condition? The cell cycle is regulated by proteins called cyclins which in
turn control cyclin-dependent kinase (CDK) enzymes.
A. HLA DR3
B. HLA A3 Phase Notes Regulatory proteins
C. HLA DR4 G0 • 'resting' phase
D. HLA DR2 • quiescent cells such as
E. HLA B27 hepatocytes and more
permanently resting cells such as
ANSWER: neurons
HLA DR4
G1 • Gap 1, cells increase in size Cyclin D / CDK4, Cyclin D /
EXPLANATION: • determines length of cell cycle CDK6 and Cyclin E / CDK2:
regulates transition from G1
Rheumatoid arthritis - HLA DR4 • under influence of p53
This patient has rheumatoid arthritis. to S phase

S • Synthesis of DNA, RNA and Cyclin A / CDK2: active in S

Please see Q-80 for HLA Associations histone phase
• centrosome duplication
Q-150
A 34-year-old patient, comes in with weight loss and
haemoptysis. On questioning, it is revealed he has significant
G2 • Gap 2, cells continue to increase Cyclin B / CDK1: regulates
in size transition from G2 to M
night sweats. On examination, he has reduced breath sounds phase
over the apex of his right lung and significant nail clubbing.
After referral to the respiratory physician, he is started on 4 M • Mitosis - cell division
antibiotics: rifampicin, ethambutol, pyrazinamide, and • the shortest phase of the cell
cycle
isoniazid. What is the mechanism of action of rifampicin?

A. Inhibit RNA synthesis

B. Inhibit cell wall formation Q-152
C. Inhibit DNA synthesis The average weight loss of a patient following a new type of
D. Inhibit 50S subunit of ribosomes bariatric surgery is 18 kg. The standard deviation of weight
E. Inhibit 30S subunit of ribosomes loss is 3kg. Assuming the weight loss is normally distributed,
what percentage of patients will loss between 9 and 27 kg?
ANSWER:
10% A. 97.4%
B. 95%
EXPLANATION: C. 95.4%
Rifampicin inhibits RNA synthesis D. 68.3%
These are the classic presentation of an individual with E. 99.7%
tuberculosis. The combination of rifampicin, ethambutol,
ANSWER:
pyrazinamide and isoniazid is the first line treatment.
99.7%
Rifampicin's mechanism of action is to inhibit RNA synthesis.
EXPLANATION:
Please see Q-55 for Antibiotics: Mechanism of Action 99.7% of values of a normally distributed variable lie within 3
Q-151 standard deviations of the mean.
In terms of the cell cycle, mitosis takes place in: Please see Q-23 for Normal Distribution
Q-153 • consist of 3 main subunits: alpha, beta and gamma
Which one of the following is most commonly secreted by T- • the alpha subunit is linked to GDP.Ligand binding causes
helper cells subset 2 (Th2 cells) ? conformational changes to receptor, GDP is
phosphorylated to GTP,and the alpha subunit is activated
A. Interleukin 2 • G proteins are named according to the alpha subunit (Gs,
B. Tumour necrosis factor Gi, Gq)
C. Interferon gamma
D. Interleukin 4
E. Interleukin 3

ANSWER:
Interleukin 4

EXPLANATION:
Please see Q-106 for T-helper cells

Q-154
The adrenergic receptor is an example of a:

A. Intracellular receptor
B. Tyrosine kinase receptor
C. Guanylate cyclase receptor
Gs Gi Gq
D. G protein-coupled receptor
Mechanism Stimulates adenylate Inhibits adenylate Activates
E. Ligand-gated ion channel
cyclase → increases cyclase → decreases phospholipase C →
cAMP → activates cAMP → inhibits splits PIP2 to IP3 &
ANSWER: protein kinase A protein kinase A DAG → activates
G protein-coupled receptor protein kinase C
Examples • Beta-1 receptors • M2 receptors • Alpha-1 receptors
EXPLANATION: (epinephrine, (acetylcholine) (epinephrine,
MEMBRANE RECEPTORS norepinephrine, • Alpha-2 receptors norepinephrine)
There are four main types of membrane receptor: ligand- dobutamine) (epinephrine, • H1 receptors
• Beta-2 receptors norephinephrine) (histamine)
gated ion channels, tyrosine kinase receptors, guanylate
(epinephrine, • D2 receptors • V1 receptors
cyclase receptors and G protein-coupled receptors salbuterol) (dopamine) (vasopressin)
• H2 receptors • GABA-B receptor • M1, M3 receptors
Ligand-gated ion channel receptors (histamine) (acetylcholine)
• generally mediate fast responses • D1 receptors
• e.g. nicotinic acetylcholine, GABA-A & GABA-C, glutamate (dopamine)
• V2 receptors
receptors
(vasopressin)
• Receptors for
Tyrosine kinase receptors ACTH, LH, FSH,
• receptor tyrosine kinase: insulin, insulin-like growth glucagon, PTH,
factor (IGF), epidermal growth factor (EGF) calcitonin,
• non-receptor tyrosine kinase: PIGG(L)ET: Prolactin, prostaglandins
Immunomodulators (cytokine, IL-2, Il-6, IFN), GH, G-CSF,
Q-155
Erythropoietin and Thromobopoietin
The atrial natriuretic peptide receptor is an example of a:
Guanylate cyclase receptors
A. Ligand-gated ion channel
• contain intrinsic enzyme activity
B. Intracellular receptor
• e.g. atrial natriuretic factor, brain natriuretic peptide
C. Guanylate cyclase receptor
D. G protein-coupled receptor
G protein-coupled receptors
E. Tyrosine kinase receptor
• generally mediate slow transmission and affect metabolic
processes ANSWER:
• activated by a wide variety of extracellular signals e.g. Guanylate cyclase receptor
Peptide hormones, biogenic amines, lipophilic hormones,
light EXPLANATION:
• 7-helix membrane-spanning domains Please see Q-154 for Membrane Receptors
Q-156 Total cholesterol 5 (Normal <5.2)
What is the main action of atrial natriuretic peptide? LDL cholesterol 2.5 (Normal <3.5)
HDL 1.1 (Normal >1)
A. Promotes renin excretion Triglycerides 2.3 (Normal <1.5)
B. Reduces excretion of sodium and water
C. Vasodilation Which would be the most appropriate management choice
D. Promotes aldosterone excretion to reduce his risk of cardiovascular events?
E. Vasoconstriction

ANSWER: A. Cholestyramine
Vasodilation B. Atorvastatin
C. Ezetimibe
EXPLANATION: D. Gemfibrozil
Atrial natriuretic peptide - powerful vasodilator E. Omega 3 fatty acids

ATRIAL NATRIURETIC PEPTIDE ANSWER:

Basics Atorvastatin
• secreted mainly from myocytes of right atrium and
ventricle in response to increased blood volume EXPLANATION:
• secreted by both the right and left atria (right >> left) The patient has an isolated hypertriglyceridaemia and
• 28 amino acid peptide hormone, which acts via cGMP significant cardiac risk factors. This is what the question is
• degraded by endopeptidases trying to demonstrate. While fibrates are well known to be
effective against hypertriglyceridaemias, his risk factor
Actions burden is enough that a statin (which is also functional on
• natriuretic, i.e. promotes excretion of sodium triglyceride levels, not just LDLs) is the first choice in this
• lowers BP situation. In particular, fibrates have not been shown to
• antagonises actions of angiotensin II, aldosterone reduce cardiovascular events in the presence of diabetes,
while statins have.
Q-157
Which one of the following types of blood vessel is first to Thus, an isolated hypertriglyceridaemia in the presence of
vasoconstrict in the presence of hypoxia? significant cardiovascular risk factors, in a patient not
currently on a statin, should be managed with the
A. Muscle arteries introduction of a statin.
B. Skin arteries
C. Hepatic arteries Please see Q-48 for Hyperlipidaemia: Management
D. Renal arteries
E. Pulmonary arteries Q-159
You are asked to review some arterial blood gases (ABGs)
ANSWER: done on a patient who has recently been admitted to the
Pulmonary arteries Emergency Department. The ABGs shown below were taken
on air:
EXPLANATION:
Pulmonary arteries vasoconstrict in the presence of hypoxia pH 7.53
pCO2 5.1 kPa
RESPIRATORY PHYSIOLOGY: HYPOXIA pO2 13.9 kPa
A fall in the partial pressure of oxygen in the blood leads to Bicarbonate 34 mmol/l
vasoconstriction of the pulmonary arteries. This allows blood
to be diverted to better aerated areas of the lung and Which one of the following is the most likely cause?
improves the efficiency of gaseous exchange
A. Chronic obstructive pulmonary disease
Q-158 B. Renal tubular acidosis
A 70-year-old male presents for advice regarding C. Mesenteric ischaemia
hyperlipidaemia. In the recent past he has trialled diet D. Anxiety
E. Vomiting
modification and exercise. He has a past history of
hypertension and Type 2 diabetes, and his medications The blood gases show a metabolic alkalosis
include aspirin, perindopril and metformin. He has a family
history of his brother and mother having a coronary artery ANSWER:
bypass grafting. Vomiting
EXPLANATION:
METABOLIC ALKALOSIS
Metabolic alkalosis may be caused by a loss of hydrogen ions
or a gain of bicarbonate. It is due mainly to problems of the
kidney or gastrointestinal tract
Causes
• vomiting / aspiration (e.g. peptic ulcer leading to pyloric
stenos, nasogastric suction)
• diuretics
• liquorice, carbenoxolone
• hypokalaemia
• primary hyperaldosteronism
• Cushing's syndrome
• Bartter's syndrome
Mechanism of metabolic alkalosis
• activation of renin-angiotensin II-aldosterone (RAA)
system is a key factor
• aldosterone causes reabsorption of Na+ in exchange for
H+ in the distal convoluted tubule
• ECF depletion (vomiting, diuretics) → Na+ and Cl- loss →
activation of RAA system → raised aldosterone levels
• in hypokalaemia, K+ shift from cells → ECF, alkalosis is
caused by shift of H+ into cells to maintain neutrality
Q-160
A 23-year-old man is referred to the ophthalmologists with
visual problems which are found to be caused by a
downward dislocation of the len in his right eye. The
ophthalmologist notices his marfarnoid habitus and history
of learning disabilities. A diagnosis of homocystinuria is
suspected. What is the pathophysiology of this condition?
A. Deficiency of S-adenosyl-methionine
B. Deficiency of homocysteine transsulfurase
C. Excess of cystathionine beta synthase
D. Deficiency of cystathionine beta synthase
E. Excess of homocysteine transsulfurase
ANSWER:
Deficiency of cystathionine beta synthase
EXPLANATION:
Homocystinuria is caused by a deficiency of cystathionine
beta synthase
Interestingly, patients with Down's syndrome have an excess
of cystathionine beta synthase.
Please see Q-24 for Homocystinuria
Q-161
A 62-year-old man with mixed hyperlipidaemia,
hypertension and ischaemic heart disease comes to the clinic
for review. He has suffered a left lower limb deep vein
thrombosis and been started on rivaroxaban for 3 months as
treatment. there are no apparent risk factors for deep vein
thrombosis and he has been fit and active, still working as a
landscape gardener.
Which of the following medications that he takes may be
associated with increased risk of deep vein thrombosis?
A. Ramipril
B. Atorvastatin
C. Fenofibrate
D. Bisoprolol
E. Indapamide
ANSWER:
Fenofibrate
EXPLANATION:
Fibrates may increase the risk of venous thromboembolism
Questions were raised as to whether fibrates may be
associated with venous thromboembolism after an
imbalance in favour of comparator therapies with respect to
thromboembolic events. A meta-analysis has now suggested
that this imbalance may represent a real risk of VTE in
patients prescribed fibrates: (OR, 1.58; 95% CI, 1.23–2.02).
https://academic.oup.com/eurheartj/article/31/10/1248/48
6868
The data from the same meta-analysis for statins suggests,
although does not confirm, that they may be associated with
reduced risk of venous thromboembolism: (OR, 0.81; 95% CI,
0.66–0.99), although the statin data was very heterogenous
and may not therefore represent a real finding. Beta-
blockers, thiazide like diuretics and ACE inhibitors are
thought to have no impact on risk of venous
thromboembolism.
FIBRATES
Fibrates are used in the management of hyperlipidaemia,
particularly raised triglycerides.
Adverse effects:
• gastrointestinal side-effects are common
• increased risk of thromboembolism
Q-162
Which one of the following statements regarding growth
hormone is incorrect?
A. Doesn't act directly on chondrocytes or osteoblasts
B. Is an anabolic hormone
C. Is responsible for changes in protein, lipid, and
carbohydrate metabolism
D. Is secreted by the somatotroph cells
E. Acts on a transmembrane receptor
ANSWER:
Doesn't act directly on chondrocytes or osteoblasts
EXPLANATION:
Growth hormone acts both directly on tissues (e.g.
stimulates division and multiplication of cartilage
chondrocytes) and also indirectly following the secretion of A. Type I reaction
insulin-like growth factor 1 B. Type II reaction
C. Type III reaction
GROWTH HORMONE D. Type IV reaction
Growth hormone (GH) is an anabolic hormone secreted by the E. Type V reaction
somatotroph cells of the anterior lobe of the pituitary gland. It
has actions on multiple organ systems and is important in ANSWER:
postnatal growth and development. Growth hormone is also Type I reaction
responsible for changes in protein, lipid, and carbohydrate
metabolism EXPLANATION:
Notes Further detail Type I hypersensitivity reaction - anaphylaxis
Source Anterior pituitary
Function Postnatal growth and Mechanism of action Please see Q-26 for Hypersensitivity
development
Numerous actions on protein, Q-164
carbohydrate and fat
• acts on a transmembrane Cystic fibrosis is due to a defect in the cystic fibrosis
metabolism (including
receptor for growth transmembrane conductance regulator (CFTR) gene. Which
increasing lipolysis and
factor chromosome is this gene located on?
gluconeogenesis)
• binding of GH to the
receptor leads to A. Chromosome 3
receptor dimerization
B. Chromosome 7
• acts directly on tissues
C. Chromosome 11
and also indirectly via
insulin-like growth factor D. Chromosome 14
1 (IGF-1), primarily E. Chromosome 15
secreted by the liver
ANSWER:
Regulation Increases secretion Conditions associated with Chromosome 7
GH disorders
• excess GH: acromegaly EXPLANATION:
• GH deficiency: resulting in Please see Q-85 for Cystic Fibrosis
• growth hormone releasing
short statu
hormone (GHRH):
released in pulses by the Q-165
hypothalamus A 42-year-old male patient presents to the GP surgery with a
• fasting 6-months history of progressive weakness of both lower
• exercise limbs. He complains of difficulty climbing stairs, lethargy and
• sleep muscle loss in the lower limbs. He had a history of type 2
diabetes mellitus and admits to heavy alcohol use for the
last 4 years. On examination, there is a marked loss of fine
Decreases secretion touch and proprioception in a stocking distribution
bilaterally. There is no evidence of ataxia.

• glucose What is the likely diagnosis?

• somatostatin (itself
increased by
A. Wernicke's encephalopathy
somatomedins, circulating
insulin-like growth factors, B. Wet beriberi
IGF-1 and IGF-2) C. Pellagra
D. Dry beriberi
E. Abetalipoproteinaemia
Q-163
A 12-year-old girl develops facial swelling and an ANSWER:
erythematous itchy rash shortly after being administered the Dry beriberi
first dose of the HPV vaccine. On arrival the paramedics note
a bilateral expiratory wheeze and blood pressure of 80/50 EXPLANATION:
mmHg. In the Gell and Coombs classification of Dry beriberi is caused by thiamine deficiency and causes
hypersensitivity reactions this is an example of a: peripheral neuropathy
This patient has a rapidly progressive polyneuropathy. Given A. Ciprofloxacin
the alcohol history, the most likely diagnosis from the B. Co-amoxiclav
options is dry beriberi, caused by thiamine deficiency. C. Trimethoprim
D. Amoxicillin
Wernicke's encephalopathy is also caused by thiamine E. Co-amoxiclav + metronidazole
deficiency but it does not usually involve peripheral
neuropathy. ANSWER:
Trimethoprim
Wet beriberi is another manifestation of thiamine deficiency
but it causes heart failure. EXPLANATION:
Trimethoprim in breastfeeding is considered safe to use
Pellagra is caused by vitamin B3 deficiency which causes Trimethoprim is considered safe to use in breastfeeding
dermatitis, dementia and diarrhoea. women.

Abetalipoproteinaemia is caused by vitamin E deficiency BREASTFEEDING: CONTRAINDICATIONS

which can present with peripheral neuropathy and cerebellar
ataxia. The absence of ataxia here makes dry beriberi more
likely.
VITAMIN B1 (THIAMINE)
Thiamine is a water soluble vitamin of the B complex group.
One of it's phosphate derivates, thiamine pyrophosphate
(TPP), is a coenzyme in the following enzymatic reactions:
• pyruvate dehydrogenase complex
• pyruvate decarboxylase in ethanol fermentation
• alpha-ketoglutarate dehydrogenase complex
• branched-chain amino acid dehydrogenase complex
• 2-hydroxyphytanoyl-CoA lyase
• transketolase
Thiamine is therefore important in the catabolism of sugars
and aminoacids. The clinical consequences of thiamine
deficiency are therefore seen first in highly aerobic tissues
such as the brain (Wenicke-Korsakoff syndrome) and the
heart (wet beriberi).
Causes of thiamine deficiency:
• alcohol excess
• malnutrition
Conditions associated with thiamine deficiency:
• Wernicke's encephalopathy: nystagmus, ophthalmoplegia
and ataxia
• Korsakoff's syndrome: amnesia, confabulation
• dry beriberi: peripheral neuropathy
• wet beriberi: dilated cardiomyopathy
Q-166
A 29-year-old woman presents with dysuria and frequency
four weeks after giving birth. The antenatal period and
delivery were unremarkable. She is exclusively breastfeeding
her child at the current time. Abdominal examination is
unremarkable and she is apyrexial. A urine dipstick shows
blood +, protein +, leucocytes +++ and nitrates positive.
What is the most appropriate management?
The major breastfeeding contraindications tested in exams
relate to drugs (see below). Other contraindications of note
include:
• galactosaemia
• viral infections - this is controversial with respect to HIV in
the developing world. This is because there is such an
increased infant mortality and morbidity associated with
bottle feeding that some doctors think the benefits
outweigh the risk of HIV transmission
Drug contraindications
The following drugs can be given to mothers who are
breastfeeding:
• antibiotics: penicillins, cephalosporins, trimethoprim
• endocrine: glucocorticoids (avoid high doses),
levothyroxine*
• epilepsy: sodium valproate, carbamazepine
• asthma: salbutamol, theophyllines
• psychiatric drugs: tricyclic antidepressants,
antipsychotics**
• hypertension: beta-blockers, hydralazine
• anticoagulants: warfarin, heparin
• digoxin
The following drugs should be avoided:
• antibiotics: ciprofloxacin, tetracycline, chloramphenicol,
sulphonamides
• psychiatric drugs: lithium, benzodiazepines
• aspirin
• carbimazole
• methotrexate
• sulfonylureas
• cytotoxic drugs
• amiodarone
*the BNF advises that the amount is too small to affect
neonatal hypothyroidism screening
**clozapine should be avoided
Q-167
An 18-year-old male is admitted to hospital for haemoptysis. Collagen diseases
He mentioned that his urine has recently become brown in Disorders of collagen range from relatively common, acquired
colour. On examination, his blood pressure is noted to be defects (typically aging), through to rarer congenital disorders.
170/110. A kidney biopsy is stained positive for The latter are exemplified by conditions such as osteogenesis
autoantibodies confirming a diagnosis of Goodpasture's imperfecta and Ehlers Danlos syndromes.
syndrome. Which type of collagen does this patient produce
autoantibodies against? Osteogenesis imperfecta:
• 8 Subtypes
A. Collagen type 1 • Defect of type I collagen
B. Collagen type 2 • In type I the collagen is normal quality but insufficient
C. Collagen type 3 quantity
D. Collagen type 4 • Type II- poor quantity and quality
E. Collagen type 5 • Type III- Collagen poorly formed, normal quantity
• Type IV- Sufficient quantity but poor quality
ANSWER: • Patients have bones which fracture easily, loose joint and
Collagen type 4 multiple other defects depending upon which sub type
they suffer from.
EXPLANATION:
Goodpasture's syndrome is caused by autoantibodies against Ehlers Danlos:
collagen type IV • Multiple sub types
Collagen IV is defective in Goodpasture's syndrome. • Abnormality of types 1 and 3 collagen
• Patients have features of hypermobility.
Ehlers-Danlos syndrome is primarily caused by a genetic
• Individuals are prone to joint dislocations and pelvic
defect in collagen type III. Collagen Type V is also affected in
organ prolapse. In addition to many other diseases
a less common variant of Ehlers-Danlos syndrome. Collagen
related to connective tissue defects.
type I is defective in osteogenesis imperfecta.
Q-168
COLLAGEN
Which one of the following statements regarding
Collagen is the main structural protein found in connective
hypocalcaemia is incorrect?
tissue and is the most common protein found in the body.
A. Most features are a result of neuromuscular excitability
Whilst over 20 types of collagen have been identified there
B. Chronic hypocalcaemia may cause cataracts
are 4-5 which are considered the most important:
C. Perioral paraesthesia is seen
D. Chvostek's sign is more sensitive and specific than
Collagen
Trousseau's sign
type Notes Associated conditions
E. Prolonged QT interval is seen
I Bone, skin, tendon Osteogenesis imperfecta
II Hyaline cartilage, vitreous
humour
ANSWER:
III Reticular fibre, granulation Vascular variant of Ehlers-
Chvostek's sign is more sensitive and specific than Trousseau's
tissue Danlos syndrome sign
IV Basal lamina, lens, basement Alport syndrome,
membrane Goodpasture's syndrome EXPLANATION:
V Most interstitial tissue, Classical variant of Ehlers- Hypocalcaemia: Trousseau's sign is more sensitive and
placental tissue Danlos syndrome specific than Chvostek's sign

Structure HYPOCALCAEMIA: FEATURES

• Composed of 3 polypeptide strands that are woven into a
helix, usually a combination of glycine with either proline
or hydroxyproline plus another amino acid
• Numerous hydrogen bonds exist within molecule to
provide additional strength
• Many subtypes but commonest subtype is I (90% of
bodily collagen), tissues with increased levels of flexibility
have increased levels of type III collagen
• Vitamin C is important in establishing cross-links
• Synthesised by fibroblasts
As extracellular calcium concentrations are important for
muscle and nerve function many of the features seen in
hypocalcaemia seen a result of neuromuscular excitability
Features
• tetany: muscle twitching, cramping and spasm
• perioral paraesthesia
• if chronic: depression, cataracts
• ECG: prolonged QT interval
Trousseau's sign ANSWER:
• carpal spasm if the brachial artery occluded by inflating A female child of a heterozygous female carrier has a 50%
the blood pressure cuff and maintaining pressure above chance of being a carrier
systolic
• wrist flexion and fingers drawn together EXPLANATION:
• seen in around 95% of patients with hypocalcaemia and Please see Q-3 for X-linked Recessive
around 1% of normocalcaemic people
Q-171
Chvostek's sign A 39-year-old male with a history of type 1 diabetes mellitus
• tapping over parotid causes facial muscles to twitch presents to his general practice with diplopia. It exacerbates
• seen in around 70% of patients with hypocalcaemia and when looking right and improved upon covering the right
around 10% of normocalcaemic people eye.

Q-169 What nerve is likely to be responsible?

A study looks at the benefits of adding a new antiplatelet
drug to aspirin following a myocardial infarction. The A. Right optic nerve
following results are obtained: B. Right trochlear
C. Right oculomotor
Percentage of patients having D. Right abducens
further MI within 3 months E. Left abducens
Aspirin 4%
Aspirin + new drug 3% ANSWER:
Right abducens
What is the number needed to treat to prevent one patient
having a further myocardial infarction within 3 months? EXPLANATION:
As the horizontal gaze to the right is where the diplopia is
A. 0.75 worst and is improved on covering the right eye then the
B. 0.33 right abducens is affected as this controls the right lateral
C. Cannot calculate without more data rectus and thus rightward gaze.
D. 1
E. 100 The trochlear nerve would lead to nystagmus on looking
down and out.
ANSWER:
100 The optic nerve would not lead to diplopia.

EXPLANATION: Please see Q-13 for Cranial Nerves

NNT = 1 / Absolute Risk Reduction
NNT = 1 / (control event rate - experimental event rate) Q-172
What is the most common cardiac defect seen in patients
= 1 / (0.04-0.03) = 1 / (0.01) = 100 with Down's syndrome?

Please see Q-92 for Numbers Needed to Treat and Absolute A. Ventricular septal defect
Risk Reduction B. Endocardial cushion defect
C. Secundum atrial septal defect
Q-170 D. Tetralogy of Fallot
Which of the following statements is true regarding X-linked E. Patent ductus arteriosus
recessive inheritance?

A. A female child of a heterozygous female carrier has a ANSWER:

50% chance of being a carrier Endocardial cushion defect
B. An example is Friedreich's ataxia
C. 50% of the male offspring of affected males will EXPLANATION:
manifest the disease Endocardial cushion defects account for about 40% of
D. An affected child's uncle on the paternal side will also congenital heart disease seen in patients with Down's
manifest the disease syndrome
E. 50% of the female offspring of affected males will be
carriers
DOWN'S SYNDROME: FEATURES
Clinical features
• face: upslanting palpebral fissures, epicanthic folds,
Brushfield spots in iris, protruding tongue, small low-set
ears, round/flat face
• flat occiput
• single palmar crease, pronounced 'sandal gap' between
big and first toe
• hypotonia
• congenital heart defects (40-50%, see below)
• duodenal atresia
• Hirschsprung's disease
Cardiac complications
• multiple cardiac problems may be present
• endocardial cushion defect (most common, 40%, also
known as atrioventricular septal canal defects)
• ventricular septal defect (c. 30%)
• secundum atrial septal defect (c. 10%)
• tetralogy of Fallot (c. 5%)
• isolated patent ductus arteriosus (c. 5%)
Later complications
• subfertility: males are almost always infertile due to
impaired spermatogenesis. Females are usually subfertile,
and have an increased incidence of problems with
pregnancy and labour
• learning difficulties
• short stature
• repeated respiratory infections (+hearing impairment
from glue ear)
• acute lymphoblastic leukaemia
• hypothyroidism
• Alzheimer's disease
• atlantoaxial instability
Q-173
A 67-year-old man with type 2 diabetes mellitus is receiving
his annual diabetic check. He is feeling more fatigued than
usual. He has not attended his previous three annual check-
ups. His blood glucose control has been poor and he has not
been compliant with his medications. Blood pressure is
170/90 mmHg. Urinalysis shows microalbuminuria. A blood
test reveals his glomerular filtration rate (GFR) is 27mL/min
per 1.73m².
EXPLANATION:
Diabetic nephropathy histological findings- Kimmelstiel-
Wilson lesions, nodular glomerulosclerosis
This patient has a poorly controlled T2DM with an underlying
diabetic nephropathy. The histological findings are
Kimmelstiel-Wilson lesions (nodular glomerulosclerosis) and
hyaline arteriosclerosis. This is due to nonenzymatic
glycosylation.
Apple-green birefringence under polarised light is seen in
amyloidosis.
Enlarged and hypercellular glomeruli is seen in acute post-
streptococcal glomerulonephritis.
Crescent moon shaped glomeruli is seen in rapidly
progressive (crescentic) glomerulonephritis.
Wire looping of capillaries in the glomeruli is seen in diffuse
proliferative glomerulonephritis (often due to SLE).
DIABETIC NEPHROPATHY
Basics
• commonest cause of end-stage renal disease (ESRD) in
the western world
• 33% of patients with type 1 diabetes mellitus have
diabetic nephropathy by the age of 40 years
• approximately 5-10% of patients with type 1 diabetes
mellitus develop (ESRD)
The pathophysiology is poorly understood, however:
• changes to the haemodynamics of the glomerulus is
thought to be key, which leads to an increased glomerular
capillary pressure
• histological changes include: basement membrane
thickening, capillary obliteration, mesangial widening.
Nodulular hyaline areas develop in the glomuli -
Kimmelstiel-Wilson nodules

If a renal biopsy was to be performed in this patient, what

would be the expected findings?

A. Nodular glomerulosclerosis and hyaline arteriosclerosis

B. Apple-green birefringence under polarised light
C. Enlarged and hypercellular glomeruli
D. Crescent moon shaped glomeruli
E. Wirelooping of capillaries in the glomeruli
Thickening of the basement membrane is seen alongside multiple Kimmelstiel-
ANSWER: Wilson nodules

Nodular glomerulosclerosis and hyaline arteriosclerosis

 EXPLANATION:
Cohort studies - relative risk

Please see Q-53 for Study Design

Q-176
Which one of the following hormones is most responsible for
the secretion of bicarbonate is the upper gastrointestinal
tract?

A. Somatostatin
B. Gastrin
C. Secretin
D. CCK
Severe arteriolosclerosis is seen in the afferent arteriole on the left of the slide.
Multiple, smaller acellular nodules are seen in the glomerulus - Kimmelstiel-
E. Vasoactive intestinal peptide
Wilson nodules. The tubular basement membrane is also thickened
ANSWER:
Risk factors for developing diabetic nephropathy Secretin

Modifiable Non-modifiable EXPLANATION:

Hypertension Male sex Please see Q-18 for Gastrointestinal Hormones
Hyperlipidaemia Duration of diabetes
Smoking Genetic predisposition (e.g. ACE gene Q-177
Poor glycaemic control polymorphisms) What is the site of action of antidiuretic hormone?
Raised dietary protein

A. Descending loop of Henle

Q-174 B. Distal convoluted tubule
Which of the following is responsible for the plateau phase C. Ascending loop of Henle
of the myocardial action potential? D. Proximal convoluted tubule
E. Collecting ducts
A. Slow calcium efflux
B. Efflux of potassium ANSWER:
C. Rapid sodium influx Collecting ducts
D. Slow influx of calcium
E. Slow sodium efflux EXPLANATION:
Antidiuretic hormone (ADH) - site of action = collecting ducts
ANSWER:
Slow influx of calcium ANTIDIURETIC HORMONE
Antidiuretic hormone (ADH) is secreted from the posterior
EXPLANATION: pituitary gland. It promotes water reabsorption in the
Slow influx of calcium is responsible for the plateau phase of collecting ducts of the kidneys by the insertion of aquaporin-2
the action potential channels.
Please see Q-62 for Cardiac Action Potential

Q-175 Notes Further detail

A cohort study is being designed to look at the relationship Source Synthesized in the supraoptic
between smoking and breast cancer. What is the usual nuclei of the hypothalamus,
released by the pituitary pituitary
outcome measure in a cohort study?
Function Conserves body water Promotes water reabsorption
A. Odds ratio in the collecting ducts of the
kidneys by the insertion of
B. Experimental event rate
aquaporin-2 channels
C. Relative risk
Regulation Increases secretion Diabetes insipidus (DI) is a
D. Absolute risk increase
condition characterised by
E. Numbers needed to harm either a deficiency of
antidiuretic hormone, ADH,
ANSWER: • extracellular fluid osmolality
(cranial DI) or an insensitivity to
Relative risk increase
antidiuretic hormone
• volume decrease
 Notes
• pressure decrease
• angiotensin II
Decreases secretion
Further detail
(nephrogenic DI)
Cranial DI can be treated by
desmopressin, an analog of
ADH
• may be useful in chronic granulomatous disease and
osteopetrosis
Q-179
A 10-year-old boy is found to have haemophilia A following
investigation for a haemoarthrosis. Which one of his
relatives is most likely to have the condition?

