MRCP Part 1 — Questions and Answers

Question 1: A 40-year-old man presents with recurrent sinopulmonary infections and chronic diarrhoea. Serum immunoglobulins show very low IgG, IgA, and IgM. B-cell numbers are markedly reduced. What is the most likely diagnosis?

DiGeorge syndrome
X-linked agammaglobulinaemia
Selective IgA deficiency
Common variable immunodeficiency (CVID) (Correct answer)

Correct answer: Common variable immunodeficiency (CVID)

Common variable immunodeficiency (CVID) is the most common symptomatic primary antibody deficiency in adults, presenting with recurrent infections and low immunoglobulin levels. Unlike X-linked agammaglobulinaemia (which presents in infancy with absent B cells), CVID typically presents in the second or third decade with reduced but not absent B cells.

Question 2: Which serological marker is most specific for coeliac disease?

Anti-endomysial IgG antibodies
Anti-nuclear antibodies
Anti-tissue transglutaminase IgA antibodies (Correct answer)
Anti-gliadin IgG antibodies

Correct answer: Anti-tissue transglutaminase IgA antibodies

Anti-tissue transglutaminase (anti-tTG) IgA antibodies are the recommended first-line serological test for coeliac disease, with sensitivity >95% and specificity >95%. Total IgA should be checked simultaneously as IgA deficiency is more common in coeliac disease and causes false negatives.

Question 3: A patient with type 2 diabetes has an eGFR of 35 mL/min/1.73m2 and persistent albuminuria (ACR 45 mg/mmol) despite maximal ACE inhibitor therapy. According to NICE, which additional medication should be considered?

Calcium channel blocker
Spironolactone
SGLT2 inhibitor (dapagliflozin) (Correct answer)
Alpha-blocker

Correct answer: SGLT2 inhibitor (dapagliflozin)

NICE recommends SGLT2 inhibitors (dapagliflozin) for patients with type 2 diabetes and CKD with ACR >=30 mg/mmol, regardless of HbA1c level. The DAPA-CKD trial demonstrated significant renal and cardiovascular benefits. They can be used down to eGFR 15 mL/min for renoprotection.

Question 4: A 45-year-old woman presents with jaundice, pruritus, elevated ALP, and positive anti-mitochondrial antibodies (AMA). What is the diagnosis?

Primary sclerosing cholangitis
Primary biliary cholangitis (Correct answer)
Autoimmune hepatitis
Wilson's disease

Correct answer: Primary biliary cholangitis

Primary biliary cholangitis (PBC, formerly called primary biliary cirrhosis) is an autoimmune cholestatic liver disease characterised by elevated ALP, positive AMA (especially anti-M2), pruritus, and jaundice. It predominantly affects middle-aged women.

Question 5: A patient with long-standing ulcerative colitis undergoes surveillance colonoscopy. Dysplasia is found in a flat non-polypoid area. What is the recommended management?

Colectomy (Correct answer)
Enhanced surveillance with narrow-band imaging annually
Argon plasma coagulation of the dysplastic area
Repeat colonoscopy in 6 months

Correct answer: Colectomy

The detection of flat (non-polypoid) dysplasia in the context of long-standing ulcerative colitis carries a high risk of synchronous or subsequent colorectal cancer. Current guidelines recommend proctocolectomy (colectomy) when flat dysplasia is confirmed by two independent pathologists.

Question 6: In obstructive sleep apnoea (OSA), which investigation is the gold standard for diagnosis?

CT neck
Epworth sleepiness scale score
Overnight oximetry alone
Polysomnography (full overnight sleep study) (Correct answer)

Correct answer: Polysomnography (full overnight sleep study)

Full polysomnography (overnight sleep study) measuring airflow, respiratory effort, oxygen saturation, EEG, EMG, and ECG is the gold standard for diagnosing OSA and characterising its severity (AHI). Limited respiratory polygraphy may be used in straightforward cases.

Question 7: A patient with known asthma has a PEFR of 33% best and cannot complete sentences. What severity of asthma attack is this?

Moderate acute asthma
Near-fatal asthma
Severe acute asthma
Life-threatening asthma (Correct answer)

Correct answer: Life-threatening asthma

Life-threatening asthma is defined by any of: PEFR <33% best/predicted, SpO2 <92%, PaO2 <8 kPa, normal/high PaCO2 (>4.6 kPa), silent chest, poor respiratory effort, cyanosis, bradycardia, confusion, or exhaustion. PEFR 33% with inability to speak indicates life-threatening severity.

Question 8: A patient with SLE develops proteinuria 3.5g/24h, haematuria, and cellular casts. Renal biopsy shows endocapillary hypercellularity affecting more than 50% of glomeruli. According to ISN/RPS classification, which class of lupus nephritis is this?

