Membership of the Royal College of General Practitioners (MRCGP) Applied Knowledge Test (AKT): Clinical Medicine Syllabus

What HbA$_1c$ value diagnoses type 2 diabetes, and what range defines pre-diabetes (non-diabetic hyperglycaemia)?

Diabetes: HbA$_1c \geq 48\ \text{mmol/mol}$ ($\geq 6.5\%$). Pre-diabetes: HbA$_1c$ of $42\text{--}47\ \text{mmol/mol}$ ($6.0\text{--}6.4\%$).

What is first-line drug therapy for type 2 diabetes, and what major comorbidity prompts adding an SGLT2 inhibitor?

Metformin is first-line. Add an SGLT2 inhibitor (e.g. dapagliflozin, empagliflozin) if there is established cardiovascular disease, heart failure, chronic kidney disease, or high QRISK.

What are the typical HbA$_1c$ targets for type 2 diabetes managed by lifestyle/single drug versus a drug with hypoglycaemia risk?

Target $48\ \text{mmol/mol}$ ($6.5\%$) on lifestyle or a drug not causing hypoglycaemia; target $53\ \text{mmol/mol}$ ($7.0\%$) if on a sulfonylurea/insulin or if intensification is needed.

What blood test confirms diabetic ketoacidosis (DKA) and what are the three biochemical diagnostic criteria?

Capillary/venous ketones and glucose/pH. DKA = ketonaemia $\geq 3.0\ \text{mmol/L}$ (or significant ketonuria), blood glucose $> 11\ \text{mmol/L}$ (or known diabetes), and bicarbonate $< 15\ \text{mmol/L}$ and/or venous pH $< 7.3$.

Describe a basal-bolus insulin regimen for type 1 diabetes.

A long-acting (basal) insulin once or twice daily (e.g. glargine, detemir, degludec) plus rapid-acting (bolus) insulin analogue (e.g. aspart, lispro) with each meal, dose-adjusted for carbohydrate counting and pre-meal glucose.

What is the recommended blood glucose target on waking and pre-meal for adults with type 1 diabetes?

On waking (fasting): $5\text{--}7\ \text{mmol/L}$; before meals at other times: $4\text{--}7\ \text{mmol/L}$. Target HbA$_1c$ is $\leq 48\ \text{mmol/mol}$ ($6.5\%$).

What biochemical pattern defines primary (overt) hypothyroidism, and what is first-line treatment?

Raised TSH with low free T4. Treat with levothyroxine, titrated to normalise TSH; recheck TSH about 6–8 weeks after each dose change.

What thyroid function pattern is seen in Graves' disease, and which antibody is characteristic?

Suppressed/low TSH with raised free T4 and/or T3. TSH-receptor antibodies (TRAb) are characteristic; thyroid peroxidase (TPO) antibodies may also be positive.

How is subclinical hypothyroidism defined biochemically?

A raised TSH (typically $4\text{--}10\ \text{mU/L}$) with a normal free T4.

What is the formula relating eGFR categories in chronic kidney disease, and what defines G3a?

CKD is staged by eGFR (mL/min/1.73 m$^2$): G1 $\geq 90$, G2 $60\text{--}89$, G3a $45\text{--}59$, G3b $30\text{--}44$, G4 $15\text{--}29$, G5 $< 15$. G3a = eGFR $45\text{--}59$ with evidence of kidney damage.

How is albuminuria categorised in CKD using the albumin:creatinine ratio (ACR)?

A1: ACR $< 3\ \text{mg/mmol}$ (normal-mildly increased); A2: ACR $3\text{--}30\ \text{mg/mmol}$ (moderately increased); A3: ACR $> 30\ \text{mg/mmol}$ (severely increased).

In CKD, which ACR value (with diabetes or otherwise) prompts an ACE inhibitor/ARB for renoprotection?

Offer an ACE inhibitor or ARB if ACR $\geq 3\ \text{mg/mmol}$ in diabetes, $\geq 30\ \text{mg/mmol}$ with hypertension, or $\geq 70\ \text{mg/mmol}$ regardless. An SGLT2 inhibitor is also added in many CKD patients.

