Rapid-recall takeaways distilled from the MRCEM Primary question bank, grouped by specialty. One pearl per high-frequency concept. Use it for last-pass revision alongside questions, not as a replacement for them.
480 pearls · 6 specialties · Generated 6 November 2026
Anatomy
80 high-yield facts
Anatomical snuffbox tenderness with a normal X-ray = treat as scaphoid fracture until proven otherwise - the scaphoid forms the snuffbox floor and the radial artery crosses its surface.
Flail arm plus Horner's syndrome indicates pan-plexus root avulsion - preganglionic injuries have the worst prognosis and cannot be repaired by direct nerve grafting.
Anterior communicating artery connects the two ACAs - most common site of anterior circulation aneurysms; the Circle of Willis provides collateral circulation but is complete in only 25-50% of people.
Pituitary gland = sella turcica = middle cranial fossa - compression of the optic chiasm above causes bitemporal hemianopia; lateral extension into cavernous sinus causes cranial nerve palsies (III, IV, V1, V2, VI).
Froment's sign = compensatory FPL flexion when adductor pollicis is paralysed (ulnar nerve) - the patient flexes the thumb IP joint to grip paper because they cannot adduct the thumb.
Subdural haematoma = bridging veins rupture - vulnerable in elderly due to brain atrophy; crescent-shaped, crosses suture lines on CT; chronic subdurals are hypodense and may present with insidious cognitive decline.
Popeye sign with mild elbow flexion weakness = long head of biceps rupture - function is largely preserved due to the intact short head, brachialis, and brachioradialis providing compensatory flexion.
Supraspinatus initiates abduction (0-15 degrees), deltoid continues it (15-90 degrees), and trapezius with serratus anterior complete it (90-180 degrees) - test each range separately to localise the lesion.
Humeral shaft fracture plus wrist drop equals radial nerve injury at the spiral groove - preserved triceps function confirms the lesion is at or below the groove.
Five muscles from the common flexor origin (medial epicondyle) - Pronator teres, FCR, Palmaris longus, FDS, FCU - use the mnemonic 'Pass Fail Pass Fail Fail' for their nerve supply (median, median, median, median, ulnar).
Regimental badge sensory loss with absent biceps reflex and weak shoulder abduction is the classic C5 triad - think upper brachial plexus injury in motorcycle RTCs.
Pterion = thinnest skull + overlies middle meningeal artery - the most important skull landmark in trauma; temporal impact → observe closely for extradural haematoma (biconvex collection, lucid interval, ipsilateral pupil dilation).
Foramen magnum transmits the medulla, vertebral arteries, spinal accessory nerve (ascending part), and anterior/posterior spinal arteries - it is the transition between the skull and the vertebral canal.
Anterior wedging is the hallmark of osteoporotic compression fractures - posterior cortex integrity distinguishes compression fractures (intact) from burst fractures (disrupted), which has critical implications for stability and neurological risk.
Dural venous sinuses drain brain venous blood and absorb CSF via arachnoid granulations - thrombosis (CVST) causes raised ICP because both venous drainage and CSF absorption are impaired; treat with anticoagulation.
Left-sided neglect = right (non-dominant) parietal lobe lesion - neglect is different from hemianopia; the patient is unaware of the deficit (anosognosia) and it carries a poor rehabilitation prognosis.
SITS muscles of the rotator cuff - Subscapularis is the only internal rotator, while Infraspinatus and Teres minor are external rotators. Teres major is NOT a rotator cuff muscle.
CN VI is the 'false localising sign' nerve - its long course and fixation at the petrous apex (Dorello's canal) makes it vulnerable to raised ICP, producing bilateral or unilateral abducens palsies that do not indicate local pathology.
CSF is produced by the choroid plexus and absorbed by arachnoid granulations into the superior sagittal sinus - normal CSF production is 500 mL/day with 150 mL total volume; impaired absorption at the granulations causes raised ICP in IIH.
Musculocutaneous nerve = biceps (elbow flexion and supination) + lateral forearm sensation - it is the nerve of the anterior compartment of the arm.
Locked-in syndrome = bilateral ventral pontine destruction (basilar artery occlusion) - the patient is conscious (tegmentum preserved) but quadriplegic and mute; only vertical eye movements and blinking are possible.
Cribriform plate fracture = CSF rhinorrhoea + anosmia + pneumocephalus - the anterior cranial fossa's weakest point; test for beta-2 transferrin to confirm CSF leak; watch for meningitis.
PIN palsy = finger drop (not wrist drop) with no sensory loss - preserved wrist extension via ECRL distinguishes it from radial nerve trunk injury at the spiral groove.
Transverse sinus → sigmoid sinus → internal jugular vein - the sigmoid sinus exits through the jugular foramen; mastoiditis can cause sigmoid sinus thrombosis due to anatomical proximity.
Always test regimental badge sensation before and after shoulder reduction - axillary nerve injury is the most important neurological complication of anterior shoulder dislocation.
Pneumococcus is the most common cause of post-traumatic meningitis through a CSF leak - recurrent pneumococcal meningitis should prompt investigation for an occult CSF leak from an unrepaired skull base fracture.
ACoA is the commonest aneurysm site (~30-35%) - aneurysms form at bifurcation points due to wall deficiency; rupture causes SAH; risk factors include hypertension, smoking, ADPKD, and family history.
Ulnar = superficial arch (main), Radial = deep arch (main) - remember 'U' for ulnar and 'upper' (superficial), though this mnemonic is imperfect, the anatomical principle is critical for hand surgery.
Dorsal hand sensation distinguishes elbow from wrist ulnar nerve lesions - the dorsal cutaneous branch arises proximal to the wrist, so dorsal sensory loss means the lesion is at or above the elbow.
Suprascapular nerve at the notch affects both supraspinatus and infraspinatus - at the spinoglenoid notch, only infraspinatus is affected. No cutaneous sensory loss occurs with either lesion.
EPL rupture after distal radius fracture is due to ischaemia at Lister's tubercle - the patient loses thumb IP extension, and diabetes increases the risk of this attritional rupture.
Dilated lateral and third ventricles with normal fourth ventricle = aqueduct stenosis - the aqueduct of Sylvius is the narrowest point and most common site of obstructive hydrocephalus.
Subfalcine herniation is the most common type - cingulate gyrus herniates under the falx; can compress the ACA causing leg weakness; midline shift on CT is the radiological indicator; it may progress to transtentorial herniation.
PICA occlusion = lateral medullary (Wallenberg) syndrome - ipsilateral Horner's + facial pain loss + cerebellar signs + contralateral body pain/temperature loss; no motor weakness because the corticospinal tract is spared.
Lateral cord = musculocutaneous nerve + lateral root of median nerve - isolated elbow flexion loss with lateral forearm numbness but preserved shoulder function points to the lateral cord.
Anterior interosseous nerve is a pure motor nerve - think of the pinch test (inability to make an 'O' with thumb and index finger) with no sensory loss to distinguish from median nerve trunk injury.
Combined thenar motor loss and lateral three and a half finger sensory loss at the wrist means median nerve main trunk injury - both motor and sensory components are affected together.
Anterior cranial fossa floor = frontal orbital plates + ethmoid cribriform plate + lesser sphenoid wing - the fragile cribriform plate is the weak point; fractures cause CSF rhinorrhoea and anosmia.
Preserved thenar eminence sensation in carpal tunnel syndrome is due to the palmar cutaneous branch arising proximal to the tunnel - loss of this sensation suggests a more proximal median nerve lesion.
Thoracic outlet syndrome presents with medial arm/hand symptoms plus vascular compromise during overhead activities - Adson's test is suggestive but has a high false-positive rate.
A2 and A4 pulleys are the biomechanically critical pulleys - A2 rupture is the classic rock climber's pulley injury causing bowstringing over the proximal phalanx.
Expanding haematomas in anticoagulated patients can cause acute nerve compression - the ulnar nerve in the medial upper arm is particularly vulnerable due to its superficial position posterior to the medial intermuscular septum.
C6 = thumb, C7 = middle finger, C8 = little finger - these three dermatomal landmarks on the hand are the most reliable and commonly tested in emergency medicine.
Radial nerve in axilla = loss of triceps + wrist extensors + finger extensors + sensory loss over posterior arm, forearm, and first dorsal web space - loss of elbow extension distinguishes axillary from spiral groove lesions.
Lunate dislocates volarly (spilled teacup on lateral X-ray) causing acute median nerve compression - this is a commonly missed ED diagnosis requiring urgent reduction.
Posterior limb of internal capsule = corticospinal tract (motor fibres) - lacunar infarcts here cause pure motor hemiplegia; lenticulostriate arteries (MCA branches) are the culprit vessels; somatotopy places face and arm anteriorly, leg posteriorly.
LMN facial palsy = entire ipsilateral face including forehead; UMN = forehead spared - the key difference is bilateral corticobulbar supply to the forehead; taste loss localises the LMN lesion proximal to the chorda tympani.
The ulnar paradox - a more distal ulnar nerve lesion produces a worse claw deformity because intact FDP allows unopposed MCP hyperextension.
Waiter's tip position with intact grasp = Erb-Duchenne palsy (C5-C6) - the opposite of Klumpke palsy (C8-T1), which has a claw hand with preserved shoulder function.
Pronator teres syndrome = median nerve symptoms PLUS forearm pronation weakness AND thenar eminence sensory loss - these extra features distinguish it from carpal tunnel syndrome.
First compartment = APL and EPB = de Quervain's - positive Finkelstein's test with radial styloid tenderness is diagnostic; be aware of the septum variant that may necessitate targeted injection.
Middle meningeal artery through foramen spinosum - temporal bone fracture at the pterion causes extradural haematoma; biconvex shape on CT; the 'lucid interval' is the classic but not universal presentation.
Cerebellar haemorrhage >3 cm is a neurosurgical emergency - the posterior fossa cannot accommodate swelling; brainstem compression and tonsillar herniation cause rapid deterioration; suboccipital craniectomy can be life-saving.
Foramen ovale = V3 + accessory meningeal artery + lesser petrosal nerve; foramen spinosum = middle meningeal artery - these two foramina are adjacent in the greater sphenoid wing and commonly confused.
Subdural = between dura and arachnoid = bridging vein rupture = crescent-shaped, crosses sutures; Extradural = between skull and dura = middle meningeal artery = biconvex, limited by sutures.