Class V
Class IV (Correct answer)
Class II
Class III

Correct answer: Class IV

Class IV (diffuse proliferative) lupus nephritis involves more than 50% of glomeruli and is the most severe form, requiring aggressive immunosuppression with cyclophosphamide or mycophenolate.

Question 9: A patient with depression has been started on an SSRI. When counselling about side effects, how long should you advise before full therapeutic effect is expected?

7 days
3 months
24-48 hours
4-6 weeks (Correct answer)

Correct answer: 4-6 weeks

SSRIs typically take 4-6 weeks to achieve full therapeutic effect in depression. Patients should be counselled about this delay and warned that side effects (nausea, anxiety, insomnia) may occur earlier. Close follow-up is important, particularly in the first few weeks due to potential increased suicidality risk before mood improves.

Question 10: Joint aspirate from a swollen knee reveals rhomboid-shaped crystals that are weakly positively birefringent under compensated polarised light. How does this differ from the crystals found in gout?

Both crystal types show identical birefringence but differ in solubility
Gout crystals are strongly negatively birefringent and needle-shaped (Correct answer)
Gout crystals are rhomboid and negatively birefringent
Gout crystals are also positively birefringent but needle-shaped

Correct answer: Gout crystals are strongly negatively birefringent and needle-shaped

Calcium pyrophosphate crystals (pseudogout) are weakly positively birefringent and rhomboid-shaped, whereas monosodium urate crystals (gout) are strongly negatively birefringent and needle-shaped.

Question 11: A patient with known asthma presents with acute breathlessness. Arterial blood gas shows pH 7.35, PaCO2 5.5 kPa, PaO2 8.0 kPa. What does the PaCO2 suggest about the severity of this exacerbation?

Life-threatening — indicates tiring and impending respiratory failure (Correct answer)
Moderate — requires nebulised salbutamol only
Resolving — the patient is improving
Mild — normal CO2 is reassuring

Correct answer: Life-threatening — indicates tiring and impending respiratory failure

In acute asthma, patients typically hyperventilate, producing a low PaCO2. A normal or rising PaCO2 (5.5 kPa) in acute asthma is a sinister sign indicating respiratory muscle fatigue and inability to maintain the hyperventilatory response. This is classified as a feature of life-threatening asthma by BTS/SIGN guidelines.

Question 12: A 48-year-old woman with long-standing Raynaud's phenomenon develops skin thickening confined to the hands and face, telangiectasia, and anti-centromere antibodies. Which long-term complication carries the greatest mortality risk in her condition?

Scleroderma renal crisis
Pulmonary arterial hypertension (Correct answer)
Diffuse alveolar haemorrhage
Rapidly progressive glomerulonephritis

Correct answer: Pulmonary arterial hypertension

Limited cutaneous systemic sclerosis with anti-centromere antibodies confers a high risk of pulmonary arterial hypertension, which is a leading cause of death in this subtype.

Question 13: A 10-year-old ANA-positive girl is diagnosed with oligoarticular juvenile idiopathic arthritis. Which potentially sight-threatening complication is classically asymptomatic and requires scheduled ophthalmological screening?

Corneal ulceration
Posterior uveitis
Optic neuritis
Anterior uveitis (iridocyclitis) (Correct answer)

Correct answer: Anterior uveitis (iridocyclitis)

Anterior uveitis in oligoarticular JIA is often asymptomatic (no red eye, no pain) and can lead to irreversible blindness if undetected; regular slit-lamp examinations every 3–6 months are mandatory.

Question 14: A patient with known IHD develops sudden-onset severe chest pain tearing to the back, unequal blood pressures in both arms, and a widened mediastinum on CXR. What is the diagnosis?

Pulmonary embolism
Aortic stenosis
STEMI
Type A aortic dissection (Correct answer)

Correct answer: Type A aortic dissection

The triad of tearing chest/back pain, unequal arm blood pressures, and widened mediastinum is classic for aortic dissection. Type A involves the ascending aorta and is a surgical emergency. CT aortogram is the investigation of choice if the patient is haemodynamically stable.

Question 15: What is the most common cause of complete heart block in the UK?

Myocardial infarction involving the right coronary artery
Digoxin toxicity
Degenerative fibrosis (Lenègre/Lev disease) (Correct answer)
Congenital abnormality

Correct answer: Degenerative fibrosis (Lenègre/Lev disease)

The most common cause of complete heart block in adults is idiopathic degenerative fibrosis of the conduction system (Lenègre's or Lev's disease), occurring with age. Inferior MI affecting the RCA is a recognised but less common cause.

