MRCP Part 1 — Questions and Answers

Question 1: A patient with end-stage renal disease on haemodialysis has a haemoglobin of 82 g/L. What is the most likely cause of anaemia?

Erythropoietin deficiency from reduced renal production (Correct answer)
Vitamin B12 deficiency
Iron deficiency from dietary restriction
Haemolytic anaemia from dialysis membranes

Correct answer: Erythropoietin deficiency from reduced renal production

Anaemia of chronic kidney disease is primarily caused by reduced erythropoietin (EPO) production by the failing kidneys, leading to normocytic normochromic anaemia. Treatment involves recombinant EPO (e.g., darbepoetin), with iron supplementation to support erythropoiesis.

Question 2: 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 III
Class IV (Correct answer)
Class V
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 3: 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?

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

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 4: A 32-year-old man develops asymmetric oligoarthritis, urethritis, and conjunctivitis 3 weeks after an episode of Campylobacter gastroenteritis. HLA-B27 is positive. What is the most likely diagnosis?

Gonococcal arthritis
Enteropathic arthritis
Ankylosing spondylitis
Reactive arthritis (Correct answer)

Correct answer: Reactive arthritis

Reactive arthritis is a seronegative spondyloarthropathy triggered by genitourinary or gastrointestinal infection, presenting with the classic triad of arthritis, urethritis, and conjunctivitis.

Question 5: A patient with ulcerative colitis presents with 8 bloody stools per day, pulse 110 bpm, temperature 38.5 degrees C, and CRP of 85 mg/L. How would you classify this flare according to the Truelove and Witts criteria?

Severe (Correct answer)
Moderate
Mild
In remission

Correct answer: Severe

Truelove and Witts criteria classify UC flares as severe when patients have 6 or more bloody stools per day PLUS at least one systemic feature: pulse >90 bpm, temperature >37.8 degrees C, Hb <10.5 g/dL, or ESR/CRP >30. This patient meets multiple severe criteria.

Question 6: Which antibody is most closely associated with diffuse cutaneous systemic sclerosis and predicts an increased risk of pulmonary fibrosis?

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

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 7: A 35-year-old woman presents with weight gain, moon face, abdominal striae, and proximal myopathy. Her 24-hour urinary free cortisol is elevated. What is the next most appropriate investigation?

ACTH stimulation test (Synacthen test)
Overnight dexamethasone suppression test (Correct answer)
MRI pituitary
CT adrenals

Correct answer: Overnight dexamethasone suppression test

After confirming hypercortisolism with elevated urinary free cortisol, the next step is to perform a low-dose (1 mg) overnight dexamethasone suppression test to confirm Cushing's syndrome. Failure to suppress cortisol (<50 nmol/L) confirms the diagnosis. ACTH levels are then measured to determine the cause.

Question 8: Which of the following best describes the pathophysiology of cardiac tamponade?

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

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

HLA-DR4
HLA-B27 (Correct answer)
HLA-DR3
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 10: Which enzyme deficiency most commonly causes congenital adrenal hyperplasia?

21-hydroxylase deficiency (Correct answer)
11-beta-hydroxylase deficiency
17-alpha-hydroxylase deficiency
3-beta-hydroxysteroid dehydrogenase deficiency

Correct answer: 21-hydroxylase deficiency

21-hydroxylase deficiency accounts for approximately 90–95% of congenital adrenal hyperplasia (CAH). It impairs the conversion of 17-hydroxyprogesterone to cortisol and aldosterone, causing cortisol deficiency, aldosterone deficiency, and excess androgen production.

Question 11: In autosomal dominant polycystic kidney disease (ADPKD), which gene mutation accounts for approximately 85% of cases?

NPHS1 on chromosome 19
PKD1 on chromosome 16 (Correct answer)
PKD2 on chromosome 4
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 12: 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?

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

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 13: 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?

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

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

Anti-nuclear antibodies
Anti-GAD65 antibodies (Correct answer)
Anti-thyroid peroxidase antibodies
Anti-smooth muscle 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 15: 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?

Spironolactone
Calcium channel blocker
Alpha-blocker
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 16: A 58-year-old woman with active rheumatoid arthritis is about to start methotrexate. Which baseline investigation is most critical before initiating this drug?

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

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

IgE
IgA
IgM
IgG (Correct answer)

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 18: A 30-year-old woman presents with a sudden severe headache she describes as 'the worst of her life', photophobia, and a normal CT head. What is the next investigation?

