MRCP Part 1 — Questions and Answers

Question 1: Which of the following is the most common cause of a spontaneous pneumothorax in a tall, thin young man?

Pulmonary embolism
Ruptured emphysematous bulla
Marfan syndrome
Idiopathic rupture of a subpleural bleb (Correct answer)

Correct answer: Idiopathic rupture of a subpleural bleb

Primary spontaneous pneumothorax typically occurs in tall, thin young men and is caused by rupture of subpleural blebs (small air-filled sacs) at the lung apex. This is idiopathic — no underlying lung disease is identified. Secondary spontaneous pneumothorax occurs in those with underlying lung disease.

Question 2: A patient with a mechanical mitral valve replacement presents with a new regurgitant murmur, fever, and splinter haemorrhages. Blood cultures grow Staphylococcus epidermidis. What is the most appropriate empirical antibiotic regimen whilst awaiting sensitivities?

Amoxicillin and gentamicin
Flucloxacillin monotherapy
Co-amoxiclav and metronidazole
Vancomycin, gentamicin, and rifampicin (Correct answer)

Correct answer: Vancomycin, gentamicin, and rifampicin

Prosthetic valve endocarditis (PVE) with coagulase-negative staphylococci requires vancomycin (covering MRSE), gentamicin (synergistic bactericidal activity), and rifampicin (penetrates biofilm on prosthetic material). This is recommended by ESC and NICE guidelines for PVE.

Question 3: Which ECG finding is most characteristic of hyperkalaemia?

Prolonged QT interval
Delta waves
ST depression
Tall tented T waves (Correct answer)

Correct answer: Tall tented T waves

Tall, peaked (tented) T waves are the earliest ECG change in hyperkalaemia, typically appearing when potassium exceeds 5.5-6.0 mmol/L. Progressive hyperkalaemia leads to widened QRS, loss of P waves, and eventually a sine wave pattern preceding cardiac arrest.

Question 4: A 30-year-old woman presents with optic neuritis. MRI brain shows periventricular white matter lesions. CSF shows oligoclonal bands not matched in serum. What is the most likely diagnosis?

Neuromyelitis optica
CNS lymphoma
Multiple sclerosis (Correct answer)
Acute disseminated encephalomyelitis

Correct answer: Multiple sclerosis

Multiple sclerosis (MS) is characterised by demyelinating lesions disseminated in time and space. Optic neuritis is a common presenting feature, and periventricular white matter lesions on MRI with unmatched CSF oligoclonal bands strongly support the diagnosis according to the McDonald criteria.

Question 5: In a patient with HOCM, which intervention is most likely to worsen outflow tract obstruction?

Squatting
Exercise in a supine position
Beta-blockers
Valsalva manoeuvre (Correct answer)

Correct answer: Valsalva manoeuvre

Valsalva manoeuvre reduces venous return, decreasing LV preload. In HOCM, reduced LV cavity size worsens the dynamic outflow tract obstruction. Squatting increases preload and reduces obstruction. Beta-blockers reduce the obstruction by slowing heart rate and reducing contractility.

Question 6: 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 7: A patient with HIV has a CD4 count of 80 cells/mm³ and presents with ring-enhancing lesions on MRI with surrounding oedema. What is the most likely diagnosis?

Cerebral toxoplasmosis (Correct answer)
Primary CNS lymphoma
Progressive multifocal leukoencephalopathy
Cryptococcal meningitis

Correct answer: Cerebral toxoplasmosis

Cerebral toxoplasmosis is the most common cause of ring-enhancing lesions in HIV-positive patients with a CD4 count below 200 cells/mm³. It is caused by reactivation of latent Toxoplasma gondii. Treatment is sulphadiazine plus pyrimethamine plus folinic acid.

Question 8: Which HLA type is most strongly associated with ankylosing spondylitis?

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

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 9: A 70-year-old man with known aortic stenosis has a systolic murmur that radiates to the carotids, a slow-rising pulse, and a narrow pulse pressure. What severity does this indicate?

Moderate aortic stenosis
Severe aortic stenosis (Correct answer)
Mild aortic stenosis
Aortic sclerosis without obstruction

Correct answer: Severe aortic stenosis

Severe aortic stenosis features include: slow-rising (anacrotisch) pulse, narrow pulse pressure, sustained apex beat, late-peaking murmur, absent A2, and the clinical triad of syncope, angina, and heart failure. These findings together indicate haemodynamically significant stenosis.

Question 10: A patient presents with AKI (creatinine 420 µmol/L, previously 85 µmol/L), oliguria, and urine sediment showing muddy brown casts. What is the most likely cause of AKI?

Acute tubular necrosis (Correct answer)
Pre-renal AKI from dehydration
Obstructive uropathy
Glomerulonephritis

Correct answer: Acute tubular necrosis

Muddy brown granular casts on urine microscopy are pathognomonic of acute tubular necrosis (ATN), caused by ischaemia or nephrotoxins damaging tubular epithelial cells that are shed and form these casts. Pre-renal AKI shows hyaline casts; GN shows red cell casts; obstruction shows few casts.

Question 11: A patient presents with symmetrical proximal muscle weakness, elevated CK, heliotrope rash, and Gottron's papules. What is the diagnosis?

Polymyalgia rheumatica
Systemic lupus erythematosus
Dermatomyositis (Correct answer)
Polymyositis

Correct answer: Dermatomyositis

Dermatomyositis is an idiopathic inflammatory myopathy characterised by proximal muscle weakness, elevated CK, and pathognomonic skin changes: heliotrope rash (violet discolouration of eyelids) and Gottron's papules (erythematous papules over knuckles). It is associated with internal malignancy in adults.

Question 12: Which spirometric pattern is characteristic of idiopathic pulmonary fibrosis?

Mixed: reduced FEV1/FVC with reduced TLC
Restrictive: reduced FVC, normal or increased FEV1/FVC ratio (Correct answer)
Obstructive: reduced FEV1/FVC ratio
Obstructive with reversibility post-bronchodilator

Correct answer: Restrictive: reduced FVC, normal or increased FEV1/FVC ratio

Idiopathic pulmonary fibrosis causes a restrictive pattern: reduced FVC, reduced TLC, preserved or elevated FEV1/FVC ratio. The fibrosis stiffens the lung, reducing volume but not obstructing flow proportionally. DLCO is also characteristically reduced.

Question 13: In nephrotic syndrome, which of the following is characteristically NOT seen?