• extracellular fluid osmolality A. Father

decrease B. Mother's brother
• volume increase C. Father's sister
• temperature decrease D. Mother
E. Father's brother

Q-178 ANSWER:
Which one of the following statements is true regarding Mother's brother
interferon?
EXPLANATION:
A. Interferon-beta is produced by leucocytes X-linked recessive conditions are only seen in males which
B. Interferon-alpha and interferon-beta bind to the same therefore excludes two of the options. As male to male
type of receptor transmission is not seen this means the answer is mother's
C. Interferon-gamma has stronger antiviral action than brother.
interferon-alpha
D. Interferon-alpha has been shown to reduce the Please see Q-3 for X-linked Recessive
frequency of exacerbations in patients with relapsing-
remitting multiple sclerosis Q-180
E. Interferon-gamma has a role in chronic hepatitis C A 36-year-old former intravenous drug user is to commence
treatment for hepatitis C with interferon-alpha and ribavirin.
ANSWER: Which of the following adverse effects are most likely to
Interferon-alpha and interferon-beta bind to the same type of occur when patients are treated with interferon-alpha?
receptor
A. Diarrhoea and transient rise in ALT
EXPLANATION: B. Cough and haemolytic anaemia
INTERFERON C. Flu-like symptoms and transient rise in ALT
Interferons (IFN) are cytokines released by the body in D. Haemolytic anaemia and flu-like symptoms
response to viral infections and neoplasia. They are classified E. Depression and flu-like symptoms
according to cellular origin and the type of receptor they bind
to. IFN-alpha and IFN-beta bind to type 1 receptors whilst IFN- ANSWER:
gamma binds only to type 2 receptors. Depression and flu-like symptoms

IFN-alpha EXPLANATION:
• produced by leucocytes Please see Q-178 for Interferon
• antiviral action
• useful in hepatitis B & C, Kaposi's sarcoma, metastatic Q-181
renal cell cancer, hairy cell leukaemia Which one of the following is in direct anatomical contact
• adverse effects include flu-like symptoms and depression with the left kidney?

IFN-beta A. Stomach
• produced by fibroblasts B. Distal part of small intestine
• antiviral action C. Spleen
• reduces the frequency of exacerbations in patients with D. Pancreas
relapsing-remitting MS E. Duodenum

IFN-gamma ANSWER:
Pancreas
• produced by T lymphocytes & NK cells
• weaker antiviral action, more of a role in
immunomodulation particularly macrophage activation
EXPLANATION: Q-182
RENAL ANATOMY A 54-year-old woman who is obese comes to the Emergency
Each kidney is about 11cm long, 5cm wide and 3cm thick. department complaining of pain at the back of her right knee
They are located in a deep gutter alongside the projecting and swelling of the right calf, which she tells you came on all
vertebral bodies, on the anterior surface of psoas major. In of a sudden. She is awaiting a knee replacement for
most cases the left kidney lies approximately 1.5cm higher osteoarthritis of the right knee. Routine blood testing
than the right. The upper pole of both kidneys approximates reveals that the D-dimer is in the normal range.
with the 11th rib (beware pneumothorax during
nephrectomy). On the left hand side the hilum is located at Which of the following is the most likely diagnosis?
the L1 vertebral level and the right kidney at level L1-2. The A. Deep vein thrombosis
lower border of the kidneys is usually alongside L3. B. Ruptured popliteal cyst
Relations C. Pseudogout
The tables below show the anatomical relations of the D. Ruptured calf muscle
kidneys: E. Septic arthritis
Relations Right Kidney Left Kidney
ANSWER:
Posterior Quadratus lumborum, Quadratus lumborum,
Ruptured popliteal cyst
diaphragm, psoas major, diaphragm, psoas major,
transversus abdominis transversus abdominis
EXPLANATION:
Anterior Hepatic flexure of colon Stomach, Pancreatic tail
Sudden onset of pain, particularly when this is associated
Superior Liver, adrenal gland Spleen, adrenal gland first with symptoms behind the knee, and calf swelling, is
If we consider relations according to whether they are in very suspicious of an underlying ruptured popliteal cyst. The
direct contact or whether there is peritoneum in-between: fact she is awaiting a right total knee replacement also
suggests significant osteoarthritis of the knee, which
Right kidney predisposes to the condition. Physiotherapy and analgesia
Direct contact Layer of peritoneum in-between
are the mainstay of therapy for the condition. Patients may
Right suprarenal gland Liver complain of posterior knee and calf pain for a number of
Duodenum Distal part of small intestine weeks after the original incident.
Colon
The fact that pain began behind the knee, and that the D-
Left kidney dimer is normal, counts against a diagnosis of deep vein
Direct contact Layer of peritoneum in-betweenthrombosis. Pseudogout is primarily associated with anterior
Left suprarenal gland Stomach knee pain and swelling, as is septic arthritis. A ruptured calf
Pancreas Spleen
muscle is more likely to present with pain in the body of the
Colon Distal part of small intestine
calf itself, rather than pain behind the knee.
Fascial covering POPLITEAL FOSSA
Each kidney and suprarenal gland is enclosed within a Boundaries of the popliteal fossa
common layer of investing fascia, derived from the Laterally Biceps femoris above, lateral head of gastrocnemius and plantaris
transversalis fascia. It is divided into anterior and posterior below
layers (Gerotas fascia). Medially Semimembranosus and semitendinosus above, medial head of
gastrocnemius below
Renal structure Floor Popliteal surface of the femur, posterior ligament of knee joint and
Kidneys are surrounded by an outer cortex and an inner popliteus muscle
medulla which usually contains between 6 and 10 pyramidal Roof Superficial and deep fascia
structures. The papilla marks the innermost apex of these.
Image showing the popliteal fossa
They terminate at the renal pelvis, into the ureter.

Lying in a hollow within the kidney is the renal sinus. This

contains:
1. Branches of the renal artery
2. Tributaries of the renal vein
3. Major and minor calyces's
4. Fat

Structures at the renal hilum

The renal vein lies most anteriorly, then renal artery (it is an
end artery) and the ureter lies most posterior.
Contents Na+ 121 mmol/l
• Popliteal artery and vein K+ 3.8 mmol/l
• Small saphenous vein Urea 9.4 mmol/l
• Common peroneal nerve Creatinine 110 umol/l
• Tibial nerve
• Posterior cutaneous nerve of the thigh His confusion screen (including CT brain) is normal. On
• Genicular branch of the obturator nerve examination he has dry mucous membranes, his blood
• Lymph nodes pressure is 104/58 mmHg, pulse 94/min and temperature
36.1ºC. With regard to his low sodium what would be the
Q-183 most appropriate management?
Each one of the following promotes the release of
endothelin, except: A. Fluid restriction
B. Demeclocycline
A. Prostacyclin C. Intravenous normal saline
B. ADH D. Tolvaptan
C. Angiotensin II E. Furosemide
D. Hypoxia
E. Mechanical shearing force ANSWER:
Intravenous normal saline
ANSWER:
Prostacyclin EXPLANATION:
This case is an example of hypovolaemic hyponatraemia. It is
EXPLANATION: important with hyponatraemia to ascertain volume status as
ENDOTHELIN this will determine management. Poor oral intake due to
Endothelin is a potent, long-acting vasoconstrictor and advancing dementia is the likely cause. This is supported by
bronchoconstrictor. It is secreted initially as a prohormone by an elevated urea suggesting dehydration. Poor oral intake
the vascular endothelium and later converted to ET-1 by the can lead to both hyper or hyponatraemia depending on the
action of endothelin converting enzyme. It acts via interaction relative proportions of sodium and water deficiency.
with a G-protein linked to phospholipase C leading to calcium
release. Endothelin is thought to be important in the The management of each is as follows:
pathogenesis of many diseases including primary pulmonary
hypertension (endothelin antagonists are now used), cardiac Hypovolaemic hyponatraemia
failure, hepatorenal syndrome and Raynaud's • rehydration with sodium chloride 0.9% or a balanced
crystalloid (Hartmann's)
Promotes release • avoid rapid correction of sodium in order to reduce the
• angiotensin II risk of osmotic complications such as central pontine
• ADH myelinolysis
• hypoxia
• mechanical shearing forces Euvolaemic hyponatraemia
• check urine and serum osmolality. Does the patient meet
Inhibits release the criteria for SIADH?
• nitric oxide • treat the underlying cause where possible in SIADH
• prostacyclin • fluid restriction (500-750mls/day)
• monitor fluid balance and perform daily weights
Raised levels in • consider demeclocycline or tolvaptan (under specialist
• MI supervision). Both inhibit the action of antidiuretic
• heart failure hormone.
• ARF
Hypervolaemic hyponatraemia
• asthma
• fluid and salt restriction
• primary pulmonary hypertension
• consider diuretics
Q-184 • treat the underlying cause (e.g. cardiac failure)
An 82-year-old male nursing home resident with advanced
vascular dementia presents with worsening confusion to the
Emergency Department. His only regular medication is Please see Q-130 for Hyponatraemia: Correction
clopidogrel. His admission blood tests are as follows:
Q-185
T-Helper cells of the Th1 subset typically secrete: ANSWER:
NMDA receptor antagonist
A. IFN-beta, IL-4, IL-8
B. IFN-gamma, IL-2, IL-3 EXPLANATION:
C. IL-1, IL-6, TNF-alpha Ketamine is an NMDA receptor antagonist
D. IL-1 Ketamine is an NMDA receptor antagonist. It can be used in
E. IL-4, IL-5, IL-6, IL-10, IL-13 neuropathic pain poorly responsive to titrated opioids and
oral adjuvant analgesics (e.g. antidepressant and/or
ANSWER: anticonvulsant) particularly when there is abnormal pain
IFN-gamma, IL-2, IL-3 sensitivity (e.g. allodynia, hyperalgesia or hyperpathia).

EXPLANATION: Gabapentin acts by modulation of the voltage-gated calcium

Please see Q-106 for T-helper cells channel.

Q-186 Pregabalin is a GABA analogue.

A 60 year-old man with haemophilia A has just become a
grandfather. He wants to know what the chances are of his Benzodiazepines are GABA agonists.
daughter's son having haemophilia. Her daughter's partner is
well with no past medical history. Local anaesthetics (e.g. lidocaine) are sodium channel
blockers.
What is the probability that his daughter's son has
haemophilia A? ANAESTHETIC AGENTS
The table below summarises some of the more commonly
A. Impossible to calculate used IV induction agents
B. 50% Agent Specific features
C. 25% Propofol • Rapid onset of anaesthesia
D. No increased risk • Pain on IV injection
E. 100% • Rapidly metabolised with little accumulation of
metabolites
ANSWER: • Proven anti emetic properties
50% • Moderate myocardial depression
• Widely used especially for maintaining sedation on ITU,
EXPLANATION: total IV anaesthesia and for daycase surgery
Haemophilia A is an X-linked recessive disease. This means
that all female offspring of affected men will be carriers. Sodium • Extremely rapid onset of action making it the agent of
There is then a 50% chance of these females passing the thiopentone choice for rapid sequence of induction
gene on. If the female's children are male, they will therefore • Marked myocardial depression may occur
have a 50% chance of having the condition. • Metabolites build up quickly
• Unsuitable for maintenance infusion
Please see Q-3 for X-linked Recessive • Little analgesic effects

Q-187 Ketamine • May be used for induction of anaesthesia

You are working in the palliative care unit. A 65-year-old • Has moderate to strong analgesic properties
female has severe neuropathic pain secondary to spinal cord • Produces little myocardial depression making it a
metastasis. It has been unresponsive to titration of opioid suitable agent for anaesthesia in those who are
and neuropathic agents. Your consultant decides to use haemodynamically unstable
ketamine. • May induce state of dissociative anaesthesia resulting
in nightmares
What is the mechanism of action of ketamine?
Etomidate • Has favorable cardiac safety profile with very little
A. GABA agonist haemodynamic instability
B. GABA analogue • No analgesic properties
C. Modulation of voltage-gated calcium channel • Unsuitable for maintaining sedation as prolonged (and
D. NMDA receptor antagonist even brief) use may result in adrenal suppression
E. Sodium channel blocker • Post operative vomiting is common
Q-188 EXPLANATION:
Which of the following is true regarding endothelin? Immune cells bind to the crystallising region (Fc) of
immunoglobulins
A. It is a potent vasodilator Antibodies (immunoglobulins) may be divided into 2 main
B. It is produced mainly by pulmonary tissue pairs:
C. It acts on target cells by stimulating guanylate cyclase Fab region: antigen-binding fragment - the region that binds
D. Release is stimulated by nitric oxide to antigens
E. Endothelin antagonists are useful in primary pulmonary Fc region: fragment crystallizable region - the tail region of
hypertension an antibody that interacts with cell surface receptors

ANSWER: IMMUNOGLOBULINS
Endothelin antagonists are useful in primary pulmonary The table below summarises the characteristics of the 5 types
hypertension of immunoglobulin found in the body:

EXPLANATION: Type Frequency Shape Notes

Please see Q-183 for Endothelin IgG 75% Monomer • Enhance phagocytosis of bacteria and viruses
• Fixes complement and passes to the fetal
Q-189 circulation
A rapid finger-prick blood test to help diagnosis deep vein • Most abundant isotype in blood serum
thrombosis is developed. Comparing the test to current IgA 15% Monomer/ • IgA is the predominant immunoglobulin
standard techniques a study is done on 1,000 patients: dimer found in breast milk. It is also found in the
secretions of digestive, respiratory and
urogenital tracts and systems
DVT present DVT absent • Provides localized protection on mucous
New test positive 200 100 membranes
New test negative 20 680 • Most commonly produced immunoglobulin
in the body (but blood serum concentrations
lower than IgG
What is the specificity of the new test?
.)
• Transported across the interior of the cell via
A. 680/880 transcytosis
B. 200/220 IgM 10% Pentamer • First immunoglobulins to be secreted in
C. 680/780 response to an infection
D. 680/700 • Fixes complement but does not pass to the
E. 200/300 fetal circulation
• Anti-A, B blood antibodies (note how they
ANSWER: cannot pass to the fetal circulation, which
could of course result in haemolysis)
680/780
Pentamer when secreted
IgD 1% Monomer • Role in immune system largely unknown
EXPLANATION: • Involved in activation of B cells
Specificity = true negatives / (true negatives + false positives) IgE 0.1% Monomer • Mediates type 1 hypersensitivity reactions
• Binds to Fc receptors found on the surface of
= 680 / (680 + 100) mast cells and basophils
• Provides immunity to parasites such as
Please see Q-8 for Screening Test Statistics helminths
• Least abundant isotype in blood serum
Q-190
Which part of an antibody do immune cells bind to? Q-191
Which one of the following organisms is most contagious?
A. Disulfide bridge
B. Heavy-chain of antigen binding site A. Varicella zoster virus
C. Light-chain of antigen binding site B. Epstein Barr virus
D. Fc region C. Rotavirus
E. Light-chain hypervariable region D. Herpes simplex virus
E. Haemophilus influenzae
ANSWER:
Fc region ANSWER:
Varicella zoster virus
EXPLANATION: *the official advice regarding school exclusion for chickenpox
CHICKENPOX has gone back and forth over recent years. In September 2017
Chickenpox is caused by primary infection with varicella zoster Public Health England advocated the 5 day rule:
virus. Shingles is reactivation of dormant virus in dorsal root
ganglion
Children should be kept away from school for at least 5 days
Chickenpox is highly infectious from onset of rash (and not developing new lesions). It is not
• spread via the respiratory route necessary for all the spots to have healed or crusted over
• can be caught from someone with shingles before return to school as the risk of transmission to other
• infectivity = 4 days before rash, until 5 days after the rash children after 5 days is minimal.
first appeared*
• incubation period = 10-21 days Q-192
Clinical features (tend to be more severe in older Where is secretin secreted from?
children/adults)
A. I cells in upper small intestine
• fever initially
B. G cells in stomach
• itchy, rash starting on head/trunk before spreading.
C. K cells in upper small intestine
Initially macular then papular then vesicular
D. D cells in the pancreas
• systemic upset is usually mild
E. S cells in upper small intestine
Management is supportive
• keep cool, trim nails ANSWER:
• calamine lotion S cells in upper small intestine
• school exclusion*: children should be kept away from
school for at least 5 days from onset of rash (and not EXPLANATION:
developing new lesions) Please see Q-18 for Gastrointestinal Hormones
• immunocompromised patients and newborns with
peripartum exposure should receive varicella zoster Q-193
immunoglobulin (VZIG). If chickenpox develops then IV A 43-year-old gentleman has returned back to the UK 2
aciclovir should be considered weeks ago following a trip to Africa. He attends his GP
complaining of a fever, chills and a bite on his left hand. On
A common complication is secondary bacterial infection of the close inspection, you can see a 1x1.5cm dark black crust over
lesions. Rare complications include the site.
• pneumonia
• encephalitis (cerebellar involvement may be seen) What is the most likely underlying organism?
• disseminated haemorrhagic chickenpox
• arthritis, nephritis and pancreatitis may very rarely be A. Rickettsial conorii
seen B. Streptococcus pyogenes
C. Borrelia burgdorferi
D. Bartonella henselae
E. Mycobacterium leprae

Rickettsial infections can occur on six continents, although

the clinical presentation may vary between each of them. As
a rule, they tend to present with a combination of rash,
headaches, and either single or multiple eschars. The clue
here is the presence of an eschar which should lead you to
consider the diagnosis along with a history of recent foreign
travel.

Borrelia burgdorferi and Bartonella henselae are the

causative organisms of Lyme disease and cat-scratch fever.
Mycobacterium leprae presents more with insensate patches
and wasting as it progresses.
Chest x-ray showing miliary opacities secondary to healed varicella pneumonia.
Multiple tiny calcific miliary opacities noted throughout both lungs. These are of ANSWER:
uniform size and dense suggesting calcification. There is no focal lung Rickettsial conorii
parenchymal mass or cavitating lesion seen.The appearances are characteristic for
healed varicella pneumonia.
EXPLANATION: On physical examination, she is in Tanner Stage I for breast
RICKETTSIAE development and in early Tanner Stage II for pubic hair
Rickettsiae are Gram-negative obligate intracellular parasites. development. She also has a webbed neck.
Types of rickettsiae cause a variety of diseases that are
typically characterised by fever, headache and rash. A notable Laboratory investigations show a significantly raised
exception is Q fever (cause by Coxiella burnetti which causes Luteinizing Hormone (LH) and Follicle-Stimulating Hormone
pneumonia but no rash. The Weil-Felix reaction is positive (FSH) with reduced oestrogen levels. Karyotyping confirms
except in Q fever. Rickettsial diseases are all treated with the diagnosis.
tetracyclines.
Which of the following cardiac pathologies is most
Disease Cause Vector Notes commonly associated with this condition?
Rocky Mountain Rickettsia Tick Headache and fever are
spotted fever ricketsii common A. Coarctation of the aorta
B. Aortic dissection
Rash starts on the peripheries C. Mitral stenosis
(wrist, ankles) before spreading
D. Hypertrophic cardiomyopathy
centrally. It is initially
maculopapular before E. Patent ductus arteriosus
becoming vasculitic
ANSWER:
Endemic to east coast of US Coarctation of the aorta
Q fever Coxiella No vector No rash but causes pneumonia
burnetti EXPLANATION:
Endemic typhus Rickettsia Flea Rash starts centrally then Please see Q-16 for Turner’s Syndrome
typhi spreads to the peripheries
Epidemic typhus Rickettsia Human Q-195
prowazekii body
You are working in oncology in the breast cancer division. A
louse
30-year-old lady has been referred to you by her GP with a
Ehrlichliosis Ehrlichia Tick
mass in her left breast. She underwent treatment for a
sarcoma of the left deltoid muscle one year previously. She
has a family history of cancer. Her mother died of a brain
tumour in her mid 40's and her brother died of an
osteosarcoma in his early teens. A mutation in which gene is
accountable for this syndrome?

A. RET
B. CMYC
C. RAS
D. P53
E. VHL

ANSWER:
P53

A dry fracture of a Vero cell exposing the contents of a vacuole where Coxiella
burnetti are busy growing. Note the intracellular nature of the organism. Credit:
NIAID
EXPLANATION:
A mutation in the P53 gene can cause Li-Fraumeni syndrome
which can present with soft tissue sarcomas, breast
carcinoma, glioblastoma, lymphoma and leukaemia. It is a
rare autosomal dominant disorder.

Q-194
A 16-year-old female is brought to her primary care
physician by her parents with a complaint of short stature
and delayed puberty. Further questioning reveals primary
amenorrhoea. The patient's height is significantly shorter
than her midparental height.
ONCOGENES
Oncogenes are cancer promoting genes that are derived from
normal genes (proto-oncogenes). Proto-oncogenes play an
important physiological role in cellular growth and
differentiation. A 'gain of function' results in an increased risk
of cancer. Only one mutated copy of the gene is needed for
cancer to occur - a dominant effect. They are implicated in the
development of up to 20% of human cancers.
Proto-oncogenes may become oncogenes via the following EXPLANATION:
processes: Managing young diabetic patients may be frustrating but
• Mutation (point mutation) needs to be approached in an empathetic manner. Taking
• Chromosomal translocation time to explore why her control is so bad is the best response
• Increased protein expression in this scenario. The GP should hopefully have a long term
relationship with the patient and may be in a position to
Examples address these problems.
Gene Category Associated cancers
ABL Cytoplasmic tyrosine Chronic myeloid leukaemia Taking no action ignores the problem. Trying to scare her by
kinase showing her patients with complications is a poor option not
c-MYC Transcription factor Burkitt's lymphoma least because it fails to respect the privacy of the other
n-MYC Transcription factor Neuroblastoma patients.
BCL-2 Apoptosis regulator Follicular lymphoma
protein Telling her she is wasting NHS resources is uncaring and
RET Tyrosine kinase receptor Multiple endocrine neoplasia unprofessional. Telling her not to turn up at hospital again is
(types II and III) indefensible from an ethical and medicolegal perspective.
RAS G-protein Many cancers
especially pancreatic Q-197
erb-B2 Tyrosine kinase receptor Breast and ovarian cancer A randomised controlled trial compares two drugs used in
(HER2/neu) the initial management of rheumatoid arthritis. After being
assigned to the randomised groups a number of patients
How are they different from tumour supressory genes? drop out due to adverse effects of the medication. How
Tumour suppressor genes restrict or repress cellular should the data be analysed?
proliferation in normal cells. Their inactivation through
mutation or germ line incorporation is implicated in renal, A. Recruit more patients
colonic, breast, bladder and many other cancers. One of the B. For each patient who drops out, remove a patient from
best known tumour suppressor genes is p53. p53 gene offers the other randomised group
protection by causing apoptosis of damaged cells. Other well C. Include the patients who drop out in the final data set
known genes include BRCA 1 and 2. D. Remove patients who drop out from final data set
E. Abandon the trial if more than 5% of patients drop out
Tumor suppressor genes - loss of function results in an increased risk of
cancer
ANSWER:
Oncogenes - gain of function results in an increased risk of cancer
Include the patients who drop out in the final data set
Q-196 EXPLANATION:
You are a ST1 doctor in general medicine. A 19-year-old INTENTION TO TREAT ANALYSIS
female who has type 1 diabetes mellitus is admitted with her Intention to treat analysis is a method of analysis for
fourth episode of diabetic ketoacidosis in the past two randomized controlled trials in which all patients randomly
months. You suspect she runs her sugars high to keep her assigned to one of the treatments are analysed together,
weight down. She is generally non-compliant and often self- regardless of whether or not they completed or received that
discharges after 24 hours. What is the most appropriate treatment
response?
Intention to treat analysis is done to avoid the effects of
A. Take her on a tour of the ward showing her patients crossover and drop-out, which may affect the randomization
with amputated legs or those on dialysis as an incentive to the treatment groups
to get better control
B. Have a chat after the ward round about why she thinks Q-198
her control is so bad A 15-year-old girl presents with an urticarial rash,
C. Write a letter to her GP advising him/her of your angioedema and wheezing. Her mother states that she has
concerns just come from her younger sister's party where she had
D. Take no action as it is her decision whether she takes been helping to blow up balloons. What is the most likely
her medication or complies with treatment diagnosis?
E. Tell her she is wasting NHS resources and you do not
want to see her turn up at your hospital again A. C1-esterase deficiency (hereditary angioedema)
B. Allergic contact dermatitis
ANSWER: C. Peanut allergy
Have a chat after the ward round about why she thinks her D. Latex allergy
control is so bad E. Irritant contact dermatitis
ANSWER: Sleep stage EEG Notes
Latex allergy REM Beta-waves Dreaming occurs
Loss of muscle tone, erections
EXPLANATION:
Type I hypersensitivity reaction - anaphylaxis N1 → N2 → N3 → REM
This is a typical history of latex allergy. Adrenaline should be
given immediately and usual anaphylaxis management Theta → Sleep spindles/K-complexes → Delta → Beta
followed
The Sleep Doctor's Brain

Please see Q-26 for Hypersensitivity

Q-200
Which of the following secondary causes of hyperlipidaemia
Q-199
result in predominantly hypercholesterolaemia, as opposed
A 22-year-old man presents with difficulties sleeping. He
to hypertriglyceridaemia?
states that as he is falling to sleep he develops an unpleasant
sensation and jerk which often causes him to awaken
A. Hypothyroidism
suddenly. They are occurring a few times a week and he is
B. Obesity
concerned they may be due to a serious underlying disorder.
C. Liver disease
D. Bendrofluazide
What stage of sleep does this phenomenon occur?
E. Chronic renal failure
A. Awake
ANSWER:
B. Non-REM stage 1 (N1)
Hypothyroidism
C. Non-REM stage 2 (N2)
D. Non-REM stage 3 (N3)
EXPLANATION:
E. REM
Hypercholesterolaemia rather than hypertriglyceridaemia:
nephrotic syndrome, cholestasis, hypothyroidism
ANSWER:
Non-REM stage 1 (N1)
HYPERLIPIDAEMIA: SECONDARY CAUSES
Causes of predominantly hypertriglyceridaemia
EXPLANATION:
• diabetes mellitus (types 1 and 2)
Non-REM stage 1 (N1) sleep is the lightest sleep which is
• obesity
associated with hypnagogic jerks
A hypnagogic jerk is a type of myoclonus. It causes an • alcohol
involuntary twitch which occurs when a person is beginning • chronic renal failure
to fall asleep, often causing them to jump and awaken • drugs: thiazides, non-selective beta-blockers, unopposed
suddenly for a moment. They occur in non-REM stage 1 (N1) oestrogen
sleep - the lightest sleep stage. There is a wide range of • liver disease
potential causes, including anxiety, caffeine, stress and
strenuous activities in the evening. However, most Causes of predominantly hypercholesterolaemia
hypnagogic jerks occur as a normal variant. • nephrotic syndrome
• cholestasis
REM sleep disorders are associated with lucid dreaming and • hypothyroidism
the absence of the normal atonia during this stage of sleep.
This can result in patients acting out their dreams and Q-201
causing themselves and others physical harm. You are designing a research project looking at the
sensitivities and specificities of various markers in relation to
SLEEP STAGES myocardial necrosis. Specifically you want to assess the
Sleep stage EEG Notes molecule which troponin C binds to.
Non-REM stage Theta waves Light sleep
1 (N1) Transition to this stage be Which molecule will you study in your research project?
associated with hypnic jerks
Non-REM stage Sleep spindles + K- Deeper sleep A. Calcium ions
2 (N2) complexes Represents around 50% of total B. Tropomyosin
sleep C. Actin
Non-REM stage Delta waves Deep sleep D. Myosin
3 (N3) Parasomnias such as night
E. Sarcoplasmic reticulum
terrors, nocturnal enuresis,
sleepwalking
ANSWER: EXPLANATION:
Calcium ions PDA is associated with a collapsing pulse

EXPLANATION: Please see Q-60 for Patent Ductus Arteriosus

Troponin C binds to calcium ions
Troponin C is responsible for binding calcium to activate Q-204
muscle contraction. Troponin C is released due to both Anti-nuclear antibodies (ANA) are commonly found in
skeletal and cardiac muscle damage resulting in poor patients with systemic lupus erythematosus (SLE). However,
specificity as a marker for myocardial necrosis. they can also be found in around 9% of people without the
condition. Therefore, as a test for diagnosing SLE, ANA has
Troponin T binds to tropomyosin, forming a troponin- low:
tropomyosin complex. It is a specific marker for myocardial
necrosis. A. Positive predictive value
B. Sensitivity
Troponin I binds to actin to hold the troponin-tropomyosin C. Specificity
complex in place. It is a specific marker for myocardial D. Negative predictive value
necrosis. E. Incidence

Myosin is the thick component of muscle fibres. Actin slides ANSWER:

along myosin to generate muscle contraction. Specificity

The sarcoplasmic reticulum regulates the calcium ion EXPLANATION:

concentration in the cytoplasm of striated muscle cells. If a test is falsely positive in 9% of the general population
then that test has poor specificity.
Please see Q-2 for Troponin
Low specificity tests have many false positives (those without
Q-202 the condition test positive).
Which one of the following drugs is contra-indicated whilst
breast feeding? Low sensitivity tests have many false negatives (those with
the condition are missed).
A. Aminophylline
B. Carbamazepine Please see Q-8 for Screening Test Statistics
C. Sodium valproate
D. Methyldopa Q-205
E. Amiodarone Which one of the following statements regarding relative
risk is correct?
ANSWER:
Amiodarone A. Relative risk = 1 - absolute risk reduction
B. It is the usual outcome measure of cohort studies
EXPLANATION: C. Risk may be defined as the odds of an outcome
Amiodarone in breastfeeding must be avoided happening
D. Relative risk = 1 / odds ratio
Please see Q-166 for Breastfeeding: Contraindications E. If the risk ratio is less than 1 then the rate of an event is
increased compared to controls
Q-203
Which of the following features is not associated with patent ANSWER:
ductus arteriosus? It is the usual outcome measure of cohort studies

A. Continuous 'machinery' murmur EXPLANATION:

B. Bisferiens pulse Remember that risk and odds are different. If 20 patients die
C. Heaving apex beat out of every 100 who have a myocardial infarction then the
D. Wide pulse pressure risk of dying is 20 / 100 = 0.2 whereas the odds are 20 / 80 =
E. Left subclavicular thrill 0.25.