What is the classic biochemistry of primary adrenal insufficiency (Addison's disease)?

Low cortisol with raised ACTH, plus hyponatraemia, hyperkalaemia, and often hypoglycaemia. Diagnosed by a short Synacthen (ACTH stimulation) test showing inadequate cortisol rise.

How do PTH and calcium levels differ between primary hyperparathyroidism and hypoparathyroidism?

Primary hyperparathyroidism: high calcium with high (or inappropriately normal) PTH. Hypoparathyroidism: low calcium with low PTH. Phosphate is often low in hyperparathyroidism and high in hypoparathyroidism.

What pituitary tumour causes hyperprolactinaemia, what symptom triad results, and what is first-line treatment?

A prolactinoma. It causes galactorrhoea, amenorrhoea/reduced libido, and (if large) visual field defects (bitemporal hemianopia). First-line treatment is a dopamine agonist (e.g. cabergoline or bromocriptine).

What waist circumference and biochemical criteria define metabolic syndrome (IDF)?

Central obesity (ethnicity-specific waist, e.g. $\geq 94\ \text{cm}$ men/$\geq 80\ \text{cm}$ women in Europids) plus any two of: triglycerides $\geq 1.7\ \text{mmol/L}$, HDL low ($< 1.0$ men/$< 1.3$ women), BP $\geq 130/85$, or fasting glucose $\geq 5.6\ \text{mmol/L}$.

What BMI thresholds define overweight, obesity class I–III in adults (WHO)?

$$\text{BMI} = \frac{\text{weight (kg)}}{[\text{height (m)}]^{2}}$$ Overweight $25.0\text{--}29.9$; Obesity I $30.0\text{--}34.9$; II $35.0\text{--}39.9$; III $\geq 40\ \text{kg/m}^{2}$.

What is the recommended first-line approach to uninvestigated dyspepsia in a patient without alarm features?

A 1-month trial of a full-dose proton pump inhibitor, OR test-and-treat for Helicobacter pylori (urea breath test or stool antigen). Address lifestyle factors and review medications.

Name two ALARM/red-flag features in dyspepsia that warrant urgent upper GI endoscopy referral.

Dysphagia, unexplained weight loss, GI bleeding (haematemesis/melaena), persistent vomiting, an epigastric mass, or age $\geq 55$ with treatment-resistant dyspepsia. Use the 2-week-wait pathway.

What is first-line H. pylori eradication therapy in UK primary care?

A 7-day course of a PPI plus two antibiotics: typically amoxicillin with either clarithromycin or metronidazole (twice daily triple therapy). Use a non-penicillin regimen if penicillin-allergic.

Which antibody and biopsy finding confirm coeliac disease, and what dietary condition must apply at testing?

Raised anti-tissue transglutaminase (anti-tTG IgA, with total IgA to exclude deficiency); confirmed by duodenal biopsy showing villous atrophy. The patient must be eating gluten ($> 1$ meal/day for $\geq 6$ weeks).

What distinguishes ulcerative colitis from Crohn's disease in terms of distribution and inflammation depth?

UC: continuous mucosal inflammation limited to the colon, starting at the rectum. Crohn's: patchy (skip lesions), transmural inflammation affecting anywhere from mouth to anus, with granulomas and a risk of fistulae/strictures.

What is first-line treatment to induce remission in mild-to-moderate ulcerative colitis?

A topical (rectal) and/or oral aminosalicylate (5-ASA, e.g. mesalazine). Add oral or topical corticosteroids if there is an inadequate response.

What positive diagnostic criteria (Rome IV) define irritable bowel syndrome?

Recurrent abdominal pain on average $\geq 1$ day/week in the last 3 months, associated with $\geq 2$ of: related to defecation, a change in stool frequency, or a change in stool form/appearance (symptom onset $\geq 6$ months before diagnosis).

In suspected IBS, which blood tests help exclude other diagnoses, and which result argues against IBS?

FBC, CRP/ESR, anti-tTG (coeliac), and faecal calprotectin. A raised faecal calprotectin suggests inflammatory bowel disease rather than IBS and warrants referral.