Falx cerebri = vertical fold separating cerebral hemispheres; Tentorium cerebelli = horizontal fold separating cerebrum from cerebellum - the tentorial notch is the critical site for transtentorial herniation in expanding supratentorial masses.
Lower pons = CN VI + VII + VIII - a lesion here produces ipsilateral lateral gaze palsy, complete facial weakness, and deafness; AICA territory stroke is the classic vascular cause.
The scaphoid has a retrograde blood supply from distal to proximal - waist and proximal pole fractures are at highest risk of AVN because they interrupt the sole blood supply to the proximal fragment.
NPH = wet, wobbly, wacky (incontinence, gait disturbance, dementia) - it is a treatable cause of dementia; ventriculomegaly out of proportion to atrophy on imaging is the key radiological finding.
Always assess the brachial artery after elbow dislocation - it lies directly anterior to the joint and is at risk from the displaced coronoid process; absent pulses mandate urgent vascular assessment.
Global aphasia = total language loss (expression + comprehension + repetition) = large left MCA territory infarct - classified as TACI when combined with contralateral motor deficit and visual field defect; this is the most severe stroke subtype.
Radial head fractures primarily impair forearm rotation (pronation/supination) - look for a posterior fat pad sign on the lateral X-ray when the fracture is not immediately visible.
SCM elevates the medial clavicle fragment while gravity and deltoid depress the lateral fragment - this understanding of deforming forces explains the typical displacement pattern of midshaft clavicle fractures.
Common extensor origin = ECRB, EDC, EDM, ECU, anconeus - note that ECRL and brachioradialis originate higher from the supracondylar ridge and are NOT part of the common extensor origin.
Carotid bifurcation is at C3-C4 (upper border of thyroid cartilage) - the ICA has no branches in the neck, distinguishing it from the ECA which has eight named branches.
Battle's sign = mastoid bruising = middle cranial fossa fracture; Raccoon eyes = periorbital bruising = anterior cranial fossa fracture - both are delayed signs appearing 24-48 hours after injury.
The arcuate artery (ascending branch of the anterior circumflex humeral artery) is the critical blood supply to the humeral head - four-part proximal humerus fractures almost invariably lead to AVN.
CSF volume = 150 mL; CSF production = 500 mL/day; turnover = 3-4 times daily; opening pressure = 7-18 cmH2O - CSF production is constant, so obstruction to flow or absorption rapidly causes hydrocephalus.
Tuffier's line (iliac crests) = L3/L4 or L4 body - LP is performed at L3/L4 or L4/L5 to avoid the conus medullaris; always below L2 in adults, below L3 in neonates.
V1 = superior orbital fissure, V2 = foramen rotundum, V3 = foramen ovale - 'Standing Room Only'; trigeminal neuralgia most commonly affects V2 and V3, with carbamazepine as first-line treatment.
CN VII and VIII traverse the petrous temporal bone - petrous fractures can cause facial palsy and hearing loss; longitudinal fractures → conductive loss, transverse fractures → sensorineural loss and facial palsy.
Vestibular schwannoma = 80% of CPA tumours - presents with unilateral sensorineural hearing loss; bilateral tumours = NF2; progressive growth can compress CN VII, V, cerebellum, and brainstem.
Rockwood Grade V = complete AC and CC ligament disruption with >100% clavicle elevation and muscle detachment - Grades IV-VI typically require surgical intervention.
LP needle order = skin → subcutaneous tissue → supraspinous ligament → interspinous ligament → ligamentum flavum → epidural space → dura → arachnoid → subarachnoid space (CSF).
Cavernous sinus lateral wall = CN III, IV, V1, V2; centre = CN VI + internal carotid artery - CN VI is most vulnerable within the sinus; bilateral spread occurs via inter-cavernous connections.
Parinaud syndrome = upward gaze palsy + convergence-retraction nystagmus = dorsal midbrain compression - pineal tumours are the classic cause; they also obstruct the aqueduct causing hydrocephalus.
Dura (outer, tough) → Arachnoid (middle, bridges over sulci) → Pia (inner, follows brain surface) - CSF is between the arachnoid and pia in the subarachnoid space; the leptomeninges (arachnoid + pia) are primarily affected in meningitis.
Nine tendons plus one nerve in the carpal tunnel - the median nerve is most vulnerable to compression because it is the only neural structure in this rigid space.
Weber syndrome = ipsilateral CN III palsy + contralateral hemiplegia = ventral midbrain lesion - the hallmark of brainstem localisation is crossed signs: ipsilateral cranial nerve deficit with contralateral long tract signs.
Jugular foramen = CN IX, X, XI; Hypoglossal canal = CN XII - combined palsies of these four nerves indicate a lesion at the skull base between the jugular foramen and hypoglossal canal; the uvula deviates away from the vagus nerve lesion.
Physiology
80 high-yield facts
Standing → blood pools in legs → reduced venous return → baroreceptor-mediated sympathetic response (↑HR, ↑vasoconstriction) - orthostatic hypotension (≥20/10 mmHg drop) indicates failure of this reflex; common causes include medications, hypovolaemia, and autonomic neuropathy.
Aortic stenosis symptom triad and survival: Angina (5 years), Syncope (3 years), Heart failure (2 years) - once symptomatic, urgent valve replacement is needed; severe AS = valve area <1.0 cm², mean gradient >40 mmHg.
SA node = unstable resting potential + slow diastolic depolarisation (If current) + calcium-dependent upstroke - this is the basis of cardiac automaticity; ivabradine blocks If to slow heart rate without reducing contractility.
Ca²⁺ binds troponin C → tropomyosin shifts → actin-myosin binding sites exposed → cross-bridge cycling → contraction; Ca²⁺ comes from the SR via ryanodine receptors; relaxation requires Ca²⁺ re-uptake by SERCA; the process requires ATP for both contraction AND relaxation.
Type I = Slow, Red, Oxidative, Fatigue-resistant (postural muscles); Type II = Fast, White, Glycolytic, Fatigable (power movements) - myoglobin gives Type I fibres their red colour and aids oxygen delivery for aerobic metabolism.
DKA = high serum K+ but low total body K+ - acidosis pushes K+ out of cells, insulin deficiency prevents K+ from entering cells; when insulin is given, K+ drops rapidly - always replace K+ during DKA treatment.
Insulin + dextrose for hyperkalaemia = transcellular shift via Na+/K+-ATPase stimulation - reduces K+ by 0.5-1.0 mmol/L for 4-6 hours; always give with calcium gluconate first for cardioprotection if ECG changes are present.
Spinal shock = temporary reflex loss below injury (flaccid, areflexic); neurogenic shock = loss of sympathetic tone → hypotension + bradycardia + warm peripheries (above T6 injuries) - they are different conditions; always exclude haemorrhage before diagnosing neurogenic shock.
CPR generates 25-33% of normal cardiac output - maximise quality with rate 100-120/min, depth 5-6 cm, full recoil, minimal interruptions; coronary perfusion pressure >15 mmHg during CPR predicts ROSC.
Pharmacology
80 high-yield facts
DOACs have minimal dietary interactions (no vitamin K restrictions); warfarin is significantly affected by vitamin K intake (green leafy vegetables); rivaroxaban should be taken WITH food (improves absorption); dabigatran capsules are moisture-sensitive (keep in blister pack); consistency is key for warfarin - patients should maintain STABLE vitamin K intake, not eliminate it.
Protamine reversal of heparin in cardiac surgery - 1 mg per 100 units residual heparin; monitor with ACT; give slowly (max 5 mg/min); adverse effects: hypotension, bradycardia, anaphylaxis, pulmonary hypertension; caution in fish allergy; excess protamine can itself cause anticoagulation; heparin t½ ~1-2h (factor into dose calculation).
Apixaban (and rivaroxaban, edoxaban) = direct factor Xa inhibitors; dabigatran = direct thrombin (IIa) inhibitor; DOACs do NOT require antithrombin as cofactor; rapid onset (2-4h); no routine monitoring; reversal: andexanet alfa for Xa inhibitors, idarucizumab for dabigatran; PCC can be used off-label if specific reversal agents unavailable.
Doxazosin = alpha-1 blocker → vasodilation → reduced BP; first-dose hypotension is the main risk; used for resistant HTN (step 4 if K⁺ >4.5 or spironolactone contraindicated) and BPH; tamsulosin = more prostate-selective alpha-1A blocker.
Salbutamol = β2 agonist → bronchodilation via cAMP increase - side effects include tremor, tachycardia, hypokalaemia, and hyperglycaemia; monitor potassium when giving repeated nebulisers per BTS/SIGN/NICE NG245.
Infliximab = chimeric anti-TNF-alpha monoclonal antibody - screen for TB and hepatitis B before starting; concurrent immunomodulator reduces anti-drug antibody formation; infusion reactions are common but manageable.
Levetiracetam binds SV2A → modulates neurotransmitter release - unique mechanism; minimal drug interactions (renal excretion); no TDM needed; low teratogenicity; behavioural side effects (irritability) are the main concern.
LMWH vs UFH - LMWH: predominantly anti-Xa, predictable PK (weight-based SC dosing), longer t½ (4-6h), lower HIT risk, partially reversed by protamine (~60-80%); UFH: equal anti-Xa/anti-IIa, unpredictable PK (needs APTT monitoring), shorter t½ (1-2h), higher HIT risk, fully reversed by protamine (100%); UFH preferred when rapid reversal may be needed.
Microbiology
80 high-yield facts
Green pigment + fruity smell + oxidase-positive + Gram-negative rod = Pseudomonas aeruginosa - intrinsically resistant to many antibiotics; anti-pseudomonal agents: Tazocin, ceftazidime, meropenem, ciprofloxacin; major pathogen in burns, ICU, CF; WHO critical priority pathogen.
Chickenpox infectious from 1-2 days PRE-rash until ALL crusted - highly contagious (>90% attack rate); VZIG for high-risk non-immune contacts within 10 days; congenital varicella syndrome if <20 weeks; neonatal varicella if maternal infection around delivery; healthcare workers must stay off until crusted.
Hypnozoites = dormant liver stages of P. vivax/P. ovale causing relapse; radical cure requires primaquine or tafenoquine; MUST check G6PD first (risk of haemolysis); chloroquine alone treats blood stages only.