Question 16: A 35-year-old woman presents with hypertension, hypokalaemia, and metabolic alkalosis. 24-hour urinary aldosterone is elevated with suppressed renin. What is the most likely diagnosis?

Renal artery stenosis
Phaeochromocytoma
Cushing's syndrome
Primary hyperaldosteronism (Conn's syndrome) (Correct answer)

Correct answer: Primary hyperaldosteronism (Conn's syndrome)

Primary hyperaldosteronism (Conn's syndrome) is characterised by hypertension, hypokalaemia, metabolic alkalosis, elevated aldosterone, and suppressed renin. The aldosterone:renin ratio (ARR) is the screening test of choice. Adrenal adenoma is the most common cause; bilateral hyperplasia is the second.

Question 17: A 52-year-old woman presents with a 2-year history of dry eyes, dry mouth, and arthralgia. Schirmer's test confirms reduced lacrimation. Which antibody is most characteristically associated with primary Sjögren's syndrome?

Anti-Jo-1
Anti-Ro (SSA) (Correct answer)
Anti-dsDNA
Anti-Scl-70

Correct answer: Anti-Ro (SSA)

Anti-Ro (SSA) antibodies are present in approximately 70% of patients with primary Sjögren's syndrome and are the hallmark serological finding.

Question 18: A 25-year-old woman presents with polyuria, polydipsia, and a random plasma glucose of 22 mmol/L. Urine dipstick shows glucose 3+ and ketones 3+. Blood gas shows pH 7.15, bicarbonate 8 mmol/L. What is the initial fluid replacement?

5% dextrose 1 litre over 1 hour
0.9% sodium chloride 1 litre over 1 hour (Correct answer)
0.45% sodium chloride 1 litre over 2 hours
Hartmann's solution 500 mL over 30 minutes

Correct answer: 0.9% sodium chloride 1 litre over 1 hour

In diabetic ketoacidosis (DKA), initial fluid resuscitation is with 0.9% sodium chloride. The JBDS DKA guideline recommends 1 litre of 0.9% saline over the first hour, followed by a fixed-rate IV insulin infusion at 0.1 units/kg/hour. 5% dextrose is added later when glucose falls below 14 mmol/L.

Question 19: A 35-year-old woman presents with fever, arthralgia, and a malar (butterfly) rash. Blood tests show pancytopaenia, raised anti-dsDNA antibodies, and low complement C3 and C4. What is the most likely diagnosis?

Systemic lupus erythematosus (SLE) (Correct answer)
Dermatomyositis
Rheumatoid arthritis
Systemic sclerosis

Correct answer: Systemic lupus erythematosus (SLE)

SLE characteristically presents in young women with multi-system involvement including malar rash, arthralgia, cytopaenias, and renal disease. Anti-dsDNA antibodies are highly specific for SLE and correlate with disease activity, particularly lupus nephritis. Low complement levels indicate active immune complex consumption.

Question 20: Which immunoglobulin class is found in highest concentration in normal human serum?

IgA
IgG (Correct answer)
IgE
IgM

Correct answer: IgG

IgG constitutes approximately 75-80% of serum immunoglobulins and is the most abundant antibody class in blood. It crosses the placenta and provides passive immunity to neonates.

Question 21: In disseminated intravascular coagulation (DIC), which coagulation profile would you expect?

Normal PT, elevated APTT, elevated fibrinogen, reduced platelets
Reduced PT, reduced APTT, elevated fibrinogen, elevated platelets
Elevated PT, elevated APTT, reduced fibrinogen, reduced platelets (Correct answer)
Elevated PT, elevated APTT, elevated fibrinogen, elevated platelets

Correct answer: Elevated PT, elevated APTT, reduced fibrinogen, reduced platelets

DIC is characterised by simultaneous microvascular thrombosis and consumption of clotting factors and platelets, leading to elevated PT, elevated APTT, reduced fibrinogen (consumed), reduced platelets, and elevated D-dimer (from fibrin degradation). Fragmented red cells (schistocytes) may be seen on blood film.

Question 22: A 45-year-old man presents with polycythaemia vera. His haematocrit is 0.56 and he complains of headaches, facial plethora, and pruritus after bathing. Which mutation is present in >95% of cases?

BCR-ABL translocation
MPL mutation
JAK2 V617F mutation (Correct answer)
CALR mutation

Correct answer: JAK2 V617F mutation

JAK2 V617F point mutation is found in over 95% of polycythaemia vera cases. The mutation leads to constitutive activation of the JAK-STAT signalling pathway, causing erythroid, myeloid, and megakaryocyte proliferation. Aquagenic pruritus (after bathing) is a classic symptom of PV.

Question 23: A patient on lithium for bipolar disorder presents with polyuria and polydipsia. Serum sodium is 148 mmol/L and urine osmolality is 180 mOsm/kg despite fluid restriction. What has lithium caused?