EEG
Lumbar puncture (Correct answer)
MRI brain
CT angiography

Correct answer: Lumbar puncture

A 'thunderclap' headache with negative CT requires lumbar puncture to exclude subarachnoid haemorrhage (SAH). LP should be performed at least 12 hours after onset to allow xanthochromia (bilirubin from haemolysed red cells) to develop. CT alone misses approximately 5% of SAH.

Question 19: 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 vivax
Plasmodium malariae
Plasmodium ovale
Plasmodium falciparum (Correct answer)

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

International Prognostic Index
Ann Arbor staging
Rai or Binet staging (Correct answer)
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 21: Which valvular lesion classically produces an early diastolic murmur best heard at the left sternal edge with the patient sitting forward?

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

Correct answer: Aortic regurgitation

Aortic regurgitation produces a high-pitched early diastolic decrescendo murmur best heard at the left sternal edge with the patient sitting forward and in held expiration. This position brings the aortic root closer to the chest wall.

Question 22: 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?

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

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 23: 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?

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

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 24: 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?

Diffuse idiopathic skeletal hyperostosis
Psoriatic spondyloarthropathy
Reactive arthritis
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 25: 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?

Methotrexate 15mg weekly
Naproxen 500mg twice daily
Prednisolone 15mg daily (Correct answer)
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 26: 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?

Lichen planus — treat with topical tacrolimus
Scabies — treat with permethrin 5% cream (Correct answer)
Eczema — treat with topical steroids
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 27: 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)
Progressive multifocal leukoencephalopathy
Cryptococcal meningitis
Primary CNS lymphoma

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 28: A 70-year-old woman with atrial fibrillation has a CHA2DS2-VASc score of 4. According to NICE guidelines, what is the recommended anticoagulation strategy?

Aspirin plus clopidogrel
No anticoagulation required
Direct oral anticoagulant (DOAC) (Correct answer)
Aspirin alone

Correct answer: Direct oral anticoagulant (DOAC)

NICE recommends anticoagulation with a DOAC (apixaban, dabigatran, edoxaban, or rivarelbana) as first-line for stroke prevention in AF when CHA2DS2-VASc score is 2 or more. Aspirin alone is no longer recommended for stroke prevention in AF.

Question 29: Which clinical sign indicates meningeal irritation when tested by flexion of the knee after passive hip flexion in a supine patient?

Romberg's sign
Babinski's sign
Kernig's sign (Correct answer)
Brudzinski's sign

Correct answer: Kernig's sign

Kernig's sign is positive when a patient in the supine position, with the hip and knee both flexed to 90°, resists or is unable to extend the knee due to pain. It indicates meningeal irritation and is positive in meningitis or subarachnoid haemorrhage.

Question 30: What is the most appropriate first-line treatment for a Wells score of 3 and a positive D-dimer in a patient with suspected PE?

Arrange echocardiogram and treat only if right heart strain is seen
Arrange V/Q scan first before treating
Commence therapeutic anticoagulation immediately
Request CT pulmonary angiography and treat if confirmed (Correct answer)

Correct answer: Request CT pulmonary angiography and treat if confirmed

A Wells score of 3 represents intermediate (moderate) probability for PE. CTPA is the investigation of choice. Anticoagulation may be started before imaging if there will be a significant delay (>1 hour) and there are no contraindications, but confirmation before committing to long-term therapy is preferred.

Question 31: A 50-year-old woman presents with lethargy, weight gain, and constipation. TSH is 45 mU/L (normal 0.4-4.0) and free T4 is 4 pmol/L (normal 9-25). Anti-TPO antibodies are strongly positive. What is the most likely diagnosis?

Subacute (de Quervain's) thyroiditis
Graves' disease
Toxic multinodular goitre
Hashimoto's thyroiditis (Correct answer)

Correct answer: Hashimoto's thyroiditis

Hashimoto's thyroiditis is the commonest cause of hypothyroidism in the UK. The markedly elevated TSH with low free T4 confirms primary hypothyroidism, and strongly positive anti-thyroid peroxidase (anti-TPO) antibodies confirm autoimmune aetiology. Treatment is lifelong levothyroxine.

Question 32: A patient presents with a painless genital ulcer. Dark-field microscopy of the ulcer exudate shows spirochaetes. What is the recommended treatment?