GBS (S. agalactiae) = Group B, beta-haemolytic - colonises 20-30% of women; causes neonatal sepsis, pneumonia, meningitis; give IV benzylpenicillin IAP in labour; risk factors: preterm, prolonged ROM, maternal fever; UK uses risk-factor-based approach, US screens all at 35-37 weeks.
Oral thrush = white scrapable plaques (Candida albicans); risk: antibiotics + steroids + HIV + diabetes; dimorphic fungus (yeast → hyphae = virulence); treat: nystatin/miconazole topical or fluconazole systemic; non-scrapable = leukoplakia not thrush.
Antibiotics within 1 hour of sepsis recognition (SSC Hour-1 Bundle); blood cultures before antibiotics but don't delay treatment; each hour delay increases mortality ~4-7%; bundle: lactate + cultures + antibiotics + fluids (30 mL/kg) + vasopressors; noradrenaline first-line vasopressor.
Proteus mirabilis = urease-positive → urine alkalinisation → struvite (staghorn) stones → catheter encrustation; swarming motility on agar; non-lactose-fermenter; common in catheter-associated UTI; often nitrofurantoin-resistant.
ESBL = extended-spectrum beta-lactamase (CTX-M most common); hydrolyses 3rd-gen cephalosporins + monobactams; inhibited by clavulanic acid; carbapenems NOT affected; treat serious infections with carbapenems; plasmid-mediated → horizontal transfer; MERINO trial: meropenem > pip-tazo for bacteraemia.
Evidence-Based Medicine
80 high-yield facts
Clinical equipoise = genuine uncertainty about treatment superiority; ethical justification for randomisation; without equipoise, randomisation would be unethical (knowingly assigning patients to inferior treatment); equipoise can be disturbed during a trial (interim analysis → DSMB may stop trial); equipoise is a COMMUNITY-level concept (individual clinicians may have preferences, but the community is uncertain); this is why placebos require careful ethical justification (is withholding active treatment ethical?).
NNT = 1/ARR; ARR = CER - EER; low NNT = more effective; NNT of 1 = perfect (everyone benefits); NNT must be interpreted with NNH (harms) and clinical context; NNH = 1/ARI; relative risk reduction (RRR) can exaggerate small absolute differences - always ask for absolute numbers; example: RRR of 25% sounds impressive, but if mortality drops from 4% to 3%, ARR is only 1% (NNT = 100).
Asymmetrical funnel plot = suggests publication bias - small negative studies are 'missing'; use Egger's test for statistical assessment; consider trim-and-fill analysis to estimate the impact on pooled results.
Multi-arm trial = multiple treatments compared simultaneously with shared control - more efficient than multiple two-arm trials; factorial designs can test interactions; platform trials allow adaptive arms (RECOVERY trial is a prime example).
ITT = analyse as randomised - preserves randomisation benefits; conservative estimate (dilutes towards null); preferred for superiority trials; per-protocol analysis may overestimate treatment effects but is preferred for non-inferiority trials.
NNH = 1/ARI; ARI = treatment adverse event rate - control adverse event rate; NNH complements NNT for benefit-harm assessment; ideal: low NNT + high NNH; compare the RATIO of NNT to NNH; also consider the severity of the benefit vs the severity of the harm; example: NNT 100 (prevent 1 death) vs NNH 500 (1 rash) = acceptable; NNT 100 (prevent 1 headache) vs NNH 10 (1 GI bleed) = not acceptable.
ROC curve = sensitivity vs (1-specificity) at all thresholds; AUC ranges 0.5 (chance) to 1.0 (perfect); 0.5 = useless, 0.7-0.8 = acceptable, 0.8-0.9 = excellent, >0.9 = outstanding; higher AUC = better discrimination; useful for comparing diagnostic tests; optimal threshold = closest to top-left corner of ROC curve; AUC is independent of prevalence; widely used in emergency medicine (e.g., HEART score AUC for MACE prediction).
Pathology
80 high-yield facts
TGF-β = most important fibrogenic cytokine; stimulates collagen synthesis + fibroblast proliferation + ECM deposition; inhibits MMPs (prevents ECM breakdown); excess → pathological fibrosis (keloids, cirrhosis, pulmonary fibrosis); TGF-β3 may promote scarless healing; also immunosuppressive.
Splenic sequestration = rapid blood pooling in spleen → acute enlargement + severe anaemia + hypovolaemia + HIGH reticulocytes (vs aplastic = LOW reticulocytes); HbSS in children <5, HbSC/S-β-thal in adults; URGENT transfusion → can be fatal; recurrent → splenectomy; parents taught to palpate spleen.
Auer rods = pathognomonic of AML (NEVER in ALL); crystallised azurophilic granules (MPO); faggot cells (bundles of Auer rods) = APL/AML-M3; APL: t(15;17)/PML-RARA + DIC + curable with ATRA + ATO (>90%); start ATRA immediately if APL suspected.
CO = HR × SV - stroke volume depends on preload, afterload, and contractility; in cardiogenic shock, target each component: fluids (preload), vasodilators/IABP (afterload), inotropes (contractility).
Winter's formula (expected PaCO₂ = 1.5 × HCO₃⁻ + 8 ±2 mmHg) checks if respiratory compensation in metabolic acidosis is appropriate; PaCO₂ lower than expected = additional respiratory alkalosis; PaCO₂ higher than expected = additional respiratory acidosis; only valid for metabolic acidosis.
Inferior = II, III, aVF; Anterior = V1-V4; Lateral = I, aVL, V5-V6; always check V4R in inferior STEMIs for RV involvement; ST elevation in aVR with diffuse ST depression suggests left main stem occlusion.
Key nephrotoxic drugs in ED: NSAIDs (prostaglandin inhibition → reduced renal perfusion), aminoglycosides (tubular toxicity), ACEi/ARBs (efferent dilation), contrast, metformin (accumulates → lactic acidosis); always review medications in AKI; NICE recommends stopping nephrotoxins as part of the AKI bundle.
Severe pancreatitis causes multi-organ failure via SIRS/cytokine storm - not direct enzyme toxicity; early organ failure is inflammatory (SIRS), late organ failure is often septic (infected necrosis); ARDS is the most common cause of death in early severe pancreatitis.
Tiered ICP management - start with basics (30° head up, sedation, normothermia, normocapnia) → CSF drainage + osmotherapy → moderate hyperventilation + deeper sedation → rescue (craniectomy, barbiturate coma, hypothermia); always address systemic factors first (hypoxia, hypotension); escalate sequentially; each tier has increasing risks.
ADH from posterior pituitary acts on V2 receptors → aquaporin-2 insertion → water reabsorption - cranial DI responds to desmopressin, nephrogenic DI does not; the water deprivation test differentiates the two.
Parietal cells produce HCl (via H⁺/K⁺-ATPase) and intrinsic factor - stimulated by ACh (vagus), histamine (ECL cells), and gastrin (G cells); PPIs block the final common pathway of acid secretion.
GABA = main brain inhibitory neurotransmitter; GABA-A = Cl⁻ channel (benzodiazepines increase frequency, barbiturates increase duration of opening); glutamate = main excitatory - the balance between GABA and glutamate determines neuronal excitability.
ATLS haemorrhage classification - Class I (<15%), II (15-30%), III (30-40%), IV (>40%) - Class III is the first class with hypotension and typically requires blood transfusion.
Troponin rises at 3-6 hours, peaks at 12-24 hours, elevated for 7-14 days - hs-troponin enables earlier detection; CK-MB is preferred for detecting reinfarction due to its shorter elevation window (48-72 hours).
Gut bacteria produce ammonia from dietary protein → liver converts it to urea (urea cycle) → kidney excretes urea - in liver failure, ammonia accumulates causing encephalopathy; lactulose and rifaximin reduce gut ammonia production/absorption.
A-a gradient = PAO₂ - PaO₂; normal <2 kPa; widened = V/Q mismatch, shunt, or diffusion impairment; normal A-a gradient with hypoxaemia = hypoventilation or low FiO₂; use the alveolar gas equation to calculate PAO₂.
the layers and their products. Phaeochromocytomas follow the 'rule of 10s': 10% bilateral, 10% extra-adrenal (paragangliomas), 10% malignant, 10% familial.
ITP = autoimmune platelet destruction (anti-GPIIb/IIIa antibodies) → isolated thrombocytopaenia with normal PT/APTT; diagnosis of exclusion; treat with steroids ± IVIg; platelet transfusion is generally ineffective (transfused platelets are rapidly destroyed) unless life-threatening bleeding.
Exercise in heat = competing demands for blood flow (muscle vs skin) + fluid loss from sweating → cardiovascular strain - heat stroke = core temp >40°C + CNS dysfunction; treat with immediate cold water immersion; stopped sweating is a danger sign.
Turner syndrome = 45,X - ovarian failure (hypergonadotrophic hypogonadism) + short stature + autoimmune thyroid disease risk; always screen for coarctation of the aorta and bicuspid aortic valve; treatment includes GH and oestrogen replacement.
Thiazides cause hyponatraemia more than loop diuretics because they preserve the medullary concentration gradient - sodium is lost (DCT) but water is still reabsorbed (collecting duct via ADH); elderly women are at highest risk.
Excitotoxicity = excessive glutamate → NMDA receptor over-activation → Ca²⁺ overload → neuronal death - this is the key mechanism of ischaemic brain injury; the penumbra is salvageable tissue at risk; 'time is brain' reflects the urgency of reperfusion.
Cranial DI = ADH deficiency → responds to desmopressin; nephrogenic DI = ADH resistance → does NOT respond to desmopressin; the desmopressin challenge test differentiates between the two.
Orthostatic hypotension = venous pooling → reduced venous return → reduced cardiac output → defined as systolic drop ≥20 mmHg or diastolic drop ≥10 mmHg on standing; commonly due to hypovolaemia or impaired baroreceptor reflex.
Post-thyroidectomy hypocalcaemia = parathyroid gland damage - treat urgently with IV calcium gluconate; test for Chvostek's and Trousseau's signs; monitor ECG for QT prolongation.
SCD in young athletes: HCM (most common), ARVC, coronary anomalies, channelopathies (long QT, Brugada, CPVT), and myocarditis; ECG screening can identify at-risk individuals; all athletes with cardiac arrest need AED and CPR; family screening is essential after SCD in a young person.