Haematuria (Correct answer)
Peripheral oedema
Hypoalbuminaemia
Proteinuria >3.5 g/day

Correct answer: Haematuria

Nephrotic syndrome is characterised by heavy proteinuria (>3.5 g/24h), hypoalbuminaemia, oedema, and hyperlipidaemia/lipiduria. Haematuria is NOT a typical feature of pure nephrotic syndrome (it is more characteristic of nephritic syndrome) though it can occasionally co-exist.

Question 14: Which pattern of inheritance does Huntington's disease follow?

Mitochondrial
X-linked recessive
Autosomal recessive
Autosomal dominant (Correct answer)

Correct answer: Autosomal dominant

Huntington's disease is caused by a CAG trinucleotide repeat expansion in the HTT gene on chromosome 4, following autosomal dominant inheritance. Anticipation occurs — subsequent generations may be affected at an earlier age with longer repeat lengths.

Question 15: 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?

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

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 16: A patient with chronic kidney disease has a corrected calcium of 1.9 mmol/L and phosphate of 2.1 mmol/L. Which is the most likely underlying mechanism?

Primary hyperparathyroidism
Increased PTH secretion
Vitamin D toxicity
Reduced renal 1-alpha-hydroxylase activity (Correct answer)

Correct answer: Reduced renal 1-alpha-hydroxylase activity

In CKD, the kidneys cannot convert 25-hydroxyvitamin D to its active form (1,25-dihydroxyvitamin D) due to reduced 1-alpha-hydroxylase activity. This leads to decreased calcium absorption, hypocalcaemia, and hyperphosphataemia from reduced renal phosphate excretion.

Question 17: A patient with heart failure has the following spirometry: FEV1 2.8L (predicted 3.5L), FVC 3.2L (predicted 4.2L), FEV1/FVC ratio 87.5%. What pattern does this show?

Normal spirometry
Mixed obstructive and restrictive
Restrictive pattern (Correct answer)
Obstructive pattern

Correct answer: Restrictive pattern

The FEV1/FVC ratio is preserved (>70%) but both FEV1 and FVC are reduced, indicating a restrictive pattern. Heart failure causes pulmonary congestion and reduced lung compliance, leading to restriction.

Question 18: Which finding on ANCA testing is associated with granulomatosis with polyangiitis (Wegener's)?

p-ANCA (anti-MPO)
ANA
Anti-GBM antibodies
c-ANCA (anti-PR3) (Correct answer)

Correct answer: c-ANCA (anti-PR3)

c-ANCA directed against proteinase 3 (PR3) is associated with granulomatosis with polyangiitis (GPA, formerly Wegener's). p-ANCA (anti-MPO) is associated with microscopic polyangiitis and eosinophilic granulomatosis with polyangiitis (Churg-Strauss). Both are ANCA-associated vasculitides.

Question 19: 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?

Resolving — the patient is improving
Life-threatening — indicates tiring and impending respiratory failure (Correct answer)
Moderate — requires nebulised salbutamol only
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 20: 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?

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

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 21: A patient presents with pleuritic chest pain, haemoptysis, and breathlessness. D-dimer is elevated and CTPA shows a filling defect in the right lower lobe pulmonary artery. What is the most appropriate initial treatment?

Oral warfarin alone
Intravenous thrombolysis with alteplase
Inferior vena cava filter
Low molecular weight heparin and arrange DOAC (Correct answer)

Correct answer: Low molecular weight heparin and arrange DOAC

For a confirmed pulmonary embolism without haemodynamic instability, initial treatment is anticoagulation with LMWH (or fondaparinux) followed by transition to a DOAC. Thrombolysis is reserved for massive PE with haemodynamic compromise.

Question 22: A patient returns from South-East Asia with cyclical fevers every 48 hours, rigors, and splenomegaly. Blood film shows ring forms and banana-shaped gametocytes within red blood cells. Which species of Plasmodium is responsible?

Plasmodium falciparum (Correct answer)
Plasmodium malariae
Plasmodium ovale
Plasmodium vivax

Correct answer: Plasmodium falciparum

Banana-shaped (crescent) gametocytes are pathognomonic of Plasmodium falciparum. While P. falciparum classically causes irregular fevers rather than strict 48-hour cycles, it can produce tertian periodicity. P. falciparum is the most dangerous species, capable of causing cerebral malaria, severe anaemia, and multi-organ failure.

Question 23: A patient returning from sub-Saharan Africa presents with fever, rigors, and splenomegaly. Thick and thin blood films show ring forms within red blood cells. What is the treatment for falciparum malaria without complications?

Chloroquine
Mefloquine
Quinine plus doxycycline
Artemether-lumefantrine (Riamet) (Correct answer)

Correct answer: Artemether-lumefantrine (Riamet)

Artemether-lumefantrine (Riamet) is the first-line treatment for uncomplicated Plasmodium falciparum malaria in the UK. Chloroquine resistance is widespread in P. falciparum. Quinine plus doxycycline/clindamycin is an alternative or second-line option.

Question 24: Which staging system is used for chronic lymphocytic leukaemia (CLL)?

Rai or Binet staging (Correct answer)
International Prognostic Index
Ann Arbor staging
Durie-Salmon staging

Correct answer: Rai or Binet staging

CLL is staged using either the Rai staging system (stages 0–IV, based on lymphocytosis, lymphadenopathy, organomegaly, anaemia, and thrombocytopenia) or the Binet staging system (stages A–C, used more commonly in Europe). Both correlate with prognosis and guide treatment decisions.

Question 25: 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?

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

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

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

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 27: 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?

Psychogenic polydipsia
SIADH
Cranial diabetes insipidus
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 28: A 28-year-old woman presents with syncope during exercise. Echocardiography shows asymmetric septal hypertrophy with systolic anterior motion of the mitral valve. What is the most likely diagnosis?

Dilated cardiomyopathy
Hypertrophic cardiomyopathy (Correct answer)
Aortic stenosis
Pulmonary hypertension

Correct answer: Hypertrophic cardiomyopathy

Hypertrophic cardiomyopathy (HCM) characteristically shows asymmetric septal hypertrophy (ASH) and systolic anterior motion (SAM) of the mitral valve on echocardiography. Exertional syncope is a concerning feature suggesting left ventricular outflow tract obstruction.