Oral azithromycin 1g single dose
Topical aciclovir
Oral doxycycline for 14 days
Intramuscular benzathine penicillin G (single dose) (Correct answer)

Correct answer: Intramuscular benzathine penicillin G (single dose)

A painless genital ulcer (chancre) with spirochaetes on dark-field microscopy is primary syphilis caused by Treponema pallidum. First-line treatment is a single intramuscular dose of benzathine penicillin G 2.4 million units. Doxycycline for 14 days is the alternative for penicillin-allergic patients.

Question 33: In obstructive sleep apnoea (OSA), which investigation is the gold standard for diagnosis?

Overnight oximetry alone
Epworth sleepiness scale score
Polysomnography (full overnight sleep study) (Correct answer)
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 34: Which pattern of inheritance does Huntington's disease follow?

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

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 35: 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?

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

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 36: 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?

Systemic lupus erythematosus
Tuberculosis
Lymphoma
Sarcoidosis (Correct answer)

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 37: A patient with a chronic leg ulcer has a painful, violaceous, undermined border wound. Skin biopsy shows neutrophilic infiltrate without infection. What is the diagnosis?

Pyoderma gangrenosum (Correct answer)
Vasculitis
Squamous cell carcinoma
Lipodermatosclerosis

Correct answer: Pyoderma gangrenosum

Pyoderma gangrenosum (PG) is a neutrophilic dermatosis presenting with rapidly progressive, painful ulcers with undermined, violaceous borders. It is associated with IBD, rheumatoid arthritis, and haematological malignancy. The pathergy phenomenon (wound worsening after trauma) is characteristic.

Question 38: Which cranial nerve is most commonly affected in raised intracranial pressure, causing a false localising sign?

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

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 39: A 45-year-old woman presents with 6 weeks of symmetrical swelling of the MCPs and PIPs, 2-hour morning stiffness, elevated CRP, positive RF, and positive anti-CCP. What is the most appropriate first-line DMARD?

Methotrexate (Correct answer)
Hydroxychloroquine
Sulfasalazine
Leflunomide

Correct answer: Methotrexate

Methotrexate is the anchor DMARD for rheumatoid arthritis and is recommended as first-line therapy by both NICE and EULAR guidelines.

Question 40: A patient presents with collapse. ECG shows torsades de pointes. What is the immediate pharmacological treatment?

Adenosine
Amiodarone
Lignocaine
IV magnesium sulphate (Correct answer)

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 41: Which investigation is used to screen for latent tuberculosis prior to starting biologic therapy, and how does it work?

Mantoux test — measures B-cell antibody response to tuberculin
Sputum culture — grows TB from respiratory secretions
Interferon-gamma release assay (IGRA) — measures T-cell IFN-gamma release in response to TB antigens (Correct answer)
Chest X-ray — identifies active pulmonary disease

Correct answer: Interferon-gamma release assay (IGRA) — measures T-cell IFN-gamma release in response to TB antigens

IGRA (e.g., QuantiFERON-TB Gold) measures interferon-gamma release from T-cells sensitised to M. tuberculosis-specific antigens (ESAT-6 and CFP-10). Unlike the Mantoux test, IGRA is not affected by prior BCG vaccination, making it preferred for screening in BCG-vaccinated populations such as the UK.

Question 42: 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?

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

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

Normal PT, elevated APTT, elevated fibrinogen, reduced platelets
Elevated PT, elevated APTT, elevated fibrinogen, elevated platelets
Elevated PT, elevated APTT, reduced fibrinogen, reduced platelets (Correct answer)
Reduced PT, reduced 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 44: A 30-year-old man from sub-Saharan Africa presents with fever, weight loss, and a CD4 count of 150 cells/microL. Chest X-ray shows bilateral upper lobe cavitating lesions. Sputum is positive for acid-fast bacilli. What is the most appropriate initial treatment regimen?

Isoniazid monotherapy for 9 months
Levofloxacin and amikacin for 3 months
Rifampicin, isoniazid, pyrazinamide, and ethambutol for 2 months then rifampicin and isoniazid for 4 months (Correct answer)
Rifampicin and isoniazid for 6 months

Correct answer: Rifampicin, isoniazid, pyrazinamide, and ethambutol for 2 months then rifampicin and isoniazid for 4 months

Standard UK treatment for pulmonary TB is 2 months of RIPE (rifampicin, isoniazid, pyrazinamide, ethambutol) followed by 4 months of rifampicin and isoniazid (total 6 months). In HIV co-infection, antiretroviral therapy should be started within 2-8 weeks, with attention to drug interactions (rifampicin with protease inhibitors).

Question 45: A patient is intubated and ventilated for ARDS. Which ventilation strategy reduces mortality?