Exercise cardiovascular response: ↑HR + ↑SV + ↑CO (up to 5-fold) + ↑systolic BP + stable/↓diastolic BP + ↓SVR; Frank-Starling mechanism increases SV; blood redistributed to working muscles; coronary stenosis causes supply-demand mismatch during exercise → angina.
Pneumothorax creates low V/Q (shunt) in the collapsed lung → hypoxaemia; hypoxic pulmonary vasoconstriction partially compensates by diverting blood to the ventilated lung; PE creates the opposite pattern - high V/Q (dead space).
Beta cells = insulin (anabolic); alpha cells = glucagon (catabolic) - beta cells are the majority in islets (~60-80%); pancreatic cancer destroying islets causes new-onset diabetes (a red flag in >50-year-olds with weight loss).
Frank-Starling law = ↑preload → ↑stroke volume (up to a limit) - the intrinsic autoregulation of cardiac output; in heart failure, the curve is depressed; excessive preload in failure worsens congestion without improving output.
Insulin = anabolic (builds up) - glucose uptake, glycogenesis, lipogenesis, protein synthesis; Glucagon = catabolic (breaks down) - glycogenolysis, gluconeogenesis, lipolysis, ketogenesis; the insulin/glucagon ratio determines metabolic direction.
Cortisol's stress response = glucose mobilisation + anti-inflammatory + vascular tone maintenance - patients on chronic steroids need stress-dose hydrocortisone during illness; the diurnal cortisol pattern peaks in the morning.
Emergency dialysis indications = AEIOU: Acidosis, Electrolytes (refractory K⁺), Intoxication, Overload, Uraemia - dialysis is indicated when medical management fails or the patient is anuric with life-threatening complications.
Central DI after head injury = hypothalamic/posterior pituitary damage → no ADH → dilute polyuria + hypernatraemia; treat with desmopressin (DDAVP) + free water; monitor Na⁺ closely (avoid rapid correction); may be part of the triphasic response; distinguish from nephrogenic DI (kidneys don't respond to ADH - treat with thiazides paradoxically).
RCA supplies the SA node (60%) and AV node (90%) - inferior MI from RCA occlusion causes bradycardia and heart block; atropine is the first-line treatment.
Spinothalamic tract = pain + temperature (crosses within 1-2 spinal segments); dorsal columns = fine touch + vibration + proprioception (crosses in medulla) - Brown-Séquard syndrome demonstrates this dissociation.
Acute post-MI VSD = left-to-right shunt → pulmonary overcirculation → biventricular volume overload → cardiogenic shock - requires urgent surgical repair with a high mortality rate.
Ischaemia → ATP depletion → Na⁺/K⁺-ATPase failure → loss of ionic gradients + cytotoxic oedema + excitotoxicity + calcium overload - DWI-MRI detects cytotoxic oedema (restricted diffusion) within minutes; CT is often normal early.
UGT1A1 conjugates bilirubin with glucuronic acid - deficiency causes unconjugated hyperbilirubinaemia (Gilbert, Crigler-Najjar); conjugated bilirubin is water-soluble and appears in urine when elevated.
Euglycaemic DKA = ketoacidosis with normal/near-normal glucose - suspect in any unwell patient on SGLT2 inhibitors; SGLT2i cause glycosuria that masks the hyperglycaemia; check ketones in any unwell diabetic regardless of glucose; sick day rules: withhold SGLT2i during acute illness; treatment = insulin + dextrose from the start.
FENa <1% = pre-renal AKI (tubules working, reabsorbing sodium avidly); FENa >2% = intrinsic renal AKI (tubular damage, sodium wasting) - use FEUrea (<35%) instead if the patient is on diuretics.
Hypernatraemia + concentrated urine = inadequate water intake (kidneys working properly); hypernatraemia + dilute urine = diabetes insipidus (renal water loss); correct hypernatraemia slowly (≤10-12 mmol/L/24h) to avoid cerebral oedema; free water deficit = 0.6 × weight × [(Na/140) - 1].
Ethanol = progressive CNS depression (disinhibition → ataxia → stupor → coma → death); enhances GABA and inhibits NMDA; withdrawal causes the opposite (excitotoxicity → seizures → DTs) due to receptor adaptation.
Cortisol = zona fasciculata + synthesised from cholesterol + not stored + regulated by ACTH - 21-hydroxylase deficiency is the commonest cause of congenital adrenal hyperplasia; cortisol production increases up to 10-fold during critical illness.
FRC = ERV + RV = the oxygen reservoir during apnoea - reduced in obesity, pregnancy, and supine position, explaining shorter safe apnoea times in these patients; pre-oxygenation fills this reservoir with oxygen.
Lactate >4 mmol/L in shock = inadequate tissue oxygenation - serial lactate measurement guides resuscitation; a falling lactate indicates improving tissue perfusion and is associated with better outcomes.
Aβ fibres = large, myelinated, fast → fine touch and vibration; Aδ fibres = thinly myelinated → fast/sharp pain; C fibres = unmyelinated, slow → dull/burning pain; large fibres are compressed first but blocked last by local anaesthetics.
Factor V Leiden = most common inherited thrombophilia (~5% of Caucasians) - APC resistance → factor Va persists → excessive thrombin generation; heterozygous = 5-7× VTE risk; prothrombin G20210A is the second most common; antithrombin III deficiency is rarest but most thrombogenic.
Cholera toxin → increased cAMP → CFTR chloride secretion → massive secretory diarrhoea - but glucose-coupled sodium absorption (SGLT1) is preserved, making ORS effective; this is why ORS is one of the greatest medical advances.
Afterload ≈ SVR - in acute pulmonary oedema with hypertension, reducing afterload (vasodilators) is a key treatment; GTN primarily reduces preload but at higher doses also reduces afterload.
In heart failure, the Starling curve is flattened and shifted right - excessive preload reduces cardiac output; diuretics and vasodilators improve function by reducing preload toward the optimal point on the curve.
Baroreceptors in the carotid sinus (CN IX) and aortic arch (CN X) - they reset in chronic hypertension; carotid sinus massage activates this reflex therapeutically in SVT.
Synchronise to the R wave to avoid the vulnerable T-wave period - a shock on the T wave can trigger VF (R-on-T phenomenon); never synchronise in VF or pulseless VT (use unsynchronised defibrillation).
SA node → AV node (delay = PR interval) → His bundle → bundle branches (right, left anterior and posterior fascicles) → Purkinje fibres - conduction velocity is fastest in Purkinje fibres and slowest at the AV node.
dP/dt (rate of rise of aortic pressure) drives dissection propagation - beta-blockers are first-line to reduce both HR and dP/dt; never give vasodilators without prior beta-blockade due to reflex tachycardia risk.
V/Q mismatch is the main cause of hypoxaemia in PE - blood redistributes from blocked vessels to remaining lung, creating low V/Q units; if hypoxaemia persists despite high-flow oxygen, suspect right-to-left shunt through a PFO.
Brugada = SCN5A loss-of-function (sodium channel) → coved ST elevation in V1-V3; unmasked by fever, sodium channel blockers; predominantly male; ICD is definitive treatment; aggressively treat fever in known Brugada patients.
RAAS in haemorrhage → angiotensin II (vasoconstriction) + aldosterone (Na+/H₂O retention) + ADH (water retention) - patients on ACE inhibitors/ARBs have impaired compensatory responses and may develop more severe hypotension during haemorrhage.
EF = (EDV - ESV) / EDV × 100 = SV/EDV × 100; normal 55-70%; <40% = HFrEF; <35% = consider ICD; EF does not measure diastolic function - patients can have heart failure with normal EF (HFpEF).
TTM reduces CMRO₂ by 6-8% per °C - limiting excitotoxicity, free radicals, and apoptosis; maintain 32-36°C for at least 24 hours; at minimum, actively prevent fever (>37.5°C) in all post-cardiac arrest patients.
WPW = accessory pathway (Bundle of Kent) → short PR + delta wave; NEVER give AV node blockers (adenosine, verapamil, digoxin) in AF with WPW - this can cause VF; procainamide or DC cardioversion are safe alternatives.
Bezold-Jarisch reflex = vagal-mediated bradycardia in inferior STEMI - usually responds to atropine and is transient; AV block in inferior STEMI is nodal (good prognosis) vs anterior STEMI is infranodal (poor prognosis, needs pacing).
Tension pneumothorax = obstructive shock from reduced venous return due to elevated intrathoracic pressure; clinical diagnosis → immediate needle decompression; JVP elevation differentiates from hypovolaemic shock.
RA collapses first in tamponade because it has the lowest pressure - RA collapse is the most sensitive sign; RV diastolic collapse is more specific; emergency pericardiocentesis is definitive; IV fluids provide temporary haemodynamic support.
COCP increases VTE risk by increasing procoagulant factors (VII, VIII, X, fibrinogen) and decreasing natural anticoagulants (protein S, antithrombin) - the oestrogen component is responsible; risk is highest in the first year and with third/fourth-generation progestogens.
DKA = high serum K⁺ but depleted total body K⁺ - acidosis + insulin deficiency shift K⁺ extracellularly while osmotic diuresis depletes total K⁺; NEVER give insulin if K⁺ <3.5 (replace K⁺ first); once insulin starts, K⁺ will fall rapidly; this is one of the most dangerous phases of DKA treatment.
Crush syndrome = reperfusion injury releasing K⁺, myoglobin, phosphate, urate → hyperkalaemia (cardiac arrest), AKI, metabolic acidosis; start IV fluids BEFORE extrication; have calcium gluconate ready; alkalinise urine with bicarbonate; target UO 200-300 mL/h; the moment of extrication is the most dangerous.
ODS = demyelination from too-rapid correction of hyponatraemia - safe rate: ≤10-12 mmol/L in 24 hours; symptoms appear 2-6 days after correction (dysarthria, dysphagia, quadriparesis, locked-in syndrome); risk factors: chronic hyponatraemia, liver disease, alcohol, malnutrition; if overcorrected, consider re-lowering sodium with desmopressin and D5W.
DKA with K⁺ <3.5 mmol/L = DO NOT start insulin until K⁺ is replaced - insulin drives K⁺ intracellularly; give KCl 40 mmol/L in fluids; recheck K⁺ hourly; hypokalaemia during DKA treatment is the most dangerous electrolyte derangement; JBDS guidelines are the UK standard for DKA management.