Interpret a predominantly raised ALT/AST versus a raised ALP/GGT pattern on LFTs.

A predominant ALT/AST rise indicates a hepatocellular pattern (e.g. viral hepatitis, NAFLD, drugs). A predominant ALP rise with raised GGT indicates a cholestatic/obstructive pattern (e.g. biliary obstruction, PBC); raised GGT confirms a hepatic source for the ALP.

What non-invasive score helps assess advanced fibrosis in non-alcoholic fatty liver disease, and what does a low result indicate?

The FIB-4 score (using age, AST, ALT, and platelets). A low score (e.g. $< 1.3$) makes advanced fibrosis unlikely; higher values prompt enhanced liver fibrosis (ELF) testing or specialist referral.

What first-line antibiotic and duration does NICE recommend for an uncomplicated lower UTI in a non-pregnant woman?

Nitrofurantoin (if eGFR $\geq 45$) for 3 days, or trimethoprim 3 days if local resistance is low. Antimicrobial stewardship: use the shortest effective course and review local resistance patterns.

What is the CURB-65 score, and what total score suggests hospital assessment for community-acquired pneumonia?

One point each for: Confusion, Urea $> 7\ \text{mmol/L}$, Respiratory rate $\geq 30$, Blood pressure ($\text{systolic} < 90$ or $\text{diastolic} \leq 60$), Age $\geq 65$. A score of $\geq 2$ suggests hospital assessment; $0\text{--}1$ can often be managed at home.

How do you distinguish iron-deficiency anaemia from anaemia of chronic disease on a blood film and iron studies?

Iron deficiency: microcytic, hypochromic (low MCV/MCH), low ferritin, low transferrin saturation, raised total iron-binding capacity (TIBC). Anaemia of chronic disease: normocytic or mildly microcytic with normal/raised ferritin and low TIBC.

What two vitamin deficiencies cause a macrocytic megaloblastic anaemia, and which antibody confirms pernicious anaemia?

Vitamin B$_{12}$ and folate deficiency. Pernicious anaemia is confirmed by intrinsic factor antibodies (and may show anti-parietal cell antibodies).

Give the diagnostic features distinguishing migraine from tension-type headache.

Migraine: moderate-severe, often unilateral, pulsating, $4\text{--}72$ hours, with nausea/vomiting and/or photophobia and phonophobia, worse with activity, $\pm$ aura. Tension-type: bilateral, pressing/tightening, mild-moderate, not aggravated by routine activity, no significant nausea.

List four red-flag headache features that warrant urgent investigation.

Thunderclap (sudden, maximal within seconds-minutes), new headache with focal neurology or papilloedema, headache worse on standing/lying or with Valsalva, new headache in over-50s (consider GCA), fever/neck stiffness, or progressive headache with morning vomiting.

What is first-line acute treatment for migraine, and what defines medication-overuse headache risk?

A triptan (e.g. sumatriptan) plus an NSAID or paracetamol. Medication-overuse headache risk: triptans/opioids/combination analgesics on $\geq 10$ days/month, or simple analgesics on $\geq 15$ days/month, for $> 3$ months.

What is the cardinal triad of Parkinson's disease, and how does Parkinsonian tremor differ from essential tremor?

Bradykinesia, rigidity, and a resting tremor (plus postural instability). Parkinsonian tremor is a 4–6 Hz resting "pill-rolling" tremor, asymmetrical, worse at rest. Essential tremor is a postural/action tremor, often symmetrical, improved by alcohol, and worse on sustained posture.

After a first unprovoked seizure, what investigations are recommended and when is anti-epileptic drug treatment usually started?

Refer to a specialist; arrange an EEG and brain MRI. AEDs are generally started after a second seizure, or after a first seizure if there is a structural lesion, an unequivocal epileptiform EEG, or the patient/clinician deems the risk of recurrence unacceptable.

Which first-line anti-epileptic drugs are used for focal versus generalised tonic-clonic seizures (and a key caution in pregnancy)?

Focal: lamotrigine or levetiracetam. Generalised tonic-clonic: sodium valproate (men) or lamotrigine/levetiracetam. Valproate must be avoided in women of childbearing potential due to teratogenicity unless conditions of the pregnancy prevention programme are met.