ANSWER: Please see Q-19 for Relative Risk

Bisferiens pulse
Q-206 A. 3.33
A 43-year-old man visits his GP because he is coughing up B. 75
green phlegm. He has chest pain on his left-hand side. On C. 10
examination, crackles can be heard in the base of his left D. 5
lung. He has bronchial breathing present too. He has reduced E. 2
chest expansion on his left side too. He has no significant
past medical history, except an allergy to penicillin. An x-ray ANSWER:
is performed and he is diagnosed with pneumonia. He is 10
started on doxycycline. What is the mechanism of action of
doxycycline? EXPLANATION:
NNT = 1 / Absolute Risk Reduction
A. Inhibit 50S subunit of ribosomes The question asks about the number needed to treat to save
B. Inhibit 30S subunit of ribosomes one life. The 'event' is therefore survival.
C. Inhibit protein wall synthesis
D. Inhibit DNA synthesis Experimental (drug A) event rate = 300 / 500 = 0.6
E. Inhibit RNA synthesis Control (placebo) event rate = 225 / 450 = 0.5

ANSWER: Absolute risk reduction = 0.6 - 0.5 = 0.1

Inhibit 30S subunit of ribosomes Number needed to treat = 1 / 0.1 = 10

EXPLANATION: Please see Q-92 for Numbers Needed to Treat and Absolute
Tetracyclines inhibit the 30S subunit of ribosomes Risk Reduction
Doxycycline is a tetracycline often prescribed for patients
allergic to penicillin and with mild pneumonia. Tetracyclines Q-208
inhibit the 30S subunit of ribosomes, which leads to an How is the left ventricular ejection fraction calculated?
inability of bacteria to produce proteins. Tetracyclines are
commonly confused with macrolides, which inhibit the 50S A. End systolic LV volume / end diastolic LV volume
subunit of ribosomes. B. End diastolic LV volume / end systolic LV volume
C. End diastolic LV volume / stroke volume
ANTIBIOTICS: PROTEIN SYNTHESIS INHIBITORS D. End systolic LV volume - end diastolic LV volume
Drug Mechanism of action Adverse effects Notes E. Stroke volume / end diastolic LV volume
Aminoglycosides Binds to 30S subunit Nephrotoxicity,
causing misreading of Ototoxicity
ANSWER:
mRNA
Stroke volume / end diastolic LV volume
Tetracyclines Binds to 30S subunit Discolouration of
blocking binding of teeth, photosensitivity
aminoacyl-tRNA EXPLANATION:
Chloramphenicol Binds to 50S subunit, Aplastic anaemia CARDIOVASCULAR PHYSIOLOGY
inhibiting peptidyl Left ventricular ejection fraction
transferase Left ventricular ejection fraction = (stroke volume / end
Clindamycin Binds to 50S subunit, Common cause of C. diastolic LV volume ) * 100%
inhibiting translocation difficilediarrhoea
(movement of tRNA Stroke volume = end diastolic LV volume - end systolic LV
from acceptor site to volume
peptidyl site)
Macrolides Binds to 50S subunit, Nausea (especially Commonly
Pulse pressure
inhibiting translocation erythromycin), P450 used for
(movement of tRNA inhibitor, prolonged patients
Pulse pressure = Systolic Pressure - Diastolic Pressure
from acceptor site to QT interval who are
peptidyl site) allergic to Factors which increase pulse pressure
penicillin • a less compliant aorta (this tends to occur with advancing
age)
Q-207 • increased stroke volume
A new drug is trialled for the treatment of lung cancer. Drug
A is given to 500 people with early stage non-small cell lung Q-209
cancer and a placebo is given to 450 people with the same Which one of the following statements best describes a type
condition. After 5 years 300 people who received drug A had II statistical error?
survived compared to 225 who received the placebo. What is
the number needed to treat to save one life?
A. The p value fails to reach statistical significance Q-210
B. A study fails to reach an appropriate power A 19-year-old female with a history of anorexia nervosa is
C. The null hypothesis is rejected when it is true admitted to hospital. Her BMI has dropped to 16. She has
D. The null hypothesis is accepted when it is false agreed to be fed by nasogastric tube. Which one of the
E. The alternative hypothesis is rejected when it is false following electrolyte disturbances is most likely to occur?

ANSWER: A. Hyperkalaemia
The null hypothesis is accepted when it is false B. Hypocalcaemia
C. Metabolic acidosis
EXPLANATION: D. Hypophosphataemia
SIGNIFICANCE TESTS E. Hypermagnesemia
A null hypothesis (H0) states that two treatments are equally
effective (and is hence negatively phrased). A significance test ANSWER:
uses the sample data to assess how likely the null hypothesis Hypophosphataemia
is to be correct.
EXPLANATION:
For example: Refeeding syndrome causes hypophosphataemia
• 'there is no difference in the prevalence of colorectal This patient is at risk of refeeding syndrome, which can lead
cancer in patients taking low-dose aspirin compared to to profound hypophosphataemia
those who are not'
HYPOPHOSPHATAEMIA
The alternative hypothesis (H1) is the opposite of the null Causes
hypothesis, i.e. There is a difference between the two • alcohol excess
treatments • acute liver failure
• diabetic ketoacidosis
The p value is the probability of obtaining a result by chance • refeeding syndrome
at least as extreme as the one that was actually observed, • primary hyperparathyroidism
assuming that the null hypothesis is true. It is therefore equal • osteomalacia
to the chance of making a type I error (see below).
Consequences
Two types of errors may occur when testing the null • red blood cell haemolysis
hypothesis • white blood cell and platelet dysfunction
• type I: the null hypothesis is rejected when it is true - i.e. • muscle weakness and rhabdomyolysis
Showing a difference between two groups when it • central nervous system dysfunction
doesn't exist, a false positive. This is determined against a
preset significance level (termed alpha). As the Q-211
significance level is determined in advance the chance of A 24-year-old female present with a tonic-clonic seizure
making a type I error is not affected by sample size. It is which self-resolved after 3 minutes. There was no warning
however increased if the number of end-points are before the seizure and her boyfriend says there was no
increased. For example if a study has 20 end-points it is incontinence or tongue biting. She complained she was
likely one of these will be reached, just by chance. having a mild headache, on and off for the last 2 weeks. Her
• type II: the null hypothesis is accepted when it is false - most recent travel history included a trip to Turkey 3 years
i.e. Failing to spot a difference when one really exists, a ago where she doesn't remember what she exactly ate.
false negative. The probability of making a type II error is There were no other symptoms. On examination, there were
termed beta. It is determined by both sample size and no signs of neurological deficit or signs of raised intracranial
alpha hypertension. She had a CT head which demonstrated
numerous small focal calcification throughout both cerebral
Study accepts H0 Study rejects H0 hemispheres with no enhancement. What is the most likely
Reality H0 Type 1 error (alpha) diagnosis?
Reality H1 Type 2 error (beta) Power (1 - beta)
A. Cerebral abscess
The power of a study is the probability of (correctly) rejecting B. Neurocysticercosis
the null hypothesis when it is false, i.e. the probability of C. Cerebral metastasis
detecting a statistically significant difference D. Amoebic encephalitis
• power = 1 - the probability of a type II error E. Tuberculomas
• power can be increased by increasing the sample size
ANSWER: Worm Notes Treatment
Neurocysticercosis eggs
Ancylostoma Larvae penetrate skin of feet; -bendazoles
EXPLANATION: duodenale, Necator gastrointestinal infection →
Neurocysticercosis often presents initially as a seizure. It also americanus(hookworms) anaemia
can present as headaches, altered mental state, and Thin-shelled ova
neurological deficits. It occurs from eating food or drinking Loa loa Transmission by deer fly and Diethylcarbamazine
mango fly
water contaminated by human faeces containing T. solium
eggs. The time between initial presentation and ingestion is Causes red itchy swellings
extremely varied. It has characteristic neuroimaging findings below the skin called
which depend on the stage of the disease. The stage 'Calabar swellings', may be
described in this patient is the nodular calcified stage which observed when crossing
is represented here by multiple calcified lesions on the CT conjunctivae
head. It is important to note neurocysticercosis is extremely Trichinella spiralis Typically develops after -bendazoles
rare and on clinical examination alone, this diagnosis would eating raw pork
be very low on the list of differential diagnosis. The other 4
Features include fever,
options can all present as a tonic-seizure and headache. periorbital oedema and
However, the CT findings are only characteristic of myositis (larvae encyst in
neurocysticercosis. The other 4 options do not have such muscle)
characteristic CT findings of numerous small focal Onchocerca volvulus Causes 'river blindness'. Ivermectin
calcification throughout both hemispheres and therefore it is Spread by female blackflies rIVERblindness
impossible for these options to be the answer. As well as the = IVERmectin
characteristic imaging findings, the trip to Turkey is another Features include blindness,
hyperpigmented skin and
clue. Cerebral abscess, cerebral metastasis and tuberculomas
possible allergic reaction to
will all typically show enhancing lesions on CT. Amoebic microfilaria
encephalitis often appears normal on CT in the early stages
Wuchereria bancrofti Transmission by female Diethylcarbamazine
and then may show some patchy low-level enhancement mosquito
after that.
Causes blockage of
HELMINTHS lymphatics → elephantiasis
Nematodes (roundworms) Toxocara canis (dog Transmitted through Diethylcarbamazine
roundworm) ingestion of infective eggs.
Worm Notes Treatment
Features include visceral
Strongyloides stercoralis Larvae are present in soil and Ivermectin and -
larva migrans and retinal
gain access to the body by bendazoles are
granulomas
penetrating the skin used
VISCious dogs → blindness
Ascaris lumbricoides(giant Eggs are visible in faeces -bendazoles
Features include diarrhoea,
roundworm)
abdominal pain,
May cause intestinal
papulovesicular lesions
obstruction and occasional
where the skin has been
migrate to lung (Loffler's
penetrated by infective
syndrome)
larvae e.g. soles of feet and
buttocks, larva currens:
pruritic, linear, urticarial rash, Cestodes (tapeworms)
if the larvae migrate to the Worm Notes Treatment
lungs a pneumonitis similar Echinococcus Transmission through ingestion of eggs -bendazoles
to Loeffler's syndrome may granulosus in dog faeces. Definite host is dog, which
be triggered ingests hydatid cysts from sheep, who act
Enterobius Threadworm infestation is -bendazoles as an intermediate host. Often seen in
vermicularis(pinworm) asymptomatic in around 90% farmers.
of cases, possible features
include perianal itching, Features include liver cysts and
particularly at night; girls anaphylaxis if cyst ruptures (e.g. during
may have vulval symptoms surgical removal)
Taenia solium Often transmitted after eating -bendazoles
Diagnosis may be made by undercooked pork. Causes cysticercosis
the applying sticky plastic and neurocysticercosis, mass lesions in
tape to the perianal area and the brain 'swiss cheese appearance'
sending it to the laboratory
Fasciola May cause biliary obstruction Triclabendazole
for microscopy to see the
 Worm Notes Treatment Q-213
hepatica(the liver Which layer of the epidermis is immediately next to the
fluke) dermis?

Trematodes (flukes) A. Stratum granulosum

Worm Notes Treatment B. Stratum lucidum
Schistosoma Hosted by snails, which release cercariae Praziquantel C. Stratum corneum
haematobium that penetrate skin. D. Stratum germinativum
Causes 'swimmer's itch' - frequency, E. Stratum spinosum
haematuria. Risk factor for squamous cell
bladder cancer
ANSWER:
Paragonimus Caused by undercooked crabmeat, Praziquantel
Stratum germinativum
westermani results in secondary bacterial infection of
lungs
Clonorchis sinensis Caused by undercooked fish Praziquantel
EXPLANATION:
Epidermis - 5 layers - bottom layer = stratum germinativum
Features include biliary tract which gives rise to keratinocytes and contains melanocytes
inflammation. Known risk factor for
cholangiocarcinoma Please see Q-111 for Epidermis

Q-212 Q-214
A 23-year-old female patient presents to the emergency Which one of the following cell organelles contains double-
department with a 24-hour-history of gradual-onset global stranded circular DNA?
headache, fever and photophobia. On examination, there is
neck stiffness and an area of non-blanching rash on the right A. Nucleus
shin. She had 3 episodes of meningococcal meningitis in the B. Ribosome
past. She was started on ceftriaxone for suspected C. Nucleolus
meningitis. In the mean time, you suspect that the patient D. Golgi apparatus
may have an immunodeficiency. E. Mitochondria

Which immunodeficiency is she likely to have? ANSWER:

Mitochondria
A. C1q, C1rs, C2, C4 deficiency
B. C10 deficiency EXPLANATION:
C. C5 deficiency Please see Q-135 for Cell Organelles
D. C1 inhibitor (C1-INH) protein deficiency
E. C5-9 deficiency Q-215
A 46-year-old female is referred to the dermatologist for a
ANSWER: rash on both her elbows. The rash is red, is papulovesicular
C5-9 deficiency in nature, and looks like it has many small blisters. The
dermatologist diagnoses her with dermatitis herpetiformis.
EXPLANATION: Which HLA haplotype is this associated with?
C5-9 deficiency predisposes to Neisseria meningitidis
infections A. HLA-A3
C5-9 deficiency predisposes to Neisseria meningitidis B. HLA-B5
infections. C. HLA-DR3
D. HLA-DR4
C1q, C1rs, C2, C4 deficiency (classic pathway components) E. HLA-B27
predisposes to SLE.
ANSWER:
C5 deficiency predisposes to Leiner disease (recurrent
HLA-DR3
diarrhoea, wasting and seborrhoeic dermatitis).

C1 inhibitor (C1-INH) protein deficiency causes hereditary EXPLANATION:

angioedema. Dermatitis herpetiformis is associated with HLA-DR3
Dermatitis herpetiformis is an autoimmune condition
There is no C10 complement. associated with HLA-DR3.

Please see Q-39 for Complement Deficiencies

HLA-A3 is associated with haemochromatosis. HLA-B5 is EXPLANATION:
most commonly associated with Behcet's disease. HLA-DR4 is By far the best option here is to speak to the consultant on-
associated with both type 1 diabetes mellitus and call. The physio may be experienced in providing NIV but it is
rheumatoid arthritis. HLA-B27 is most commonly associated ultimately a medical decision about whether to start a
with several diseases, most commonly ankylosing treatment.
spondylitis.
Accepting her opinion is a poor option as she has not
Please see Q-80 for HLA Associations reviewed the patient herself and is only giving an opinion on
the basis of blood gases.
Q-216
Which one of the following immunoglobulins are present in Setting up NIV equipment requires training. If done
the lowest concentration in blood? incorrectly it could potentially harm a patient. Transferring
an acutely unwell patient simply because the physio won't
A. IgA come in is not appropriate. Lying about clinical information is
B. IgE a very poor option.
C. IgG
D. IgM Q-218
E. IgD A scientist is investigating Chronic Myeloid Leukaemia (CML).
He develops a fluorescent DNA probe to bind to BCR-ABL
ANSWER: fusion gene for direct visualisation of Philadelphia
IgE translocation.

EXPLANATION: Which molecular technique is he using?

Whilst the majority of IgA is found in secretions there is a
significant quantity present in blood. IgE makes up less than A. Southern blot
0.1% of immunoglobulins B. DNA Microarray
C. Fluorescence In Situ Hybridisation (FISH)
Please see Q-190 for Immunoglobulins D. Northern blot
E. Flow cytometry
Q-217
You are a ST1 doctor in medicine. Whilst on-call you review a ANSWER:
60-year-old woman who is known to have COPD. She has Fluorescence In Situ Hybridisation (FISH)
been admitted with an infective exacerbation and has not
responded to nebulisers and intravenous aminophylline. Her EXPLANATION:
most recent blood gases show a worsening respiratory Fluorescence in situ hybridization uses fluorescent DNA or
acidosis. You feel that non-invasive ventilation (NIV) is RNA probe to bind to specific gene site of interest for direct
needed and bleep the on-call physio. After discussing the visualisation of chromosomal anomalies
blood gas results over the phone she says that NIV is not Fluorescence in situ hybridization uses fluorescent DNA or
indicated in her opinion and refuses to set it up. What is the RNA probe to bind to specific gene site of interest for direct
most appropriate action? visualisation of chromosomal anomalies.

A. Phone her back in 30 minutes and exaggerate the clinical
picture to persuade her to come in
B. Accept her professional opinion and reassess the
situation in 30 minutes
C. Set-up the NIV equipment yourself to avoid any further
delay
D. As there is a disagreement on management speak to the
consultant on-call
E. Transfer the patient to another hospital
Please see Q-15 for Molecular Biology Techniques
Q-219
A randomised controlled trial is performed to look at a new
drug to prevent hip fractures in postmenopausal women.
Group A consists of 1,000 women who take the new drug
whilst group B contains 1,400 women taking a placebo. The
hip fracture rate in group A is 2% and in group B is 4%. What
is the number needed to treat to prevent one hip fracture?

ANSWER: A. 10
As there is a disagreement on management speak to the B. 50
consultant on-call C. 6
D. 12
E. 2
ANSWER:
50
EXPLANATION:
NNT = 1 / Absolute Risk Reduction
They key to answering this question is to ignore irrelevant
data such as the number of patients in each group.
Control event rate = 4% = 0.04
Experimental event rate = 2% = 0.02
Absolute risk reduction = 0.04 - 0.02 = 0.02
Number needed to treat = 1 / 0.02 = 50
Please see Q-92 for Numbers Needed to Treat and Absolute
Risk Reduction
Q-220
Which one of the following statements regarding
epidemiological measures is correct?
A. Cross-sectional surveys can be used to estimate the
prevalence of a condition in the population
B. In chronic diseases the incidence is much greater than
the prevalence
C. Incidence = prevalence * duration of condition
D. The prevalence is the number of new cases per
population in a given time period
E. Pre-test probability = 1 / incidence
ANSWER:
Cross-sectional surveys can be used to estimate the
prevalence of a condition in the population
EXPLANATION:
Please see Q-7 for Incidence and Prevalence
Q-221
A case-control study is being designed to look at the
relationship between epilepsy and a new vaccine for
varicella. What is the usual outcome measure in a case-
control study?
A. Numbers needed to harm
B. Odds ratio
C. Experimental event rate
D. Absolute risk increase
E. Relative risk
ANSWER:
Odds ratio
EXPLANATION:
Case-control studies - odds ratio
Please see Q-53 for Study Design
Q-222
Which one of the following statements is true regarding the
radial nerve?
A. Damage at the axilla would lead to wrist drop
B. Damage at the wrist leads to wasting of the thenar
muscles
C. It supplies the lateral 2 lumbricals
D. It supplies sensation to the lateral one and a half fingers
E. It is derived from C6-8 and T1
ANSWER:
Damage at the axilla would lead to wrist drop
EXPLANATION:
RADIAL NERVE
Continuation of posterior cord of the brachial plexus (root
values C5 to T1)
Path
• In the axilla: lies posterior to the axillary artery on
subscapularis, latissimus dorsi and teres major.
• Enters the arm between the brachial artery and the long
head of triceps (medial to humerus).
• Spirals around the posterior surface of the humerus in the
groove for the radial nerve.
• At the distal third of the lateral border of the humerus it
then pierces the intermuscular septum and descends in
front of the lateral epicondyle.
• At the lateral epicondyle it lies deeply between brachialis
and brachioradialis where it then divides into a superficial
and deep terminal branch.
• Deep branch crosses the supinator to become the
posterior interosseous nerve.
In the image above the relationships of the radial nerve can be appreciated
Regions innervated
Motor (main nerve) • Triceps
• Anconeus
• Brachioradialis
• Extensor carpi radialis
Motor (posterior • Supinator Q-223
interosseous • Extensor carpi ulnaris A 43-year-old man requests a 'medical' as he is concerned
branch)
• Extensor digitorum about his risk of heart disease. His father died at the age of
• Extensor indicis 45-years following a myocardial infarction. His lipid profile is
• Extensor digiti minimi as follows:
• Extensor pollicis longus and brevis
• Abductor pollicis longus HDL 1.4 mmol/l
LDL 5.7 mmol/l
Sensory The area of skin supplying the proximal phalanges on Triglycerides 2.3 mmol/l
the dorsal aspect of the hand is supplied by the radial Total cholesterol 8.2 mmol/l
nerve (this does not apply to the little finger and part
of the ring finger) Clinical examination reveals tendon xanthomata around his
ankles. What is the most likely diagnosis?
Muscular innervation and effect of denervation
Anatomical A. Familial hypercholesterolaemia (heterozygous)
location Muscle affected Effect of paralysis B. Nephrotic syndrome
Shoulder Long head of triceps Minor effects on shoulder stability C. Mixed hyperlipidaemia
in abduction D. Familial hypercholesterolaemia (homozygous)
Arm Triceps Loss of elbow extension E. Hypothyroidism
Forearm Supinator Weakening of supination of prone
Brachioradialis hand and elbow flexion in mid
ANSWER:
Extensor carpi radialis prone position
Familial hypercholesterolaemia (heterozygous)
longus and brevis

EXPLANATION:
Patterns of damage
The presence of tendon xanthomata and cholesterol levels
• wrist drop
meet the diagnostic criteria for familial
• sensory loss to small area between the dorsal aspect of
hypercholesterolaemia. Homozygous familial
the 1st and 2nd metacarpals
hypercholesterolaemia is exceedingly rare - most patients die
in their teenage years from a myocardial infarction.
Axillary damage
• as above
Please see Q-33 for Familial Hypercholesterolaemia
• paralysis of triceps
Q-224
A 67-year-old man presents to the emergency department
with lethargy, abdominal pain and polyuria. He underwent a
cadaveric renal transplant for end-stage renal disease two
months ago. He has a background of type 2 diabetes mellitus
and diabetic nephropathy.

Bloods indicate the following:

Na+ 135 mmol/l

K+ 4.6 mmol/l
Urea 8 mmol/l
Creatinine 110 µmol/l
Corrected Ca2+ 3.16 mmol/l
Phosphate 0.6 mmol/l
HbA1C 48 mmol/l
Parathyroid hormone 100 ng/l
(reference range 10-65ng/l)

What is the most likely diagnosis?

A. Tertiary hyperparathyroidism
B. Secondary hyperparathyroidism
The cutaneous sensation of the upper limb- illustrating the contribution of the
radial nerve C. Graft rejection
D. Vitamin D deficiency
E. Poorly controlled diabetes
ANSWER: Differential diagnoses
Tertiary hyperparathyroidism It is important to consider the rare but relatively benign
condition of benign familial hypocalciuric hypercalcaemia,
EXPLANATION: caused by an autosomal dominant genetic disorder. Diagnosis
Tertiary hyperparathyroidism is an important differential in is usually made by genetic testing and concordant
hypercalcaemia post renal replacement therapy biochemistry (urine calcium : creatinine clearance ratio <0.01-
This is tertiary hyperparathyroidism. Most patients with distinguished from primary hyperparathyroidism).
chronic kidney disease develop a degree of secondary
hyperparathyroidism prior to renal transplantation. Treatment
Secondary hyperparathyroidism is associated with hypo- or
normocalcaemia. Following renal replacement therapy, up to Primary hyperparathyroidism
half of these patients develop persistent Indications for surgery
hyperparathyroidism with or without hypercalcaemia, this is • Elevated serum Calcium > 1mg/dL above normal
termed tertiary hyperparathyroidism. A minority of these • Hypercalciuria > 400mg/day
patients will become symptomatic.
• Creatinine clearance < 30% compared with normal
• Episode of life threatening hypercalcaemia
Graft rejection would not be most likely here, the creatinine
• Nephrolithiasis
is only mildly elevated, other electrolytes are within normal
• Age < 50 years
limits. Vitamin D deficiency would not be associated with
hypercalcaemia. Diabetic control is good. • Neuromuscular symptoms
• Reduction in bone mineral density of the femoral neck,
PARATHYROID GLANDS AND DISORDERS OF CALCIUM lumbar spine, or distal radius of more than 2.5 standard
METABOLISM deviations below peak bone mass (T score lower than -
Hyperparathyroidism 2.5)
Disease type Hormone profile Clinical features Cause
Primary • PTH • May be Most cases due Secondary hyperparathyroidism
hyperparathyroidism (Elevated) asymptomatic if to solitary Usually managed with medical therapy.
• Ca2+(Elevated) mild adenoma
• Recurrent (80%), •
• Phosphate Indications for surgery in secondary (renal)
abdominal pain multifocal
(Low) hyperparathyroidism:
(pancreatitis, disease occurs
• Urine calcium
renal colic) in 10-15% and • Bone pain
: creatinine •
• Changes to parathyroid Persistent pruritus
clearance
ratio > 0.01
emotional or carcinoma in • Soft tissue calcifications
cognitive state 1% or less
Tertiary hyperparathyroidism
Secondary • PTH • May have few Parathyroid
Allow 12 months to elapse following transplant as many cases
hyperparathyroidism (Elevated) symptoms gland
• Eventually hyperplasia will resolve
• Ca2+ (Low or
normal) may develop occurs as a The presence of an autonomously functioning parathyroid
bone disease, result of low gland may require surgery. If the culprit gland can be
• Phosphate
osteitis fibrosa calcium, almost identified then it should be excised. Otherwise total
(Elevated)
cystica and soft always in a parathyroidectomy and re-implantation of part of the gland
• Vitamin D
tissue setting of
levels (Low) may be required.
calcifications chronic renal
failure
Q-225
Tertiary • Ca2+(Normal • Metastatic Occurs as a
hyperparathyroidism calcification result of A study is designed to see whether the degree of chest pain
or high)
• Bone pain and ongoing is linked to the troponin I value for patients admitted
• PTH
(Elevated) / or fracture hyperplasia of following a myocardial infarction. The pain is assessed using
• the parathyroid a scale of 1-10, with 10 representing the worst pain that the
• Phosphate
Nephrolithiasis glands after patient has ever experienced. Which one of the following
levels
• Pancreatitis correction of
(Decreased significance tests is it most appropriate to use to investigate
underlying
or Normal) this link?
renal disorder,
• Vitamin D
hyperplasia of
(Normal or A. Student's t-test
all 4 glands is
decreased)
usually the B. Chi-squared test
• Alkaline cause C. Spearman's rank correlation coefficient
phosphatase
(Elevated)
D. Pearson's product-moment coefficient
E. Mann-Whitney test
ANSWER:
Spearman's rank correlation coefficient
EXPLANATION:
This scenario looks at whether the values are correlated. As
the data is non-parametric, particularly the observation
based pain scale, Spearman's rank correlation coefficient
should be used.
Please see Q-30 for Significance Tests: Types
Q-226
A newborn female baby is diagnosed with cystic fibrosis
following an episode of meconium ileus shortly after birth.
Which one of the following is least likely to occur as a
consequence of her underlying diagnosis?
EXPLANATION:
Liddle's syndrome: hypokalaemia + hypertension
Liddle's syndrome is an autosomal dominant disorder that
mimics hyperaldosteronism, resulting in hypokalaemia
associated with hypertension.
Bartter's syndrome is an inherited cause (usually autosomal
recessive) of severe hypokalaemia due to defective chloride
absorption at the Na+ K+ 2Cl- cotransporter in the ascending
loop of Henle. It should be noted that it is associated with
normotension.
Gitelman's syndrome is due to a defect in the thiazide-
sensitive Na+ Cl- transporter in the distal convoluted tubule.
It is associated with hypokalaemia and normotension.

A. Delayed puberty HYPOKALAEMIA AND HYPERTENSION

B. Nasal polyps For exams it is useful to be able to classify the causes of
C. Diabetes mellitus hypokalaemia in to those associated with hypertension, and
D. Rectal prolapse those which are not
E. Arthropathy
Hypokalaemia with hypertension
ANSWER: • Cushing's syndrome
Arthropathy • Conn's syndrome (primary hyperaldosteronism)
• Liddle's syndrome
EXPLANATION: • 11-beta hydroxylase deficiency*
Arthropathy is not a common feature of cystic fibrosis
Carbenoxolone, an anti-ulcer drug, and liquorice excess can
CYSTIC FIBROSIS: FEATURES potentially cause hypokalaemia associated with hypertension
Presenting features
• neonatal period (around 20%): meconium ileus, less Hypokalaemia without hypertension
commonly prolonged jaundice • diuretics
• recurrent chest infections (40%) • GI loss (e.g. Diarrhoea, vomiting)
• malabsorption (30%): steatorrhoea, failure to thrive • renal tubular acidosis (type 1 and 2**)
• other features (10%): liver disease • Bartter's syndrome
• Gitelman syndrome
Other features of cystic fibrosis
• short stature *21-hydroxylase deficiency, which accounts for 90% of
• diabetes mellitus congenital adrenal hyperplasia cases, is not associated with
• delayed puberty hypertension
• rectal prolapse (due to bulky stools)
• nasal polyps **type 4 renal tubular acidosis is associated with
• male infertility, female subfertility hyperkalaemia

Q-227 Q-228
Which one of the following is a recognised cause of Which foramen does the maxillary nerve go through?
hypokalaemia associated with hypertension
A. Jugular foramen
A. Liddle's syndrome B. Foramen ovale
B. Bartter's syndrome C. Superior orbital fissure
C. Gitelman syndrome D. Optic canal
D. Ciclosporin E. Foramen rotundum
E. Renal tubular acidosis
ANSWER:
ANSWER: Foramen rotundum
Liddle's syndrome
EXPLANATION: A. 20 extra patients in the placebo group had a stroke
FORAMINA OF THE SKULL B. For 1000 patients treated with active therapy, there
Questions asking about foramina of the skull have come up in would be 50 fewer strokes
the exam in previous years. Below is a brief summary of the C. For 1000 patients treated with active therapy, there
major foramina, please see the Wikipedia link for a full list. would be 20 fewer strokes
D. For every 1000 patients treated with active therapy
Foramen Bone Vessels Nerves there would be 100 fewer strokes
Optic canal Sphenoid Ophthalmic artery Optic nerve (II) E. 20 patients in the treatment group were protected from
Superior Sphenoid Superior Oculomotor nerve (III) stroke
orbital fissure ophthalmic vein Trochlear nerve (IV)
Inferior lacrimal, frontal and ANSWER:
ophthalmic vein nasociliary branches of For 1000 patients treated with active therapy, there would be
ophthalmic nerve (V1)
50 fewer strokes
Abducent nerve (VI)
Inferior orbital Sphenoid and Inferior Zygomatic nerve and
fissure maxilla ophthalmic veins infraorbital nerve of
EXPLANATION:
Infraorbital artery maxillary nerve (V2) This prevention study for stroke reveals that 20 patients
Infraorbital vein Orbital branches of need to be treated to prevent one event.
pterygopalatine
ganglion Thus if you treat 1000 patients then you will expect to have
Foramen Sphenoid - Maxillary nerve (V2) 50 fewer strokes.
rotundum
Foramen ovale Sphenoid Accessory Mandibular nerve (V3) NNT is a time-specific epidemiological measure of the
meningeal artery
number of patients who need to be treated in order to
Jugular Occipital and Posterior Glossopharyngeal nerve prevent one adverse outcome. A perfect NNT would be 1,
foramen temporal meningeal artery (IX)
where everyone improves with treatment, thus the higher
Ascending Vagus nerve (X)
pharyngeal artery Accessory nerve (XI) the NNT, the less effective the treatment.
Inferior petrosal
sinus Please see Q-92 for Numbers Needed to Treat and Absolute
Sigmoid sinus Risk Reduction
Internal jugular
vein
Q-231
A male child from a travelling community is diagnosed with
Q-229
measles. Which one of the following complications is he at
Which one of the following techniques would be most
risk from in the immediate aftermath of the initial infection?
suitable to detect and quantify a viral protein?

A. Polymerase chain reaction A. Arthritis

B. Northern blotting B. Pancreatitis
C. Western blotting C. Infertility
D. Southern blotting D. Subacute sclerosing panencephalitis
E. Eastern blotting E. Pneumonia

ANSWER: ANSWER:
Western blotting Pneumonia
EXPLANATION:
EXPLANATION:
Molecular biology techniques
Subacute sclerosing panencephalitis is seen but develops 5-
SNOW (South - NOrth - West)
10 years following the illness. Pancreatitis and infertility may
DROP (DNA - RNA - Protein)
follow mumps infection
Please see Q-15 for Molecular Biology Techniques
MEASLES
Q-230 Measles is now rarely seen in the developed world following
A 64-year-old woman, whose husband had a TIA one month the adoption of immunisation programmes. Outbreaks are
ago brings you a newspaper article with the headline 'new occasionally seen, particularly when vaccinations rates drop,
super drug prevents stroke'. Reading through the article with for example after the MMR controversy of the early 2000's.
her, it states that a recent clinical trial has shown that a new
lipid-lowering therapy for stroke had a number needed to Overview
treat (NNT) of 20 for the prevention of the primary end- • RNA paramyxovirus
point. How do you best describe these results to her?
• spread by droplets
• infective from prodrome until 4 days after rash starts
• incubation period = 10-14 days
Features
• prodrome: irritable, conjunctivitis, fever
• Koplik spots (before rash): white spots ('grain of salt') on
buccal mucosa
• rash: starts behind ears then to whole body, discrete
maculopapular rash becoming blotchy & confluent
Management of contacts
• if a child not immunized against measles comes into
contact with measles then MMR should be offered
(vaccine-induced measles antibody develops more rapidly
than that following natural infection)
• this should be given within 72 hours
Q-232
A 36-year-old woman presents with a 3 week history of
weakness worse at the end of the day. In particular she
noticed difficulty getting out of her chair in the evening. Her
husband has noticed that whilst driving at night she
complains of difficulty keeping her eyes open, despite not
being tired.