CKD acidosis = reduced ammonium production + reduced bicarbonate regeneration → daily acid retention; early CKD = normal AG acidosis, late CKD = high AG acidosis; treat with oral sodium bicarbonate (target HCO₃⁻ >22 mmol/L); chronic acidosis causes muscle wasting and bone disease and accelerates CKD.
Salicylate poisoning = respiratory alkalosis (direct respiratory centre stimulation) + metabolic acidosis (uncoupled oxidative phosphorylation) - the pH may look deceptively normal; DO NOT intubate unless absolutely necessary (removing hyperventilation worsens acidosis); urinary alkalinisation with IV sodium bicarbonate enhances salicylate excretion; haemodialysis for severe poisoning.
Lactate in sepsis = tissue hypoperfusion marker + prognostic indicator; lactate >4 mmol/L = high mortality; serial measurements guide resuscitation; aim for >10% clearance per hour; persistent elevation suggests inadequate resuscitation or hepatic dysfunction; lactate is more useful than central venous oxygen saturation as a resuscitation target.
Normal anion gap metabolic acidosis (NAGMA) + hypokalaemia = diarrhoea or RTA; use urine anion gap to differentiate: negative UAG = GI loss (diarrhoea), positive UAG = renal cause (RTA); type 4 RTA causes hyperKALAEMIA (not hypokalaemia) - associated with hypoaldosteronism.
Paracetamol overdose = NAPQI depletion of glutathione → hepatotoxicity - NAC replenishes glutathione; use the single 100 mg/L treatment line at 4 hours per MHRA 2012/RCEM guidance; most effective within 8 hours of ingestion (RCEM Best Practice Guideline; MHRA/CHM 2012; TOXBASE).
Fidaxomicin = narrow-spectrum anti-C. difficile → preserves normal flora → lower recurrence (~13% vs ~27% with vancomycin); inhibits RNA polymerase and spore formation; NICE first-line alongside vancomycin; FMT is most effective for recurrent CDI.
Adenosine = A₁ receptor → K⁺ channel opening → AV nodal block; ultra-short half-life (~10-15 seconds) - must give as rapid bolus + flush; dose: 6 → 12 → 12 mg; CONTRAINDICATED in asthma (bronchospasm); use verapamil instead in asthma.
Ciclosporin = calcineurin inhibitor → blocks IL-2 → T-cell suppression; major toxicity = nephrotoxicity - monitor levels (narrow therapeutic index), renal function, and blood pressure; numerous CYP3A4 drug interactions.
Rate control of AF = IV beta-blocker or diltiazem first-line - avoid beta-blockers in severe asthma (use diltiazem); avoid diltiazem + beta-blocker combination; digoxin is second-line due to slow onset.
NSAID gastroprotection = PPI for high-risk patients (age >65, ulcer history, concurrent anticoagulants/steroids/SSRIs) - NICE recommends co-prescription; use lowest NSAID dose for shortest duration.
Triple whammy = ACEi/ARB + diuretic + NSAID → 30× increased AKI risk - each drug impairs renal perfusion through a different mechanism; implement sick day rules during acute illness; substitute paracetamol for NSAIDs in at-risk patients.
Fentanyl and buprenorphine are safest in renal failure (inactive metabolites); morphine → M6G accumulation (dangerous); pethidine → norpethidine accumulation (seizures, CONTRAINDICATED); always reduce doses and extend intervals in renal impairment.
Naloxone wears off (30-90 min) before most opioids - monitor for re-sedation for ≥2 hours (longer for long-acting opioids); consider naloxone infusion for sustained reversal; methadone overdose may need monitoring for 24+ hours.
Mechanical aortic valve = INR 2.0-3.0; mechanical mitral valve = INR 2.5-3.5; lifelong warfarin required; DOACs are CONTRAINDICATED for mechanical valves (RE-ALIGN trial stopped); bioprosthetic valves = anticoagulation for 3 months then aspirin.
Massive PE treatment escalation - systemic thrombolysis (first-line) → catheter-directed therapy (CDT - lower bleeding risk, local delivery) → surgical embolectomy (if catheter fails or unavailable) → VA-ECMO (bridge); PERT teams coordinate care; CDT uses lower tPA doses (10-20 mg vs 100 mg systemic); mechanical thrombectomy devices avoid thrombolytic risk entirely; decision depends on local expertise and availability.
Theophylline = PDE inhibitor + adenosine antagonist → bronchodilation; narrow therapeutic index (10-20 mg/L); toxicity causes seizures and arrhythmias; CYP1A2 metabolised (levels increased by ciprofloxacin/erythromycin, decreased by smoking).
Montelukast = leukotriene receptor antagonist (CysLT1) - useful in exercise-induced asthma and AERD; oral once daily; be aware of neuropsychiatric side effects (agitation, sleep disturbance, depression).
TXA = lysine analogue → blocks plasminogen-fibrin binding → inhibits fibrinolysis → stabilises clots; CRASH-2: TXA within 3 hours of trauma reduces mortality; dose: 1 g IV over 10 min then 1 g over 8h; also used in PPH (WOMAN trial), menorrhagia, dental extractions; contraindicated in active DIC with predominant thrombotic phenotype; also used topically for wound bleeding.
Amiodarone in cardiac arrest: 300 mg after 3rd shock + 150 mg after 5th shock (for refractory VF/pVT); adrenaline 1 mg every 3-5 min (after 3rd shock in shockable, ASAP in non-shockable); post-ROSC = amiodarone 900 mg/24h infusion.
Gabapentin binds α2δ calcium channel subunit → reduces excitatory neurotransmitter release - does NOT act on GABA despite its name; effective for neuropathic pain; renally cleared; now a controlled substance in the UK due to abuse potential.
DAPT = aspirin (COX-1/TXA₂) + P2Y₁₂ inhibitor (ADP pathway) - blocks two platelet activation pathways; ACS/STEMI: aspirin + ticagrelor or prasugrel × 12 months; stable angina post-PCI: aspirin + clopidogrel × 6 months; then aspirin monotherapy; stent thrombosis risk highest in first 30 days; premature DAPT cessation is the strongest risk factor for stent thrombosis.
Severe lithium toxicity → haemodialysis; lithium = MW 7 Da, no protein binding, small Vd - ideal for dialysis; activated charcoal does NOT adsorb lithium; therapeutic range 0.4-1.0 mmol/L; >2.0 = serious toxicity; >4.0 = potentially fatal; rebound after dialysis (tissue redistribution) - may need repeated dialysis; clinical features: tremor, hyperreflexia, seizures, renal failure.
Flumazenil = benzodiazepine competitive antagonist - AVOID in chronic benzodiazepine users (seizure risk), mixed overdoses with TCAs, and epilepsy; mainly used for iatrogenic oversedation reversal; supportive care is usually safer than flumazenil in overdose.
Prilocaine = safest amide LA for Bier's block (lowest systemic toxicity, rapid metabolism) - risk of methaemoglobinaemia at high doses (>600 mg) from metabolite o-toluidine; treat with IV methylene blue.
Ivabradine = selective If (funny current) inhibitor in the SA node → reduces heart rate without affecting contractility or BP; only works in sinus rhythm; used in angina + HFrEF (if HR >70-75 despite beta-blocker); phosphenes are a unique side effect.
topical NSAIDs = effective local analgesia with minimal systemic side effects - NICE NG226 first-line for knee and hand OA; best for superficial joints; ideal for patients with GI, renal or CV risk factors.
Toxin-induced seizures → benzodiazepines FIRST (lorazepam 4 mg IV); avoid phenytoin (worsens TCA cardiotoxicity); second-line: phenobarbital or propofol; treat aggressively - toxicological seizures can be refractory; always check glucose; common seizure-causing toxins: TCAs, tramadol, isoniazid (treat with pyridoxine), organophosphates, theophylline, cocaine.
Spironolactone = aldosterone antagonist at MR → potassium-sparing + anti-fibrotic/anti-remodelling in heart failure; RALES: 30% mortality reduction; side effects: hyperkalaemia + gynaecomastia (anti-androgen); eplerenone = more selective (fewer hormonal side effects).
Dobutamine = predominantly beta-1 agonist → positive inotrope (increased contractility/CO); relatively BP-neutral; used in acute HF with low CO; increases myocardial O₂ demand - use with caution; noradrenaline is first-line vasopressor in cardiogenic shock.
HIT type II = immune-mediated (anti-heparin/PF4 IgG) → platelet activation → thrombocytopenia + PARADOXICAL THROMBOSIS; onset day 5-14; 4T score for risk assessment; STOP all heparin; start alternative anticoagulant (argatroban or fondaparinux); NEVER give platelets (fuel the fire); HIT type I is non-immune, mild, and benign (occurs day 1-2, self-limiting).
Sudden sniffing death syndrome = volatile substance sensitises myocardium to catecholamines → fatal VF triggered by sympathetic surge; can occur on FIRST use; avoid adrenaline in cardiac arrest if volatile substance use suspected; most common cause of death in volatile substance abuse; affects adolescents disproportionately; educate about dangers of 'experimenting' - there is no safe way to inhale solvents.
Beta-blockers reduce myocardial O₂ demand = ↓HR + ↓contractility + ↓BP; first-line for angina; avoid combining with verapamil/diltiazem (amlodipine is safe); decreased HR also increases coronary perfusion time (diastole).
Rivaroxaban = direct factor Xa inhibitor (as are apixaban and edoxaban); dabigatran = direct thrombin inhibitor; reversal: andexanet alfa for Xa inhibitors, idarucizumab for dabigatran; all DOACs need dose adjustment in renal impairment.
Alteplase (tPA) converts plasminogen → plasmin → fibrin degradation (fibrinolysis); fibrin-selective; used for massive PE, acute stroke (<4.5h), and STEMI; main risk = haemorrhagic transformation (~1-2%); tenecteplase = single bolus alternative.
ACE inhibitors block angiotensin I → II conversion → vasodilation + reduced aldosterone + reduced remodelling; also increase bradykinin (→ cough + angioedema); monitor K⁺ and creatinine; switch to ARB for cough; contraindicated in bilateral RAS.