What tool stratifies early stroke risk after a TIA, and what is the immediate antiplatelet management?

The ABCD$^2$ score historically estimated risk, but current UK practice treats all suspected TIAs urgently. Give aspirin 300 mg immediately (unless contraindicated) and refer for specialist assessment within 24 hours.

What is the time window for thrombolysis with alteplase in acute ischaemic stroke, and what must be excluded first?

Within $4.5$ hours of symptom onset. A CT/MRI brain must first exclude haemorrhage. Mechanical thrombectomy may be offered up to 6 hours (or later in selected patients with favourable imaging) for large-vessel occlusion.

What is the long-term antiplatelet regimen after a non-cardioembolic ischaemic stroke or TIA?

Clopidogrel 75 mg once daily long-term (first-line). If clopidogrel is unsuitable, use aspirin plus modified-release dipyridamole. High-intensity statin and blood pressure control are also indicated.

What clinical features distinguish mechanical low back pain from cauda equina syndrome (a red flag)?

Cauda equina red flags: bilateral sciatica, saddle (perianal) anaesthesia, bladder/bowel dysfunction (urinary retention/incontinence, faecal incontinence), and reduced anal tone — these require emergency MRI and surgical referral.

What is the typical history and examination finding in lateral epicondylitis (tennis elbow)?

Pain over the lateral epicondyle radiating down the forearm, worsened by resisted wrist extension and gripping. Tenderness over the common extensor origin; provoked by resisted middle-finger extension.

What antibody is most specific for rheumatoid arthritis, and which joints are characteristically involved?

Anti-cyclic citrullinated peptide (anti-CCP) antibody is most specific (rheumatoid factor is also used). It causes a symmetrical polyarthritis affecting the small joints — MCPs, PIPs, and wrists — with early-morning stiffness lasting $> 30$ minutes.

What is first-line treatment to control synovitis in newly diagnosed rheumatoid arthritis?

A conventional DMARD as monotherapy (methotrexate first-line, or leflunomide/sulfasalazine), ideally started within 3 months, with a short-term bridging glucocorticoid. Treat-to-target aiming for remission/low disease activity.

What crystal and joint fluid finding confirm gout, and what is the first-line acute treatment?

Negatively birefringent, needle-shaped monosodium urate crystals on polarised microscopy. First-line acute treatment: an NSAID or colchicine (or a short course of oral corticosteroid). Serum urate target for prophylaxis is $< 360\ \mu\text{mol/L}$ (or $< 300$ in tophaceous/severe disease).

What are the classic clinical and laboratory features of polymyalgia rheumatica, and its first-line treatment?

Bilateral shoulder and pelvic girdle pain and stiffness (worse in the morning) in over-50s, with a raised ESR/CRP. First-line treatment is oral prednisolone (typically 15 mg daily) with a dramatic response within days; be alert for coexisting giant cell arteritis.

What is the first-line management of mild-to-moderate plaque psoriasis in primary care?

A potent topical corticosteroid plus a topical vitamin D analogue (e.g. calcipotriol) applied separately (one in the morning, one in the evening), or as a combined product, for up to 4 weeks initially.

How do you distinguish the typical lesion of basal cell carcinoma from a malignant melanoma?

BCC: a slow-growing, pearly, rolled-edge papule with telangiectasia, often with central ulceration (rodent ulcer), rarely metastasises. Melanoma: a pigmented lesion meeting ABCDE criteria — Asymmetry, irregular Border, Colour variation, Diameter $> 6\ \text{mm}$, Evolving — warranting urgent 2-week-wait referral.

What is the first-line treatment for moderate acne vulgaris, and which agent is teratogenic and prescriber-restricted?

A topical combination (e.g. a topical retinoid with benzoyl peroxide, or with a topical antibiotic), or a fixed combination; an oral antibiotic (e.g. lymecycline/doxycycline) for up to 12 weeks if widespread. Oral isotretinoin (specialist-only) is highly teratogenic and requires a pregnancy prevention programme.