Question 29: A 28-year-old man presents with 4 months of insidious lower back pain and stiffness lasting more than 1 hour each morning, relieved by exercise but not rest. X-ray shows bilateral sacroiliac joint erosions. HLA-B27 is positive. What is the most likely diagnosis?

Reactive arthritis
Psoriatic spondyloarthropathy
Diffuse idiopathic skeletal hyperostosis
Ankylosing spondylitis (Correct answer)

Correct answer: Ankylosing spondylitis

Ankylosing spondylitis is characterised by bilateral sacroiliitis, inflammatory back pain that improves with exercise (not rest), and strong association with HLA-B27 in young men.

Question 30: A 70-year-old man develops profuse watery diarrhoea and abdominal cramping 5 days after completing a course of co-amoxiclav. Stool toxin assay is positive. What is the first-line treatment?

Fidaxomicin
Oral vancomycin (Correct answer)
Oral metronidazole
IV vancomycin

Correct answer: Oral vancomycin

NICE and PHE guidelines now recommend oral vancomycin (125 mg QDS for 10 days) as first-line treatment for all severities of Clostridioides difficile infection, replacing metronidazole which was previously first-line for mild cases. Fidaxomicin is an alternative, particularly for recurrent episodes.

Question 31: A 55-year-old man presents with progressive weakness affecting both upper and lower motor neurones but with no sensory involvement. Fasciculations are noted in multiple limbs. What is the most likely diagnosis?

Motor neurone disease (amyotrophic lateral sclerosis) (Correct answer)
Cervical myelopathy
Multiple sclerosis
Guillain-Barre syndrome

Correct answer: Motor neurone disease (amyotrophic lateral sclerosis)

Motor neurone disease (MND/ALS) characteristically presents with mixed upper and lower motor neurone signs WITHOUT sensory involvement. Fasciculations, progressive weakness, and wasting are typical. The combination of UMN and LMN signs without sensory loss is virtually pathognomonic.

Question 32: A 25-year-old woman presents with an intensely pruritic papular rash in the finger webs, wrists, and waistline, worse at night. What is the most likely diagnosis and treatment?

Scabies — treat with permethrin 5% cream (Correct answer)
Eczema — treat with topical steroids
Lichen planus — treat with topical tacrolimus
Dermatitis herpetiformis — treat with dapsone

Correct answer: Scabies — treat with permethrin 5% cream

Scabies is caused by Sarcoptes scabiei mite infestation, presenting with intense nocturnal pruritus, burrows in the finger webs, wrists, and genitalia. First-line treatment is permethrin 5% cream applied from neck to toes. All household contacts must be treated simultaneously.

Question 33: A 30-year-old woman has a serum sodium of 118 mmol/L, serum osmolality of 260 mOsm/kg, and urine osmolality of 550 mOsm/kg. She is clinically euvolaemic. What is the most likely diagnosis?

Psychogenic polydipsia
Nephrotic syndrome
Syndrome of inappropriate ADH secretion (SIADH) (Correct answer)
Addison's disease

Correct answer: Syndrome of inappropriate ADH secretion (SIADH)

SIADH presents with hyponatraemia, low serum osmolality, and inappropriately concentrated urine (>100 mOsm/kg) in a euvolaemic patient. Psychogenic polydipsia would show dilute urine, and Addison's would typically show hypovolaemia.

Question 34: Which investigation is the gold standard for diagnosing Cushing's syndrome?

Single morning cortisol
Overnight 1mg dexamethasone suppression test (Correct answer)
24-hour urinary free cortisol
ACTH stimulation test

Correct answer: Overnight 1mg dexamethasone suppression test

The overnight low-dose dexamethasone suppression test (1mg at midnight, cortisol at 9am) is the most commonly used first-line screening test. In healthy individuals, cortisol is suppressed to <50 nmol/L. Failure to suppress suggests autonomous cortisol secretion. Multiple tests may be needed.

Question 35: A patient presents with dysphagia to solids and liquids from onset, with a bird's beak appearance on barium swallow. Manometry shows absent peristalsis and failure of LOS relaxation. What is the diagnosis?

Diffuse oesophageal spasm
Achalasia (Correct answer)
Benign oesophageal stricture
Oesophageal carcinoma

Correct answer: Achalasia

Achalasia presents with dysphagia to both solids and liquids from onset (unlike mechanical obstruction which starts with solids). The bird's beak sign on barium swallow, absent peristalsis, and failure of lower oesophageal sphincter (LOS) relaxation on manometry are diagnostic.

Question 36: What is the most appropriate management for a haemodynamically stable patient with AF of known duration less than 48 hours?

Rhythm or rate control after anticoagulation initiation, with cardioversion if appropriate (Correct answer)
Immediate DC cardioversion without anticoagulation
Long-term anticoagulation and acceptance of permanent AF
Urgent pacemaker insertion

Correct answer: Rhythm or rate control after anticoagulation initiation, with cardioversion if appropriate

For AF of less than 48 hours duration, cardioversion (chemical or electrical) can be considered without prolonged anticoagulation, though DOAC or LMWH should be started before cardioversion and continued for at least 4 weeks after. Rate control is an alternative for stable patients.

Question 37: 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?

Phaeochromocytoma
Cushing's syndrome
Renal artery stenosis
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 38: A 58-year-old woman with active rheumatoid arthritis is about to start methotrexate. Which baseline investigation is most critical before initiating this drug?

Dual-energy X-ray absorptiometry
Liver function tests and full blood count (Correct answer)
Pulmonary function tests
Echocardiogram

Correct answer: Liver function tests and full blood count

Methotrexate is hepatotoxic and myelosuppressive; baseline liver function tests and full blood count are mandatory before starting therapy, with regular monitoring every 4–12 weeks thereafter.

Question 39: A 55-year-old man has a plasma osmolality of 295 mOsm/kg but his urine remains maximally dilute at 80 mOsm/kg despite water deprivation. After desmopressin administration, urine osmolality rises to 600 mOsm/kg. What is the diagnosis?

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

Correct answer: Cranial diabetes insipidus

The failure to concentrate urine despite water deprivation (raised plasma osmolality) indicates diabetes insipidus. The response to desmopressin (synthetic ADH) confirms the kidneys can respond, meaning the problem is insufficient ADH production — cranial diabetes insipidus.

Question 40: A patient taking hydralazine for hypertension develops arthralgia, pleuritis, and a positive ANA. Anti-histone antibodies are positive but anti-dsDNA and complement levels are normal. What is the most likely diagnosis?