Beta-blockers in HFrEF block chronic catecholamine toxicity → reduce remodelling, arrhythmias, and death; start low, go slow; specific agents: bisoprolol, carvedilol, metoprolol succinate, nebivolol; four pillars: ACEi + BB + MRA + SGLT2i.
Amlodipine = dihydropyridine CCB → blocks L-type Ca²⁺ channels in vascular smooth muscle → vasodilation; verapamil/diltiazem also affect heart (rate-limiting); NICE step 1: ACEi (<55) or CCB (>55/Black); ankle oedema is the main side effect.
Life-threatening warfarin bleeding = IV vitamin K 5 mg + PCC (Beriplex - factors II, VII, IX, X); PCC works in 10-15 min; give vitamin K alongside to prevent INR rebound when PCC wears off; FFP is inferior to PCC.
Sacubitril = neprilysin inhibitor → prevents breakdown of natriuretic peptides (ANP, BNP) → natriuresis + vasodilation; combined with valsartan as ARNI (Entresto); PARADIGM-HF: 20% reduction in CV death vs enalapril; NEVER combine with ACE inhibitors (angioedema risk).
Nitrates → NO → guanylyl cyclase → cGMP → vasodilation (predominantly venodilation = reduced preload); need nitrate-free interval to prevent tolerance; ABSOLUTELY CONTRAINDICATED with PDE5 inhibitors (sildenafil) - fatal hypotension risk.
Lidocaine = Class Ib (Na⁺ channel blocker) - shortens APD, preferentially acts on ischaemic/depolarised tissue (use-dependent); rapid bind/unbind kinetics; used for ventricular (not supraventricular) arrhythmias; CNS toxicity at high levels.
Noradrenaline = predominantly alpha-1 (vasoconstriction) + beta-1 (cardiac) → first-line vasopressor in septic shock (target MAP ≥65); add vasopressin as second agent; adrenaline is second-line vasopressor; adrenaline IM is first-line in anaphylaxis.
Statins = HMG-CoA reductase inhibitors → reduced hepatic cholesterol synthesis → upregulated LDL receptors → lower LDL; myalgia is common; rhabdomyolysis is rare but serious; atorvastatin 80 mg for secondary prevention (NICE).
SGLT2 inhibitors = proximal tubule SGLT2 blockade → glucosuria + natriuresis + multiple cardioprotective effects; benefit HFrEF regardless of diabetes (DAPA-HF); four pillars: ACEi + BB + MRA + SGLT2i; watch for genital candidiasis and euglycaemic DKA.
Fondaparinux = synthetic pentasaccharide → selective anti-Xa via AT-III (no anti-IIa activity); does NOT cause HIT; 2.5 mg SC OD for NSTEMI; renally excreted; NOT reversed by protamine; long half-life (~17-21 hours).
LMWH doesn't cross the placenta (too large) = safe in pregnancy; warfarin crosses freely and is teratogenic (embryopathy weeks 6-12); DOACs contraindicated in pregnancy; exception: mechanical valves may need warfarin (specialist decision).
Aortic dissection - SBP <120 mmHg and HR <60 bpm; beta-blocker FIRST then vasodilator (never vasodilator alone - reflex tachycardia worsens dissection); labetalol/esmolol first-line; Type A = emergency surgery, Type B = medical unless complicated.
Idarucizumab = specific reversal agent for dabigatran (5 g IV, >98% reversal in minutes); andexanet alfa = reverses factor Xa inhibitors; dabigatran is 80% renally excreted - dose reduce/avoid in renal impairment; can be dialysed (low protein binding).
Sequential nephron blockade = loop diuretic + thiazide → blocks Na⁺ reabsorption at two sites → overcomes diuretic resistance; metolazone works even in renal failure; monitor K⁺, Na⁺, Mg²⁺, and renal function closely - can cause profound diuresis and electrolyte derangement.
Unprovoked PE = at least 3 months then consider extended/indefinite anticoagulation (balance recurrence vs bleeding risk); provoked PE = 3 months; cancer-associated = ongoing; reduced-dose DOACs available for extended treatment.
NEVER give AV nodal blockers (adenosine, verapamil, digoxin, beta-blockers) in pre-excited AF (WPW) - forces conduction through the accessory pathway → VF risk; treat with DC cardioversion (unstable) or flecainide/procainamide (stable); definitive = catheter ablation.
Vaughan-Williams: I = Na⁺ (Ia prolong, Ib shorten, Ic no change APD); II = beta-blockers; III = K⁺ (prolong APD/ERP); IV = Ca²⁺ - amiodarone is Class III but has all class properties; adenosine and digoxin don't fit the classification.
H-ISDN = hydralazine (arterial vasodilator - ↓afterload) + ISDN (venous vasodilator - ↓preload) - balanced haemodynamic effect; A-HeFT showed mortality benefit in African Americans with HFrEF; hydralazine can cause drug-induced lupus (anti-histone antibodies).
Vasodilators in severe aortic stenosis = dangerous (fixed CO cannot compensate for reduced preload/afterload → severe hypotension); maintain preload and SVR; symptomatic AS triad: angina, syncope, HF - prognosis is poor without valve replacement.
Naloxone = competitive opioid antagonist - titrate to respiratory rate >12, not full consciousness; shorter acting than most opioids so monitor for re-sedation; may precipitate acute withdrawal in dependent patients.
Codeine is a prodrug activated by CYP2D6 to morphine - poor metabolisers get no effect, ultra-rapid metabolisers risk toxicity; avoid in children <12, breastfeeding mothers, and known CYP2D6 variants.
Paracetamol acts centrally (not peripherally like NSAIDs) - analgesic and antipyretic without anti-inflammatory effect; no GI, renal, or platelet toxicity at therapeutic doses; hepatotoxicity in overdose via NAPQI.
Ketamine = NMDA receptor antagonist → dissociative anaesthesia - preserves airway reflexes and respiratory drive; sympathomimetic; bronchodilator; ideal for procedural sedation and analgesia in the ED.
Phenytoin has saturation (zero-order) kinetics at therapeutic levels - small dose changes cause large concentration changes; nystagmus at >20, ataxia at >30, confusion at >40 mg/L; correct for albumin in hypoalbuminaemia.
Local anaesthetics block intracellular sodium channels - use-dependent and size-dependent (small pain fibres blocked first); work poorly in infected (acidic) tissue because ionised form cannot cross the membrane.
LAST = circumoral tingling → tinnitus → seizures → cardiac arrest - treat with IV lipid emulsion (Intralipid 20%); bupivacaine is the most cardiotoxic LA; always calculate maximum doses before injection.
COX-1 = constitutive (stomach, platelets, kidney); COX-2 = inducible (inflammation) - COX-2 selective inhibitors spare the stomach but increase cardiovascular risk by shifting the prostacyclin/thromboxane balance.
Valproate = highest AED teratogenicity risk (~10% major malformations, 30-40% neurodevelopmental effects) - contraindicated in childbearing women unless Pregnancy Prevention Programme; levetiracetam and lamotrigine are safer alternatives.
TCA cardiotoxicity → QRS >100 ms → IV sodium bicarbonate 8.4% (50-100 mL boluses) - target pH 7.45-7.55; AVOID amiodarone; QRS >100 ms predicts seizures, >160 ms predicts VT/VF.
Adrenaline in LA = vasoconstriction → reduced absorption + prolonged block + reduced bleeding - increases maximum safe dose of lidocaine from 3 to 7 mg/kg; modern evidence supports safe use in digits (WALANT technique).
NSAIDs → COX inhibition → reduced renal prostaglandins → afferent arteriolar constriction → reduced GFR → AKI; the 'triple whammy' (NSAID + ACEi + diuretic) is a dangerous combination; risk is highest in dehydrated, elderly, or CKD patients.
Ketamine emergence phenomena = hallucinations/agitation during recovery - more common in adults (10-30%) than children; reduced by co-administered midazolam (0.03 mg/kg) and a calm recovery environment; not a reason to avoid ketamine - its safety profile still makes it an excellent ED sedation agent.
Ketorolac = potent parenteral NSAID without opioid side effects (no respiratory depression, sedation, or dependence) - but limited to short-term use (≤5 days); contraindicated in renal impairment, GI ulceration, and coagulopathy; excellent opioid-sparing agent.
Lamotrigine = voltage-gated sodium channel blocker → reduced glutamate release - broad-spectrum AED; low teratogenicity (good for women); risk of SJS/TEN reduced by slow titration; valproate doubles lamotrigine levels (halve the dose).
Lidocaine max dose: 3 mg/kg without adrenaline, 7 mg/kg with adrenaline; 1% = 10 mg/mL; always calculate before injecting; bupivacaine max 2 mg/kg (more cardiotoxic, lower maximum); early signs of LAST include circumoral tingling and tinnitus.
Carbamazepine → SIADH-like hyponatraemia (enhanced ADH sensitivity) - occurs in 5-40% of patients; monitor sodium early; elderly patients at highest risk; oxcarbazepine has even higher rates; manage with fluid restriction or drug switch.
Bupivacaine = 'fast-in, slow-out' cardiac sodium channel binding → cumulative blockade → refractory VT/VF - most cardiotoxic LA; treat with lipid emulsion + prolonged CPR; levobupivacaine and ropivacaine are safer alternatives.
IV paracetamol = 100% bioavailability, faster peak levels than oral (60-90% due to first-pass) - use IV when oral route unavailable; for most patients who can swallow, oral is equally effective and much cheaper; rectal absorption is erratic.
Barbiturates increase DURATION of GABA-A Cl- channel opening; benzodiazepines increase FREQUENCY - barbiturates can directly open channels without GABA (no ceiling effect, more dangerous); no specific antidote for barbiturate overdose.
Levobupivacaine = S-enantiomer of bupivacaine → less cardiotoxic, less CNS toxic, same efficacy - preferred over racemic bupivacaine for large-volume regional blocks; ropivacaine is another safer alternative; the R-enantiomer is the 'bad' enantiomer for cardiac safety.
Beta-lactams (penicillins, cephalosporins, carbapenems) inhibit cell wall synthesis via PBP binding → bactericidal; clavulanic acid inhibits beta-lactamase → extends spectrum; beta-lactams are most effective against dividing bacteria.