On examination you note a bilateral facial nerve weakness,

complex ophthalmoplegia and symmetrical proximal power
loss (MRC power 4/5). Upon repetitive stimulation of
movements fatigability is noted.

What Gell and Coombs hypersensitivity class is she likely to

Koplik spots be suffering from?

Investigations A. Type 1
• IgM antibodies can be detected within a few days of rash B. Type 2
onset C. Type 3
D. Type 4
Management E. Type 5
• mainly supportive
• admission may be considered in immunosuppressed or ANSWER:
pregnant patients Type 5
• notifiable disease → inform public health
EXPLANATION:
Complications The patient is a young female presenting with a proximal
• encephalitis: typically occurs 1-2 weeks following the myopathy with complex ophthalmoplegia with evidence of
onset of the illness) fatigability. This picture is classic for myasthenia gravis. An
• subacute sclerosing panencephalitis: very rare, may autoimmune disease caused by antibodies to acetylcholine
present 5-10 years following the illness nicotinic postsynaptic receptors.
• febrile convulsions
Please see Q-26 for Hypersensitivity
• giant cell pneumonia
• keratoconjunctivitis, corneal ulceration
Q-233
• diarrhoea
A 22-year-old male university student presents to the GP
• increased incidence of appendicitis surgery with a 2-week history of a patch of red and flaky skin
• myocarditis at the corners of the mouth. On examination, angular
cheilitis is evident. On further questioning, he reports that
for the last 3-4 months he has been drinking alcohol
excessively and not eating well.

What is the most likely vitamin deficiency to cause this

clinical picture?

A. Vitamin B2 (riboflavin) deficiency

B. Vitamin B6 deficiency
C. Vitamin D deficiency
D. Vitamin A deficiency
The rash typically starts behind the ears and then spreads to the whole body E. Vitamin K deficiency
ANSWER: hepatosplenomegaly. The family history in the history
Vitamin B2 (riboflavin) deficiency indicates Gaucher's disease as the most likely.

EXPLANATION: Heart failure is unusual in children and does not usually

Riboflavin deficiency causes angular cheilitis cause massive splenomegaly.
Vitamin B2 (riboflavin) deficiency is a cause of angular
cheilitis. 3-4 months of inadequate intake of riboflavin is Chronic myeloid leukaemia can cause massive splenomegaly
sufficient to lead to depletion and becoming symptomatic. but it is unusual in children.

Vitamin B6 deficiency causes peripheral neuropathy.
Vitamin D deficiency causes osteomalacia.
Vitamin A deficiency causes visual deterioration and night
blindness.
Acute myeloid leukaemia can cause splenomegaly but
massive splenomegaly is rare. It is not usually inherited.
Kala azar, also known as visceral leishmaniasis, is a cause of
massive splenomegaly but given the lack of travel history, it
is unlikely.

Vitamin K deficiency causes easy bruising and bleeding. INHERITED METABOLIC DISORDERS
Glycogen storage disease
VITAMIN B2 (RIBOFLAVIN) Disorder Deficient enzyme Notes
Riboflavin is a cofactor of flavin adenine dinucleotide (FAD) Von Gierke's Glucose-6-phosphatase Hepatic glycogen accumulation. Key
and flavin mononucleotide (FMN) and is important in energy disease (type I) features include hypoglycaemia,
metabolism. lactic acidosis, hepatomegaly
Pompe's Lysosomal alpha-1,4- Cardiac, hepatic and muscle
Consequences of riboflavin deficiency: disease (type II) glucosidase glycogen accumulation. Key features
include cardiomegaly
• angular cheilitis
Cori disease Alpha-1,6-glucosidase Hepatic, cardiac glycogen
(type III) (debranching enzyme) accumulation. Key features include
Q-234 muscle hypotonia
A 3-year-old boy has been brought into the GP surgery by his McArdle's Glycogen phosphorylase Skeletal muscle glycogen
parents. He presents with pallor, lethargy and enlargement disease (type V) accumulation. Key features include
of the abdomen. The boy’s parents said that they only myalgia, myoglobulinaemia with
noticed these symptoms for the past 2 weeks but it has been exercise
gradually worsening over the longer period. The boy was
born in the UK by normal vaginal delivery following an Lysosomal storage disease
uncomplicated pregnancy. There is no significant past Disorder Defect Notes
medical history or recent travel history. The mother reports Gaucher's disease Beta- Most common lipid storage disorder
a family history of a form of metabolic disorder but couldn’t glucocerebrosidase resulting in accumulation of
remember the name. On examination, there is generalised glucocerebrosidase in the brain, liver
pallor. There is enlargement of the abdomen with massive and spleen. Key features include
hepatosplenomegaly, aseptic necrosis
splenomegaly which is firm but not tender. Hepatomegaly is
of the femur
also noted. There is no jaundice or lymphadenopathy.
Tay-Sachs disease Hexosaminidase A Accumulation of GM2 ganglioside
within lysosomes. Key features
What is the most likely diagnosis? include developmental delay, cherry
red spot on the macula, liver and
A. Gaucher's disease spleen normal size (cf. Niemann-Pick)
B. Heart failure Niemann-Pick Sphingomyelinase Key features include
C. Chronic myeloid leukaemia disease hepatosplenomegaly, cherry red spot
D. Acute myeloid leukaemia on the macula
E. Kala azar Fabry disease Alpha-galactosidase- Accumulation of ceramide
A trihexoside. Key features include
angiokeratomas, peripheral
ANSWER: neuropathy of extemeties, renal
Gaucher’s disease failure
Krabbe's disease Galactocerebrosidase Key features include peripheral
EXPLANATION: neuropathy, optic atrophy, globoid
Gaucher's disease is the most common lipid storage disorder cells
and a cause of hepatosplenomegaly Metachromatic Arylsulfatase A Demyelination of the central and
Gaucher's disease is an autosomal recessive disease and it is leukodystrophy peripheral nervous system
the most common lipid storage disorder. It's a cause of
Mucopolysaccharidoses
Disorder Defect Notes Latex-fruit syndrome
Hurler Alpha-1- Accumulation of glycosaminoglycans (heparan It is recognised that many people who are allergic to latex are
syndrome iduronidase and dermatan sulfate). Key features include also allergic to fruits, particularly banana, pineapple, avocado,
(type I) gargoylism, hepatosplenomegaly, corneal chestnut, kiwi fruit, mango, passion fruit and strawberry.
clouding
Hunter Iduronate Accumulation of glycosaminoglycans (heparan Q-237
syndrome sulfatase and dermatan sulfate). Key features include
Which one of the following may be used to calculate the
(type II) coarse facial features, behavioural
problems/learning difficulties short stature, no number needed to treat?
corneal clouding
A. 1 / (Absolute risk reduction)
Q-235 B. (Absolute Risk Reduction) / (Number of people in trial)
The chance of a 45-year-old mother giving birth to a child C. ((Control event rate) - (Experimental event rate)) /
with Down's syndrome is approximately: (Control event rate)
D. 1 / (Relative risk)
A. 1 in 5 E. 1 / (Hazard ratio)
B. 1 in 10
C. 1 in 50 ANSWER:
D. 1 in 100 1 / (Absolute risk reduction)
E. 1 in 500
EXPLANATION:
ANSWER: NNT = 1 / Absolute Risk Reduction
1 in 50
Please see Q-92 for Numbers Needed to Treat and Absolute
EXPLANATION: Risk Reduction
Down's syndrome risk - 1/1,000 at 30 years then divide by 3
for every 5 years Q-238
A study is designed to compare the calcium levels of males
Please see Q-14 for Down’s Syndrome: Epidemiology and and females who have Crohn's disease. The investigators aim
Genetics to discover whether there is a difference between the
average calcium level in males compared to females. From
Q-236 previous studies it is known that the calcium levels are
A nurse who is known to have an allergy to latex develops a normally distributed. Which one of the following statistical
widespread urticarial rash and facial oedema shortly after tests is it most appropriate to use?
eating lunch. Which food is she most likely to have
consumed? A. Pearson's test
B. Mann-Whitney test
A. Peanut C. Chi-squared test
B. Apple D. Student's unpaired t-test
C. Grapes E. Student's paired t-test
D. Pear
E. Banana ANSWER:
Student's unpaired t-test
ANSWER:
Banana EXPLANATION:
As the data is parametric and compares two independent
EXPLANATION: sample from the same population an unpaired t-test is the
The nurse is likely to suffer from latex-fruit syndrome. most appropriate test to use

LATEX ALLERGY Please see Q-30 for Significance Tests: Types

Sensitivity to latex may cause a number of problems:
• type I hypersensitivity (anaphylaxis) Q-239
• type IV hypersensitivity (allergic contact dermatitis) Which of the following statements is true regarding
• irritant contact dermatitis hyponatraemia?

Latex allergy is more common in children with

myelomeningocele spina bifida.
A. In a dehydrated patient with urinary sodium < A. Sensitivity / (1 - specificity)
20mmol/L it may be due to the diuretic stage of renal B. TP / (TP + FP)
failure C. TN / (TN + FP)
B. SIADH typically leads to urine osmolality of < 500 D. TN / (TN + FN)
mmol/kg E. TP / (TP + FN )
C. Hyperlipidaemia may cause pseudohyponatraemia
D. Cardiac failure and liver cirrhosis may lead to primary ANSWER:
hyperaldosteronism TP / (TP + FP)
E. It is known to cause a long QT interval
EXPLANATION:
ANSWER: Positive predictive value = TP / (TP + FP)
Hyperlipidaemia may cause pseudohyponatraemia
Please see Q-8 for Screening Test Statistics
EXPLANATION:
Please see Q-43 for Hyponatraemia Q-242
A 49-year-old man comes into clinic. One of his friends has
Q-240 recently had a myocardial infarction and he is concerned
A 10-year-old male is referred to an oncologist for suspected about his own risk of coronary heart disease. He has no past
lymphoma. His symptoms include fever, night sweats, medical history of note other than anxiety for which he is
weight loss and lymphadenopathy is present on not currently taking any medication. He does however
examination. Molecular testing and histological analysis of a smoke around 20 cigarettes a day. Cardiovascular
lymph node biopsy suggest a diagnosis of Burkitt's examination is unremarkable. His BMI is 26 kg/m² and blood
lymphoma. Which oncogene is associated with Burkitt's pressure is 126/82 mmHg.
lymphoma?
You strongly advise him to stop smoking. What is the most
A. ABL appropriate further course of action?
B. p53
C. n-MYC A. Reassure him that he has a very low risk of coronary
D. c-MYC heart disease given his age
E. HER2 B. Arrange a 24 hour blood pressure monitor
C. Arrange a lipid profile then calculate his QRISK2 score
ANSWER: D. Start orlistat
c-MYC E. Refer him for an exercise tolerance test

EXPLANATION: ANSWER:
Burkitt's lymphoma is commonly associated with c-MYC Arrange a lipid profile then calculate his QRISK2 score
Burkitt's lymphoma is classically associated with the
translocation: t(8;14). Here, the c-MYC gene is translocated EXPLANATION:
next to the gene for IgH. IgH is highly expressed in the body If we feed his age, gender and smoking history into QRISK2
(as it codes for the heavy chain of antibodies), and this leads this gives a 10-year-risk of cardiovascular disease (CVD) of
to an overamplification c-MYC. 13.9%. He is therefore an appropriate person to have a
'formal' assessment of CVD risk using a lipid profile to further
p53 is a tumour suppressor gene, not an oncogene. n-MYC inform the QRISK2 score.
comes from the same family as c-MYC but is found in
neuroblastoma. HER2 is found in breast cancer. ABL is found Please see Q-48 for Hyperlipidaemia: Management
chronic myeloid leukaemia.
Q-243
Please see Q-195 for Oncogenes Which one of the following best describes the function of the
p53 gene?
Q-241
What is the correct formula to calculate the positive A. Inhibits angiogenesis
predictive value? B. Oncogene
C. Encodes proteins which regulate the cell cycle
TP = true positive; FP = false positive; TN = true negative; FN D. Encodes proteins which activate of natural killer cells
= false negative E. Encodes proteins which directly repair damaged DNA
ANSWER:
Encodes proteins which regulate the cell cycle ANSWER:
Type IV reaction
EXPLANATION:
Whilst p53 can trigger cell cycle arrest to allow DNA to be EXPLANATION:
repaired the encoded proteins do not directly repair DNA. Type IV hypersensitivity reaction - allergic contact dermatitis
This patient has allergic contact dermatitis, which is
p53 commonly precipitated by nickel
p53 is a tumour suppressor gene located on chromosome 17p.
It is the most commonly mutated gene in breast, colon and Please see Q-26 for Hypersensitivity
lung cancer
Q-246
p53 is thought to play a crucial role in the cell cycle, A 45-year-old female with poorly controlled rheumatoid
preventing entry into the S phase until DNA has been checked arthritis attends a rheumatology appointment. She is started
and repaired. It may also be a key regulator of apoptosis on a new medication called anakinra, an IL-1 receptor
antagonist. Which cell is responsible for the production of IL-
Li-Fraumeni syndrome is a rare autosomal dominant disorder 1?
characterised by the early onset of a variety of cancers such as
sarcomas and breast cancer. It is caused by mutation in the A. Neutrophils
p53 gene B. Basophils
C. Eosinophils
Q-244 D. T cells
The parents of a 3-year-old boy with cystic fibrosis ask for E. Macrophages
advice. They are considering having more children. Neither
of the parents have cystic fibrosis. What is the chance that ANSWER:
their next child will be a carrier of the cystic fibrosis gene? Macrophages

A. 50% EXPLANATION:
B. 100% The main source of IL-1 is macrophages
C. 1 in 25 IL-1, an acute inflammatory cytokine, is mostly produced by
D. 25% innate immune cells. Within the innate immune system,
E. 66.6% macrophages are responsible for the production of cytokines,
including IL-1. Basophils, Neutrophils and Eosinophils all
ANSWER: produce proinflammatory cytokines but in lower volumes
50% than macrophages. T cells don't produce IL-1.

EXPLANATION: Please see Q-88 for Cytokines

As cystic fibrosis is an autosomal recessive condition there is
a 50% chance that their next child will be a carrier of cystic Q-247
fibrosis (i.e. be heterozygous for the genetic defect) and a Which of the following statements is true regarding the p53
25% chance that the child will actually have the disease (be gene?
homozygous).
A. It is an oncogene
Please see Q-85 for Cystic Fibrosis B. Mutation results in a gain of function
C. 50% of families with a strong history of breast cancer
Q-245 have a p53 mutation
A patient develops an eczematous, weeping rash on his wrist D. Li-Fraumeni syndrome predisposes to the development
following the purchase of a new watch. In the Gell and of sarcomas
Coombs classification of hypersensitivity reactions this is an E. It is located on chromosome 13
example of a:
ANSWER:
A. Type I reaction Li-Fraumeni syndrome predisposes to the development of
B. Type II reaction sarcomas
C. Type III reaction
D. Type IV reaction EXPLANATION:
E. Type V reaction Please see Q-243 for p53
Q-248 Deficiency of HGPRT and glucocerebrosidase are associated
Patients with deficiencies of which one of the following with Lesch-Nyhan syndrome and Gaucher disease
complement proteins are predisposed to Leiner disease? respectively. Hexosaminidase A deficiency is linked with Tay-
Sachs.
A. C1
B. C2 Fabry disease
C. C3 Fabry disease is an X-linked recessive disorder characterised
D. C4 by the deficiency of alpha-galactosidase A. This leads to
E. C5 accumulation of glycosphingolipids, namely
globotriaosylceramide, within the lysosomes of cells. It is the
ANSWER: second most prevalent lysosomal storage disorder after
C5 Gaucher disease.

EXPLANATION: Clinical features:

Please see Q-39 for Complement Deficiencies • Severe neuropathic/limb pain brought on by stress, heat,
or cold
Q-249 • Angiokeratomas
In terms of the cell cycle, which one of the following phases • Renal features: proteinuria, polyuria, polydipsia
determine the length of the cell cycle: • Cardiac: left ventricular hypertrophy, coronary artery
disease, valvular abnormalities and heart failure
A. M • Cerebrovascular: TIAs/strokes
B. M0
C. G1 Management:
D. S • Enzyme replacement therapy with agalsidase alfa
E. G2
Please see Q-234 for Inherited Metabolic Disorders
ANSWER:
G1 Q-251
During cell division, at what stage do sister chromatids move
EXPLANATION: to opposite ends of the cell?
Please see Q-151 for Cell Cycle
A. Prometaphase
Q-250 B. Metaphase
A 40-year-old man is admitted with an MI and transferred C. Anaphase
for an urgent PCI. On closer questioning, he has been D. Telophase
complaining of a severe burning sensation of his hands and E. Cytokinesis
feet. On examination, you notice multiple angiokeratomas in
a bathing-suit distribution. A urine dip reveals protein +++. A ANSWER:
diagnosis of Fabry disease is suspected. What is the most Anaphase
likely pathophysiology of the condition?
EXPLANATION:
A. Deficiency of HGPRT During mitosis, sister chromatids move to opposite ends of
B. Deficiency of TPMT the cell during anaphase
C. Deficiency of glucocerebrosidase Anaphase is split into 2 parts:
D. Deficiency of alpha-galactosidase A • anaphase A: cohesins that bind sister chromatids
E. Deficiency of hexosaminidase A together are cleaved, followed by shortening of the
kinetochore microtubules which pulls the daughter
ANSWER: chromosomes to opposite ends of the cell
Deficiency of alpha-galactosidase A • anaphase B: polar microtubules push against each other,
causing the cell to elongate
EXPLANATION: Please see Q-108 for Cell Division
Fabry disease is an X-linked recessive disorder characterised
by a deficiency of alpha-galactosidase A. Q-252
A 40-year-old woman with rheumatoid arthritis is diagnosed
A deficiency of TPMT is linked with severe bone marrow as having type 1 renal tubular acidosis. Which one of the
failure when these patients are given azathioprine of 6- following features is most likely to be seen as a
mercaptopurine. consequence?
A. Hyperkalaemia Type 4 RTA (hyperkalaemic)
B. Osteomalacia • reduction in aldosterone leads in turn to a reduction in
C. Decreased bicarbonate reabsorption in the proximal proximal tubular ammonium excretion
tubule • causes hyperkalaemia
D. Raised anion gap metabolic acidosis • causes include hypoaldosteronism, diabetes
E. Nephrocalcinosis
Q-253
ANSWER:
A 32-year-old female patient is referred by GP to the urology
Nephrocalcinosis
clinic for 6-months non-specific pain in the right lower back
EXPLANATION: and the abdomen, urinary frequency and haematuria. She is
Osteomalacia is more commonly seen in type 2 renal tubular originally from Ghana and moved to the UK 3 months ago.
acidosis. Ultrasound of the kidney ureters and bladder (KUB) shows
thickening of the bladder wall. CT KUB shows linear
RENAL TUBULAR ACIDOSIS calcification of the entire surface area of the bladder wall as
All three types of renal tubular acidosis (RTA) are associated well as part of the left ureter. On further questioning, the
with hyperchloraemic metabolic acidosis (normal anion gap) patient reports when she was living in Ghana, she has been
swimming in the local lake on a regular basis.
Type 1 RTA (distal)
• inability to generate acid urine (secrete H+) in distal Given the likely diagnosis, what would be the most
tubule appropriate treatment?
• causes hypokalaemia
• complications include nephrocalcinosis and renal stones A. Linezolid
• causes include idiopathic, RA, SLE, Sjogren's, B. Amoxicillin
amphotericin B toxicity, analgesic nephropathy C. Co-trimoxazole
D. Bendazole
E. Praziquantel

ANSWER:
Praziquantel

EXPLANATION:
Schistosoma haematobium can be treated with praziquantel
This patient likely has Schistosoma haematobium, which can
be treated with praziquantel.

Helminth infections are not usually treatable with antibiotics

such as linezolid and amoxicillin.

Co-trimoxazole is not usually used for the treatment of

helminth infections.

Bendazole is used to treat a variety of helminth infections

but not Schistosoma haematobium.

Please see Q-211 for Helminths

Q-254
A study is designed to look at the efficacy of a mandible
advancement device in reducing snoring. The severity of
Abdominal x-ray showing nephrocalcinosis - a classical finding in type 1 RTA snoring was assessed by the partner using a 10 point scale
before and after using the device. Fifty people were involved
Type 2 RTA (proximal) in the study. What is the most appropriate statistical test to
• decreased HCO3- reabsorption in proximal tubule apply to this data?
• causes hypokalaemia
• complications include osteomalacia A. Unpaired Student's t-test
• causes include idiopathic, as part of Fanconi syndrome, B. Pearson's product-moment coefficient
Wilson's disease, cystinosis, outdated tetracyclines, C. Wilcoxon signed-rank test
carbonic anhydrase inhibitors (acetazolamide, D. Chi-squared test
topiramate) E. Mann-Whitney test
ANSWER:
Wilcoxon signed-rank test
EXPLANATION:
The data in this study is non-parametric, paired and comes
from the same population. These factors make the Wilcoxon
signed-rank test the most appropriate statistical hypothesis
test to use.
Please see Q-30 for Significance Tests: Types
Q-255
Which one of the following statements regarding the normal
distribution is correct?
A. Is a discrete probability distribution
B. 99.7% of values lie within 2 standard deviations of the
mean
C. Mean = mode = median
D. Standard deviation = mean / square root (variance)
E. Is also referred to as the binomial distribution
ANSWER:
Mean = mode = median
EXPLANATION:
The Normal distribution is a continuous probability
distribution
Please see Q-23 for Normal Distribution
Q-256
A 68-year-old man is admitted with haematemesis. A
gastroscopy performed as an inpatient shows a carcinoma
which is confirmed on biopsy. Who is the most appropriate
person to inform the patient of the diagnosis?
A. The F2 doctor on the ward who has most contact with
the patient
B. The doctor who performed the gastroscopy
C. His GP following discharge
D. The consultant in-charge of his care
E. His next-of-kin after you have told him/her
ANSWER:
The consultant in-charge of his care
EXPLANATION:
One of the key aims of the entrance exam is to assess a
doctors ability to act in a compassionate and empathetic
way. Many of you may recall incidences of patients being
told about a cancer diagnosis in inappropriate
circumstances.
The most appropriate person to inform the patient is the
consultant in this scenario. He/she is currently in charge of
their care and will be best placed to answer questions about
management and prognosis. The F2 doctor will be less able
to do this but will at least be known to the patient.
The doctor who performed the gastroscopy is unlikely to
know the patient apart from their brief meeting prior to the
procedure. Asking the GP to tell the patient is a 'cop-out' on
a number of levels. Firstly the patient may feel that the
hospital team 'could not be bothered' to tell him themselves.
Secondly it results in an unnecessary delay and thirdly the GP
may not be best placed to give information on management
and prognosis.
Telling the next-of-kin is the worst option as it breaks
confidentiality.
Q-257
A 24-year-old male is admitted with a head injury.
Approximately one hour ago he was hit on the lateral aspect
of his head by a high velocity cricket ball. A collateral history
reveals that he lost consciousness immediately after the
impact. Paramedics on the scene noted his Glasgow coma
score of 15. On examination he has Glasgow coma score of
13 (M5, V4, E4) on arrival in the department. He has
anterograde and retrograde amnesia to events. You arrange
an urgent CT scan.
Which clinical sign would be most concerning in this patient?
A. Pyrexia
B. Hypotension
C. Bradycardia
D. Tachycardia
E. Decreased pulse pressure
ANSWER:
Bradycardia
EXPLANATION:
The Cushing reflex is a physiological nervous system
response to increased intracranial pressure (ICP) that results
in hypertension and bradycardia
The mechanism of injury, loss of consciousness and 'lucid
interval' should ring alarm bells for an extradural
haematoma. The Cushing reflex is a physiological nervous
system response to increased intracranial pressure that
results in hypertension and bradycardia. Cerebral perfusion
pressure (CPP) = mean arterial pressure (MAP) - intracranial
pressure. Therefore if intracranial pressure is high, the only
way the body can compensate to increase CPP is by
increasing MAP. A sympathetic reflex therefore results in
hypertension. This results in a counter parasympathetic
reflex by stimulation of the baroreceptors resulting in
bradycardia.
CEREBRAL PERFUSION PRESSURE
The cerebral perfusion pressure (CPP) is defined as being the
net pressure gradient causing blood flow to the brain. The CPP
is tightly autoregulated to maximise cerebral perfusion. A
sharp rise in CPP may result in a rising ICP, a fall in CPP may ANSWER:
result in cerebral ischaemia. It may be calculated by the Bicuspid aortic valve
following equation:
EXPLANATION:
CPP= Mean arterial pressure - Intra cranial pressure Please see Q-16 for Turner’s Syndrome

Following trauma, the CPP has to be carefully controlled and Q-261

the may require invasive monitoring of the ICP and MAP. A 23-year-old gentleman is referred to the respiratory clinic
with a possible diagnosis of bronchiectasis. He has been
Q-258 suffering from recurrent chest infections his entire life and
Which one of the following is not a recognised cause of has also struggled to maintain a healthy weight. He has no
hypocalcaemia? smoking history and no notable family history. He has tried
inhalers but these have had no noticeable effect. He is
A. Hypoparathyroidism suspected of having cystic fibrosis and genetic tests are sent
B. Bendroflumethiazide for analysis.
C. Pseudohypoparathyroidism
D. Acute pancreatitis What is the normal function of the cystic fibrosis
E. Acute rhabdomyolysis transmembrane regulator?

ANSWER: A. Signalling molecule

Bendroflumethiazide B. Water channel
C. Potassium channel
EXPLANATION: D. Chloride channel
Please see Q-32 for Hypocalcaemia: Causes and E. Sodium channel
Management
ANSWER:
Q-259 Chloride channel
Each one of the following statements regarding atrial
natriuretic peptide are true, except: EXPLANATION:
The correct answer is chloride channel, specifically a cyclic-
A. Lowers blood pressure AMP regulated chloride channel. There are many different
B. Degraded by endopeptidases mutations which can cause cystic fibrosis but they all disrupt
C. Promotes excretion of sodium the same gene, the cystic fibrosis transmembrane
D. Secreted mainly by the left atrium conductance regulator gene. This is a chloride channel which
E. Antagonises actions of angiotensin II and aldosterone when not functioning leads to increased viscosity of
secretions, which leads to the pathology of cystic fibrosis.
ANSWER:
Secreted mainly by the left atrium Please see Q-85 for Cystic Fibrosis

EXPLANATION: Q-262
Please see Q-156 for Atrial Natriuretic Peptide Where are G protein-coupled receptors located?

Q-260 A. Nucleus
An 18-year-old female who is known to have Turner's B. Golgi apparatus
syndrome is referred to cardiology as she has a murmur. On C. Ribosome
examination a soft ejection systolic murmur is heard. What D. Cell membrane
is the most likely cause of this finding? E. Mitochondria

A. Coarctation of the aorta ANSWER:

B. Ventricular septal defect Cell membrane
C. Pulmonary stenosis
D. Supravalvular aortic stenosis EXPLANATION:
E. Bicuspid aortic valve G protein-coupled receptors span the cell membrane

Turner's syndrome - most common cardiac defect is bicuspid Please see Q-154 for Membrane Receptors
aortic valve
Q-263 WILMS' TUMOUR
A 64-year-old female patient is referred to the Wilms' nephroblastoma is one of the most common childhood
gastroenterology clinic with a 6-month history of recurrent malignancies. It typically presents in children under 5 years of
epigastric pain, acid reflux unresponsive to antacids and a age, with a median age of 3 years old.
trial of proton-pump inhibitor. Gastroscopy is arranged
which shows an ulcer in the descending duodenum and a Features
tumour in the antrum of the stomach. • abdominal mass (most common presenting feature)
• painless haematuria
Which type of cell this does this tumour originates from? • flank pain
• other features: anorexia, fever
A. S cells • unilateral in 95% of cases
B. G cells • metastases are found in 20% of patients (most commonly
C. I cells lung)
D. D cells
E. H cells Associations
• Beckwith-Wiedemann syndrome
ANSWER: • as part of WAGR syndrome with Aniridia, Genitourinary
G cells malformations, mental Retardation
• hemihypertrophy
EXPLANATION:
• around one-third of cases are associated with a loss-of-
Gastrin is produced by the G cells in the antrum of the
function mutation in the WT1 gene on chromosome 11
stomach
The tumour in this patient is most likely a gastrinoma.
Management
Gastrinoma secretes excessive gastrin which causes
• nephrectomy
increased HCL production, resulting in peptic ulcers. Gastrin
• chemotherapy
is usually produced by the G cells in the antrum of the
• radiotherapy if advanced disease
stomach.
• prognosis: good, 80% cure rate
S cells secrete secretin.

I cells secrete CCK.

D cells secrete somatostatin.

There is no such cell as H cell in the stomach.