Rheumatoid arthritis with ANA positivity
Drug-induced lupus erythematosus (Correct answer)
Undifferentiated connective tissue disease
Systemic lupus erythematosus

Correct answer: Drug-induced lupus erythematosus

Drug-induced lupus caused by hydralazine (also procainamide, isoniazid) is characterised by anti-histone antibodies, positive ANA, absence of anti-dsDNA, and normal complement; it resolves on drug withdrawal.

Question 41: A 45-year-old man presents with muscle weakness and hypokalaemia. His arterial blood gas shows metabolic alkalosis. Which hormone, if produced in excess, is most likely responsible?

Thyroxine
Adrenaline
Cortisol
Aldosterone (Correct answer)

Correct answer: Aldosterone

Excess aldosterone (Conn's syndrome) causes sodium retention and potassium excretion, leading to hypokalaemia and metabolic alkalosis. This is a classic presentation of primary hyperaldosteronism.

Question 42: Which prophylaxis is recommended for a patient with HIV and a CD4 count below 200 cells/mm³ to prevent Pneumocystis jirovecii pneumonia?

Dapsone
Aciclovir
Co-trimoxazole (trimethoprim-sulfamethoxazole) (Correct answer)
Fluconazole

Correct answer: Co-trimoxazole (trimethoprim-sulfamethoxazole)

Co-trimoxazole (trimethoprim-sulfamethoxazole) is the first-line prophylaxis for PCP (Pneumocystis jirovecii pneumonia) in patients with HIV and CD4 count below 200 cells/mm³. Alternatives for those with sulfonamide allergy include dapsone, atovaquone, or aerosolised pentamidine.

Question 43: 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-Scl-70
Anti-dsDNA

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 44: Which investigation is the gold standard for diagnosing coronary artery disease?

Invasive coronary angiography (Correct answer)
Exercise stress test
CT coronary angiography
Cardiac MRI

Correct answer: Invasive coronary angiography

Invasive coronary angiography (cardiac catheterisation) remains the gold standard for diagnosing coronary artery disease, as it provides real-time visualisation of coronary anatomy, allows assessment of stenosis severity, and permits simultaneous intervention (PCI).

Question 45: A 45-year-old woman has recurrent palpitations. A 24-hour Holter shows intermittent delta waves and short PR interval. What is the diagnosis?

Wolff-Parkinson-White syndrome (Correct answer)
Complete heart block
Lown-Ganong-Levine syndrome
Brugada syndrome

Correct answer: Wolff-Parkinson-White syndrome

Wolff-Parkinson-White syndrome is characterised by a delta wave (slurred upstroke of QRS), short PR interval (<120ms), and wide QRS. It results from an accessory conduction pathway (Bundle of Kent) bypassing the AV node.

Question 46: A 68-year-old man presents with acute onset of a hot, erythematous, severely swollen right knee. Joint aspirate shows cloudy fluid with WBC 85,000/mm³ (92% neutrophils) and Gram-positive cocci in clusters on Gram stain. What is the most appropriate immediate management?

Colchicine and naproxen
IV flucloxacillin and urgent joint washout (Correct answer)
Oral flucloxacillin and outpatient review in 48 hours
Intra-articular corticosteroid injection

Correct answer: IV flucloxacillin and urgent joint washout

Septic arthritis (most likely Staphylococcus aureus) is a medical emergency requiring IV antibiotics and surgical joint washout to prevent irreversible cartilage destruction.

Question 47: Which drug used for type 2 diabetes has been shown to reduce cardiovascular death and hospitalisation for heart failure in patients with established CVD?

Pioglitazone
Empagliflozin (Correct answer)
Sitagliptin
Glipizide

Correct answer: Empagliflozin

SGLT2 inhibitors, particularly empagliflozin (EMPA-REG OUTCOME trial) and canagliflozin (CANVAS trial), have demonstrated significant reductions in cardiovascular death, hospitalisation for heart failure, and renal progression in patients with type 2 diabetes and established CVD or high CV risk.

Question 48: Which score is used to assess severity and 30-day mortality in acute upper GI bleeding?

MELD score
Glasgow-Blatchford score (Correct answer)
Maddrey's discriminant function
Child-Pugh score

Correct answer: Glasgow-Blatchford score

The Glasgow-Blatchford score (GBS) uses clinical and biochemical parameters (blood urea, haemoglobin, pulse, systolic BP, history of liver disease/heart failure, and syncope/melaena) to assess the need for clinical intervention and risk of mortality in acute upper GI bleeding.

Question 49: A patient on warfarin has an INR of 8.5 with no active bleeding. According to NICE guidelines, what is the most appropriate management?

Give intravenous vitamin K 10 mg
Continue warfarin at a reduced dose
Give fresh frozen plasma
Stop warfarin and give oral vitamin K 1-5 mg (Correct answer)

Correct answer: Stop warfarin and give oral vitamin K 1-5 mg

For an INR >8.0 without major bleeding, NICE recommends stopping warfarin and administering 1-5 mg of oral vitamin K. FFP or IV vitamin K at high doses is reserved for major bleeding. The INR should be rechecked within 24 hours.

Question 50: What is the mechanism of action of rifaximin in hepatic encephalopathy?

Increases renal ammonia clearance
Reduces gut motility
Acts as a GABA receptor antagonist
Minimally absorbed antibiotic that alters gut flora to reduce ammonia production (Correct answer)

Correct answer: Minimally absorbed antibiotic that alters gut flora to reduce ammonia production

Rifaximin is a minimally absorbed antibiotic that acts locally in the gut to alter the gut microbiome, reducing ammonia-producing bacteria. This lowers portal and systemic ammonia levels, which is thought to be the primary driver of hepatic encephalopathy.

Question 51: A patient with known type 2 diabetes presents with confusion, blood glucose 58 mmol/L, and serum osmolality 360 mOsm/kg. There is no ketoacidosis. What is the diagnosis?

Lactic acidosis
Hyperosmolar hyperglycaemic state (Correct answer)
Euglycaemic DKA
Diabetic ketoacidosis

Correct answer: Hyperosmolar hyperglycaemic state

Hyperosmolar hyperglycaemic state (HHS) is characterised by severe hyperglycaemia (>30 mmol/L), hyperosmolality (>320 mOsm/kg), dehydration, and absence of significant ketoacidosis. It typically occurs in elderly type 2 diabetic patients and carries higher mortality than DKA.