WHO Critical Priority = carbapenem-resistant Acinetobacter, Pseudomonas, and Enterobacterales; MRSA/VRE = High Priority; S. pneumoniae = Medium; critical because carbapenems are last-resort beta-lactams; limited remaining options: colistin, ceftazidime-avibactam, cefiderocol.
C. difficile spores = sodium hypochlorite (bleach) 1000-5000 ppm for environmental decontamination; alcohol and quaternary ammonium compounds ineffective; soap and water handwashing (not ABHR); contact isolation; restrict 4 Cs antibiotics; HPV for terminal clean.
HSV encephalitis = temporal lobe predilection - start IV aciclovir 10 mg/kg TDS EMPIRICALLY, do NOT wait for PCR results; untreated mortality 70%; even with treatment, significant morbidity; CSF: lymphocytes + raised protein + RBCs; MRI: temporal lobe signal change.
SBP = E. coli and Klebsiella most common - diagnose with ascitic PMN ≥250 cells/mm³; treat with ceftriaxone + IV albumin; if anaerobes isolated, suspect secondary peritonitis (bowel perforation); prophylaxis with norfloxacin; 20-30% 30-day mortality.
Rabies = retrograde axonal transport to CNS → fatal encephalitis (virtually 100% once symptomatic) - incubation varies; PEP is effective (wound washing + RIG + vaccine); hydrophobia is pathognomonic; wash wounds thoroughly immediately after any bite from a potentially rabid animal.
Mucormycosis first-line = liposomal amphotericin B (high-dose 5-10 mg/kg/day); Mucor is RESISTANT to voriconazole and echinocandins; management triad: surgery + amphotericin + correct underlying condition; posaconazole/isavuconazole as alternatives; mortality remains high.
Meningitis + non-blanching petechial rash = Neisseria meningitidis until proven otherwise - Gram-negative diplococcus; give pre-hospital benzylpenicillin; treat with ceftriaxone; notify public health; close contacts need ciprofloxacin prophylaxis.
S. pyogenes = Group A, beta-haemolytic - causes pharyngitis, skin infections, necrotising fasciitis; post-infectious complications: rheumatic fever and PSGN; M protein is the major virulence factor; always penicillin-sensitive; Lancefield grouping classifies streptococci by cell wall carbohydrate.
HUS = MAHA + thrombocytopenia + AKI - usually follows STEC O157:H7 bloody diarrhoea in children; Shiga toxin damages glomerular endothelium; do NOT give antibiotics for STEC (increases toxin release); treatment is supportive; 25% have long-term renal damage.
Uncomplicated lower UTI = nitrofurantoin or trimethoprim for 3 days (NICE first-line) - narrow spectrum to protect microbiome; nitrofurantoin needs eGFR ≥45; trimethoprim can cause hyperkalaemia; save ciprofloxacin for complicated UTI/pyelonephritis.
IVDU endocarditis = TRICUSPID valve + S. aureus - presents with septic pulmonary emboli; modified Duke criteria for diagnosis; treat MSSA with high-dose IV flucloxacillin for 6 weeks; right-sided endocarditis has better prognosis than left-sided.
C. difficile = Gram-positive, spore-forming, obligate anaerobe - spores resist alcohol gel (hand WASHING required), persist on surfaces; toxins A and B cause pseudomembranous colitis; risk factors: antibiotics, elderly, PPIs; treatment: oral vancomycin or fidaxomicin.
Hib = Gram-negative coccobacillus requiring factors X and V - historically caused epiglottitis and meningitis in children; Hib vaccine reduced invasive disease by >99%; now epiglottitis is rare in children and more common in unvaccinated adults; NTHi causes sinusitis/otitis/COPD exacerbations.
Flucloxacillin = beta-lactamase-resistant penicillin for MSSA - narrow-spectrum (good stewardship); superior to vancomycin for MSSA infections; does NOT cover MRSA; risk of cholestatic hepatitis with prolonged courses.
Malignant otitis externa = Pseudomonas + elderly diabetic - starts as severe OE, progresses to skull base osteomyelitis; facial nerve palsy is the earliest cranial nerve sign; granulation tissue in ear canal; treat with prolonged anti-pseudomonal antibiotics (6-8 weeks); can be fatal.
Foul-smelling wound/abscess = think anaerobes → Bacteroides fragilis is the most common anaerobic pathogen; resistant to aminoglycosides and penicillin; treat with metronidazole (gold standard for anaerobes); capsule promotes abscess formation; most important in intra-abdominal infections.
Post-bowel-surgery SSI = polymicrobial (E. coli + Bacteroides + Enterococcus) - needs broad-spectrum cover for aerobes AND anaerobes; source control is essential; prophylaxis with co-amoxiclav at induction; one-third of all SSIs are polymicrobial.
Thick film = sensitive (detects low parasitaemia, RBCs lysed); Thin film = specific (species ID, morphology preserved, parasitaemia %) - both needed; P. falciparum: banana gametocytes, high parasitaemia, cerebral malaria; treat severe malaria with IV artesunate.
Influenza = segmented RNA virus (Orthomyxoviridae) - H (attachment) and N (release); antigenic SHIFT = reassortment → pandemics; antigenic DRIFT = point mutations → seasonal epidemics; treat with oseltamivir within 48 hours; annual vaccine needed due to drift.
Oseltamivir = neuraminidase inhibitor → prevents virion release from infected cells - start within 48 hours; oral; reduces symptoms by ~1 day and complications in high-risk patients; zanamivir is the inhaled alternative; only effective against influenza A and B.
Shingles = VZV reactivation from dorsal root ganglia → dermatomal vesicular rash - treat with aciclovir within 72 hours; complications: PHN, zoster ophthalmicus (V1), Ramsay Hunt (CN VII); Shingrix vaccine for ≥50 years; do NOT cross midline (if bilateral, consider immunosuppression).
Painful genital vesicles/ulcers = HSV-2 (or HSV-1) - latency in sacral ganglia (S2-S4); primary worse than recurrences; asymptomatic shedding is the main transmission route; treat with aciclovir; suppressive therapy for frequent recurrences; neonatal herpes is a medical emergency.
RECOVERY trial: dexamethasone 6 mg × 10 days → reduced mortality in COVID-19 patients requiring O2 or ventilation - NO benefit in non-hypoxic patients (may cause harm); rationale = suppress cytokine storm in severe disease; one of the most impactful COVID-19 treatments.
Hepatitis A = faecal-oral transmission, acute self-limiting, NO chronic state - RNA picornavirus; children often asymptomatic; vaccine available for travellers; post-exposure vaccine within 14 days; fulminant hepatitis rare but more common in elderly and those with pre-existing liver disease.
HEV in pregnancy = 15-25% mortality (especially third trimester) - fulminant hepatic failure; genotypes 1-2 = faecal-oral (developing world), genotypes 3-4 = zoonotic (developed world); genotype 3 can become chronic in immunocompromised; ribavirin for chronic HEV; no widely available vaccine outside China.
Aciclovir = guanosine analogue activated by viral TK → chain termination of viral DNA - selective because only virus-infected cells activate it; effective against HSV and VZV; valaciclovir has better oral absorption; resistance via TK mutation; CMV needs ganciclovir (different TK).
Parvovirus B19 = slapped cheek + lacy rash - only significant ssDNA human virus; infects erythroid precursors via P antigen; aplastic crisis in sickle cell; hydrops fetalis in pregnancy (<20 weeks); child NOT infectious when rash appears; arthropathy in adult women.
HPV 16 and 18 = high-risk → 70% of cervical cancers - E6 degrades p53, E7 inactivates pRb; HPV 6 and 11 = low-risk → genital warts; Gardasil 9 vaccine covers both; UK programme gender-neutral from age 12-13; cervical screening still needed post-vaccination.
Croup = parainfluenza virus (types 1, 3) → subglottic oedema → barking cough + stridor + hoarse voice; worse at night; treat with single-dose dexamethasone (all severities); nebulised adrenaline for moderate-severe; steeple sign on X-ray; usually resolves in 48-72 hours.
Anti-HCV antibody = exposure (not necessarily active infection); HCV RNA PCR = active viraemia confirmation; antibodies persist after clearance; treat with DAAs (>95% cure); SVR12 = cure; 1985 blood transfusion is a recognised risk factor (screening introduced later).
HBV → HCC through: chronic inflammation/cirrhosis + DNA integration (insertional mutagenesis) + HBx protein (transcriptional activation) - unique: HCC can occur without cirrhosis; 6-monthly USS surveillance; HBV vaccination = cancer prevention; second most carcinogenic infection globally.
Ramsay Hunt = VZV in geniculate ganglion → facial palsy + ear vesicles + hearing loss - worse prognosis than Bell's palsy (50-70% recovery vs 85%); treat with aciclovir + prednisolone; eye protection essential; refer ENT and ophthalmology.
Live attenuated vaccines (MMR, BCG, varicella, rotavirus) = stronger immunity but CONTRAINDICATED in immunosuppressed and pregnancy; Inactivated/subunit (hep B, IPV, flu injection, HPV) = safe in immunosuppressed but may need boosters; mRNA vaccines = newest platform (COVID-19).
Zika = Flavivirus, Aedes mosquito + sexual transmission - causes congenital microcephaly; mild illness in adults; defer pregnancy and use condoms after travel to endemic areas; cross-reacts with dengue serology; no specific treatment or vaccine widely available.
Dengue = Aedes mosquito + fever + retro-orbital pain + myalgia + thrombocytopenia - 4 serotypes; secondary infection risk of severe dengue (antibody-dependent enhancement); no specific treatment; avoid NSAIDs; warning signs predict progression to severe disease.
PrEP = TDF/FTC for HIV-negative individuals at risk → >99% effective with consistent use; available on NHS; daily or event-based dosing; monitor renal function and HIV/STI status; does NOT prevent other STIs; cabotegravir injection is a newer option; U=U for partners on ART.
Sofosbuvir = NS5B polymerase inhibitor (nucleotide analogue → chain termination) - pangenotypic backbone of HCV DAA therapy; combined with NS5A inhibitor (velpatasvir) or NS3/4A protease inhibitor; >95% cure rate (SVR12); 8-12 week oral treatment; HCV is now CURABLE.
Classic whooping cough = B.
Severe varicella in immunocompromised → IV aciclovir 10 mg/kg TDS - NOT oral antivirals; varicella pneumonia = bilateral nodular infiltrates; prevent with VZIG in exposed high-risk contacts; varicella vaccine is LIVE → contraindicated in immunocompromised; adult chickenpox is more severe than childhood.