Please see Q-18 for Gastrointestinal Hormones

Q-264
A two-year old boy presents with an abdominal mass. Which
of the following is associated with Wilm's tumour
(nephroblastoma)?
Histological features include epithelial tubules, areas of necrosis, immature
glomerular structures, stroma with spindle cells and small cell blastomatous
A. Deletion on short arm of chromosome 12
tissues resembling the metanephric blastema
B. Tuberose sclerosis
C. Beckwith-Wiedemann syndrome Q-265
D. Autosomal dominant polycystic kidney disease You are caring for a local cardiology consultant's father who
E. Autosomal recessive polycystic kidney disease has been admitted following a myocardial infarction. He
bleeps you from the switchboard and asks how his father is
ANSWER: doing. You recognise his voice on the phone. What is the
Beckwith-Wiedemann syndrome most appropriate response?
EXPLANATION: A. Decline to give any details over the phone but offer to
Beckwith-Wiedemann syndrome is a inherited condition meet the consultant face-to-face for a chat
associated with organomegaly, macroglossia, abdominal B. As a matter of professional courtesy ask for his advice
wall defects, Wilm's tumour and neonatal hypoglycaemia. on post-myocardial infarction care
C. Ask permission from his father then give relevant details
D. Give full details include the troponin I value and offer to Q-267
fax the ECG A scientist is studying the role of regulatory proteins in
E. Say he is 'doing fine' intracellular trafficking. He has isolated and identified
various intracellular proteins tagged with extensive
ANSWER: ubiquitination.
Ask permission from his father then give relevant details
These proteins are destined to which of the following
EXPLANATION: organelles?
The main nub of this question relates to confidentiality. You
cannot give details over the phone to anyone, even his son, A. Smooth endoplasmic reticulum
without the patient's express permission. Whilst it may be B. Rough endoplasmic reticulum
presumed that this is what the patient would want it is C. Golgi apparatus
impossible to be sure of the family dynamics. D. Proteasome
E. Peroxisome
If the patient has given permission and you are sure you are
speaking to the son then giving relevant details is the best ANSWER:
option. Asking the consultant to come in as an option but Proteasome
may not be necessary if the previous conditions are met.
Saying he is 'doing fine' is unlikely to satisfy a consultant EXPLANATION:
cardiologist. Ubiquitin tagging destines proteins to proteasome for
degradation
Giving details without first getting permission from the Ubiquitin tags proteins for degradation in proteasome and
patient is breaking confidentiality, however well intentioned. lysosome.
Involving a relative in the management of a patient is
inappropriate and the worst option. Please see Q-135 for Cell Organelles

Q-266 Q-268
A 34-year-old female is referred to the oncologist due to a A 22 year-old man is referred to clinic with refractory
suspicion of lymphoma. She has suffered from a fever and hypertension.
night sweats. Moreover, she has previously suffered from
glandular fever. On examination, her cervical lymph nodes Potassium 2.7mmol/l
are swollen. She undergoes a lymph node biopsy with
staining for a cell surface marker. This reveals the presence Other U&E, FBC, calcium and LFTs are normal. Which would
of Reed-Sternberg cells, confirming a diagnosis of Hodgkin's be the most appropriate next investigation?
lymphoma. Which cell surface marker is associated with
Reed-Sternberg cells? A. CT abdomen
B. MR angiography renal tract
A. CD3 C. 24 hour urinary catecholamines
B. CD4 D. USS abdomen
C. CD15 E. Plasma renin and aldosterone levels
D. CD16
E. CD21 ANSWER:
Plasma renin and aldosterone levels
ANSWER:
CD15 EXPLANATION:
The differential for hypertension with low potassium includes
EXPLANATION: Conn's, Cushing's, renal artery stenosis and Liddle's. The first
CD15 is found on Reed-Sternberg cells step in this case should be further simple investigations.
CD15 is found on Reed-Sternberg cells. Reed-Sternberg cells Quantifying the renin and angiotensin levels will help to
are found in those with Hodgkin's lymphoma. distinguish the cause here, before going on to more
specialised tests.
CD3 is found on all T cells. CD4 is found on T helper cells. Cushing's and Conn's would be associated with a high
CD16 binds to the Fc portion of IgG. CD21 is the receptor for aldosterone and a low renin, renal artery stenosis would be
the Epstein-Barr virus. associated with a high renin and aldosterone, Liddle's is
associated with a low renin and aldosterone.
Please see Q-97 for Cell Surface Proteins
Please see Q-227 for Hypokaleimia and Hypertension
Q-269 ANSWER:
Which one of the following statements best describes a type Cod liver oil
I statistical error?
EXPLANATION:
A. The null hypothesis is rejected when it is true Cod liver oil provides around 1,300 IU per 15 ml serving
B. The null hypothesis is accepted when it is false
C. The p value fails to reach statistical significance VITAMIN DEFICIENCY
D. The alternative hypothesis is rejected when it is true The table below summarises vitamin deficiency states
E. A study fails to reach an appropriate power

ANSWER: Vitamin Chemical name Deficiency state

The null hypothesis is rejected when it is true A Retinoids Night-blindness (nyctalopia)
B1 Thiamine Beriberi
EXPLANATION:
Please see Q-209 for Significance Tests
• polyneuropathy, Wernicke-Korsakoff
Q-270 syndrome
A patient comes into the GP due to a dry cough. He mentions • heart failure
that he becomes very easily short of breath and feels
feverish. He admits to being an intravenous drug user. He is B3 Niacin Pellagra
referred to the sexual health clinic and is diagnosed with HIV
after blood tests. Which cell surface protein does HIV use to
enter cells? • dermatitis
• diarrhoea
A. CD3 • dementia
B. CD4
C. CD5 B6 Pyridoxine Anaemia, irritability, seizures
D. CD8 B7 Biotin Dermatitis, seborrhoea
E. CD14 B9 Folic acid Megaloblastic anaemia, deficiency during
pregnancy - neural tube defects
ANSWER:
B12 Cyanocobalamin Megaloblastic anaemia, peripheral
CD4 neuropathy

EXPLANATION: C Ascorbic acid Scurvy

HIV uses CD4 to enter cells
The patient in this scenario has Pneumocystis pneumonia, a
lung infection from the fungus Pneumocystis jiroveci, which • gingivitis
affects immunocompromised patients. HIV uses CD4 to enter • bleeding
cells - this is why specifically T helper cells are reduced in
patients with HIV. D Ergocalciferol, Rickets, osteomalacia
cholecalciferol
CD3 is a cell surface protein found on all T cells. CD5 is a cell E Tocopherol, tocotrienol Mild haemolytic anaemia in newborn
surface marker commonly found in mantle cell lymphomas. infants, ataxia, peripheral neuropathy
CD8 is a cell surface marker found on cytotoxic T cells. CD14 K Naphthoquinone Haemorrhagic disease of the newborn,
is a cell surface marker found on macrophages. bleeding diathesis

Please see Q-97 for Cell Surface Proteins Q-272

Q-271 Which one of the following statements regarding nitric oxide
A 61-year-old female who has recently emigrated from the is incorrect?
Indian subcontinent presents with muscle weakness. Bloods A. Promotes platelet aggregation
reveal a low serum calcium. A diagnosis of osteomalacia is B. Raises intracellular cGMP levels
suspected. Which one of the following, per average serving, C. An inducible form of NOS is present in macrophages
provides the best source of vitamin D? D. In sepsis increased levels of NO contribute to septic
A. Lentils shock
B. Sunflower seeds E. Causes venodilation
C. Salmon
D. Cod liver oil ANSWER:
E. Milk Promotes platelet aggregation
EXPLANATION: A. Apolipoprotein SP-B
Nitric oxide - vasodilation + inhibits platelet aggregation B. Phosphatidylglycerol
Nitric oxide inhibits, rather than promotes, platelet C. Pulmonary elastase
aggregation D. Apolipoprotein SP-A
E. Dipalmitoyl phosphatidylcholine
Please see Q-118 for Nitric Oxide
ANSWER:
Q-273 Dipalmitoyl phosphatidylcholine
A 3-year-old boy is investigated for lethargy. Examination is
unremarkable with a blood pressure of 90/46 mmHg (normal EXPLANATION:
for his age). Blood tests reveal: Pulmonary surfactant - main constituent is dipalmitoyl
phosphatidylcholine (DPPC)
Na+ 140 mmol/l
K+ 2.6 mmol/l Please see Q-59 for Pulmonary Surfactant
Bicarbonate 33 mmol/l
Urea 4.2 mmol/l Q-276
Creatinine 91 µmol/l You are a ST1 doctor in medicine. A 67-year-old man has
been investigated for anaemia and weight loss. Endoscopy
Which one of the following conditions is most likely to be shows a gastric tumour which is confirmed as an
responsible? adenocarcinoma on biopsy. On discussing the diagnosis the
patient states that he has had 'a good life' and doesn't want
A. Cushing's syndrome any treatment. Clinical examination is unremarkable. He is
B. Conn's syndrome able to retain and understand the information you give to
C. 11-beta hydroxylase deficiency him, including the likely curative nature of surgery. What is
D. Bartter's syndrome the most appropriate action?
E. Liddle's syndrome
A. Respect his wishes and book a follow-up appointment
ANSWER: for four weeks
Bartter's syndrome B. Arrange a CT head and check bloods to exclude cerebral
metastases and hypercalcaemia
EXPLANATION: C. Arrange an appointment with a psychiatrist
Bartter's syndrome is associated with normotension D. Detain him under the Mental Health Act
Bartter's syndrome is an inherited cause (usually autosomal E. Ask to speak to his wife alone to find out why he is
recessive) of severe hypokalaemia due to defective chloride refusing surgery
absorption at the Na+ K+ 2Cl- cotransporter in the ascending
loop of Henle ANSWER:
Respect his wishes and book a follow-up appointment for four
Please see Q-227 for Hypokaleimia and Hypertension weeks

EXPLANATION:
Q-274 This question is ultimately about autonomy. By being able to
Which one of the following serum proteins is most likely to understand and retain the information you give him the
increase in a patient with severe pneumococcal pneumonia? patient has demonstrated that he is competent to make
decisions. It should be noted that the Mental Capacity Act
A. Transferrin 2005 states that 'a person is not to be treated as unable to
B. Transthyretin make a decision merely because he makes an unwise
C. Ferritin decision'.
D. Albumin
E. Cortisol binding protein A CT head and bloods may exclude causes that would impair
judgement but would you override his decision even if you
ANSWER: noticed evidence of a cerebral metastase? As there is no
Ferritin evidence that this man is suffering from a mental illness
referral to a psychiatrist would be inappropriate.
EXPLANATION:
Please see Q-27 for Acute Phase Proteins By speaking to the wife alone you are risking breaching
confidentiality. Detaining him under the Mental Health Act
Q-275 simply because you disagree with his decision is clearly
What is the main constituent of pulmonary surfactant? wrong
Q-277 Q-279
Which one of the following foods is the best source of folic A 25-year-old female patient presents to the emergency
acid? department with a 2-day history of bloody diarrhoea and
abdominal pain. She was admitted under the medical team
A. Cheese for intravenous rehydration therapy. The next day, she
B. Red meat developed general oedema with sudden drop in her urine
C. Liver output. An urgent blood sample was sent with the results
D. Fish below.
E. Milk

ANSWER: Hb 9.0 g/dL

Liver Urea 30.3 mmol/L
Creatinine 285μmol/L
EXPLANATION: Peripheral blood film presence of schistocytes
Folic acid is also present in green vegetables and nuts
What is the likely infection causing this clinical picture?
FOLATE METABOLISM
Drugs which interfere with metabolism A. Salmonella
• trimethoprim B. Shigella
• methotrexate C. Campylobacter
• pyrimethamine D. E. coli O157: H7
E. Cholera
Drugs which can reduce absorption
• phenytoin ANSWER:
E.coli O157: H7
Q-278
You are trying to assess the risk of hepatic dysfunction
EXPLANATION:
associated with a new drug for the treatment of cardiac
E.coli O157: H7 is the strain causing haemolytic uraemic
failure. In total there have been 5 phase 3 studies and a
syndrome
cardiac outcome study has been published.
The clinical picture suggests the haemolytic uraemic
Which of the following is the optimal way to assess the risk syndrome. The patient has a combination of bloody
of hepatic dysfunction? diarrhoea, acute renal failure with a high urea and
haemolytic anaemia (as confirmed by the presence of
A. Case control study schistocytes). E.coli O157: H7 is the strain causing haemolytic
B. Cohort study uraemic syndrome.
C. Mechanistic study in patients with hepatic dysfunction
D. Meta-analysis of published randomised controlled trials Salmonella, shigella and campylobacter can cause bloody
E. New prospective randomised controlled trial diarrhoea but do not commonly cause haemolytic anaemia.
ANSWER:
Cholera is not a cause of bloody diarrhoea.
Meta-analysis of published randomised controlled trials

EXPLANATION: ESCHERICHIA COLI

In this situation, time is of the essence in evaluating the Escherichia coli is a facultative anaerobic, lactose-fermenting,
possible signal of hepatic dysfunction because of risk to Gram negative rod which is a normal gut commensal.
patients. By amalgamating data from published randomised
controlled trials, one single study which would not have the E. coli infections lead to a variety of diseases in humans
power to detect a signal for hepatic dysfunction could be including:
combined with others to confirm or refute any risk of • diarrhoeal illnesses
incident liver disease. This is, therefore, the preferred option. • UTIs
• neonatal meningitis
A case-control study is unlikely to have the granularity to
confirm or refute risk of incident liver disease, and a cohort Serotypes
study would be a massive and lengthy undertaking. A new E. coli may be classified according to the antigens which may
prospective randomised controlled trial would have to be trigger an immune response:
large and long to confirm a liver signal, and a mechanistic
study in patients with hepatic dysfunction may well not be Antigen Origin Notes
reflective of the population of clinical use. O Lipopolysaccharide
Please see Q-53 for Study Design layer
Antigen Origin Notes Student's paired t-test
K Capsule Neonatal meningitis secondary to E. coli is usually caused
by a serotype that contains the capsular antigenEXPLANATION:
K-1
H Flagellin Please see Q-30 for Significance Tests: Types

E. coli O157:H7 is a particular strain associated with severe, Q-282

haemorrhagic, watery diarrhoea. It has a high mortality rate Which one of the following is in direct anatomical contact
and can be complicated by haemolytic uraemic syndrome. It is with the right kidney?
often spread by contaminated ground beef.
A. Gallbladder
B. Liver
C. Stomach
D. Distal part of small intestine
E. Duodenum

ANSWER:
Duodenum

EXPLANATION:
Please see Q-181 for Renal Anatomy
Scanning electron micrograph of Escherichia coli, grown in culture and adhered to
a cover slip. Credit: NIAID
Q-283
Q-280 A 36-year-old female comes in complaining of back pain. On
A 23-year-old man presents with a three day history of examination, she has a loss of sensation of the kneecaps.
general malaise and low-grade temperature. Yesterday he Which dermatome has been compromised?
developed extensive painful ulceration of his mouth and
gums. On examination his temperature is 37.4ºC, pulse 84 / A. L2
min and there is submandibular lymphadenopathy. What is B. L3
the most likely diagnosis? C. L4
D. L5
A. Epstein Barr virus E. S1
B. Lichen planus
C. HIV seroconversion illness ANSWER:
D. Herpes simplex virus infection L4
E. Oral Candida
EXPLANATION:
ANSWER: The L4 dermatome is located at the knee caps
Herpes simplex virus infection The L4 dermatome is most easily tested at the kneecaps.

EXPLANATION: Please see Q-31 for Dermatomes

This man has gingivostomatitis, a characteristic feature of
primary herpes simplex virus infection Q-284
A 45-year-old female is brought to the emergency
Please see Q-17 for Herpes Simplex Virus department by an ambulance after she was found collapsed
on the street by a bystander. Within few minutes of arrival,
Q-281 she developed severe abdominal pain. She became severely
A study measures a patients serum cholesterol before and agitated. Her respiratory rate is 35 breaths per minute, heart
after a new lipid-lowering therapy has been given. What rate 110 beats per minute, temperature 39.3ºC. Her
type of significance test should be used to analyse the data? prothrombin time and activated partial thromboplastin time
are increased, and his fibrinogen levels are lower than
A. Student's paired t-test normal. His D-dimer is positive.
B. Student's unpaired t-test
C. Chi-squared test Hb 96 g/l
D. Pearson's test Platelets 85 * 109/l
E. Spearman test WBC 14 * 109/l

ANSWER: Blood smears are sent to the laboratory.


What is most likely to be seen in the blood smears?
A. Heinz bodies
B. Bite cells
C. Dacrocytes
D. Schistocytes
E. Elliptocytes
ANSWER:
Schistocytes
EXPLANATION:
Schistocytes are seen on blood smears in DIC
Also known as 'consumptive coagulopathy,' DIC is a
syndrome in which the coagulation cascade is activated to
the point in which normal mechanisms of clotting are
exhausted, which in turn produces unchecked haemorrhage.
Typically, haemostasis is maintained by maintaining a
balance between clot formation (i.e. coagulation) and
breakdown (i.e. fibrinolysis). Thrombin is produced through
the activation of the coagulation cascade. Thrombin converts
fibrinogen to fibrin (the final product of clotting). Fibrinolysis
is the breakdown of fibrinogen and fibrin. In the presence of
thrombin, a substance called plasmin is generated, breaking
down formed clots. Fibrin degradation products (FDPs) or
fibrin split products (FSPs) are produced as a result.
Thrombin plays a key role in hemostasis, in both coagulation
and fibrinolysis.
Patients with DIC can present with a wide range of
abnormalities in their laboratory values. Typically, prolonged
coagulation times, thrombocytopenia, high levels of fibrin
degradation products (FDPs), elevated D-dimer levels, and
microangiopathic pathology (schistocytes) on peripheral
smears are suggestive findings.
The activation of the cascade leads to thrombi formation
which causes an accumulation of excess fibrin formation in
the intravascular circulation. The excess fibrin strands cause
mechanical damage to the red blood cells resulting in
schistocyte formation and also thrombocytopenia and
consumption of clotting factors.
A bite cell is an abnormally shaped red blood cell with one or
more semicircular portions removed from the cell margin.
These “bites” result from the removal of denatured
haemoglobin by macrophages in the spleen. Glucose-6-
phosphate dehydrogenase deficiency (G6PD), in which
uncontrolled oxidative stress causes haemoglobin to
denature and form Heinz bodies, is a common disorder that
leads to the formation of bite cells.
The Heinz Bodies are seen as antigenic and are quickly
phagocytosed. Because the Heinz Bodies are derivatives of
haemoglobin, they are located inside the cell, and thus
phagocytosis takes a significant “bite” out of the cell.
Dacrocytes (teardrop cells) are usually characteristic of
myelofibrosis and seen with marrow disorders or marrow
infiltrations, really because of improper production of blood
cells from the bone marrow. In post-splenectomy patients,
the number of dacrocytes drastically increases, since the
spleen cannot remove the improperly formed cells.
Red cells varying in shape from elongated to oval, and rich in
haemoglobin, are called elliptocytes. They can be seen in
hereditary disorders, such as hereditary elliptocytosis, or in
acquired disorders, such as iron deficiency anaemia,
infectious anaemias, thalassaemia, and in newborn babies.
DISSEMINATED INTRAVASCULAR COAGULATION
Simultaneous coagulation and haemorrhage caused by initially
formation of thrombi which consume clotting factors (factors
5,8) and platelets, ultimately leading to bleeding
Causes include:
• Infection
• Malignancy
• Trauma e.g. major surgery, burns, shock, dissecting aortic
aneurysm
• Liver disease
• Obstetric complications
Key points
• Clinically bleeding is usually a dominant feature, bruising,
ischaemia and organ failure
• Blood tests: prolonged clotting times, thrombocytopenia,
decreased fibrinogen, increased fibrinogen degradation
products
• Treat the underlying cause and supportive management
Q-285
A 15-year-old boy is reviewed. He has been referred by his
GP with ptosis, diplopia and night blindness. On examination
he is noted to have a degree of ophthalmoplegia, bilateral
partial ptosis and evidence of retinitis pigmentosa during
fundoscopy. His mother developed a similar problem when
she was 18-years-old. What is the most likely diagnosis?
A. Kearns-Sayre syndrome
B. Alport's syndrome
C. Usher syndrome
D. Refsum disease
E. Lawrence-Moon-Biedl syndrome
ANSWER:
Kearns-Sayre syndrome
EXPLANATION:
Kearns-Sayre syndrome
• mitochondrial inheritance
• onset < 20-years-old
• external ophthalmoplegia
• retinitis pigmentosa
Please see Q-76 for Mitochondrial Diseases
Q-286
In 2015 The New England Journal of Medicine reported that
that the sodium-glucose co-transporter 2 inhibitor,
empagliflozin, resulted in a reduction in cardiovascular
deaths, non- fatal myocardial infarction and non-fatal stroke
when added to standard care in patients with type 2
diabetes at high risk of cardiovascular events. They
expressed the result per 1000 patient years, with
empagliflozin having an event rate of 37.3/1000 patient
years and placebo an event rate of 43.9/1000 patient years.
Using this information, approximately how many patients at
high risk of adverse cardiovascular outcome need to be
treated with empagliflozin to prevent one cardiovascular
death, non-fatal myocardial infarction or non-fatal stroke?
A. 1000
B. 150
C. 200
D. 50
E. 100
ANSWER:
150
EXPLANATION:
It is important to be able to interpret clinical papers correctly
so that information can be expressed in a clinically
meaningful way. The number needed to treat (NNT) is one
such method and is the inverse of the absolute risk reduction:
NNT= 1/ Absolute risk reduction
The absolute risk reduction is the change in the risk of an
outcome of a given treatment in relation to the comparison
treatment. It is the difference between the treatment event
rate and the control event rate.
The tricky part of this question is that the data is expressed
per 1000 patient years. When a study outcome is based on
time of exposure (patient-years), the NNT is calculated based
on cumulative event proportions. This requires some complex
calculations which you would never be expected to perform
in an exam (you aren't allowed calculators); however, a
quick way to get an estimate of the number needed to treat
is by performing the following calculation:
ARR=(Control event rate expressed per 1000 patient years) -
(Experimental event rate expressed per 1000 patient years)
For the above question:
ARR=43.9-37.3
ARR= 6.6/1000 patient years
NNT=(Patient years)/ARR
NNT= 1000/ 6.6
NNT= 151.5 (which is closest to 150, the correct answer here)
Please see Q-92 for Numbers Needed to Treat and Absolute
Risk Reduction
Q-287
A 28-year-old man is admitted to the Emergency Department
with dyspnoea and fever. Two days ago he developed an
itchy, vesicular rash after coming into contact with a child
who had chickenpox. On examination his temperature is
38.6ºC, respiratory rate 24 / min, pulse 120 / min and blood
pressure 135/68 mmHg. Oxygen saturations are 95% on
room air. Examination of chest reveals only occasional fine
crackles bilaterally. What is the most important
intervention?
A. Elective intubation within the next 2 hours
B. Prednisolone
C. Varicella zoster immunoglobulin
D. IV aciclovir
E. Paracetamol
ANSWER:
IV aciclovir
EXPLANATION:
Varicella pneumonia is the most common and serious
complication of chickenpox infection in adults. Auscultation
of the chest is often unremarkable. Varicella zoster
immunoglobulin is used for the prevention of varicella in at-
risk groups (e.g. Immunocompromised, pregnant women),
rather than for treatment
Please see Q-191 for Chickenpox
Q-288
A new blood test which can show signs of myocardial
damage within one hour of the onset of chest pain is
developed. In a trial of 100 patients presenting with chest
pain, 40 of the patients are later proven to have had
myocardial ischaemia by conventional troponin tests. Of
these patients the new test was positive in 20 cases. The
new test was also positive in 20 of the remaining 60 patients
later shown to have a negative troponin. What is the
negative predictive value of the new test for myocardial
ischaemia?
A. 0.5 A. 15%
B. 0.66 B. 10%
C. 0.8 C. 12
D. Cannot calculate D. 5%
E. 0.33 E. 20

ANSWER: ANSWER:
0.66 5%

EXPLANATION:
The new test was negative in 20 of the patients later shown
to have myocardial ischaemia (false negative) and negative
in 40 patients confirmed not to have myocardial ischaemia
(true negative)
Negative predictive value = TN / (TN + FN)
= 40 / (40 + 20) = 0.66
Please see Q-8 for Screening Test Statistics
EXPLANATION:
Absolute risk reduction = (Control event rate) - (Experimental
event rate)
Control event rate = 60 / 240 = 0.25
Experimental event rate = 24 / 120 = 0.2
Absolute risk reduction = 0.25 - 0.2 = 0.05 = 5% reduction
Please see Q-92 for Numbers Needed to Treat and Absolute
Risk Reduction

Q-289 Q-291
A 23-year-old man is admitted with sepsis. Blood cultures A 23-year-old female with Down's syndrome is reviewed in
are reported as follows: clinic. Which one of the following features is least associated
with her condition?
Neisseria gonorrhoeae
A. Infertility
Which of the following complement proteins is the patient B. Hypothyroidism
most likely to deficient in? C. Alzheimer's disease
D. Short stature
A. C1q, C1rs, C2, C4 E. Ventricular septal defect
B. C3a + C5a
C. C5-9 ANSWER:
D. C4 Infertility
E. C2
EXPLANATION:
ANSWER: As this patient is female she is likely to be subfertile rather
C5-9 than infertile - please see the notes below

EXPLANATION: Please see Q-172 for Down’s Syndrome: Features

Whilst C3 deficiency is associated with recurrent bacterial
infections, C5 deficiency is more characteristically associated
with disseminated meningococcal infection and other Gram
negative diplococcal infections
Please see Q-39 for Complement Deficiencies
Q-290
A study is designed to assess a new proton pump inhibitor
(PPI) in elderly patients who are taking aspirin. The new PPI
is given to 120 patients whilst a control group of 240 is given
the standard PPI. Over a five year period 24 of the group
receiving the new PPI had an upper GI bleed compared to 60
who received the standard PPI. What is the absolute risk
reduction?
Q-292
A 30-year-old male patient is referred by the GP to the
infectious disease team with a 10-months history of the
gradual appearance of an increasing number of painless
nodules on the neck, face and arms. He admits to travelling
to India 4 months prior to the appearance of the first nodule.
Whilst he was in India, he stayed with a local family for one
month, during which he was served meat including pork. On
further questioning, he admits that 6 months ago, he noticed
passing a noodle-like material in his stool but did not seek
medical attention. He also admits to general weight loss for
the last 8 months but he has been going to the gym. On
examination, there are 10 different subcutaneous nodules in
total. The skin biopsy of one of the nodules on the arm
shows the nodule to be a white cystic structure.
Given the likely diagnosis, what would be the most Q-294
appropriate treatment to start him on? Which one of the following statements regarding
leukotrienes is not true?
A. Praziquantel
B. Bendazoles A. Secreted by leukocytes
C. Quinine B. Formed from arachidonic acid
D. Penicillin C. Attract leukocytes
E. Flucloxacillin D. Cause bronchodilation
ANSWER: E. Increase vascular permeability
Bendazoles
ANSWER:
EXPLANATION: Cause bronchodilation
Cysticercosis can be treated with bendazoles
This patient has disseminated cysticercosis. Cysticercosis can EXPLANATION:
be treated with bendazoles. LEUKOTRIENES

Praziquantel is used to treat schistosomiasis. Function

Quinine is an anti-malarial.
Penicillin and flucloxacillin are not usually used to treat
cysticercosis.
Please see Q-211 for Helminths
Q-293
A study looks at the use of bisphosphonates in controlling
the pain associated with bone metastases. One hundred and
twenty patients (120) are enrolled in the study, 40 of whom
are given conventional treatment with NSAIDs and
radiotherapy. Of the 80 patients who were given
bisphosphonates, 40 received significant pain relief.
What is the odds of a patient with bone metastases receiving
significant pain relief from bisphosphonates?
• mediators of inflammation and allergic reactions
• cause bronchoconstriction, mucous production
• increase vascular permeability, attract leukocytes
• leukotriene D4 has been identified as the SRS-A (slow
reacting substance of anaphylaxis)
Production
• secreted by leukocytes
• formed from arachidonic acid by action of lipoxygenase
• it is thought that the NSAID induced bronchospasm in
asthmatics is secondary to the express production of
leukotrienes due to the inhibition of prostaglandin
synthetase
Q-295
Which of the following conditions is inherited in an
autosomal recessive fashion?

A. 0.33 A. Familial adenomatous polyposis

B. 3 B. Noonan syndrome
C. 2 C. Malignant hyperthermia
D. 1 D. Antithrombin III deficiency
E. 0.5 E. Congenital adrenal hyperplasia

ANSWER: ANSWER:
1 Congenital adrenal hyperplasia

EXPLANATION:
The question is limited to the 80 patients who've been given
bisphosphonates. Odds are a ratio of the number of people
who incur a particular outcome to the number of people who
do not incur the outcome.
40 of the 80 patients received significant pain relief
EXPLANATION:
Autosomal recessive conditions are 'metabolic' - exceptions:
inherited ataxias
Autosomal dominant conditions are 'structural' - exceptions:
hyperlipidaemia type II, hypokalaemic periodic paralysis

It can therefore be inferred that 40 of the 80 patients did not Please see Q-54 for Autosomal Recessive Conditions
receive significant pain relief.

Therefore the odds are 40 / 40 = 1

Please see Q-93 for Odds and Odds Ratio

Q-296 CLINICAL TRIAL: PHASES
A 34-week-old baby was born by emergency caesarean Clinical trials are commonly classified into 4 phases;
section due to placental abruption. Polyhydramnios was
detected antenatal but no cause found. Whilst on the Phase Goal Notes
neonatal unit, the baby showed failure to thrive, occasional I Determines pharmacokinetics Conducted on healthy volunteers
vomiting. Blood gas showed hypokalaemia, hyponatraemia, and pharmacodynamics and side-
hypochloraemia and metabolic alkalosis. Subsequently effects prior to larger studies
excessive sodium, potassium and chloride were found in the II Assess efficacy + dosage Involves small number of patients
urine. affected by particular disease

May be subdivided into

What is the most likely diagnosis?

A. Diabetes insipidus
• IIa - assesses optimal
B. Syndrome of inappropriate ADH
dosing
C. Addison's disease
• IIb - assesses efficacy
D. Bartter's syndrome
E. Diabetes mellitus
III Assess effectiveness Typically involves 100-1000's of
people, often as part of a
ANSWER: randomised controlled trial,
Bartter's syndrome comparing new treatment with
established treatments
EXPLANATION: IV Postmarketing surveillance Monitors for long-term
Bartter's syndrome is a cause of metabolic alkalosis effectiveness and side-effects
This baby presents with symptoms and signs of Bartter's
syndrome. Bartter's syndrome is a cause of metabolic Q-298
alkalosis along with excessive loss of sodium, potassium and Which one of the following cardiac tissue types has the
chloride. Polyhydramnios is typical in the neonatal form of highest conduction velocity?
Bartter's syndrome.
A. Atrial myocardial tissue
Diabetes insipidus typically presents with hypernatraemia B. Ventricular myocardial tissue
rather than hyponatraemia as in this case. C. Purkinje fibres
D. Atrioventricular node
Addison's disease typically presents with hyperkalaemia and E. Sinoatrial node
in some cases metabolic acidosis.
ANSWER:
Diabetes mellitus does not typically cause metabolic Purkinje fibres
alkalosis.
EXPLANATION:
Please see Q-159 for Metabolic Alkalosis Please see Q-62 for Cardiac Action Potential

Q-297 Q-299
A new drug is being developed by a pharmaceutical company A new drug designed to prevent exacerbations of genital
to help treat ovarian cancer. Which phase of clinical trials herpes undergoes clinical trials. One hundred patients are
specifically looks at the efficacy of the drug? given the new drug. During a three month period 10 of the
patients have an episode of genital herpes. In the control
A. Phase I group there are 300 patients who are given a placebo. In this
B. Phase IIa group 50 people have an exacerbation during the same time
C. Phase IIb period. What is the relative risk of having an exacerbation of
D. Phase III genital herpes whilst taking the new drug?
E. Phase IV
A. 0.8
ANSWER: B. 0.2
Phase IIb C. 1.66
D. 0.6
EXPLANATION: E. 0.06

ANSWER:
0.6
 ANSWER:
EXPLANATION: C5
Experimental event rate, EER = 10 / 100 = 0.10

Control event rate, CER = 50 / 300 = 0.166 EXPLANATION:

Therefore the relative risk = EER / CER = 0.1 / 0.166 = 0.6
Please see Q-19 for Relative Risk
Q-300
A 13-year-old girl presents with palpitations, fatigue and
dyspnoea. She has had symptoms for around a year. There is
no history of syncope or chest pain. On examination she has
a pan-systolic murmur associated with giant V waves in the
jugular venous pulse. Auscultation of the chest is
unremarkable. A resting ECG is normal but a 24 hour tape
shows a short burst of supraventricular tachycardia. What is
the most likely diagnosis?
A. Atrial septal defect
B. Pulmonary stenosis
C. Hypertrophic obstructive cardiomyopathy
D. Arrhythmogenic right ventricular cardiomyopathy
E. Ebstein's anomaly
ANSWER:
Ebstein's anomaly
EXPLANATION:
EBSTEIN'S ANOMALY
Ebstein's anomaly is a congenital heart defect characterised
by low insertion of the tricuspid valve resulting in a large
atrium and small ventricle. It is sometimes referred to as
'atrialisation' of the right ventricle.
C5 is cleaved into C5a and C5b, C5a is involved in chemotaxis,
and C5b forms the first part of the membrane attack
complex. Deficiencies of the membrane attack complex, (C5-
C9) are particularly associated with meningococcal infection.
C5 activation may also have a role in progression of fibrotic
liver disease.
Deficiencies of the C1 complex are recognised to be closely
associated with the development of systemic lupus
erythematosus. C3 deficiency is associated with a
predisposition to infection with capsulated bacterial
infections such as pneumococcus and Haemophilus which
begins quite soon after birth. C4 deficiency is rare and is
associated with early onset systemic lupus erythematosus.
CD59 deficiency is involved in the pathogenesis of
paroxysmal nocturnal haemoglobinuria.
Please see Q-39 for Complement Deficiencies
Q-302
Which one of the following best describes the Haldane
effect?
A. Increase in pO2 means CO2 binds less well to Hb
B. Increasing acidity (or pCO2) means oxygen binds less
well to Hb
C. Decreasing acidity (or pCO2) means oxygen binds less
well to Hb
D. Raised 2,3-DPG enhances oxygen delivery to the tissues
E. Decrease in pO2 means CO2 binds less well to Hb

Associations ANSWER:
• tricuspid incompetence (pan-systolic murmur, giant V Increase in pO2 means CO2 binds less well to Hb
waves in JVP)
• Wolff-Parkinson White syndrome EXPLANATION:
Please see Q-103 for Respiratory Physiology
Ebstein's anomaly may be caused by exposure to lithium in-
utero Q-303
A study is designed to assess the efficacy of a new anti-
Q-301
hypertensive medication. Two groups of patients are
An 18-year-old man is seen in the infectious diseases clinic
randomly assigned, one to take the established drug for 3
some 6 weeks after admission to the Emergency department
months whilst the other takes the new drug for 3 months.
with meningococcal meningitis. This was confirmed on
Blood pressure is measured before and after the
lumbar puncture and represented his second episode of
intervention. There is then a period off medication for 1
meningitis over the last 6 months. He has no other past
month. After this period has elapsed the medication that the
medical history and takes no regular medication.
groups receive is swapped around and again blood pressure
Which of the following is most likely to be deficient? is measured before and 3 months later. The difference in
blood pressure after the respective medications is calculated
A. C1 for each patient. Which one of the following significance
B. C3 tests is it most appropriate to apply?
C. C4
D. C5
E. CD59
A. Student's unpaired t-test
B. Student's paired t-test
C. Pearson's test
D. Mann-Whitney test
E. Chi-squared test

ANSWER:
Student's paired t-test

EXPLANATION:
This describes a crossover study. As we are comparing
parametric data from the same patients (they swapped
medication halfway through the study) the Student's paired
t-test should be used.