Question 52: What is the most common cause of complete heart block in the UK?

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

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 53: A 22-year-old university student presents with low mood, anhedonia, poor concentration, early morning wakening, and weight loss for 3 months. She expresses passive suicidal ideation. According to NICE, what severity of depression is this?

Moderate to severe depression (Correct answer)
Mild depression
Subthreshold depressive symptoms
Psychotic depression

Correct answer: Moderate to severe depression

This patient has five core and additional symptoms of depression persisting for over 2 weeks, with functional impairment and suicidal ideation, indicating moderate to severe depression. NICE recommends a combination of antidepressant medication and high-intensity psychological therapy (CBT or IPT) for this severity.

Question 54: A 35-year-old man presents with epigastric pain and a duodenal ulcer is found on endoscopy. CLO test is positive. What is the recommended first-line eradication therapy in the UK?

PPI, metronidazole, and levofloxacin
PPI and amoxicillin for 14 days
Bismuth quadruple therapy
PPI, amoxicillin, and clarithromycin for 7 days (Correct answer)

Correct answer: PPI, amoxicillin, and clarithromycin for 7 days

NICE recommends triple therapy with a PPI, amoxicillin 1g BD, and clarithromycin 500mg BD for 7 days as first-line H. pylori eradication in the UK. If penicillin allergic, metronidazole replaces amoxicillin.

Question 55: A patient with end-stage renal disease on haemodialysis has a PTH of 85 pmol/L (normal 1.6-6.9), low calcium, and high phosphate. What is this condition called?

Tertiary hyperparathyroidism
Secondary hyperparathyroidism (renal osteodystrophy) (Correct answer)
Primary hyperparathyroidism
Hypoparathyroidism

Correct answer: Secondary hyperparathyroidism (renal osteodystrophy)

Secondary hyperparathyroidism occurs in CKD due to phosphate retention, reduced 1,25-dihydroxyvitamin D production, and hypocalcaemia. The parathyroid glands respond appropriately by increasing PTH secretion. Management includes phosphate binders, active vitamin D (alfacalcidol), and cinacalcet if refractory.

Question 56: A 67-year-old postmenopausal woman has a femoral neck T-score of –2.7 on DEXA scan with no previous fragility fractures. She takes no current medications. What is the most appropriate pharmacological treatment?

Calcium and vitamin D supplementation alone
Denosumab 60mg subcutaneously every 6 months
Teriparatide 20 micrograms subcutaneously daily
Alendronic acid 70mg weekly plus calcium and vitamin D (Correct answer)

Correct answer: Alendronic acid 70mg weekly plus calcium and vitamin D

A bisphosphonate (alendronic acid) combined with calcium and vitamin D is first-line treatment for osteoporosis; teriparatide and denosumab are reserved for very high-risk patients or those who fail bisphosphonate therapy.

Question 57: Which investigation is the gold standard for diagnosing chronic pancreatitis when cross-sectional imaging is equivocal?

Serum amylase
Faecal elastase
Plain abdominal X-ray
Endoscopic ultrasound (EUS) (Correct answer)

Correct answer: Endoscopic ultrasound (EUS)

Endoscopic ultrasound (EUS) is the most sensitive investigation for diagnosing chronic pancreatitis, capable of detecting early parenchymal and ductal changes that CT and MRI may miss. It uses the Rosemont classification criteria for standardised diagnosis.

Question 58: A 74-year-old woman presents with 6 weeks of bilateral shoulder and hip girdle aching, 90-minute morning stiffness, ESR 92 mm/hr, and CRP 58 mg/L. There are no features of giant cell arteritis. What is the first-line treatment?

Prednisolone 15mg daily (Correct answer)
Methotrexate 15mg weekly
Naproxen 500mg twice daily
Hydroxychloroquine 400mg daily

Correct answer: Prednisolone 15mg daily

Polymyalgia rheumatica is treated with prednisolone 15mg daily initially, with gradual dose reduction guided by symptoms and inflammatory markers; NSAIDs alone are insufficient.

Question 59: A patient with asthma fails to respond to salbutamol and ipratropium nebulisers. Which additional treatment should be given for a life-threatening attack?

Oral prednisolone and discharge
IV magnesium sulphate 1.2–2g over 20 minutes (Correct answer)
Intubation as first step
IV theophylline only

Correct answer: IV magnesium sulphate 1.2–2g over 20 minutes

IV magnesium sulphate (1.2–2g over 20 minutes) is indicated for life-threatening asthma that fails to respond to initial bronchodilator therapy. It causes bronchial smooth muscle relaxation by inhibiting calcium-mediated bronchoconstriction. This is a BTS/SIGN guideline recommendation.

Question 60: A 55-year-old man with gout whose serum urate is well controlled at 0.26 mmol/L on allopurinol develops an acute flare 2 months after his dose was increased. What is the most likely explanation?

Allopurinol resistance
Mobilisation of urate crystals during changes in serum urate (Correct answer)
Dietary non-compliance with a high-purine diet
Worsening renal impairment reducing urate clearance

Correct answer: Mobilisation of urate crystals during changes in serum urate

During initiation or dose adjustment of urate-lowering therapy, fluctuations in serum urate cause dissolution and mobilisation of existing crystal deposits, triggering acute flares despite adequate control.

Question 61: A patient presents with collapse. ECG shows torsades de pointes. What is the immediate pharmacological treatment?

Lignocaine
Amiodarone
IV magnesium sulphate (Correct answer)
Adenosine

Correct answer: IV magnesium sulphate

Torsades de pointes is a polymorphic ventricular tachycardia associated with prolonged QTc. IV magnesium sulphate is the first-line treatment regardless of the patient's magnesium level. It stabilises the cardiac membrane and suppresses early afterdepolarisations.

Question 62: A 60-year-old man with a history of alcohol excess presents with haematemesis. Endoscopy shows oesophageal varices with active bleeding. After resuscitation, what is the most appropriate acute pharmacological intervention?

Intravenous terlipressin (Correct answer)
Intravenous omeprazole
Oral lactulose
Oral propranolol

Correct answer: Intravenous terlipressin

Terlipressin (a vasopressin analogue) reduces portal pressure by causing splanchnic vasoconstriction and is the recommended first-line vasoactive drug for acute variceal bleeding. It should be started as soon as variceal bleeding is suspected, even before endoscopy, according to NICE guidelines.