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

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 46: 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?

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

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

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 48: 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
Aldosterone (Correct answer)
Cortisol
Adrenaline

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 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
Stop warfarin and give oral vitamin K 1-5 mg (Correct answer)
Give fresh frozen plasma

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: A patient presents to A&E having taken 40 paracetamol tablets 4 hours ago. The plasma paracetamol level is above the treatment line on the nomogram. What is the antidote?

N-acetylcysteine (NAC) (Correct answer)
Activated charcoal
Naloxone
Flumazenil

Correct answer: N-acetylcysteine (NAC)

N-acetylcysteine (NAC) is the antidote for paracetamol overdose. It works by replenishing glutathione stores and enhancing sulphation, preventing accumulation of the toxic metabolite NAPQI. It is most effective within 8 hours of ingestion but can still be beneficial up to 24 hours and beyond.

Question 51: 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)
Rheumatoid arthritis
Systemic sclerosis
Dermatomyositis

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

IV magnesium sulphate 1.2–2g over 20 minutes (Correct answer)
Intubation as first step
Oral prednisolone and discharge
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 53: 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 rhomboid and negatively birefringent
Both crystal types show identical birefringence but differ in solubility
Gout crystals are strongly negatively birefringent and needle-shaped (Correct answer)
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 54: 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
Teriparatide 20 micrograms subcutaneously daily
Alendronic acid 70mg weekly plus calcium and vitamin D (Correct answer)
Denosumab 60mg subcutaneously every 6 months

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

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 56: A 45-year-old woman presents with jaundice, pruritus, and fatigue. Blood tests show raised ALP (450 U/L), mildly raised ALT (65 U/L), and positive anti-mitochondrial antibodies (AMA). What is the most likely diagnosis?

Primary sclerosing cholangitis
Drug-induced liver injury
Autoimmune hepatitis
Primary biliary cholangitis (Correct answer)

Correct answer: Primary biliary cholangitis

Primary biliary cholangitis (PBC, formerly primary biliary cirrhosis) characteristically presents in middle-aged women with cholestatic liver enzymes (raised ALP) and positive anti-mitochondrial antibodies (AMA), which are present in over 95% of cases. Pruritus and fatigue are common symptoms.

Question 57: Which ECG finding is most characteristic of hyperkalaemia?

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

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 58: 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?

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

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 59: Which antibody is associated with myasthenia gravis?

Anti-Ro/La
Anti-Jo-1
Anti-AChR (acetylcholine receptor antibody) (Correct answer)
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 60: A chest physician suspects mesothelioma in a patient with a unilateral pleural effusion and a history of asbestos exposure. Which investigation is most likely to confirm the diagnosis?

Pleural fluid cytology alone
Serum mesothelin level alone
Sputum cytology
CT-guided or thoracoscopic pleural biopsy (Correct answer)

Correct answer: CT-guided or thoracoscopic pleural biopsy

Mesothelioma diagnosis requires histological confirmation from pleural tissue. Pleural fluid cytology has low sensitivity for mesothelioma. CT-guided biopsy or thoracoscopy with directed biopsies provides histological tissue with adequate yield for diagnosis and subtyping (epithelioid, sarcomatoid, biphasic).

Question 61: A 5-year-old child presents with fever, petechial rash, and neck stiffness. CSF shows raised WCC (predominantly neutrophils), raised protein, low glucose, and Gram-negative diplococci. What is the most likely causative organism?

Streptococcus pneumoniae
Neisseria meningitidis (Correct answer)
Haemophilus influenzae
Listeria monocytogenes

Correct answer: Neisseria meningitidis

Neisseria meningitidis (meningococcus) is a Gram-negative diplococcus and the most common cause of bacterial meningitis in children and young adults in the UK. The petechial/purpuric rash is characteristic of meningococcal disease. Close contacts require ciprofloxacin chemoprophylaxis.

Question 62: A 65-year-old right-handed man suddenly develops expressive dysphasia with comprehension preserved. He can understand commands but struggles to produce fluent speech. Which area of the brain is most likely affected?

Right inferior frontal gyrus
Wernicke's area (left superior temporal gyrus)
Broca's area (left inferior frontal gyrus) (Correct answer)
Bilateral occipital lobes

Correct answer: Broca's area (left inferior frontal gyrus)

Broca's area, located in the left inferior frontal gyrus (in right-handed individuals), is responsible for speech production. Damage causes expressive (non-fluent) dysphasia where comprehension is preserved but speech output is effortful and telegraphic.