Please see Q-30 for Significance Tests: Types

Q-304
A 45-year-old woman was commenced on treatment for a
tuberculosis infection, 3 months ago. She has since
developed a burning sensation at the base of her feet.
Diagram showing the biochemical role of vitamin B12 and vitamin B6
Which of the following medications may have caused this
new 'burning sensation'? Q-305
A study is carried out to assess the potential of hip
A. Rifampicin protectors to reduce femoral neck fractures in elderly
B. Isoniazid nursing home patients. The average age of the patients was
C. Pyrazinamide 82 years. Over a two-year period 800 patients were recruited
D. Ethambutol and assigned randomly either to the hip protector group or
E. Amoxicillin standard care group.

ANSWER: The results:

Isoniazid
Hip protector group: 400 patients - 10 of whom had a
EXPLANATION: femoral neck fracture over the two year period
Isoniazid therapy can cause a vitamin B6 deficiency causing
peripheral neuropathy Control group: 400 patients - 20 of whom had a femoral neck
TB drugs have a variety of side effects, many of which are fracture over the two year period
widely tested in medical school examinations. This patient is
reporting evidence of a peripheral neuropathy which can be What is the absolute risk reduction?
caused by the vitamin b6 deficiency that can result with
Isoniazid therapy. Usually, prophylactic pyridoxine A. 0.025
hydrochloride is prescribed at the same time as Isoniazid to B. 0.05
prevent the peripheral neuropathy. C. 2
D. 10
VITAMIN B6 (PYRIDOXINE) E. 0.5
Vitamin B6 is a water soluble vitamin of the B complex group.
It is converted to pyridoxal phosphate (PLP) which is a ANSWER:
cofactor for many reactions including transamination, 0.025
deamination and decarboxylation.
EXPLANATION:
Causes of vitamin B6 deficiency Absolute risk reduction = (Control event rate) - (Experimental
• isoniazid therapy event rate)
The absolute risk reduction = CER-EER, where:
Consequences of vitamin B6 deficiency
• peripheral neuropathy Control event rate (CER) = (Number who had particular
• sideroblastic anemia outcome with the control/ (Total number who had the
control)

Experimental event rate (EER) = (Number who had particular
outcome with the intervention) / (Total number who had the
intervention)
CER = 20 / 400 = 1 / 20 = 0.05
EER = 10 / 400 = 1 / 40 = 0.025
ARR = CER - EER = 0.05 - 0.025 = 0.025
Please see Q-92 for Numbers Needed to Treat and Absolute
Risk Reduction
Alkaptonuria is generally a benign and often asymptomatic
condition. Possible features include:
• pigmented sclera
• urine turns black if left exposed to the air
• intervertebral disc calcification may result in back pain
• renal stones
Treatment
• high-dose vitamin C
• dietary restriction of phenylalanine and tyrosine

Q-306
A 35-year-old gentleman has attended his GP due to joint
pains and reported skin changes.

On examination, you note a brownish/bluish pigment to his

ears. On closer inspection, you also note a similar
discolouration of his sclera bilaterally. His past history
includes a prior knee joint replacement. A specialist urine
sample is sent away, which ultimately shows elevated levels
of homogentisic acid. What is the most likely unifying
diagnosis?
Multi-level intervertebral disc calcification with disc space narrowing
A. Osteogenesis imperfecta
B. Alkaptonuria Q-307
C. Porphyria cutanea tarda Patients with deficiencies of which one of the following
D. Wilson disease complement proteins are most predisposed to disseminated
E. Phenylketonuria meningococcal infection?

ANSWER: A. C1
Alkaptonuria B. C2
C. C3
EXPLANATION: D. C4
Alkaptonuria is an autosomal recessive disorder that is a E. C5
result of a deficiency of homogentisic acid dioxygenase
leading to elevated levels of homogentisic acid (HGA). HGA ANSWER:
then polymerises and forms a pigment that is deposited in C5
connective tissue throughout the body (ochronosis). Clinically
features include brown/bluish pigment of the ear cartilage or EXPLANATION:
sclera, arthropathy, renal stones, cardiac valve involvement Whilst C3 deficiency is associated with recurrent bacterial
and coronary calcification. infections, C5 deficiency is more characteristically associated
with disseminated meningococcal infection
Osteogenesis imperfecta causes blue sclera but is not
associated with elevated HGA. Porphyria cutanea tarda, Please see Q-39 for Complement Deficiencies
Wilson disease and phenylketonuria do not cause cartilage
discolouration nor elevated HGA. Q-308
Which one of the following reduces the secretion of renin?
ALKAPTONURIA
Alkaptonuria (ochronosis) is a rare autosomal recessive A. Erect posture
disorder of phenylalanine and tyrosine metabolism caused by B. Adrenaline
a lack of the enzyme homogentisic dioxygenase (HGD) which C. Hyponatraemia
results in a build-up of toxic homogentisic acid. The kidneys D. Hypotension
filter the homogentisic acid (hence black urine) but eventually E. Beta-blockers
it accumulates in cartilage and other tissues.
ANSWER:
Beta-blockers
EXPLANATION:
RENIN
Renin is secreted by juxtaglomerular cells and hydrolyses
angiotensinogen to produce angiotensin I
Factors stimulating renin secretion
• hypotension causing reduced renal perfusion
• hyponatraemia
• sympathetic nerve stimulation
• catecholamines
• erect posture
Factors reducing renin secretion
• drugs: beta-blockers, NSAIDs
Q-309
A 55-year-old lady with known metastatic breast cancer
presents to the acute medical take with hypercalcaemia. She
has no other co-morbidities, is a non-smoker and works in an
office based job. She is treated with intravenous fluid and
bisphosphonates, after which her calcium normalises and
she is discharged.
At discharge, she is referred to the endocrinology
department for outpatient follow-up, alongside regular
blood calcium monitoring. What verbal advice is it most
important to give her on discharge from hospital?
A. Avoid excess exercise until treated
B. Low calcium diet
C. Reduce alcohol intake
D. Ensure adequate sunlight exposure
E. Increase fluid intake
ANSWER:
Increase fluid intake
EXPLANATION:
In the context of hypercalcaemia secondary to malignancy
the below advice is suggested by NICE:
Advice about maintaining good hydration (drinking 3-4 L of
fluid per day), provided there are no contraindications (such
as severe renal impairment or heart failure).
Reassure that a low calcium diet is not necessary, as
intestinal absorption of calcium is usually reduced.
Advise the person to avoid any drugs or vitamin supplements
that could exacerbate the hypercalcaemia.
Encourage mobilization where possible to avoid
exacerbating the hypercalcaemia.
Advise the person to report any symptoms of
hypercalcaemia.
Please see Q-1 for Hypercalcaemia: Management
Q-310
A 24-year-old man who has been discharged following
admission for a spontaneous pneumothorax ask for advice
about flying. During his stay in hospital the pneumothorax
was aspirated and a check x-ray revealed no residual air.
What is the earliest time he should fly?
A. Immediately
B. 24 hours
C. 3 days
D. 2 weeks
E. 2 months
ANSWER:
2 weeks
EXPLANATION:
Please see the text below for an explanation about the
competing and changing guidelines.
Please see Q-29 for Fitness to Fly
Q-311
Which one of the following statements regarding the power
of a study is correct?
A. Is the probability of rejecting the null hypothesis when it
is false
B. Decreases with increasing sample size
C. Lies within 2 standard deviations of the mean
D. Is the chance a significant p value will be reached
E. Is equal to 1 - (the probability of a type I error)
ANSWER:
Is the probability of rejecting the null hypothesis when it is
false
EXPLANATION:
Power = 1 - the probability of a type II error
The power of a study may be defined in a number of ways:
in general terms, the probability that a statistically
significant difference will be detected
probability of (correctly) rejecting the null hypothesis when it
is false
which also means the probability of confirming the
alternative hypothesis when the alternative hypothesis is
true
power = 1 - the probability of a type II error or 1 - β
Please see Q-209 for Significance Tests
Q-312
A 67-year-old man is discharged after having a percutaneous
coronary intervention following an acute coronary syndrome
(ACS). He had no past medical of note prior to the ACS.
Which type of lipid modification therapy should he have
been started on during the admission?
 Typical
A. Simvastatin 40mg on mechanism of
B. Atorvastatin 10mg on Nerve Motor Sensory injury & notes
C. Atorvastatin 20mg on metacarpals in wrist drop
D. Atorvastatin 40mg on Median nerve (C6, LOAF* muscles Palmar aspect of Wrist lesion
E. Atorvastatin 80mg on C8, T1) lateral 3½ → carpal tunnel
Features fingers syndrome
depend on the
ANSWER: site of the
Atorvastatin 80mg on lesion:

EXPLANATION:
Patients with established CVD should take atorvastatin 80mg • wrist:
on paralysis of
thenar
Please see Q-48 for Hyperlipidaemia: Management muscles,
opponens
pollicis
Q-313
• elbow: loss
A 50-year-old man is reviewed in the neurology clinic. For
of
the past four months he has been experiencing problems pronation
with his right shoulder. On examination he has weakness of of forearm
shoulder abduction and to a lesser extent weak elbow and weak
flexion. A small patch of numbness is noted over the deltoid wrist
muscle but otherwise sensation is normal. Where is the flexion
neurological lesion?
Ulnar nerve (C8, T1) Intrinsic hand Medial 1½ Medial epicondyle
A. C4 muscles except fingers fracture
B. C5 LOAF*
Damage may result
C. C6
Wrist flexion in a 'claw hand'
D. C7
Long thoracic nerve Serratus Often during sport
E. C8 (C5-C7) anterior e.g. following a
blow to the ribs.
ANSWER: Also possible
C5 complication of
mastectomy
EXPLANATION:
Damage results in
This man has weakness of both the deltoid (C5, C6) and the
a winged scapula
biceps muscle (C5, C6, C7). The location of the sensory loss
points to a C5 lesion however

UPPER LIMB ANATOMY

The information below contains selected facts which
commonly appear in examinations:

Typical
mechanism of
Nerve Motor Sensory injury & notes
Musculocutaneous Elbow flexion Lateral part of Isolated injury rare
nerve (C5-C7) (supplies biceps the forearm - usually injured as
brachii) and part of brachial
supination plexus injury
Axillary nerve Shoulder Inferior region Humeral neck
(C5,C6) abduction of the deltoid fracture/dislocation
(deltoid muscle) muscle
Results in flattened
deltoid
Radial nerve (C5- Extension Small area Humeral midshaft Diagram of the brachial plexus
C8) (forearm, wrist, between the fracture
fingers, thumb) dorsal aspect of
the 1st and 2nd Palsy results
Erb-Duchenne palsy ('waiter's tip') A. Prevents ethical dilemmas
• due to damage of the upper trunk of the brachial plexus B. Robust results are produced
(C5,C6) C. Useful for conditions where there is no proven drug
• may be secondary to shoulder dystocia during birth treatment
• the arm hangs by the side and is internally rotated, elbow D. Useful for conditions where there is a high placebo
extended response rate
E. Small sample size is required
Klumpke injury
• due to damage of the lower trunk of the brachial plexus ANSWER:
(C8, T1) Small sample size is required
• as above, may be secondary to shoulder dystocia during
birth. Also may be caused by a sudden upward jerk of the EXPLANATION:
hand Please see Q-71 for Study Design: New Drugs
• associated with Horner's syndrome
Q-316
*LOAF muscles Which foramen does the oculomotor nerve go through?
• Lateral two lumbricals
• Opponens pollis A. Superior orbital fissure
• Abductor pollis brevis B. Foramen ovale
C. Foramen rotundum
• Flexor pollis brevis
D. Optic canal
E. Inferior orbital fissure
Q-314
A 45-year-old lady was discharged from hospital following
ANSWER:
treatment with pamidronate for hypercalcaemia. She now
Superior orbital fissure
presents with symptoms consistent of hypocalcaemia
including muscle spasms and tetany. Which ECG changes are
EXPLANATION:
most likely to be present?
Please see Q-228 for Foramina of the Skull
A. T wave inversion
Q-317
B. Peaked T waves
A 72-year-old woman who is diagnosed with osteoporosis
C. Corrected QT interval prolongation
after suffering a Colles' fracture is prescribed vitamin D
D. U waves
supplementation. Which one of the following benefits will
E. Corrected QT interval shortening
vitamin D result in?
ANSWER:
A. Increased calcium absorption in the gut
13%
B. Promoting renal phosphate excretion
C. Decreased osteoclastic activity
EXPLANATION:
D. Inhibition of the proliferation and differentiation of
The clinical picture presented is not atypical when a patient
osteoblasts
who initially has hypercalcaemia is treated with
E. Decreases osteocalcin release
bisphosphonates and rapidly develops hypocalcaemia.
ANSWER:
The following ECG changes are associated with Increased calcium absorption in the gut
hypocalcaemia:
EXPLANATION:
Common: Corrected QT interval prolongation The effects of vitamin D on osteoblasts are complex and not
Rare: Atrial fibrillation or torsade de pointes fully understood. Inhibition of osteoblastic activity would not
however be in keeping with a beneficial effect on
(Note: In hypercalcaemia shortening of the QT interval may osteoporosis.
be observed, in severe cases Osborn (or J-waves) may be VITAMIN D
present)/ Vitamin D is a fat soluble vitamin that plays a key role in
Please see Q-168 for Hypocalcaemia: Features calcium and phosphate metabolism.

Q-315 Sources
What is the main advantage of non-inferiority trials when • vitamin D2 (ergocalciferol): plants
testing a new drug? • vitamin D3 (cholecalciferol): dairy products, can be
synthesised by the skin from sunlight
 ANSWER:
Functions Lung distension causing slowing of the respiratory rate
• increases plasma calcium and plasma phosphate
EXPLANATION:
• increases renal tubular reabsorption and gut absorption
Please see Q-124 for Respiratory Physiology: Control
of calcium
• increases osteoclastic activity Q-321
• increases renal phosphate reabsorption A 52-year-old man presents to the emergency department
with a 5-day history of abdominal pain. He reports a history
Consequences of vitamin D deficiency: of recurrent abdominal pain in the right upper abdomen but
• rickets: seen in children they have always been self-resolving. On examination, he is
• osteomalacia: seen in adults jaundiced. Tenderness is elicited on palpating the right upper
quadrant. Murphy's sign is negative. His basic observations
Q-318 include temperature 38.7°C, heart rate 100 beats per minute,
Where is CCK secreted from? respiratory rate 24 breaths per minute, blood pressure
110/62 mmHg.
A. I cells in upper small intestine
What is the first-line investigation for this patient?
B. G cells in stomach
C. K cells in upper small intestine A. Magnetic resonance cholangiopancreatography (MRCP)
D. D cells in the pancreas B. CT abdomen and pelvis
E. S cells in upper small intestine C. Endoscopic retrograde cholangiopancreatography
(ERCP)
ANSWER: D. Ultrasound scan (USS)
I cells in upper small intestine E. CT abdomen

EXPLANATION: ANSWER:
Please see Q-18 for Gastrointestinal Hormones Ultrasound scan (USS)
EXPLANATION:
Q-319 USS is the first line investigation for suspected cholangitis
A patient receives vincristine to help treat non-Hodgkin's This patient has the Charcot's triad of right upper quadrant
lymphoma. What stage in the cell cycle does vincristine act? pain, fever and jaundice. USS is the first line investigation for
suspected cholangitis.
A. G1
B. M0 MRCP is helpful to visualise the biliary tree but not the first
C. M line investigation.
D. G2
ERCP is helpful for the investigation of biliary pathology and
E. S
therapeutic removal of gallstones but it is not the first line
investigation for suspected cholangitis.
ANSWER:
M CT abdomen (and pelvis) is helpful to rule out other
abdominal pathologies but ultrasound is usually the first
EXPLANATION: line.
Vincristine inhibits formation of microtubules and arrests
mitosis CHOLANGITIS
• Combination of bacterial infection and biliary obstruction
Please see Q-151 for Cell Cycle • Most common organisms are: (most frequent at top of
list)
Q-320
Which one of the following best describes the Hering-Bruer Escherichia coli
reflex? Klebsiella species
Enterococcus species
A. Lung distension causing slowing of the respiratory rate Streptococcus species
B. Raised hydrogen ion concentration in the ECF
Clinical features
stimulating respiration
Charcot's triad:
C. Low pO2 stimulating the carotid and aortic bodies
Fever (90% cases)
D. Lung distension causing increase of the respiratory rate
Right upper quadrant pain
E. Decreased hydrogen ion concentration in the ECF
Jaundice
stimulating respiration
Reynolds pentad: Above plus confusion and hypotension
Investigations A. C7
USS 1st line B. Median nerve
CT scan C. Radial nerve
ERCP: may be 1st line if high clinical suspicion and suitable for D. Anterior interosseous nerve
treatment E. Ulnar nerve
Treatment
ERCP -usually after 72 hours of antibiotics ANSWER:
Percutaneous transhepatic cholangiogram and biliary drain Ulnar nerve

Q-322 EXPLANATION:
A 60-year-old man presents to the clinic with breathlessness. ULNAR NERVE
An urgent chest X-ray is arranged. Sputum cultures reveal Overview
that he has pneumonia. He is started on erythromycin. What • arises from medial cord of brachial plexus (C8, T1)
is the mechanism of action of erythromycin?
A. Inhibit 50S subunit of ribosomes Motor to
B. Inhibit 30S subunit of ribosomes • medial two lumbricals
C. Inhibit protein wall synthesis • aDductor pollicis
D. Inhibit DNA synthesis • interossei
E. Inhibit RNA synthesis • hypothenar muscles: abductor digiti minimi, flexor digiti
minimi
ANSWER: • flexor carpi ulnaris
Inhibit 50S subunit of ribosomes
EXPLANATION: Sensory to
Macrolides inhibit the 50S subunit of ribosomes • medial 1 1/2 fingers (palmar and dorsal aspects)
Erythromycin is a macrolide, which works by inhibiting the
50S subunit of ribosomes. This prevents the production of Path<
proteins from bacteria. Macrolides are commonly confused • posteromedial aspect of upper arm to flexor
with tetracyclines, which inhibit the 30S subunit of compartment of forearm, then along the ulnar. Passes
ribosomes. beneath the flexor carpi ulnaris muscle, then superficially
through the flexor retinaculum into the palm of the hand.
Please see Q-206 for Antibiotics: Protein Synthesis Inhibitors
Q-323
Which of the following conditions is inherited in an
autosomal dominant fashion?
A. Noonan syndrome
B. Homocystinuria
C. Cystinuria
D. Congenital adrenal hyperplasia
E. Fanconi anaemia
ANSWER:
Noonan syndrome
EXPLANATION:
Autosomal recessive conditions are 'metabolic' - exceptions:
inherited ataxias
Autosomal dominant conditions are 'structural' - exceptions:
Gilbert's, hyperlipidaemia type II
Please see Q-4 for Autosomal Dominant Conditions
Q-324
A 75-year-old female presents with weakness of her left
hand. On examination, wasting of the hypothenar eminence
is seen and there is weakness of finger abduction. Thumb
adduction is also weak. Where is the lesion most likely to
be?
Branches
Branch Supplies
Muscular branch Flexor carpi ulnaris
Medial half of the flexor digitorum profundus
Palmar cutaneous branch Skin on the medial part of the palm
(Arises near the middle of
the forearm)
Dorsal cutaneous branch Dorsal surface of the medial part of the hand
Superficial branch Cutaneous fibres to the anterior surfaces of the
medial one and one-half digits
Deep branch Hypothenar muscles
All the interosseous muscles
Third and fourth lumbricals
Adductor pollicis Features
Medial head of the flexor pollicis brevis • usually presents by 6 months e.g. with developmental
delay
Patterns of damage • child classically has fair hair and blue eyes
Damage at wrist • learning difficulties
• 'claw hand' - hyperextension of the metacarpophalangeal • seizures, typically infantile spasms
joints and flexion at the distal and proximal • eczema
interphalangeal joints of the 4th and 5th digits • 'musty' odour to urine and sweat*
• wasting and paralysis of intrinsic hand muscles (except
lateral two lumbricals) Diagnosis
• wasting and paralysis of hypothenar muscles • Guthrie test: the 'heel-prick' test done at 5-9 days of life -
• sensory loss to the medial 1 1/2 fingers (palmar and also looks for other biochemical disorders such as
dorsal aspects) hypothyroidism
• hyperphenylalaninaemia
Damage at elbow • phenylpyruvic acid in urine
• as above (however, ulnar paradox - clawing is more
severe in distal lesions) Management
• radial deviation of wrist • poor evidence base to suggest strict diet prevents
learning disabilities
Q-325 • dietary restrictions are however important during
Each one of the following features is seen in pregnancy as genetically normal fetuses may be affected
phenylketonuria, except: by high maternal phenylalanine levels

A. Learning difficulties *secondary to phenylacetate, a phenylketone

B. Seizures
C. Eczema Q-326
D. Recurrent infections A 22-year-old female student presents to the medical team
E. 'Musty' urine with a 7-day history of frontal headache, fever, abdominal
pain and severe myalgia. She thought it was flu so just
ANSWER: stayed at home without seeking medical help. 24 hours ago,
Recurrent infections she noticed a rash starting in both her arms and now
becoming more generalised. On further questioning, she
EXPLANATION: admitted to having just returned from an extended
PHENYLKETONURIA excursion in Central America and had tick bites. On
Phenylketonuria (PKU) is an autosomal recessive condition examination, there is a generalised petechial rash covering
caused by a disorder of phenylalanine metabolism. This is the arms and small areas of the trunk. Rocky Mountain
usually due to defect in phenylalanine hydroxylase, an enzyme spotted fever was suspected.
which converts phenylalanine to tyrosine. In a small number
of cases the underlying defect is a deficiency of the What is the organism implicated in this case?
tetrahydrobiopterin-deficient cofactor, e.g. secondary to
A. Coxiella burnetti
defective dihydrobiopterin reductase. High levels of
B. Rickettsia typhi
phenylalanine lead to problems such as learning difficulties
C. Rickettsia prowazekii
and seizures. The gene for phenylalanine hydroxylase is
D. Ehrlichia
located on chromosome 12. The incidence of PKU is around 1
E. Rickettsia rickettsii
in 10,000 live births.
ANSWER: Pre-test odds = pre-test probability / (1 - pre-test probability)
Rickettsia rickettsii
Post-test odds
EXPLANATION: The odds that the patient has the target disorder after the test
Rickettsia ricketsii is the causative organism for rocky is carried out
mountain spotted fever
Post-test odds = pre-test odds x likelihood ratio
Coxiella burnetti is the organism causing Q fever.
where the likelihood ratio for a positive test result = sensitivity
Rickettsia typhi is the organism causing endemic typhus. / (1 - specificity)

Rickettsia prowazekii is the organism causing epidemic Q-328

typhus. Northern blotting is used to:

Ehrlichia is the organism causing ehrlichiosis. A. Detect and quantify proteins

B. Amplify DNA
Please see Q-193 for Rickettsiae C. Detect RNA
D. Detect DNA
Q-327 E. Amplify RNA
Which one of the following is equivalent to the pre-test
probability? ANSWER:
Detect RNA
A. Post test odds / (1 + post-test odds)
B. Pre-test odds x likelihood ratio EXPLANATION:
C. The prevalence of a condition Molecular biology techniques
D. The incidence of a condition SNOW (South - NOrth - West)
E. Post-test odds / likelihood ratio DROP (DNA - RNA - Protein)

ANSWER: Please see Q-15 for Molecular Biology Techniques

The prevalence of a condition
EXPLANATION:
The prevalence is the proportion of a population that have
the condition at a point in time whilst the incidence is the
rate at which new cases occur in a population during a
specified time period.
PRE- AND POST- TEST ODDS AND PROBABILITY
Q-329
You are called to see a patient overnight who had a total
parathyroidectomy earlier in the day for primary
hyperparathyroidism. The patient is experiencing perioral
tingling and leg cramps. The nurse tells you that his hand
clenched into a claw when she took his blood pressure. You
suspect an electrolyte imbalance. Which ECG finding are you
most likely to see with this electrolyte disorder?

Pre-test probability A. Tented T waves

The proportion of people with the target disorder in the B. Flattening of the P wave
population at risk at a specific time (point prevalence) or time C. Prolongation of the QTc interval
interval (period prevalence) D. Prolongation of the QRS interval
E. Torsades de pointes
For example, the prevalence of rheumatoid arthritis in the UK
is 1% ANSWER:
Prolongation of the QTc interval
Post-test probability
The proportion of patients with that particular test result who EXPLANATION:
have the target disorder The most common ECG change in hypocalcaemia is
prolongation of the QTc interval
Post-test probability = post test odds / (1 + post-test odds) The correct answer is a prolongation of the QTc interval. The
patient has the classic symptoms of acute hypocalcaemia.
Pre-test odds This is common after parathyroidectomy for primary
The odds that the patient has the target disorder before the hyperparathyroidism, due to rapid absorption of calcium into
test is carried out the bones after removal of excess PTH (often called ‘hungry
bones syndrome.’) QTc prolongation in hypocalcaemia is
mainly due to prolongation of the ST segment as a result of ANSWER:
the slowing of ventricular repolarisation. Acetazolamide

Torsades de pointes can be seen in hypocalcaemia but it is EXPLANATION:

more commonly seen with hypokalaemia or
hypomagnesaemia. Tented T waves and flattening of the P
wave are seen in hyperkalaemia.
Please see Q-168 for Hypocalcaemia: Features
HYPOKALAEMIA
Potassium and hydrogen can be thought of as competitors.
Hyperkalaemia tends to be associated with acidosis because
as potassium levels rise fewer hydrogen ions can enter the
cells

Q-330 Hypokalaemia with alkalosis

A 19-year-old man from a travelling community presents to • vomiting
the Emergency Department with breathing difficulties. On • diuretics
examination he has a temperature of 38.2ºC and stridor. A • Cushing's syndrome
diagnosis of acute epiglottitis is suspected. Which one of the • Conn's syndrome (primary hyperaldosteronism)
following organisms is most likely to be responsible?
Hypokalaemia with acidosis
A. Epstein Barr Virus • diarrhoea
B. Streptococcus pneumoniae • renal tubular acidosis
C. Neisseria meningitidis • acetazolamide
D. Haemophilus influenzae • partially treated diabetic ketoacidosis
E. Staphylococcus aureus
Magnesium deficiency may also cause hypokalaemia. In such
ANSWER: cases, normalizing the potassium level may be difficult until
Haemophilus influenzae the magnesium deficiency has been corrected

EXPLANATION: Q-332
Patients from travelling communities may not always receive Which type of secondary messenger system does nitric oxide
a full course of immunisation. stimulate?