Question 63: A 50-year-old man with a 30-pack-year smoking history presents with haemoptysis and a right hilar mass on CXR. CT confirms a central lung mass with mediastinal lymphadenopathy. What is the most likely histological type?

Small cell lung cancer
Adenocarcinoma
Mesothelioma
Squamous cell carcinoma (Correct answer)

Correct answer: Squamous cell carcinoma

Squamous cell carcinoma is the most common central lung tumour in smokers, arising from bronchial epithelium. It is associated with haemoptysis, central location, and hilar masses. Adenocarcinoma is more common peripherally. Small cell is central but has distinct paraneoplastic syndromes.

Question 64: A healthcare worker sustains a needlestick injury from a patient known to be HIV positive with a detectable viral load. The injury is deep and from a hollow-bore needle. When should post-exposure prophylaxis (PEP) ideally be started?

Within 72 hours
Within 1 hour (as soon as possible) (Correct answer)
Within 1 week
Within 24 hours

Correct answer: Within 1 hour (as soon as possible)

HIV PEP should be started as soon as possible, ideally within 1 hour of exposure. The recommended regimen is a 28-day course of two NRTIs plus a third agent (usually raltegravir or dolutegravir). PEP is unlikely to be effective if started more than 72 hours after exposure.

Question 65: What is the mechanism by which montelukast acts in asthma?

Beta-2 adrenoceptor agonism
Leukotriene receptor antagonism (Correct answer)
Phosphodiesterase inhibition
Mast cell stabilisation

Correct answer: Leukotriene receptor antagonism

Montelukast is a leukotriene receptor antagonist (LTRA) that blocks cysteinyl leukotriene receptors (CysLT1). Leukotrienes are inflammatory mediators that cause bronchoconstriction, mucus secretion, and airway oedema. Blocking them reduces these effects in asthma and allergic rhinitis.

Question 66: A 45-year-old man presents with episodic headaches, sweating, and palpitations. His blood pressure is 220/130 mmHg. 24-hour urine metanephrines are markedly elevated. What is the diagnosis?

Cushing's syndrome
Conn's syndrome
Phaeochromocytoma (Correct answer)
Essential hypertension

Correct answer: Phaeochromocytoma

Phaeochromocytoma presents with the classic triad of episodic headaches, sweating, and palpitations with paroxysmal hypertension. Elevated urinary metanephrines confirm catecholamine excess. It must be excluded before any surgery, and alpha-blockade (phenoxybenzamine) must precede beta-blockade to prevent hypertensive crisis.

Question 67: 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?

Diffuse alveolar haemorrhage
Pulmonary arterial hypertension (Correct answer)
Scleroderma renal crisis
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 68: A 65-year-old man presents with resting tremor, bradykinesia, and rigidity. Dopamine transporter (DAT) imaging shows reduced uptake in the striatum. What is the diagnosis?

Parkinson's disease (Correct answer)
Wilson's disease
Essential tremor
Drug-induced tremor

Correct answer: Parkinson's disease

Parkinson's disease is characterised by the triad of resting tremor, bradykinesia, and rigidity (plus postural instability), with reduced dopaminergic neurone activity in the substantia nigra. DAT scan (DaTSCAN) shows reduced striatal dopamine transporter uptake, distinguishing it from essential tremor.

Question 69: A 40-year-old Afro-Caribbean woman presents with bilateral hilar lymphadenopathy, erythema nodosum, and arthralgia. Serum ACE is elevated. What is the most likely diagnosis?

Tuberculosis
Systemic lupus erythematosus
Sarcoidosis (Correct answer)
Lymphoma

Correct answer: Sarcoidosis

This is Löfgren syndrome, an acute presentation of sarcoidosis characterised by bilateral hilar lymphadenopathy, erythema nodosum, fever, and polyarthralgia. It carries a good prognosis. Elevated serum ACE and raised calcium support the diagnosis. Sarcoidosis is more prevalent in Afro-Caribbean populations.

Question 70: 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?

Sumatriptan
Propranolol (Correct answer)
Paracetamol
Codeine phosphate

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.

Question 71: Which cranial nerve is most commonly affected in raised intracranial pressure, causing a false localising sign?

Oculomotor nerve (CN III)
Facial nerve (CN VII)
Abducens nerve (CN VI) (Correct answer)
Trochlear nerve (CN IV)

Correct answer: Abducens nerve (CN VI)

The abducens nerve (CN VI) has the longest intracranial course and is most susceptible to stretching from raised intracranial pressure. This causes a lateral rectus palsy (inability to abduct the eye) which is a false localising sign — it does not indicate the site of the pathology.

Question 72: A 65-year-old man taking hydrochlorothiazide presents with acute severe pain in the right first metatarsophalangeal joint. Joint aspirate reveals needle-shaped crystals that are strongly negatively birefringent under polarised light. What is the deposited substance?

Monosodium urate (Correct answer)
Calcium pyrophosphate
Calcium oxalate
Hydroxyapatite

Correct answer: Monosodium urate

Monosodium urate crystals are negatively birefringent and needle-shaped, causing gout; thiazide diuretics reduce renal urate excretion, raising serum urate levels.

Question 73: A patient is found to have a serum calcium of 2.95 mmol/L, low PTH, and high phosphate. What is the most likely diagnosis?

Primary hyperparathyroidism
Hypercalcaemia of malignancy
Sarcoidosis
Hypoparathyroidism (Correct answer)

Correct answer: Hypoparathyroidism

Low PTH with high phosphate and hypercalcaemia (or hypocalcaemia) in the context of low PTH indicates hypoparathyroidism. Wait — in hypoparathyroidism, calcium is LOW. If calcium is high with low PTH and high phosphate, consider vitamin D toxicity or granulomatous disease. A low PTH with hypocalcaemia and hyperphosphataemia is hypoparathyroidism.

Question 74: A patient with known hepatitis B has the following serology: HBsAg positive, HBeAg negative, anti-HBe positive, HBV DNA 1500 IU/mL, ALT normal. What phase of hepatitis B is this?

Immune tolerant phase
Immune active phase (HBeAg-positive chronic hepatitis)
Inactive carrier (HBeAg-negative chronic infection) (Correct answer)
HBeAg-negative chronic hepatitis

Correct answer: Inactive carrier (HBeAg-negative chronic infection)

The inactive carrier phase is characterised by HBsAg positive, HBeAg negative, anti-HBe positive, low HBV DNA (<2000 IU/mL), and persistently normal ALT. These patients have low risk of disease progression but require regular monitoring as reactivation can occur.