Question 63: A 25-year-old woman presents with haematuria, bilateral renal cysts on ultrasound, and a family history of renal failure. Genetic testing reveals a PKD1 mutation. What is the diagnosis?

Tuberous sclerosis
Medullary sponge kidney
Autosomal dominant polycystic kidney disease (Correct answer)
Von Hippel-Lindau syndrome

Correct answer: Autosomal dominant polycystic kidney disease

Autosomal dominant polycystic kidney disease (ADPKD) is caused by mutations in PKD1 (chromosome 16, 85% of cases) or PKD2 (chromosome 4). It is the most common inherited kidney disease, presenting with bilateral cysts, haematuria, hypertension, and progressive renal failure.

Question 64: A 25-year-old non-smoker presents with progressive dyspnoea and a CXR showing bilateral basal emphysematous changes. What rare condition should be considered?

Lymphangioleiomyomatosis
Sarcoidosis
Hypersensitivity pneumonitis
Alpha-1-antitrypsin deficiency (Correct answer)

Correct answer: Alpha-1-antitrypsin deficiency

Alpha-1-antitrypsin (AAT) deficiency should be suspected in young, non-smoking patients with premature emphysema, particularly with a basal distribution (unlike smoking-related emphysema which is upper lobe). Serum AAT levels and phenotyping confirm the diagnosis.

Question 65: A patient with haemophilia A has a factor VIII level of 3%. What severity does this represent?

Moderate haemophilia A (1–5% factor VIII) (Correct answer)
Severe haemophilia A (<1% factor VIII)
Carrier state only
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 66: What is the mechanism by which montelukast acts in asthma?

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

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 67: 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?

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

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 68: Which enzyme deficiency is responsible for acute intermittent porphyria?

Porphobilinogen deaminase (Correct answer)
ALA synthase
Ferrochelatase
Uroporphyrinogen decarboxylase

Correct answer: Porphobilinogen deaminase

Acute intermittent porphyria is caused by deficiency of porphobilinogen (PBG) deaminase (also called hydroxymethylbilane synthase), the third enzyme in the haem biosynthesis pathway. This leads to accumulation of ALA and PBG, causing neurovisceral attacks.

Question 69: 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
Glipizide
Sitagliptin
Empagliflozin (Correct answer)

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 70: 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?

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

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 71: Which ECG finding is most specific for hyperkalaemia?

U waves
Peaked T waves (Correct answer)
Shortened PR interval
Prolonged QTc

Correct answer: Peaked T waves

Tall, peaked (tented) T waves are the earliest and most characteristic ECG change in hyperkalaemia. As potassium rises further, the PR prolongs, QRS widens, P waves disappear, and a sine wave pattern can develop, eventually leading to VF.

Question 72: Which HLA type is strongly associated with ankylosing spondylitis?

HLA-B27 (Correct answer)
HLA-A2
HLA-DR4
HLA-DR3

Correct answer: HLA-B27

HLA-B27 is present in approximately 90–95% of patients with ankylosing spondylitis in the UK Caucasian population. Although it has high sensitivity for AS, it has low specificity as 8% of the general population carry HLA-B27 without developing AS. Its exact pathogenic role remains under investigation.

Question 73: 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-Ro (SSA) (Correct answer)
Anti-dsDNA
Anti-Scl-70
Anti-Jo-1

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 74: 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?

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

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 75: 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?

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

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 76: 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?

Primary Sjögren's syndrome
Mixed connective tissue disease (Correct answer)
Undifferentiated connective tissue disease
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 77: 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
Anywhere from mouth to anus (Correct answer)
Small bowel only
Colon and rectum 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 78: 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?

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

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 79: A 62-year-old man presents with acute chest pain. His ECG shows ST elevation in leads II, III, and aVF with reciprocal changes in I and aVL. Which coronary artery is most likely occluded?

Right coronary artery (Correct answer)
Left anterior descending artery
Left circumflex artery
Left main stem

Correct answer: Right coronary artery

ST elevation in leads II, III, and aVF indicates an inferior myocardial infarction. The right coronary artery (RCA) supplies the inferior surface of the heart in approximately 85% of patients (right-dominant circulation).

Question 80: 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 81: 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?

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

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 82: 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?

Severe aortic stenosis (Correct answer)
Mild aortic stenosis
Moderate 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 83: A patient presents with severe hypercalcaemia (corrected calcium 3.8 mmol/L) causing confusion and dehydration. What is the most important initial treatment?