Acute epiglottitis is of course much more common in young A. Cyclic GMP

children B. Cyclic AMP
C. Phosphoinositide
ACUTE EPIGLOTTITIS D. Protein kinase
Acute epiglottitis is rare but serious infection caused by E. Calcium
Haemophilus influenzae type B. Prompt recognition and
treatment is essential as airway obstruction may develop. ANSWER:
Epiglottitis was generally considered a disease of childhood Cyclic GMP
but in the UK it is now more common in adults due to the
immunisation programme. The incidence of epiglottitis has EXPLANATION:
decreased since the introduction of the Hib vaccine SECOND MESSENGERS
Overview
Features • many different types
• rapid onset • allow amplification of external stimulus
• high temperature, generally unwell
• stridor Tyrosine
• drooling of saliva Phosphoinositol cGMP kinase
cAMP system system system system
Q-331 Ligand: Epinephrine (α2, Epinephrine (α1) - -
Which of the following is most likely to cause hypokalaemia Neurotransmitters β1, β2) Acetylcholine
associated with acidosis? (Receptor) Acetylcholine (M2) (M1, M3)
Ligand: ACTH, ADH, angiotensin II, ANP, insulin,
A. Cushing's syndrome Hormones calcitonin, FSH, GnRH, GHRH*, Nitric growth
B. Vomiting glucagon, hCG,LH, Oxytocin, TRH oxide hormone,
C. Conn's syndrome MSH, PTH, TSH, IGF, PDGF
GHRH*
D. Diuretics
Primary effector Adenylyl cyclase Phospholipase C Guanylate Receptor
E. Acetazolamide
cyclase tyrosine
 TyrosineANSWER:
Phosphoinositol cGMP kinase Left-to-right shunt
cAMP system system system system
kinase EXPLANATION:
Secondary cAMP (cyclic IP3 (inositol 1,4,5 cGMP Protein Right-to-left shunting is characteristic of Fallot's. It is
messenger adenosine trisphosphate) phosphatas
however known that a small number of asymptomatic
monophosphate) and DAG e
infants may initially have a degree of left-to-right shunting
(Diacylglycerol)
through the ventricular septal defect
*the cAMP pathway is the most important
TETRALOGY OF FALLOT
Tetralogy of Fallot (TOF) is the most common cause of
Q-333
cyanotic congenital heart disease*. It typically presents at
A case-control study is designed to investigate whether
around 1-2 months, although may not be picked up until the
being exposed to passive smoking as a child is a risk factor
baby is 6 months old
for asthma. Two hundred patients with asthma are
recruited. Of these 200, 40 report either one or both parents
TOF is a result of anterior malalignment of the
smoking in the house when they were a child. A further 200
aorticopulmonary septum. The four characteristic features
controls who do not have asthma are recruited. Of these
are:
people 20 report that one or both parents smoked in the
• ventricular septal defect (VSD)
house. What is the odds ratio of asthmatics having been
• right ventricular hypertrophy
exposed to passive smoking as a child?
• right ventricular outflow tract obstruction, pulmonary
A. 2.25 stenosis
B. 0.66 • overriding aorta
C. 0.5
D. 1.5
E. 4

ANSWER:
2.25

EXPLANATION:
Odds - remember a ratio of the number of people who incur
a particular outcome to the number of people who do not
incur the outcome

NOT a ratio of the number of people who incur a particular

outcome to the total number of people
The odds of asthmatics being exposed to passive smoking is
40 / 160 = 1 / 4

The odds of the controls being exposed to passive smoking is The severity of the right ventricular outflow tract obstruction
20 / 180 = 1 / 9 determines the degree of cyanosis and clinical severity

The odds ratio is therefore 1/4 / 1/9 = 9/4 = 2.25 Other features
• cyanosis
Please see Q-93 for Odds and Odds Ratio • causes a right-to-left shunt
• ejection systolic murmur due to pulmonary stenosis (the
Q-334 VSD doesn't usually cause a murmur)
Which one of the following is least associated with Tetralogy • a right-sided aortic arch is seen in 25% of patients
of Fallot? • chest x-ray shows a 'boot-shaped' heart, ECG shows right
ventricular hypertrophy
Right ventricular outflow tract obstruction
Overriding aorta Management
Ejection systolic murmur • surgical repair is often undertaken in two parts
Left-to-right shunt • cyanotic episodes may be helped by beta-blockers to
Right ventricular hypertrophy reduce infundibular spasm
*however, at birth transposition of the great arteries is the Q-336
more common lesion as patients with TOF generally present A study is performed comparing two chemotherapy regimes
at around 1-2 months for patients with small cell lung cancer. The end point of the
study is survival time. Which one of the following types
Q-335 statistical measures is it most appropriate to compare
A 22-year-old gentleman is admitted to the Emergency survival time with?
Department with worsening shortness of breath with signs
of left ventricular failure. He has a known genetic condition. A. Odds ratio
B. Pearson's product-moment coefficient
On examination, you note an ejection systolic murmur C. Relative risk
loudest over the aortic area radiating to the carotids, bibasal D. Hazard ratio
crepitations and pitting oedema to the knees bilaterally. On E. Absolute risk reduction
closer inspection of the patient, you note a wide vermillion
border, small spaced teeth and a flat nasal bridge. The ANSWER:
patient also has a disinhibited friendly demeanour. Hazard ratio

What is the likely precipitating valvular issue? EXPLANATION:

HAZARD RATIO
A. Subvalvular aortic stenosis The hazard ratio (HR) is similar to relative risk but is used
B. Supravalvular aortic stenosis when risk is not constant to time. It is typically used when
C. Valvular aortic stenosis analysing survival over time
D. Aortic sclerosis
E. Aortic regurgitation Q-337
Which one of the following best describes the characteristics
ANSWER: of a negatively skewed distribution?
Supravalvular aortic stenosis
A. Median < mode < mean
EXPLANATION: B. Mean < median < mode
The answer is supravalvular aortic stenosis, which is C. Mode < mean < median
associated with a condition called William's syndrome. This D. Median < mean < mode
syndrome is a genetic condition associated with transient E. Mean < mode < median
neonatal hypercalcaemia, short stature, and a friendly
demeanour. ANSWER:
Mean < median < mode
A subvalvular aortic stenosis is associated with hypertrophic
obstructive cardiomyopathy. Aortic sclerosis does not EXPLANATION:
typically cause radiation to the carotids and associated with Skewed distributions
a more senior demographic. Aortic regurgitation is alphabetical order: mean - median - mode
associated with an early diastolic murmur and valvular aortic '>' for positive, '<' for negative
stenosis tends to be related to senile calcification or a
bicuspid aortic valve. SKEWED DISTRIBUTIONS
Normal (Gaussian) distributions: mean = median = mode
WILLIAM'S SYNDROME
William's syndrome is an inherited neurodevelopmental Positively skewed distribution: mean > median > mode
disorder caused by a microdeletion on chromosome 7
Negatively skewed distribution mean < median < mode
Features
• elfin-like facies To remember the above note how they are in alphabetical
• characteristic like affect - very friendly and social order, think positive going forward with '>', whilst negative
• learning difficulties going backwards '<'
• short stature
• transient neonatal hypercalcaemia Q-338
• supravalvular aortic stenosis Which of the following secondary causes of hyperlipidaemia
result in predominantly hypercholesterolaemia, as opposed
Diagnosis is made by FISH studies to hypertriglyceridaemia?
A. Diabetes mellitus A. The p value
B. Bendrofluazide B. Specificity
C. Nephrotic syndrome C. Likelihood ratio for a negative test result
D. Alcohol D. Sensitivity
E. Obesity E. Negative predictive value

ANSWER: ANSWER:
Nephrotic syndrome Specificity

EXPLANATION: EXPLANATION:
Hypercholesterolaemia rather than hypertriglyceridaemia: Increasing the cut-off of a positive test result will decrease
nephrotic syndrome, cholestasis, hypothyroidism the number of false positives and hence increase the
specificity
Please see Q-200 for Hyperlipidaemia: Secondary Causes
Please see Q-8 for Screening Test Statistics
Q-339
Which of the following is most likely to cause hypokalaemia Q-341
associated with alkalosis? You review a 29-year-old woman who is recovering from a
fracture of the right olecranon. Since the fracture she has
A. Acetazolamide noticed that the little finger on her right hand is numb.
B. Partially treated diabetic ketoacidosis Which nerve is likely to have been damaged?
C. Diarrhoea
D. Cushing's syndrome A. Ulnar nerve
E. Renal tubular acidosis B. Radial nerve
C. Axillary nerve
ANSWER: D. Musculocutaneous nerve
Cushing's syndrome E. Median nerve

EXPLANATION:
HYPOKALAEMIA
Potassium and hydrogen can be thought of as competitors.
Hyperkalaemia tends to be associated with acidosis because
as potassium levels rise fewer hydrogen ions can enter the
cells
Hypokalaemia with alkalosis
• vomiting
• diuretics
• Cushing's syndrome
• Conn's syndrome (primary hyperaldosteronism)
Hypokalaemia with acidosis
• diarrhoea
• renal tubular acidosis
• acetazolamide
• partially treated diabetic ketoacidosis
Magnesium deficiency may also cause hypokalaemia. In such
cases, normalizing the potassium level may be difficult until
the magnesium deficiency has been corrected
Q-340
A new screening test is developed for colorectal cancer. It is
a blood test which detects a protein; the higher the level of
the protein, the more likely a patient is to have colorectal
cancer. If the cut-off for a positive test is increased, which
one of the following will also be increased?
ANSWER:
Ulnar nerve
EXPLANATION:
Please see Q-324 for Ulnar Nerve
Q-342
Which one of the following is the best definition of the p
value?
A. The probability of obtaining a similar result, assuming
that the null hypothesis is true
B. The probability that a replicating experiment would not
yield the same conclusion
C. The probability of obtaining a result at least as extreme,
assuming that the null hypothesis is true
D. The probability that the null hypothesis is true
E. The probability of obtaining a result at least as extreme,
assuming that the null hypothesis is false
ANSWER:
The probability of obtaining a result at least as extreme,
assuming that the null hypothesis is true
EXPLANATION:
Please see Q-209 for Significance Tests
Q-343 Q-344
A 40-year-old man is admitted to the intensive care unit A study is performed looking at the chance of stroke in high-
following a severe episode of acute pancreatitis. On the third risk patients taking a new oral antithrombotic drug
day of his admission he becomes pyrexial. A septic screen is compared to warfarin. The following results are obtained:
ordered including cultures taken from both peripheral blood
and the internal jugular line. There is no signs of infection on Number who had a stroke within a
the chest x-ray or urine sample. The microbiology laboratory Total number of patients 3 year period
phone to report signs of bacterial infection in the sample New drug 200 10
from the central line. What is the most likely organism to be Warfarin 600 12
isolated?
What is the relative risk of having a stroke within a 3 year
A. Pseudomonas aeruginosa period for patients taking the new drug compared to
B. Escherichia coli warfarin?
C. Staphylococcus epidermidis
D. Streptococcus pneumoniae A. 3.33
E. Staphylococcus aureus B. 0.66
C. 1.2
ANSWER: D. 2.5
Staphylococcus epidermidis E. Cannot calculate from above data

EXPLANATION: ANSWER:
Most common organism found in central line infections - 2.5
Staphylococcus epidermidis
EXPLANATION:
STAPHYLOCOCCI Relative risk = EER / CER
Staphylococci are a common type of bacteria which are often Experimental event rate, EER = 10 / 200 = 0.05
found normal commensal organisms but may also cause
invasive disease. Some basic facts include: Control event rate, CER = 12 / 600 = 0.02
• Gram-positive cocci
• facultative anaerobes Therefore the relative risk = EER / CER = 0.05 / 0.02 = 2.5
• produce catalase
Please see Q-19 for Relative Risk
The two main types of Staphylococci you need to know about
are Staphylococcus aureus and Staphylococcus epidermidis. Q-345
A 52-year-old man presents to the medical team with a 6-
Staphylococcus aureus Staphylococcus epidermidis day history of fever, headache, rigors, diarrhoea and
• Coagulase-positive • Coagulase-negative vomiting. His observations include temperature 39 °C, heart
• Causes skin infections (e.g. cellulitis), • Cause of central line infections and rate 110 beats per minute, respiratory rate 22, blood
abscesses, osteomyelitis, toxic shock infective endocarditis pressure 143/92 mmHg. He has been previous fit and well
syndrome and has been working on a farm for the last 6 months. A
diagnosis of Q fever is confirmed via PCR testing.

What is the organism implicated in this condition?

A. Rickettsia rickettsii
B. Coxiella burnetti
C. Rickettsia typhi
D. Rickettsia prowazekii
E. Ehrlichia

ANSWER:
Coxiella burnetti

EXPLANATION:
Coxiella burnetti is the causative organism in Q fever
Coxiella burnetti is the causative organism in Q fever.
Scanning electromicrograph of Staphylococcus aureus bacteria. Credit: NIAID
Rickettsia rickettsii is the causative organism in Rocky ANSWER:
Mountain spotted fever. Type II reaction

Rickettsia typhi is the causative organism in endemic typhus. EXPLANATION:

Type II hypersensitivity reaction - ITP
Rickettsia prowazekii is the causative organism in epidemic
typhus. Please see Q-26 for Hypersensitivity

Ehrlichia is the causative organism in ehrlichiosis. Q-348

Vitamin D causes which one of the following:
Please see Q-193 for Rickettsiae
A. Increased plasma phosphate
Q-346 B. Decreased plasma calcium
You are reviewing the blood results for a patient who was C. Decreased osteoclastic activity
started on atorvastatin 20mg on for primary prevention 3 D. Decreased gut absorption of calcium
months ago: E. Decreased renal tubular absorption of calcium

Recent 3 months ago prior to starting treatment ANSWER:

Total cholesterol 4.2 mmol/l 6.3 mmol/l
Increased plasma phosphate
HDL cholesterol 1.1 mmol/l 1.0 mmol/l
EXPLANATION:
Non-HDL cholesterol 2.1 mmol/l 4.0 mmol/l Vitamin D increases plasma calcium and plasma phosphate
Triglyceride 1.2 mmol/l 1.3 mmol/l levels by promoting renal tubular absorption and gut
absorption of calcium and increasing renal phosphate
Liver function tests are normal. reabsorption

What is the most appropriate course of action? CALCIUM METABOLISM

The two hormones which primarily control calcium
A. Reduce atorvastatin to 10mg on metabolism are:
B. Make no changes to medication • parathyroid hormone (PTH)
C. Increase atorvastatin to 40mg on • 1,25-dihydroxycholecalciferol (calcitriol, the active form
D. Check creatine kinase of vitamin D)
E. Check compliance
Other hormones include
ANSWER: • calcitonin: secreted from the parafollicular cells (C-cells)
Make no changes to medication of the thyroid gland
• thyroxine
EXPLANATION: • growth hormone
NICE look for a 40% reduction in non-HDL cholesterol after 3
months. A 10% reduction in a non-HDL cholesterol of 4.0 Actions of parathyroid hormone
would be 0.4 so a 40% reduction would take it down to (4.0 - • increases plasma calcium, decreases plasma phosphate
1.6 = 2.4 mmol/l). This patients non-HDL cholesterol of 2.1 • increases renal tubular reabsorption of calcium
mmol/l is therefore acceptable. • increases osteoclastic activity*
• increases renal conversion of 25-hydroxycholecalciferol to
Please see Q-48 for Hyperlipidaemia: Management 1,25-dihydroxycholecalciferol
• decreases renal phosphate reabsorption
Q-347
In the Gell and Coombs classification of hypersensitivity Actions of 1,25-dihydroxycholecalciferol
reactions idiopathic thrombocytopenic purpura is an • increases plasma calcium and plasma phosphate
example of a: • increases renal tubular reabsorption and gut absorption
of calcium
A. Type I reaction • increases osteoclastic activity
B. Type II reaction • increases renal phosphate reabsorption
C. Type III reaction
D. Type IV reaction *this is actually via an indirect mechanism as osteoclasts don't
E. Type V reaction have PTH receptors
Q-349 Q-352
A 25-year-old man who has been morbidly obese for the past A patient presents with an inability to abduct his right
five years is reviewed in the endocrinology clinic. In this shoulder. Which nerve supplies the deltoid muscle?
patient, which one of the following hormones would
increase appetite as levels increase? A. Lateral cutaneous
B. Suprascapular
A. Leptin C. Musculocutaneous
B. Thyroxine D. Axillary
C. Adiponectin E. Median
D. Ghrelin
E. Serotonin ANSWER:
ANSWER: 3%
Ghrelin
EXPLANATION:
EXPLANATION: Shoulder abduction - deltoid muscle - axillary nerve (C5,C6)
Obesity hormones
Leptin Lowers appetite Please see Q-313 for Upper Limb Anatomy
Ghrelin Gains appetite
Whilst thyroxine can increase appetite it does not fit with the Q-353
clinical picture being described A 61-year-old woman presents to the emergency
department with morning headaches, nausea and vomiting.
Please see Q-64 for Obesity: Physiology An urgent CT head reveals a mass within the right frontal
lobe. An MRI head is performed which shows what is likely a
Q-350 glioblastoma surrounded by oedema.
Which one of the following diseases is most strongly
associated with HLA antigen DR2? What medication is used in this context to treat oedema?

A. Haemochromatosis A. Hydrocortisone
B. Type 1 diabetes mellitus B. Dexamethasone
C. Goodpasture's syndrome C. Hypertonic saline
D. Behcet's disease D. Mannitol
E. Coeliac disease E. Furosemide

ANSWER: ANSWER:
Goodpasture's syndrome Dexamethasone

EXPLANATION: EXPLANATION:
Please see Q-80 for HLA Associations Dexamethasone is used to treat cerebral oedema in patients
with brain tumours
Q-351 Dexamethasone is a potent steroid with predominantly
A man with glucose-6-phosphate dehydrogenase deficiency glucocorticoid effects. It is used to treat vasogenic oedema
asks for advice regarding his son. What is the chance his son that occurs due to the break down of the blood-brain barrier.
will also develop the disease? A common use within neurosurgery is to treat oedema
caused by brain tumours.
A. 2 in 3
B. No increased risk CNS TUMOURS
C. Will definitely be affected
D. 1 in 2 - 60% = Glioma and metastatic disease
E. 1 in 4 • 20% = Meningioma
• 10% = Pituitary lesions
ANSWER:
No increased risk In paediatric practice medulloblastomas (neuroectodermal
tumours) were the commonest lesions, astrocytomas now
EXPLANATION: account for the majority.
X-linked recessive conditions - no male-to-male transmission Tumours arising in right temporal and frontal lobe may reach
considerable size before becoming symptomatic. Whereas
Please see Q-3 for X-linked Recessive
tumours in the speech and visual areas will typically produce
early symptoms.
Diagnosis
MRI Scanning provides the best resolution.
Treatment
Usually surgery, even if tumour cannot be completely
resected conditions such as rising ICP can be addressed with
tumour debulking and survival and quality of life prolonged.
Curative surgery can usually be undertaken with lesions such
as meningiomas. Gliomas have a marked propensity to invade
normal brain and resection of these lesions is nearly always
incomplete.
Q-354
A 12-year-old child comes into the GP clinic with her mother
due to a sore throat and fever. On examination, the GP
diagnoses the patient with viral tonsillitis and recommends
paracetamol to alleviate the fever. Her mother is curious as
to how her daughter will fight off the infection. Which
cytokine is responsible for differentiating Th0 cells to Th1
cells?
A. Tumour necrosis factor-α
B. Interferon-γ
C. IL-12
D. IL-4
E. IL-5
ANSWER:
IL-12
EXPLANATION:
IL-12 stimulates the differentiation of Th0 cells to Th1 cells
IL-12 is responsible for the differentiation of Th0 cells to Th1
cells. Interferon-γ is produced by Th1 cells and is not
responsible for the differentiation. IL-4 stimulates
differentiation of Th0 cells to Th1 cells. IL-5 is secreted from
Th2 cells. Tumour necrosis factor-α is a proinflammatory
cytokine not involved in the adaptive immune response.
Please see Q-88 for Cytokines
Q-355
You are a ST1 doctor on a gastroenterology ward. The F2
doctor has asked you to supervise him putting in an ascitic
drain for a patient with liver cirrhosis. He is keen to get it
signed off for his portfolio. He has never seen one put in
before but has read around the subject. What is the most
appropriate action?
A. You do the procedure but sign him off as you know he
will do many more over the next 3 months
B. Get the F2 doctor to insert the drain under your careful
guidance, avoid telling the patient to prevent
unnecessary anxiety
C. Suggest it would be better if he watches you insert the
drain before attempting one himself
D. If he is confident ask him to do it so you can spend your
time more efficiently on other ward jobs and sign him
off
E. Ask the patient if he minds the F2 doctor doing the
procedure and get the F2 doctor to insert the drain
under your careful guidance
ANSWER:
Suggest it would be better if he watches you insert the drain
before attempting one himself
EXPLANATION:
It used to be said that for procedures 'see one, do one, teach
one'. These days have long gone. Doctors are now expected
to show proof of competency before performing procedures
alone. In this scenario the F2 doctor has never seen one
previously so it is not appropriate for him to insert the drain
today. The best option is for him to watch you.
If you are going to let the F2 doctor insert the drain you
should be honest with the patient about his lack of
experience.
Signing him off without seeing him perform the procedure is
a very poor option which could result in a GMC referral if
found out. It also puts future patients at risk
Letting him insert the drain today without supervision is
again a very poor option as it puts the patient at risk.
Q-356
You are reviewing a new study on the benefit of omega-3
fish oils in patients with established ischaemic heart disease.
What does the power of the study equate to?
A. = 1 / p value
B. = standard deviation / square root of sample size
C. = 1 - probability of making a type II error
D. = 1 - probability of making a type I error
E. = 1 / probability of making a type I error
ANSWER:
= 1 - probability of making a type II error
EXPLANATION:
Power = 1 - the probability of a type II error
Please see Q-209 for Significance Tests
Q-357
Which one of the following stimulates the release of gastrin
from G-cells?
A. Histamine ANSWER:
B. Somatostatin Poor genotype:phenotype correlation
C. Gastric acid
D. Cholecystokinin EXPLANATION:
E. Luminal peptides Please see Q-76 for Mitochondrial Diseases

ANSWER: Q-361
Luminal peptides A study looks at the use of amoxicillin in the treatment of
acute sinusitis compared to placebo. The following results
EXPLANATION: are obtained:
Please see Q-18 for Gastrointestinal Hormones
Total number of Number who achieved resolution of
Q-358 patients symptoms at 7 days
Each one of the following is associated with hyperkalaemia, Amoxicillin 100 60
except: Placebo 75 30

A. Rhabdomyolysis What is the odds ratio a patient achieving resolution of

B. Carbenoxolone symptoms at 7 days if they take amoxicillin compared to
C. Acute renal failure placebo?
D. Ciclosporin
E. Addison's A. 1.5
B. 0.5
ANSWER: C. 2.25
Carbenoxolone D. 0.6
E. 1.66
EXPLANATION:
Please see Q-9 for Hyperkaleimia ANSWER:
2.25
Q-359
Which type of secondary messenger system does adrenaline EXPLANATION:
stimulate? The odds of symptoms resolution with amoxicillin = 60 / 40 =
1.5
A. Calcium
B. Protein kinase The odds of symptoms resolution with placebo = 30 / 45 =
C. Phosphoinositide (2/3)
D. Cyclic AMP
E. Cyclic GMP Therefore the odds ratio = 1.5 / (2/3) = 2.25

ANSWER: Please see Q-93 for Odds and Odds Ratio

Cyclic AMP
Q-362
EXPLANATION: A 17-year-old girl presents with a 6 week history of nausea
Please see Q-332 for Second Messengers and abdominal discomfort. Routine blood tests reveal the
following.
Q-360
Which one of the following statements regarding Hb 10.9 g/dl
mitochondrial inheritance is true? WBC 6.7 *109/l
Platelets 346 *109/l
A. Friedreich's ataxia is caused by defects in mitochondrial
DNA Calcium 2.33 mmol/l
B. There is a 50% chance that the female offspring of an Bilirubin 7 µmol/l
affected male will inherit the disease ALP 262 u/l
C. Affected females cannot pass on the disease ALT 35 u/l
D. Most cases of spinocerebellar ataxia are caused by
defects in mitochondrial DNA What is the most likely diagnosis?
E. Poor genotype:phenotype correlation
A. Alcoholic liver disease ANSWER:
B. Cholangiocarcinoma HIV is an RNA virus
C. Pregnancy
D. Gallstones EXPLANATION:
E. Primary biliary cirrhosis HIV is an RNA retrovirus
The correct answer is 3 - HIV is an RNA virus in the retrovirus
ANSWER: class. It uses a reverse transcriptase to convert its RNA
Pregnancy genome into DNA, which it then integrates into the host cell
EXPLANATION: genome.
Alkaline phosphatase is significantly elevated in pregnancy.
This would also explain the borderline anaemia The other answers are incorrect. HIV 2 is less pathogenic
than HIV 1. HIV leads to depletion of T cells. HIV enters the
ALKALINE PHOSPHATASE cell primarily via the CD4 receptor.
Causes of raised alkaline phosphatase (ALP)
• liver: cholestasis, hepatitis, fatty liver, neoplasia Please see Q-10 for HIV: The Virus
• Paget's
• osteomalacia Q-365
• bone metastases A 4-year-old female is referred to the paediatrician due to a
swollen abdomen. She has lost considerable weight and says
• hyperparathyroidism
she is never hungry. Moreover, her bowel movements
• renal failure
suggest she is constipated. An MRI reveals a lesion in the
• physiological: pregnancy, growing children, healing
adrenal glands. A biopsy of this lesion is taken and
fractures
undergoes molecular testing for an oncogene. Which of the
following is an oncogene for neuroblastoma?
The table below splits the causes according to the calcium
level
A. ABL
B. c-MYC
Raised ALP and raised calcium Raised ALP and low calcium
C. n-MYC
• Bone metastases • Osteomalacia
D. BCL-2
• Hyperparathyroidism • Renal failure
E. Ras
Q-363
ANSWER:
The nicotinic acetylcholine receptor is an example of a:
n-MYC
A. Ligand-gated ion channel
EXPLANATION:
B. Tyrosine kinase receptor
n-MYC is an oncogene for neuroblastoma
C. Guanylate cyclase receptor
n-MYC is an oncogene for neuroblastoma. The number of n-
D. G protein-coupled receptor
MYC repeats often correlates with prognosis. ABL is an
E. Intracellular receptor
oncogene found in chronic myeloid leukaemia. c-MYC is an
oncogene found in Burkitt's lymphoma. Ras is an oncogene
ANSWER:
found in many cancers, but mostly pancreatic cancer.
Ligand-gated ion channel
Please see Q-195 for Oncogenes
EXPLANATION:
Please see Q-154 for Membrane Receptors
Q-366
Q-364 Which one of the following types of immunoglobulins are
A 45-year-old man presents to his GP with a severe sore responsible for haemolytic blood transfusion reactions?
throat and difficulty swallowing. He is found to have
oesophageal candidiasis and an HIV test returns as positive. A. IgD
The medical student attached to the GP practice asks the GP B. IgE
about the HIV virus. Which of the following is correct? C. IgM
D. IgA
A. HIV is a DNA virus E. IgG
B. HIV 2 is more pathogenic than HIV 1
C. HIV is an RNA virus ANSWER:
D. HIV leads to depletion of B cells IgM
E. HIV enters the cells using the CD3 receptor
EXPLANATION: • macroorchidism
Please see Q-190 for Immunoglobulins • hypotonia
• autism is more common
Q-367 • mitral valve prolapse
You are a ST1 doctor in General Medicine. During an on-call
you are in A&E seeing a patient who has a pneumothorax. Features in females (who have one fragile chromosome and
On arriving you find the A&E ST2 doctor attempting to one normal X chromosome) range from normal to mild
perform an aspiration. He appears to about to insert the
needle at the wrong landmark. What is the most appropriate Diagnosis
action? • can be made antenatally by chorionic villus sampling or
amniocentesis
A. Tell your colleagues about what happened in the mess • analysis of the number of CGG repeats using restriction
to ensure they are aware of the doctors limitations endonuclease digestion and Southern blot analysis
B. Say nothing, stay with the patient and take over when
he asks for help Q-369
C. Go and get the A&E consultant A 61-year-old woman is admitted to the Acute Medical Unit
D. Say nothing at the time but fill in a clinical incident form as she is generally unwell with muscle twitching. Blood
E. Immediately voice your concerns and ask him to stop pressure is recorded at 114/78 mmHg, pulse 84/min and she
is apyrexial. Blood tests reveal the following:
ANSWER:
Immediately voice your concerns and ask him to stop Calcium 1.94 mmol/l
Albumin 38 g/l
EXPLANATION:
If you have concerns regarding the management of a patient Which one of the following tests is most useful in elucidating
it is important to act on them. It may be that you are wrong - the cause of her symptoms?
the ST2 doctor may actually be performing the aspiration
using a recognised, safe technique. This should not however A. Urea
stop you voicing your concerns - failing to do so may put the B. Vitamin D
patient at risk. C. Phosphate
D. Parathyroid hormone
If you feel unable to do you should discuss your concerns E. Magnesium
with someone who is in a position to act. Saying nothing puts
the patient at potential harm. Filling in a clinical incident ANSWER:
form after the event will not alter this. Parathyroid hormone

Spreading rumours in the mess about a doctors ability is EXPLANATION:

unprofessional and unlikely to lead to a resolution of the Parathyroid hormone is the single most useful test in
problem. determining the cause of hypocalcaemia

Q-368 Please see Q-32 for Hypocalcaemia: Causes and

ragile X is associated with each one of the following, except: Management

A. Small, firm testes Q-370

B. Mental retardation An elderly patient is admitted to hospital following blood in
C. Hypotonia her urine and severe abdominal pain. She has a blood
D. Short stature pressure of 90/60 and a heart rate of 140bpm. Her
E. Large low set ears respiratory rate is 30 breaths per minute with oxygen sats at
90%. She is started on high-flow oxygen, given antibiotics
ANSWER: and a fluid bolus. Moreover, blood cultures, lactate and
Small, firm testes urine output are measured. Over the next 10 minutes, her
heart rate and blood pressure stabilise. Her family are told
EXPLANATION: that she is most likely suffering from sepsis secondary to a
FRAGILE X SYNDROME urinary tract infection. Which cytokine is responsible for the
Fragile X syndrome is a trinucleotide repeat disorder. chemotaxis of neutrophils?
Features in males
• learning difficulties
• large low set ears, long thin face, high arched palate
A. Il-1 X-linked recessive conditions - there is no male-to-male
B. IL-2 transmission. Affected males can only have unaffected sons
C. IL-5 and carrier daughters.
D. IL-8 As we now know that mother is not a carrier of the disease
E. IL-12 there is no chance that any future children could develop
haemophilia. You should of course also discuss with him that
ANSWER: any daughters that he has will be carriers of the condition.
IL-8
Please see Q-3 for X-linked Recessive
EXPLANATION:
IL-8 encourages chemotaxis of neutrophils Q-373
IL-8 is responsible for the chemotaxis of neutrophils. It is A neonate female born at 37 weeks gestation develops
secreted from macrophages and some epithelial tissues. severe cyanosis 1 hour after birth. She develops worsening
respiratory distress and becomes highly tachypnoeic with
IL-1 is responsible for acute inflammation. IL-2 is secreted difficulty feeding. She is soon transferred to the neonatal
from Th1 cells and is responsible for proliferation and intensive care unit for supportive treatment. Her mother did
differentiation of T cells. IL-5 stimulates proliferation of not seek any antenatal care and the baby was born via an
eosinophils. IL-12 is secreted from antigen presenting cells uncomplicated spontaneous vaginal delivery.
and encourages the differentiation of Th0 cells into Th1 cells.
On physical examination, the neonate is cyanosed and
Please see Q-88 for Cytokines lethargic. Her vital signs were as follows: respiratory rate
62/min, oxygen saturation 84% (on 60% oxygen), heart rate
Q-371 160/min, blood pressure 96/66 mmHg. Cardiac auscultation
Which one of the following immunoglobulins is involved in reveals a loud S2 heart sound.
the activation of B-cells?
Chest x-ray shows the cardiac silhouette with an 'eggs on a
A. IgD string' appearance. Electrocardiogram (ECG) shows a right
B. IgM ventricular dominance. Further diagnostic workup with
C. IgE echocardiography confirms a congenital heart defect.
D. IgG
E. IgA Which of the following is the most likely underlying
embryological pathology in this neonate's congenital heart
ANSWER: defect?
IgD
A. Absent tricuspid valve and hypoplastic right ventricle
EXPLANATION: B. Anterosuperior displacement of the infundibular septum
IgD is involved in the activation of B-cells C. Defect in interatrial septum
D. Failure of the aorticopulmonary septum to spiral
Please see Q-190 for Immunoglobulins E. Aortic narrowing near insertion of ductus arteriosus

Q-372 ANSWER:
You are speaking to a 24-year-old man who is known to have Failure of the aorticopulmonary septum to spiral
haemophilia A. His wife has had genetic testing and was
found not to be a carrier of haemophilia. He asks you what EXPLANATION:
the chances are of his future children developing Transposition of great vessels is due to the failure of the
haemophilia. What is the correct answer? aorticopulmonary septum to spiral
The clinical stem here is significant for a cyanotic heart
A. 0% disease. The clinical findings as well as the classic X-ray
B. 25% description point towards a diagnosis of transposition of
C. 50% great vessels which is caused by the failure of the
D. 50% if male, 0% if female aorticopulmonary septum to spiral during early life.
E. 100% Absent tricuspid valve and hypoplastic right ventricle are
seen in tricuspid atresia (cyanotic heart defect).
ANSWER:
0% Anterosuperior displacement of the infundibular septum is
seen in Tetralogy of Fallot (cyanotic heart defect). The x-ray
EXPLANATION: in this condition would show a 'boot-shaped' heart.
A defect in the interatrial septum is present in the atrial
septal defect (non-cyanotic).
Aortic narrowing near the insertion of ductus arteriosus
occurs in aortic coarctation.
TRANSPOSITION OF THE GREAT ARTERIES
Transposition of the great arteries (TGA) is a form of cyanotic
congenital heart disease. It is caused from the failure of the
aorticopulmonary septum to spiral during septation. Children
of diabetic mothers are at an increased risk of TGA.
Other effects include increasing the expression of adhesion
molecules on the endothelium. By stimulating the release by
the endothelium of vasoactive factors such as PAF, nitric oxide
and prostacyclin it also causes vasodilation and increases
vascular permeability. It is therefore one of the mediators of
shock in sepsis. Along with IL-6 and TNF, it acts on the
hypothalamus causing pyrexia.
Q-376
A cohort study is designed to look at the association
between working long hours and blood pressure.