Question 75: Which antibody is most closely associated with diffuse cutaneous systemic sclerosis and predicts an increased risk of pulmonary fibrosis?

Anti-Jo-1
Anti-Scl-70 (anti-topoisomerase I) (Correct answer)
Anti-Mi-2
Anti-centromere

Correct answer: Anti-Scl-70 (anti-topoisomerase I)

Anti-Scl-70 (anti-topoisomerase I) antibodies are associated with diffuse cutaneous SSc and predict a substantially higher risk of interstitial lung disease.

Question 76: A 25-year-old man presents with a 2-week history of productive cough, night sweats, and weight loss after returning from India. Sputum AFB smear is positive. He lives with his partner and 2-year-old child. What is the most important public health action?

Contact tracing and screening of household contacts (Correct answer)
Notifying the WHO directly
Isolating the patient in a negative pressure room permanently
Vaccinating all contacts with BCG immediately

Correct answer: Contact tracing and screening of household contacts

Active pulmonary TB is notifiable, and contact tracing is the most important public health intervention. Household contacts, especially children under 5, are at highest risk. Contacts should be screened with symptom assessment, chest X-ray, and interferon-gamma release assay (IGRA). The child may need chemoprophylaxis regardless of screening results due to young age.

Question 77: Which of the following best describes the pathophysiology of cardiac tamponade?

Aortic regurgitation causing volume overload
Increased left ventricular preload from fluid accumulation
Elevated intrapericardial pressure compressing all four chambers, reducing cardiac filling and output (Correct answer)
Left ventricular systolic dysfunction from ischaemia

Correct answer: Elevated intrapericardial pressure compressing all four chambers, reducing cardiac filling and output

Cardiac tamponade occurs when fluid accumulates in the pericardium, raising intrapericardial pressure above right atrial pressure, impeding cardiac filling. The result is reduced stroke volume, hypotension, and compensatory tachycardia. Beck's triad: hypotension, raised JVP, muffled heart sounds.

Question 78: A patient with known SLE presents with a butterfly rash, arthritis, positive anti-dsDNA, and low complement levels (C3, C4). What does this combination suggest?

Active lupus nephritis (Correct answer)
Inactive SLE
Drug-induced lupus
Antiphospholipid syndrome

Correct answer: Active lupus nephritis

Active SLE is indicated by rising anti-dsDNA titres, falling complement (C3/C4 consumed by immune complex deposition), and clinical features. The combination of butterfly rash, arthritis, high anti-dsDNA, and low complement raises concern for active disease including lupus nephritis, requiring urinalysis and renal biopsy consideration.

Question 79: Which immunoglobulin class is found in highest concentration in normal human serum?

IgG (Correct answer)
IgA
IgM
IgE

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

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

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 81: In autosomal dominant polycystic kidney disease (ADPKD), which gene mutation accounts for approximately 85% of cases?

PKD2 on chromosome 4
PKD1 on chromosome 16 (Correct answer)
NPHS1 on chromosome 19
WT1 on chromosome 11

Correct answer: PKD1 on chromosome 16

PKD1 mutations on chromosome 16 account for approximately 85% of ADPKD cases and are associated with more severe disease and earlier onset of end-stage renal failure compared to PKD2 mutations on chromosome 4.

Question 82: A 40-year-old man with known psoriasis develops diffuse swelling of the entire right index finger, giving it a sausage-like appearance. What is the correct term for this finding?

Dactylitis (Correct answer)
Boutonnière deformity
Heberden's node
Swan-neck deformity

Correct answer: Dactylitis

Dactylitis (sausage digit) results from simultaneous inflammation of all compartments of a digit including tendons and joints, and is a hallmark feature of psoriatic arthritis.

Question 83: A 28-year-old man of Turkish origin presents with recurrent painful oral ulcers, genital ulcers, inflammatory uveitis, and erythema nodosum. A pathergy test shows a pustule forming 48 hours after a needle prick. What is the most likely diagnosis?

Systemic lupus erythematosus
Behçet's disease (Correct answer)
Reactive arthritis
Stevens–Johnson syndrome

Correct answer: Behçet's disease

Behçet's disease is a systemic vasculitis characterised by the triad of oral ulcers, genital ulcers, and uveitis, with a positive pathergy test; it is more prevalent along the ancient Silk Road including Turkey and the Middle East.

Question 84: 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 IV (Correct answer)
Class V
Class III
Class II

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 85: Which acid-base disturbance is most commonly seen in pyloric stenosis?

Mixed respiratory and metabolic acidosis
Respiratory alkalosis
Hypochloraemic hypokalaemic metabolic alkalosis (Correct answer)
Metabolic acidosis

Correct answer: Hypochloraemic hypokalaemic metabolic alkalosis

Pyloric stenosis causes persistent vomiting of gastric acid (HCl), leading to loss of hydrogen and chloride ions. The kidneys compensate by retaining hydrogen ions and excreting potassium, resulting in hypochloraemic hypokalaemic metabolic alkalosis.

Question 86: A 40-year-old woman presents with abdominal pain and diarrhoea. Colonoscopy shows skip lesions with cobblestoning and non-caseating granulomas on biopsy. Where else might you expect to find disease?

Oesophagus only
Colon and rectum only
Anywhere from mouth to anus (Correct answer)
Small bowel only

Correct answer: Anywhere from mouth to anus

Crohn's disease can affect any part of the gastrointestinal tract from mouth to anus, though the terminal ileum and colon are most commonly affected. The skip lesions (normal bowel between affected segments), cobblestoning, and non-caseating granulomas are characteristic histological features.

Question 87: A patient with COPD has an FEV1/FVC ratio of 0.6 and an FEV1 of 45% predicted. According to GOLD criteria, what severity is this?

GOLD 2 (moderate)
GOLD 4 (very severe)
GOLD 1 (mild)
GOLD 3 (severe) (Correct answer)

Correct answer: GOLD 3 (severe)

GOLD severity is based on FEV1 % predicted (post-bronchodilator): GOLD 1 ≥80%, GOLD 2 50–79%, GOLD 3 30–49%, GOLD 4 <30%. An FEV1 of 45% predicted places this patient in GOLD 3 (severe). The FEV1/FVC <0.7 confirms obstruction.