Intravenous zoledronic acid
Intravenous 0.9% sodium chloride (Correct answer)
Calcitonin injection
Oral prednisolone

Correct answer: Intravenous 0.9% sodium chloride

Aggressive IV fluid resuscitation with 0.9% saline is the first priority in severe hypercalcaemia. Patients are typically volume depleted due to hypercalcaemia-induced nephrogenic diabetes insipidus. Rehydration alone can reduce calcium significantly. Bisphosphonates (zoledronic acid) are given once rehydrated but take 2-4 days to work.

Question 84: A patient presents with sudden onset worst headache of their life, neck stiffness, and photophobia. CT head is normal. What is the next most appropriate investigation?

MRI brain
Repeat CT head in 24 hours
CT angiography immediately
Lumbar puncture (after 12 hours from onset) (Correct answer)

Correct answer: Lumbar puncture (after 12 hours from onset)

When subarachnoid haemorrhage (SAH) is suspected but CT head is negative (sensitivity drops after 6 hours), lumbar puncture should be performed at least 12 hours after symptom onset to allow time for xanthochromia to develop. Xanthochromia (yellow discolouration from bilirubin) distinguishes SAH from a traumatic tap.

Question 85: 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?

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

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 86: A 60-year-old man with CKD stage 4 has a potassium of 6.8 mmol/L. ECG shows tall tented T waves but no QRS broadening. After IV calcium gluconate, what is the next most appropriate treatment to lower potassium?

Oral furosemide
Oral calcium resonium
Insulin-dextrose infusion (10 units actrapid in 50 mL 50% glucose) (Correct answer)
IV sodium bicarbonate alone

Correct answer: Insulin-dextrose infusion (10 units actrapid in 50 mL 50% glucose)

After cardioprotection with calcium gluconate, insulin-dextrose infusion is the fastest way to shift potassium intracellularly. 10 units of short-acting insulin with 50 mL of 50% glucose typically reduces potassium by 0.5-1.0 mmol/L within 15-30 minutes. Blood glucose monitoring is essential to prevent hypoglycaemia.

Question 87: Which condition is associated with a 'saddle-shaped' ST elevation pattern across multiple leads without reciprocal changes?

STEMI
Left bundle branch block
Acute pericarditis (Correct answer)
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 88: A 45-year-old woman has recurrent palpitations. A 24-hour Holter shows intermittent delta waves and short PR interval. What is the diagnosis?

Complete heart block
Brugada syndrome
Wolff-Parkinson-White syndrome (Correct answer)
Lown-Ganong-Levine 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 89: 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?

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

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 90: 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?

Bismuth quadruple therapy
PPI and amoxicillin for 14 days
PPI, metronidazole, and levofloxacin
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 91: 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?

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

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 92: 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)
Heberden's node
Swan-neck deformity
Boutonnière 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 93: In a patient with HOCM, which intervention is most likely to worsen outflow tract obstruction?

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

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 94: 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?

Mobilisation of urate crystals during changes in serum urate (Correct answer)
Allopurinol resistance
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 95: A patient with small cell lung cancer presents with hyponatraemia (Na 118 mmol/L) and inappropriately concentrated urine. What paraneoplastic syndrome does this represent?

Hypercalcaemia of malignancy
Eaton-Lambert syndrome
SIADH (Correct answer)
Cushing syndrome

Correct answer: SIADH

SIADH (Syndrome of Inappropriate Antidiuretic Hormone secretion) is the most common paraneoplastic syndrome in small cell lung cancer. Ectopic ADH production causes dilutional hyponatraemia with inappropriately concentrated urine (urine osmolality >100 mOsm/kg despite low plasma osmolality).

Question 96: 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)
Hydroxyapatite
Calcium oxalate
Calcium pyrophosphate

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 97: 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?

Codeine phosphate
Paracetamol
Propranolol (Correct answer)
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.

Question 98: What is the most common cause of complete heart block in the UK?

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

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 99: 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?

Nephrotic syndrome
Psychogenic polydipsia
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 100: 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
Benign oesophageal stricture
Achalasia (Correct answer)
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.

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

Questions

180 min

Time Limit

60%

To Pass

Checking for saved progress...

Exam Rules

You can skip questions and return to them later
Flag questions for review before submitting
No feedback shown until you submit the entire exam
Unanswered questions count as wrong — answer everything
10 pretest questions are mixed in and don't affect your score
Timer auto-submits when time runs out
Your progress is auto-saved every 30 seconds