Key features The following results are obtained after 10 years of follow-
• aorta leaves the right ventricle up:
• pulmonary trunk leaves the left ventricle
Number of patients Number of patients
Surgical correction is the definite treatment. with normal blood diagnosed with
pressure after 10 years hypertension after 10 years Total
Q-374 Working < 40 1000 50 1,050
A new blood test is developed to screen for prostate cancer. hours/ week
Trials have shown it has a sensitivity for detecting clinically Working > 40 600 60 660
hours/ week
significant prostate cancer of 80% but a specificity of 60%.
What is the likelihood ratio for a positive test result?
What is the odds ratio of developing hypertension if you
A. Cannot be calculated work more than 40 hours/week compared to people who
B. 2 work less than 40 hours/week?
C. 4
D. 0.8 A. 60/600
E. 0.2 B. 0.5
C. 2
ANSWER: D. 50/60
2 E. 60/50

EXPLANATION: ANSWER:
Please see Q-8 for Screening Test Statistics 2

Q-375 EXPLANATION:
Which one of the following statements regarding interleukin The odds of developing hypertension if you work < 40
1 (IL-1) is true? hours/week is 50 / 1000 = 1 / 20 or 0.05

A. It is released mainly by macrophages/monocytes
B. It causes vasoconstriction
C. It reduces expression of selectin molecules on the
endothelium
D. IL-1 antagonists are currently licensed for use in
colorectal cancer
E. It inhibits the release of nitric oxide by the endothelium
The odds of developing hypertension if you work > 40
hours/week is 60 / 600 = 1 / 10 or 0.1
The odds ratio is therefore = (odds of developing
hypertension if you work > 40 hours/week) / (odds of
developing hypertension if you work < 40 hours/week) =
0.1/0.05 = 2

ANSWER: Please see Q-93 for Odds and Odds Ratio

It is released mainly by macrophages/monocytes
EXPLANATION:
IL-1
Interleukin 1 (IL-1) is a key mediator of the immune response.
It is secreted mainly by macrophages and monocytes and acts
as a costimulator of T cell and B cell proliferation.
Q-377
A 28-year-old woman presents with a 3-day history of
dysuria and increased urinary frequency. She denies any
vaginal discharge or menorrhagia. Urine dipstick is positive
for leukocytes and nitrites. Urine culture grows a urease-
bacteria that is identified as Proteus mirabilis. She is treated
with antibiotics.
Chronic and recurrent infections with this bacteria Type of Percentage of
predispose patients to which of the following types of renal stones Features all calculi
stones? May precipitate when urinary pH low
May be caused by diseases with extensive tissue
A. Calcium oxalate breakdown e.g. malignancy
More common in children with inborn errors of
B. Calcium phosphate
metabolism
C. Ammonium magnesium phosphate (struvite) Radiolucent
D. Uric acid Calcium May occur in renal tubular acidosis, high urinary 10%
E. Cystine phosphate pH increases supersaturation of urine with
calcium and phosphate
ANSWER: Renal tubular acidosis types 1 and 3 increase
Ammonium magnesium phosphate (struvite) risk of stone formation (types 2 and 4 do not)
Radio-opaque stones (composition similar to
bone)
EXPLANATION:
Struvite Stones formed from magnesium, ammonium 2-20%
Recurrent urease-positive bacteria (eg. proteus mirabilis)
and phosphate
infections predispose individuals to struvite renal stones Occur as a result of urease producing bacteria
Struvite accounts for 15% of stones. It is caused by infections (and are thus associated with chronic infections)
with urease-positive bacteria (e.g. Proteus mirabilis) that Under the alkaline conditions produced, the
hydrolyze urea to ammonia and alkalize the urine. They crystals can precipitate
commonly form staghorn calculi. Slightly radio-opaque

Calcium-based renal stones account for 80% of all stones. Effect of urinary pH on stone formation
They are mostly idiopathic but may result from antifreeze Urine pH will show individual variation (from pH 5-7). Post
ingestion, vitamin C abuse, hypocitraturia and prandially the pH falls as purine metabolism will produce uric
malabsorption (e.g. Crohn disease). acid. Then the urine becomes more alkaline (alkaline tide).
When the stone is not available for analysis the pH of urine
Uric acid renal stones account for about 5% of all stones. Risk may help to determine which stone was present.
factors include reduced urine volume, arid climates, acidic
pH. It is strongly associated with hyperuricaemia (e.g. gout) Stone type Urine acidity Mean urine pH
and is often seen in diseases with high cell turnover (e.g. Calcium phosphate Normal- alkaline >5.5
leukaemia) Calcium oxalate Variable 6
Uric acid Acid 5.5
Cystine renal stones result from a hereditary condition in Struvate Alkaline >7.2
which cystine-reabsorbing PCT transporter loses function, Cystine Normal 6.5
causing cystinuria. Cystine is poorly soluble, thus stones form
in the urine. They can also form staghorn calculi. Q-378
Which one of the following occurs during reverse
RENAL STONES transcriptase polymerase chain reaction?

Type of Percentage ofA. Proteins are converted to DNA

stones Features all calculi B.DNA is converted to RNA
Calcium Hypercalciuria is a major risk factor (various 85% C. Used to amplify DNA
oxalate causes) D. RNA is converted to DNA
Hyperoxaluria may also increase risk E. Proteins are converted to RNA
Hypocitraturia increases risk because citrate
forms complexes with calcium making it more
soluble ANSWER:
Stones are radio-opaque (though less than RNA is converted to DNA
calcium phosphate stones)
Hyperuricosuria may cause uric acid stones to EXPLANATION:
which calcium oxalate binds Please see Q-6 for Polymerase Chain Reaction
Cystine Inherited recessive disorder of transmembrane 1%
cystine transport leading to decreased Q-379
absorption of cystine from intestine and renal
Patients with deficiencies of which one of the following
tubule
Multiple stones may form complement protein(s) are predisposed to immune complex
Relatively radiodense because they contain diseases?
sulphur
Uric acid Uric acid is a product of purine metabolism 5-10%
A. C1-INH Which of the following is the most likely diagnosis?
B. C1q, C1rs, C2, C4
C. C5-9 A. Adverse reaction to patient controlled analgesia
D. C3 B. Hyperosmolar hyperglycaemic state
E. C3bBb C. Hyponatraemic encephalopathy
D. Normal pressure hydrocephalus
ANSWER: E. Central pontine myelinolysis
C1q, C1rs, C2, C4
ANSWER:
EXPLANATION: Hyponatraemic encephalopathy
Please see Q-39 for Complement Deficiencies
EXPLANATION:
Q-380 POST OPERATIVE FLUID MANAGEMENT
Which one of the following syndromes is associated with an Composition of commonly used intravenous fluids mmol-1
increased risk of Crohn's disease?
Na K Cl Bicarbonate Lactate
A. Turner's syndrome Plasma 137-147 4-5.5 95-105 22-25 -
B. Down's syndrome 0.9% Saline 153 - 153 - -
C. Fragile X syndrome Dextrose / saline 30.6 - 30.6 - -
D. Patau syndrome Hartmans 130 4 110 - 28
E. Edward's syndrome
Post operative fluid management
ANSWER: In the UK the GIFTASUP guidelines (see reference below) were
Turner's syndrome devised to try and provide some consensus guidance as to
how intravenous fluids should be administered. A decade ago
EXPLANATION: it was a commonly held belief that little harm would occur as
Please see Q-16 for Turner’s Syndrome a result of excessive administration of normal saline and many
oliguric post operative patients received enormous quantities
Q-381 of IV fluids. As a result they developed hyperchloraemic
Which one of the following is least associated with acidosis. With greater understanding of this potential
homocystinuria? complication the use of electrolyte balanced solutions
(Ringers lactate/ Hartmans) is now favored over normal
A. Recurrent renal stones saline. In addition to this solutions of 5% dextrose and
B. Downwards lens dislocation dextrose/saline combinations are now generally not
C. Deep vein thrombosis recommended for surgical patients. The other guidance
D. Arachnodactyly includes:
E. Learning difficulties • Fluids given should be documented clearly and easily
available
ANSWER:
• Assess the patient's fluid status when they leave theatre
Recurrent renal stones
• If a patient is haemodynamically stable and euvolaemic,
aim to restart oral fluid intake as soon as possible
EXPLANATION:
• Review patients whose urinary sodium is < 20
Please see Q-24 for Homocystinuria
• If a patient is oedematous, hypovolaemia if present
should be treated first. This should then be followed by a
Q-382
negative balance of sodium and water, monitored using
An 8-year-old is admitted with suspected appendicitis and
urine Na excretion levels.
has a laparoscopic appendicectomy. He is given 0.45 %
sodium chloride post-operatively. When reviewed by the • Solutions such as Dextran 70 should be used in caution in
surgical team he has developed features of a headache, patients with sepsis as there is a risk of developing acute
confusion, and disturbance to his gait. renal injury.

Na+ 128 mmol/l References

K+ 4.0 mmol/l British Consensus Guidelines on Intravenous Fluid Therapy for
Urea 5 mmol/l Adult Surgical Patients
Creatinine 60µmol/l GIFTASUP (2009)
Glucose 4.0mmol/l
Q-383 CD3 is a cell surface marker found on all T cells. CD4 is a cell
A 68-year-old man presents to the clinic with his wife. His surface marker found on T helper cells. CD14 is a cell surface
wife is very concerned about his behaviour during sleep. She marker found on macrophages. CD15 is a cell surface marker
states that he appears to be lucidly dreaming and acting out found on Reed-Sternberg cells.
his dreams, which has resulted in him physically hurting her
a few times. ANSWER:
CD21
What stage of sleep does this phenomenon occur?
EXPLANATION:
A. Awake Please see Q-97 for Cell Surface Proteins
B. Non-REM stage 1 (N1)
C. Non-REM stage 2 (N2) Q-385
D. Non-REM stage 3 (N3) Which one of the following conditions may cause
E. REM hypokalaemia in association with hypertension?

ANSWER: A. Gitelman syndrome

REM B. 21-hydroxylase deficiency
C. Bartter's syndrome
EXPLANATION: D. Phaeochromocytoma
REM sleep is the deepest stage of sleep which is associated E. 11-beta hydroxylase deficiency
with dreaming and loss of muscle tone
During the REM stage of sleep there is normally atonia to ANSWER:
prevent individuals acting out their dreams. REM sleep 11-beta hydroxylase deficiency
behaviour disorders (REM parasomnias) are characterised by
loss of this normal atonia during REM sleep. REM sleep is the EXPLANATION:
deepest stage of sleep where dreaming occurs. It is believed 21-hydroxylase deficiency, which accounts for 90% of
that loss of muscle tone during this stage of sleep is partly a congenital adrenal hyperplasia cases, is not associated with
protective factor to prevent harm to oneself and others. In hypertension
REM sleep disorders, the paralysis that normally occurs
during REM sleep is incomplete or absent, allowing the Please see Q-227 for Hypokaleimia and Hypertension
person to 'act out' his or her dreams, which are often vivid,
intense, and violent. Q-386
Which one of the following is true regarding Escherichia coli
Non-REM stage 1 (N1) sleep is the lightest sleep which is infection?
associated with hypnagogic jerks.
A. It is a Gram negative coccus
Please see Q-199 for Sleep Stages B. E. coli is an important cause of neonatal meningitis
C. The O157:H7 strain is typically spread via shellfish
Q-384 D. Severe infection should be treated with teicoplanin
An 18-year-old university student goes to see her GP due to E. It is an aerobic bacteria
a sore throat. She also has a marked fever and says she has ANSWER:
been feeling tired for the past three weeks. On examination, E coli is an important cause of neonatal meningitis
she has swollen cervical lymph nodes. An antibody test
confirms infectious mononucleosis. Which cell surface EXPLANATION:
protein does the Ebstein-Barr virus bind to? Escherichia coli is classified as a facultative anaerobe

A. CD3 Please see Q-279 for Eschericia coli

B. CD4 Q-387
C. CD14 Which one of the following statements regarding
D. CD15 galactosaemia is incorrect?
E. CD21
A. Autosomal recessive inheritance
CD21 is the receptor for the Ebstein-Barr virus B. May cause cataracts
Infectious mononucleosis is caused by the Epstein-Barr virus C. Caused by the absence of galactose-1-phosphate uridyl
(EBV) - CD21 is the receptor for EBV. transferase
D. May cause jaundice
E. May cause peripheral neuropathy
ANSWER: • atrial septal defect (ASD)
May cause peripheral neuropathy • patent ductus arteriosus (PDA)
• coarctation of the aorta
EXPLANATION: • aortic valve stenosis
GALACTOSAEMIA
Galactosaemia is a rare autosomal recessive condition caused VSDs are more common than ASDs. However, in adult patients
by the absence of galactose-1-phosphate uridyl transferase. ASDs are the more common new diagnosis as they generally
This results in intracellular accumulation of galactose-1- presents later
phosphate
Cyanotic - most common causes
Features • tetralogy of Fallot
• jaundice • transposition of the great arteries (TGA)
• failure to thrive • tricuspid atresia
• hepatomegaly
• cataracts Fallot's is more common than TGA. However, at birth TGA is
• hypoglycaemia after exposure to galactose the more common lesion as patients with Fallot's generally
• Fanconi syndrome presenting at around 1-2 months

Diagnosis The presence of cyanosis in pulmonary valve stenosis depends

• urine reducing substances very much on the severity and any other coexistent defects.

Management is with a galactose free diet Q-389

A 29-year-old man presents with a productive cough, fever
Q-388 and pleuritic chest pain. A chest x-ray shows lobar
A 2-day-old baby girl is noted to become cyanotic whilst consolidation and a sputum culture grows Haemophilus
feeding and crying. A diagnosis of congenital heart disease is influenzae. This is his fourth chest infection in the past seven
suspected. What is the most likely cause? months. Streptococcus pneumoniae has been grown from
the sputum of the previous three episodes. Six-weeks
A. Transposition of the great arteries following the latest infection a full blood count, urea and
B. Coarctation of the aorta electrolytes, CRP and chest x-ray are all reported as normal.
C. Patent ductus arteriosus What is the most appropriate next investigation?
D. Tetralogy of Fallot
E. Ventricular septal defect A. Serum immunoglobulins
B. Spirometry
ANSWER: C. HIV test
Transposition of the great arteries D. Colonoscopy
E. Urinalysis
EXPLANATION:
Congenital heart disease ANSWER:
• cyanotic: TGA most common at birth, Fallot's most Serum immunoglobulins
common overall
• acyanotic: VSD most common cause EXPLANATION:
This patient has had repeated infections with encapsulated
The key point to this question is that whilst tetralogy of bacteria which should raise the suspicion of immunoglobulin
Fallot is more common than transposition of the great deficiency. HIV would be suggested by infections associated
arteries (TGA), Fallot's doesn't usually present until 1-2 with impaired cellular immunity.
months following the identification of a murmur or cyanosis. Please see Q-190 for Immunoglobulins
In the neonate, TGA is the most common presenting cause of
cyanotic congenital heart disease Q-390
A 20-year-old Chinese woman, who came to the UK on
The other 3 options are causes of acyanotic congenital heart holiday, was brought into the emergency department
disease following a road traffic accident. On physical examination,
apart from the traumatic injuries and bruises, there is absent
CONGENITAL HEART DISEASE: TYPES axillary and pubic hair as well as minimal breast
Acyanotic - most common causes development and hyperpigmentation of the oral mucosa and
• ventricular septal defects (VSD) - most common, accounts axilla. CT traumagram (head, occiput to T1, chest including
for 30% aortic arch, abdomen, and pelvis) reveals a cervical fracture
but also bulky adrenal glands and an atrophic uterus. She
reports a history of primary amenorrhoea which was
thought to be due to pubertal delay. Her basic observations
include heart rate 58 beats per minute, blood pressure
182/102 mmHg, Saturation 99% on room air, respiratory rate
18 breaths per minute. An arterial blood gas(ABG) was done.
Hypokalaemia was found with a potassium of 2.9 mmol.
Given the likely diagnosis, what do you expect the rest of the
ABG result to be?
A. pH = 7.34, pO2 = 14 kPa, pCO2 = 5.2 kPa, bicarbonate =
20 mEq/L
B. pH = 7. 42, pO2 = 14 kPa, pCO2 = 3.9 kPa, bicarbonate =
28 mEq/L
C. pH = 7.49, pO2 = 14 kPa, pCO2 = 5.0 kPa, bicarbonate =
32 mEq/L
D. pH = 7.32, pO2 = 7 kPa, pCO2 = 6.8 kPa, bicarbonate = 37
mEq/L
E. pH = 7.39, pO2 = 14, pCO2 = 4.9 kPa, bicarbonate = 25
mEq/L
ANSWER:
pH = 7.49, pO2 = 14 kPa, pCO2 = 5.0 kPa, bicarbonate = 32
mEq/L
EXPLANATION:
Congenital adrenal hyperplasia is a cause of metabolic
alkalosis
This patient has signs of undiagnosed congenital adrenal
hyperplasia. Even though the classic 21-hydroxylase
deficiency commonly presents in infancy, other rarer forms
such as 17-alpha-hydroxylase deficiency could remain
undiagnosed till adulthood, especially in the case of this
patient who comes from a country where good paediatric
care may not be easily accessible. Congenital adrenal
hyperplasia is a cause of metabolic alkalosis. The ABG
readings in Option 3 shows metabolic alkalosis.
Option 1 shows metabolic acidosis.
Option 2 shows metabolic acidosis with respiratory
compensation.
Option 4 shows Type 2 respiratory failure, respiratory
acidosis with partial metabolic compensation.
Option 5 shows a normal ABG.
Please see Q-159 for Metabolic Alkalosis
Q-391
A 34-year-old man is stabbed in the back causing a
hemisection of the spinal cord at the level T5. You assess the
patient's sensory function, with respect to temperature,
vibration, fine touch. You also assess the patient's muscle
strength. Which signs would you expect to see?
A. Ipsilateral loss of temperature, contralateral loss of fine
touch and vibration, ipsilateral spastic paresis
B. Contralateral loss of temperature, ipsilateral loss of fine
touch and vibration, contralateral spastic paresis
C. Contralateral loss of temperature, contralateral loss of
fine touch and vibration, contralateral spastic paresis
D. Ipsilateral loss of temperature, ipsilateral loss of fine
touch and vibration, ipsilateral spastic paresis
E. Contralateral loss of temperature, ipsilateral loss of fine
touch and vibration, ipsilateral spastic paresis
ANSWER:
Contralateral loss of temperature, ipsilateral loss of fine touch
and vibration, ipsilateral spastic paresis
EXPLANATION:
The spinothalamic tract decussates at the same level the
nerve root enters the spinal cord. The corticospinal tract,
dorsal column medial lemniscus, and spinocerebellar tracts
decussate at the medulla
The spinothalamic tract is responsible for carrying sensory
fibres for pain and temperature. It decussates at the same
level the nerve root enters the spinal cord, and hence
temperature loss is contralateral. The dorsal column medial
lemniscus carries sensory fibres for fine touch and vibration
(and unconscious proprioception). It decussates at the
medulla and hence the fine touch and vibration loss is
ipsilateral. The corticospinal tract is a descending tract which
has already decussated (at the medulla). It is responsible for
inhibiting movement of muscles. Loss of its function causes
an upper motor neuron lesion on the ipsilateral side (if
affected in the spinal cord)
SPINAL CORD
- Located in a canal within the vertebral column that affords it
structural support.
• Rostrally it continues to the medulla oblongata of the
brain and caudally it tapers at a level corresponding to
the L1-2 interspace (in the adult), a central structure, the
filum terminale anchors the cord to the first coccygeal
vertebra.
• The spinal cord is characterised by cervico-lumbar
enlargements and these, broadly speaking, are the sites
which correspond to the brachial and lumbar plexuses
respectively.
There are some key points to note when considering the
surgical anatomy of the spinal cord:
* During foetal growth the spinal cord becomes shorter than
the spinal canal, hence the adult site of cord termination at
the L1-2 level.
* Due to growth of the vertebral column the spine segmental
levels may not always correspond to bony landmarks as they
do in the cervical spine.
* The spinal cord is incompletely divided into two symmetrical EXPLANATION:
halves by a dorsal median sulcus and ventral median fissure. For normally distributed data 95.4% of values lie within 2
Grey matter surrounds a central canal that is continuous standard deviations of the mean, leaving 4.6% outside this
rostrally with the ventricular system of the CNS. range. Therefore 2.3% of values will be higher and 2.3% will
be lower than 2 standard deviations from the mean. This
* The grey matter is sub divided cytoarchitecturally into figure is sometimes approximated to 2.5%
Rexeds laminae.
* Afferent fibres entering through the dorsal roots usually Please see Q-23 for Normal Distribution
terminate near their point of entry but may travel for varying
distances in Lissauers tract. In this way they may establish Q-393
synaptic connections over several levels Which one of the following statements regarding gastrin is
true?
* At the tip of the dorsal horn are afferents associated with
nociceptive stimuli. The ventral horn contains neurones that A. Secreted by D cells in the stomach
innervate skeletal muscle. B. Secretion is inhibited by high antral pH
C. Reduces acid secretion in the stomach
The key point to remember when revising CNS anatomy is to D. Increases gastric motility
keep a clinical perspective in mind. So it is worth classifying E. Distension of the stomach inhibits secretion
the ways in which the spinal cord may become injured. These
include: ANSWER:
Increases gastric motility
• Trauma either direct or as a result of disc protrusion
• Neoplasia either by direct invasion (rare) or as a result of EXPLANATION:
pathological vertebral fracture Please see Q-18 for Gastrointestinal Hormones
• Inflammatory diseases such as Rheumatoid disease, or
OA (formation of osteophytes compressing nerve roots Q-394
etc. A new blood test to screen patients for heart failure is
• Vascular either as a result of stroke (rare in cord) or as trialled on 500 patients. The test was positive in 40 of the 50
complication of aortic dissection patients shown to have heart failure by echocardiography. It
• Infection historically diseases such as TB, epidural was also positive in 20 patients who were shown not to have
abscesses. heart failure. What is the positive predictive value of the
test?
The anatomy of the cord will, to an extent dictate the clinical
presentation. Some points/ conditions to remember: A. 0.8
B. 0.66
• Brown- Sequard syndrome-Hemisection of the cord C. 0.33
producing ipsilateral loss of proprioception and upper D. 0.1
motor neurone signs, plus contralateral loss of pain and E. Cannot be calculated
temperature sensation. The explanation of this is that the
fibres decussate at different levels. ANSWER:
• Lesions below L1 will tend to present with lower motor 0.66
neurone signs
EXPLANATION:
Q-392 A contingency table can be constructed from the above data,
A study is performed to find the normal reference range for as shown below:
IgE levels in adults. Assuming IgE levels follow a normal
distribution, what percentage of adults will have an IgE level Heart failure No heart failure
higher than 2 standard deviations from the mean? Test positive 40 20
Test negative 10 430
A. 1.25%
B. 2.3% Positive predictive value = TP / (TP + FP) = 40 / (40 + 20) =
C. 1.96% 0.66
D. 5%
E. 0.5% Please see Q-8 for Screening Test Statistics

ANSWER:
2.3%
Q-395 These proteins are destined to which of the following
A 4-month-old female infant was admitted to hospital for organelles?
diarrhoea and abdominal distension. She had a complicated
birth with resuscitation attempts necessary. On A. Lysosome
examination, it is apparent she appears to be malnourished, B. Smooth endoplasmic reticulum
has axial hypotonia and she has abnormal facial features. C. Rough endoplasmic reticulum
Blood tests elevated long-chain fatty acids levels. Which D. Nucleus
organelle is responsible for the catabolism of long chain fatty E. Mitochondria
acids?
ANSWER:
A. Rough endoplasmic reticulum Lysosome
B. Nucleus
C. Proteasome EXPLANATION:
D. Peroxisome Golgi adds mannose-6-phosphate to proteins for trafficking
E. Lysosome to lysosomes
Golgi adds mannose-6-phosphate to proteins for trafficking
ANSWER: to lysosomes
Peroxisome
Please see Q-135 for Cell Organelles
EXPLANATION:
Peroxisomes are responsible for the catabolism of long chain Q-398
fatty acids A 17-year-old male with a history of cystic fibrosis presents
This patient is presenting with symptoms of Zellweger to clinic for annual review. What is the most appropriate
syndrome a genetic disease which causes peroxisome advice regarding his diet?
dysfunction. Peroxisomes are the principle organelle
responsible for the catabolism of long chain fatty acids. A. High calorie and low fat with pancreatic enzyme
supplementation for every meal
Rough endoplasmic reticulum is responsible for the B. High calorie and low fat with pancreatic enzyme
translation and folding of new proteins. The nucleus is supplementation for evening meal
responsible for containing and maintaining DNA, and the C. Normal calorie and low fat with pancreatic enzyme
transcription of RNA Proteasomes are responsible for the supplementation for every meal
breakdown of proteins tagged with ubiquitin. Lysosomes are D. High calorie and high fat with pancreatic enzyme
responsible for the catabolism of polysaccharides and supplementation for evening meal
proteins. E. High calorie and high fat with pancreatic enzyme
supplementation for every meal
Please see Q-135 for Cell Organelles
ANSWER:
Q-396 High calorie and high fat with pancreatic enzyme
Interferon-alpha may be used in the management of each supplementation for every meal
one of the following, except:
EXPLANATION:
A. Metastatic renal cell cancer CYSTIC FIBROSIS: MANAGEMENT
B. Hepatitis B Management of cystic fibrosis involves a multidisciplinary
C. Kaposi's sarcoma approach
D. Hepatitis C
E. Chronic granulomatous disease Key points
• regular (at least twice daily) chest physiotherapy and
ANSWER:
postural drainage. Parents are usually taught to do this.
Chronic granulomatous disease
Deep breathing exercises are also useful
EXPLANATION: • high calorie diet, including high fat intake*
Please see Q-178 for Interferon • vitamin supplementation
• pancreatic enzyme supplements taken with meals
Q-397 • heart and lung transplant
A scientist is studying the role of regulatory proteins in
intracellular trafficking. He has isolated and identified *this is now the standard recommendation - previously high
various intracellular proteins tagged with mannose-6- calorie, low-fat diets have been recommended to reduce the
phosphate. amount of steatorrhoea
Q-399 ANSWER:
You are a ST1 doctor in medicine doing a nightshift. An Chi-squared test
elderly patient with colorectal cancer has been admitted to
the Emergency Department with suspected bowel EXPLANATION:
obstruction. The Emergency Department F2 doctor has tried As percentages are being compared the chi-squared test
to refer the patient to the surgeons but was told that as no should be used
surgical intervention is likely the patient should be admitted
to the medics. The F2 doctor therefore phones yourself and Please see Q-30 for Significance Tests: Types
asks you to accept the patient. What is the most appropriate
response? Q-401
Which one of the following is involved in the degradation of
A. Accept the patient and ask the staff to transfer her to polypeptides?
the medical assessment unit
B. Simply refuse in order to avoid the patient being A. Peroxisome
admitted under an inappropriate specialty B. Endoplasmic reticulum
C. Tell the surgical registrar that you will contact the on- C. Proteasome
call surgical consultant if he refuses to accept the patient D. Ribosome
D. Go down to the emergency department and review the E. Golgi apparatus
patient ANSWER:
E. Phone the surgical team yourself to discuss the matter Proteasome
ANSWER: EXPLANATION:
Go down to the emergency department and review the
patient Please see Q-135 for Cell Organelles

Q-402
EXPLANATION:
A 30-year-old man is referred to ophthalmology due to
Scenarios similar to this occur on an almost daily basis for
deteriorating visual acuity. Both his brother and uncle on his
admitting medical teams. The priority in all of this has to be
mother's side have developed similar problems. What is the
the patient. It may be the case if the patient is end-stage
most likely mode of inheritance of his condition?
then medical admission is more appropriate. If they are
Duke's A and awaiting an operation then clearly they are A. Autosomal dominant
surgical. Until you review the patient yourself you will not B. Autosomal recessive
have all the facts and this is therefore the best option. C. X-linked recessive
D. X-linked dominant
Discussing the matter with the surgical team will help to E. Polygenic
clarify their opinion about the patient and is the next best
option. Accepting the patient without review risks placing a ANSWER:
patient with an acute surgical problem on a medical ward. X-linked recessive
This may delay or compromise care.
EXPLANATION:
Getting into an argument with the surgical registrar is not This first clue is the nature of the disease - many of the
constructive and is a poor choice, as is simply refusing to see inherited eye disorders such as retinitis pigmentosa and
the patient as this indicates a disregard for the patient. ocular albinism are inherited in an x-linked recessive pattern.

For this disorder to be autosomal recessive both the patient's

Q-400 parents would need to be carriers (heterozygous) as well as
A study compares the sensitivity of two tests for colorectal both his maternal aunt and uncle. Even for common
cancer. The first test has a sensitivity of 85% whilst the autosomal recessive disorders such as cystic fibrosis the
second test has a sensitivity of 91%. What type of carrier rate is around 1 in 25 making this statistically less
significance test should be used for comparing the two likely.
results?
Please see Q-3 for X-linked Recessive
A. Wilcoxon matched-pairs
B. Mann-Whitney test Q-403
C. Student's t-test A 90-year-old man is admitted to hospital. He is taking no
D. Chi-squared test regular medication. On admission his blood pressure is
E. Pearson's test 170/68 mmHg. Which one of the following is the main factor
which accounts for the large pulse pressure?
A. Calcified brachial arteries A. Chi-squared test
B. Autonomic dysfunction B. Spearman's rank correlation coefficient
C. Reduced aortic compliance C. Wilcoxon matched-pairs
D. Reduced left ventricular ejection fraction D. Mann-Whitney test
E. Reduced circulating volume E. Student's t-test

ANSWER: ANSWER:
Reduced aortic compliance Student's t-test

EXPLANATION: EXPLANATION:
Please see Q-208 for Cardiovascular Physiology Student's t-test is used to analyse parametric data. The other
tests are used on non-parametric data
Q-404
A 64-year-old woman who is reviewed due to multiple non- Please see Q-30 for Significance Tests: Types
healing leg ulcers. She reports feeling generally unwell for
many months. Examination findings include a blood pressure Q-406
of 138/72 mmHg, pulse 90 bpm, pale conjunctivae and poor A 33-year-old woman who is known to have familial
dentition associated with bleeding gums. What is the most hypercholesterolaemia comes for review. She is planning to
likely underlying diagnosis? have children and asks for advice regarding medication as
she currently takes atorvastatin 80mg on. What is the most
A. Thyrotoxicosis appropriate advice?
B. Vitamin B12 deficiency
C. Vitamin C deficiency A. Switch to atorvastatin 10mg
D. Diabetes mellitus B. Continue current drug at same dose
E. Sarcoidosis C. Stop atorvastatin before trying to conceive
D. Switch to ezetimibe
ANSWER: E. Switch to simvastatin 40mg
Vitamin C deficiency
ANSWER:
EXPLANATION: Stop atorvastatin before trying to conceive
VITAMIN C (ASCORBIC ACID)
Vitamin C is a water soluble vitamin. EXPLANATION:
Statins should be discontinued in women 3 months before
Functions conception due to the risk of congenital defects
• antioxidant
• collagen synthesis: acts as a cofactor for enzymes that are Please see Q-33 for Familial Hypercholesterolaemia
required for the hydroxylation proline and lysine in the
synthesis of collagen
• facilitates iron absorption
• cofactor for norepinephrine synthesis

Vitamin C deficiency (scurvy) leads to defective synthesis of

collagen resulting in capillary fragility (bleeding tendency) and
poor wound healing

Features vitamin C deficiency

• gingivitis, loose teeth
• poor wound healing
• bleeding from gums, haematuria, epistaxis
• general malaise

Q-405
Which one of the following significance tests is used to
analyse data which is measured and follows a normal
distribution?