Question 88: 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?

JAK2 V617F mutation (Correct answer)
CALR mutation
BCR-ABL translocation
MPL 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 89: A 45-year-old woman presents with jaundice, pruritus, elevated ALP, and positive anti-mitochondrial antibodies (AMA). What is the diagnosis?

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

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 90: A 30-year-old man presents with profuse watery diarrhoea, terminal ileum disease on colonoscopy, and perianal fistulae. What is the most likely diagnosis?

Ulcerative colitis
Crohn's disease (Correct answer)
Microscopic colitis
Coeliac disease

Correct answer: Crohn's disease

Crohn's disease is characterised by transmural, discontinuous ('skip lesions') inflammation that can affect any part of the GI tract from mouth to anus, with predominance for the terminal ileum and colon. Perianal disease (fistulae, abscesses) occurs in up to one-third and is highly characteristic of Crohn's.

Question 91: A patient is intubated and ventilated for ARDS. Which ventilation strategy reduces mortality?

Lung-protective ventilation (tidal volume 6 mL/kg, plateau pressure <30 cmH2O) (Correct answer)
High tidal volume ventilation (12–15 mL/kg)
High FiO2 ventilation targeting SpO2 >99%
Frequent disconnections for suctioning

Correct answer: Lung-protective ventilation (tidal volume 6 mL/kg, plateau pressure <30 cmH2O)

The ARMA trial demonstrated that lung-protective ventilation with low tidal volumes (6 mL/kg ideal body weight) and a plateau pressure below 30 cmH2O reduces mortality in ARDS compared to high tidal volume ventilation by minimising ventilator-induced lung injury.

Question 92: Which antibody is associated with myasthenia gravis?

Anti-Ro/La
Anti-AChR (acetylcholine receptor antibody) (Correct answer)
Anti-Jo-1
Anti-dsDNA

Correct answer: Anti-AChR (acetylcholine receptor antibody)

Myasthenia gravis is an autoimmune neuromuscular junction disorder caused in approximately 85% of cases by anti-acetylcholine receptor (AChR) antibodies that block, accelerate degradation, or destroy AChR at the postsynaptic membrane. Anti-MuSK antibodies account for most seronegative cases.

Question 93: What is the target blood pressure in a patient with CKD and proteinuria (urine ACR >70 mg/mmol) according to NICE guidelines?

<140/90 mmHg
<120/75 mmHg
<150/90 mmHg
<130/80 mmHg (Correct answer)

Correct answer: <130/80 mmHg

NICE CKD guidelines recommend a target blood pressure of <130/80 mmHg in patients with CKD who have significant proteinuria (ACR ≥70 mg/mmol) or diabetes. ACE inhibitors or ARBs are first-line for CKD with proteinuria due to their nephroprotective effects.

Question 94: Which organism is the most common cause of infective endocarditis in IV drug users?

Enterococcus faecalis
Streptococcus viridans
HACEK organisms
Staphylococcus aureus (Correct answer)

Correct answer: Staphylococcus aureus

Staphylococcus aureus is the most common cause of infective endocarditis in IV drug users. It typically affects the tricuspid valve (right-sided endocarditis) due to direct injection into venous circulation. It causes an aggressive, destructive infection with high mortality.

Question 95: A 70-year-old man has a haemoglobin of 70 g/L, MCV 120 fL, and hypersegmented neutrophils on blood film. Vitamin B12 is low. What is the most likely cause of B12 deficiency?

Metformin therapy
Pernicious anaemia (Correct answer)
Dietary deficiency in a vegan
Terminal ileal resection

Correct answer: Pernicious anaemia

Pernicious anaemia is the most common cause of B12 deficiency in older adults in the UK. It is an autoimmune condition where anti-intrinsic factor antibodies prevent B12 absorption in the terminal ileum. Hypersegmented neutrophils and macrocytosis are classic blood film findings.

Question 96: Which condition is associated with a 'saddle-shaped' ST elevation pattern across multiple leads without reciprocal changes?

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

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 97: A 47-year-old woman presents with 3 months of proximal muscle weakness, CK 3,800 U/L, heliotrope discolouration of the eyelids, and Gottron's papules over the knuckles. Which investigation is most important to arrange urgently?

Nerve conduction studies
Tensilon test
CT thorax, abdomen and pelvis (Correct answer)
Anti-dsDNA antibody titre

Correct answer: CT thorax, abdomen and pelvis

Adult-onset dermatomyositis has a strong association with underlying malignancy; CT TAP is mandatory to screen for occult cancer at diagnosis.

Question 98: Which antibody is most specific for type 1 diabetes mellitus?

Anti-thyroid peroxidase antibodies
Anti-smooth muscle antibodies
Anti-GAD65 antibodies (Correct answer)
Anti-nuclear antibodies

Correct answer: Anti-GAD65 antibodies

Anti-glutamic acid decarboxylase (anti-GAD65) antibodies are the most commonly tested and most persistent autoantibodies in type 1 diabetes. Other relevant antibodies include IA-2 antibodies and zinc transporter 8 (ZnT8) antibodies. They are useful for confirming autoimmune aetiology, particularly in LADA (latent autoimmune diabetes in adults).

Question 99: A 33-year-old woman presents with puffy oedematous fingers, proximal muscle weakness, and pleuritis. Serology shows a very high-titre anti-U1 RNP antibody with no other specific autoantibodies detected. What is the most likely diagnosis?

Mixed connective tissue disease (Correct answer)
Undifferentiated connective tissue disease
Primary Sjögren's syndrome
Drug-induced lupus

Correct answer: Mixed connective tissue disease

Mixed connective tissue disease is defined by overlapping features of SLE, systemic sclerosis, and inflammatory myositis in the context of high-titre anti-U1 RNP antibodies as the sole specific autoantibody.

Question 100: Which cytokine is most important in the pathogenesis of septic shock?

Tumour necrosis factor alpha (TNF-alpha) (Correct answer)
Interleukin-10
Interleukin-4
Interferon-gamma

Correct answer: Tumour necrosis factor alpha (TNF-alpha)

TNF-alpha is the key pro-inflammatory cytokine released by macrophages in response to bacterial lipopolysaccharide. It triggers the inflammatory cascade leading to vasodilation, increased vascular permeability, myocardial depression, and multi-organ failure in septic shock.

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.

100

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180 min

Time Limit

60%

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