Cranial diabetes insipidus
Psychogenic polydipsia
SIADH
Nephrogenic diabetes insipidus (Correct answer)

Correct answer: Nephrogenic diabetes insipidus

Lithium is the most common cause of acquired nephrogenic diabetes insipidus. It accumulates in collecting duct cells and inhibits aquaporin-2 expression, rendering the kidney resistant to ADH. This results in inability to concentrate urine, causing polyuria, polydipsia, and hypernatraemia.

Question 24: A 35-year-old woman with SLE has suffered three first-trimester miscarriages and one DVT. Lupus anticoagulant and anti-cardiolipin IgG are positive on two occasions 12 weeks apart. What is the most appropriate long-term antithrombotic treatment?

Rivaroxaban 20mg daily
Low molecular weight heparin indefinitely
Warfarin with target INR 2–3 (Correct answer)
Aspirin 75mg daily alone

Correct answer: Warfarin with target INR 2–3

Antiphospholipid syndrome with confirmed venous thrombosis requires long-term warfarin targeting an INR of 2–3; direct oral anticoagulants are not recommended in APS due to evidence of higher recurrence rates.

Question 25: Which HLA type is most strongly associated with ankylosing spondylitis?

HLA-B51
HLA-B27 (Correct answer)
HLA-DR4
HLA-DR3

Correct answer: HLA-B27

HLA-B27 is present in over 90% of patients with ankylosing spondylitis, making it one of the strongest HLA-disease associations known. However, only about 5% of HLA-B27 positive individuals develop the condition.

Question 26: Which valve lesion produces a mid-diastolic rumbling murmur best heard at the apex with the bell in the left lateral position?

Mitral stenosis (Correct answer)
Tricuspid regurgitation
Pulmonary stenosis
Aortic regurgitation

Correct answer: Mitral stenosis

Mitral stenosis produces a low-pitched, mid-diastolic rumbling murmur, heard best at the apex with the bell of the stethoscope, with the patient in the left lateral position. It is often preceded by an opening snap and is accentuated by exercise.

Question 27: A patient with haemophilia A has a factor VIII level of 3%. What severity does this represent?

Carrier state only
Mild haemophilia A (>5% factor VIII)
Severe haemophilia A (<1% factor VIII)
Moderate haemophilia A (1–5% factor VIII) (Correct answer)

Correct answer: Moderate haemophilia A (1–5% factor VIII)

Haemophilia A severity is classified by factor VIII activity: mild (>5–40%), moderate (1–5%), and severe (<1%). A level of 3% places this patient in the moderate category, characterised by bleeding with significant trauma or surgery, but not usually spontaneous bleeding.

Question 28: Which condition is associated with a 'saddle-shaped' ST elevation pattern across multiple leads without reciprocal changes?

Acute pericarditis (Correct answer)
Left bundle branch block
STEMI
Prinzmetal angina

Correct answer: Acute pericarditis

Acute pericarditis classically causes diffuse, saddle-shaped ST elevation across multiple leads without the reciprocal ST depression seen in STEMI. It is accompanied by PR depression (especially in limb leads) and is caused by inflammation of the pericardium.

Question 29: A 78-year-old man presents with visual hallucinations, fluctuating cognition, and parkinsonism that preceded dementia onset. What is the most likely diagnosis?

Vascular dementia
Dementia with Lewy bodies (Correct answer)
Frontotemporal dementia
Alzheimer's disease

Correct answer: Dementia with Lewy bodies

Dementia with Lewy bodies (DLB) is characterised by the core features of fluctuating cognition, recurrent visual hallucinations, and spontaneous parkinsonism. REM sleep behaviour disorder is also a core feature. Importantly, patients with DLB are exquisitely sensitive to neuroleptics, which should be avoided.

Question 30: A 25-year-old woman presents with episodic severe unilateral headache with visual aura lasting 20 minutes followed by nausea and photophobia. She has 4 attacks per month. What is the most appropriate prophylactic medication?

Propranolol (Correct answer)
Paracetamol
Codeine phosphate
Sumatriptan

Correct answer: Propranolol

Propranolol is a first-line prophylactic agent for migraine recommended by NICE. Prophylaxis is considered when patients have 4 or more attacks per month. Topiramate and amitriptyline are alternatives. Sumatriptan is an acute treatment, not prophylaxis.

MRCP Part 1

The MRCP Part 1 is a two-paper written examination testing broad knowledge of general medicine across clinical specialties, required for entry to core medical training in the UK. Each paper contains 100 single best answer questions in 'best of five' format over 3 hours.

Questions

55 min

Time Limit

60%

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