P. falciparum = multiple ring forms + banana gametocytes + high parasitaemia + sequestration via PfEMP1; infects all RBC ages; no hypnozoites but most lethal species; predominates in sub-Saharan Africa.
Pregnancy + uncomplicated P. falciparum: ACT (artemether-lumefantrine) in 2nd/3rd trimester, quinine + clindamycin in 1st trimester; avoid doxycycline, primaquine; placental sequestration via VAR2CSA; IPTp with SP in endemic areas.
Chloroquine inhibits haem → haemozoin polymerisation in parasite digestive vacuole → toxic free haem accumulates; resistance via PfCRT mutations (efflux pump); P. falciparum widely resistant; P. vivax generally still sensitive.
Hypoglycaemia (<2.2 mmol/L) = severe malaria criterion + mortality predictor; correct immediately with IV dextrose; caused by parasite glucose consumption + impaired gluconeogenesis; quinine worsens it (hyperinsulinaemia); artesunate does not cause hyperinsulinaemia.
P. vivax = enlarged RBCs + Schüffner's dots + amoeboid trophozoites + reticulocytes only (Duffy antigen); 48h tertian cycle; hypnozoites → relapse; rare in Duffy-negative West Africans; primaquine for radical cure.
Giardia = pear-shaped flagellated trophozoite with ventral disc + 'face-like' appearance; chronic diarrhoea + bloating + malabsorption; faecal-oral via cysts (10 cysts infectious); duodenum/jejunum; treat with metronidazole; most common parasitic cause of chronic diarrhoea.
Giardiasis first-line = metronidazole 400 mg TDS for 5 days (or tinidazole 2 g single dose); avoid alcohol (disulfiram-like reaction); cure rate 85-95%; treatment failure → longer course or combination therapy; stool antigen test is sensitive diagnostic method.
Giardia cysts resist standard chlorination; low infectious dose (10-100 cysts); survive months in cold water; need filtration + boiling + UV for reliable removal; common waterborne outbreaks; cyst wall = GalNAc polymer.
Stool antigen test (EIA/ICT) = most sensitive routine test for Giardia (85-98%); not operator-dependent; single microscopy only 50-70% sensitive; three stools improve microscopy to 85-90%; PCR is gold standard in reference labs; Giardia does not invade - non-invasive pathogen.
Catheterised candiduria → remove/change catheter first (resolves 40%); usually colonisation not infection; treat if symptomatic/neutropenic/transplant/planned procedure; fluconazole 200-400 mg for 14 days when treatment needed; caspofungin has poor urinary penetration.
Aspergillus = septate hyphae + 45° dichotomous branching; Mucor = pauci-septate + 90° irregular branching; critical distinction for treatment: voriconazole (Aspergillus) vs amphotericin/posaconazole (Mucor); A. fumigatus most common pathogenic species.
Candida species identification guides therapy: C. albicans = fluconazole-sensitive; C. glabrata = dose-dependent/use echinocandin; C. krusei = fluconazole-resistant intrinsically; C. auris = multi-drug resistant; candidaemia: start echinocandin + remove lines + ophthalmology review.
Invasive aspergillosis first-line = voriconazole; inhibits CYP51 (ergosterol synthesis); Herbrecht trial showed superiority over amphotericin; TDM essential (trough 1-5.5); side effects: visual, hepatotoxicity, photosensitivity, CYP450 interactions; fluconazole has NO activity against Aspergillus.
Interdigital tinea pedis = most common pattern; 4th-5th toe web space; maceration + scaling + fissuring; T. rubrum most common organism; moccasin-type = chronic sole scaling; vesiculobullous = inflammatory blisters; topical terbinafine first-line for localised disease.
RVVC = ≥4 episodes in 12 months; fluconazole induction (150 mg × 3 doses) then weekly maintenance for 6 months; 90% C. albicans, 10% non-albicans; exclude diabetes/HIV; C. glabrata → boric acid or nystatin; 50% relapse after stopping maintenance.
Amphotericin B = binds ergosterol → forms membrane pores → ion leakage → cell death; broadest antifungal spectrum; major toxicity: nephrotoxicity + infusion reactions ('shake and bake'); liposomal formulation (AmBisome) = less nephrotoxic; polyene class.
Visceral leishmaniasis = fever + massive splenomegaly + pancytopenia; L. donovani via sandfly; amastigotes (Leishman-Donovan bodies) in macrophages; treat: liposomal amphotericin B or miltefosine; fatal if untreated; kala-azar = 'black fever'.
Thick film = sensitive screening (concentrated); thin film = species ID + parasitaemia %; repeat q12-24h × 3 if negative; urgent test for febrile travellers from endemic areas; RDTs are useful adjuncts; results needed within 2 hours in UK hospitals.
Cutaneous leishmaniasis = painless papule → nodule → ulcer at sandfly bite site; amastigotes in dermal macrophages; L. braziliensis (New World) → risk of mucocutaneous disease (espundia) → must treat systemically; L. major (Old World) → often self-heals; diagnosis: biopsy + PCR.
Co-trimoxazole = first-line treatment AND prophylaxis for PCP; double folate blockade (DHPS + DHFR); high-dose for 21 days (treatment); adjunctive steroids if PaO₂ <9.3 kPa; Pneumocystis lacks ergosterol → azoles/amphotericin ineffective; prophylaxis if CD4 <200 or immunosuppressed.
Sandflies (Phlebotomus - Old World; Lutzomyia - New World) transmit Leishmania; tiny 2-3 mm flies; inject promastigotes → transformed to amastigotes in macrophages; fine-mesh nets needed (smaller than mosquitoes); crepuscular/nocturnal biters; 12 million infected globally.
Autoclave = gold standard sterilisation (134°C/3 min or 121°C/15 min); moist heat > dry heat; kills all organisms including spores; Spaulding: critical = sterilise, semi-critical = HLD, non-critical = clean; sterility assurance level ≤10⁻⁶.
Sterilisation = ALL organisms including spores (SAL ≤10⁻⁶); Disinfection = reduces organisms but spores may survive; HLD for semi-critical items (endoscopes); prions resist standard autoclaving - need NaOH or incineration; Spaulding classification guides processing level.
Transduction = phage-mediated DNA transfer between bacteria; generalised (any gene) vs specialised (adjacent genes); conjugation = pilus/plasmid transfer (most important for AMR spread); transformation = naked DNA uptake; all three enable horizontal gene transfer and resistance spread.
Surgical prophylaxis within 60 minutes of incision (120 min for vancomycin); single dose sufficient (no benefit from prolonged courses); cover likely organisms for site; re-dose if long procedure or major blood loss; NICE: single dose; extending >24h increases C. difficile/resistance risk.
Fluoroquinolones inhibit DNA gyrase (Gram-neg primary target) and topoisomerase IV (Gram-pos target); bactericidal; resistance via gyrA mutations + efflux + PMQR; serious side effects: tendon rupture, QT prolongation, neuropathy, aortic dissection; restricted use (MHRA/FDA).
Norovirus outbreak = cohort isolation + soap and water (NOT alcohol gel) + chlorine-based cleaning (1000-5000 ppm) + staff exclusion 48h post-symptoms + consider ward closure; non-enveloped virus = alcohol-resistant; infectious dose as low as 18 particles; no vaccine or antiviral.
Procalcitonin rises in bacterial infection (LPS + cytokine-induced), stays low in viral (IFN-γ inhibits); <0.25 = likely viral (withhold antibiotics); >0.5 = likely bacterial; guides antibiotic duration (reduced without harm); interpret in context; not a replacement for cultures.
CLABSI = BSI with CVC in situ, not from another source; CoNS (S. epidermidis) most common - biofilm-forming; prevention: central line bundle (hand hygiene, barriers, chlorhexidine, subclavian preferred, daily review); treatment: remove line + antibiotics.
Type I (alpha) = false positive (rejecting a true null hypothesis); Type II (beta) = false negative (accepting a false null hypothesis); Power = 1 - beta - alpha is typically set at 0.05; power is typically set at 0.80.
Regression to the mean = extreme values naturally tend toward the average on remeasurement - a major confounder in before-and-after studies; use interrupted time series or concurrent controls to distinguish true intervention effects from regression to the mean.
or report exposures. Performance bias occurs when the groups receive different care apart from the intervention (related to blinding). Detection bias occurs when outcomes are assessed differently between groups (related to outcome assessor blinding).
P-value = probability of the observed result (or more extreme) IF the null hypothesis is true - it is NOT the probability that the null is true or that the treatment works; statistical significance ≠ clinical significance.
Kaplan-Meier = survival probability over time with censoring - log-rank test compares curves between groups; read median survival from the 50% line; each step = one or more events; handles variable follow-up times.
The evidence hierarchy for therapy = systematic review of RCTs > individual RCTs > cohort > case-control > case series > expert opinion - however, a well-conducted cohort study can be more reliable than a poorly conducted RCT.
Diagnostic test evaluation = cross-sectional study comparing index test vs reference standard - use STARD guidelines for reporting; avoid case-control design which creates spectrum bias; report sensitivity, specificity, PPV, NPV, and likelihood ratios.
Non-inferiority trial = new treatment is not worse than standard by more than delta - per-protocol analysis is preferred (ITT is anti-conservative); watch for bio-creep in sequential non-inferiority trials.
Concealed allocation ≠ blinding - concealment prevents knowledge of FUTURE allocation (pre-randomisation bias); blinding prevents knowledge of CURRENT allocation (post-randomisation bias); both are essential for trial validity.
Prevalence → cross-sectional study; incidence → cohort study - cross-sectional studies provide a snapshot but cannot establish temporality; ensure adequate response rates to minimise non-response bias.
Interrupted time series = multiple data points before and after intervention - stronger than simple before-and-after studies because it accounts for pre-existing trends; commonly used in quality improvement alongside SPC charts.
Prospective cohort = define exposure → follow forward → measure outcomes - can calculate incidence, relative risk, and attributable risk; establishes temporal sequence; expensive and time-consuming but high-quality observational evidence.
Primary outcome = what the study is powered to detect - should be patient-centred, predefined, and singular; secondary outcomes are exploratory and may be underpowered; trial registration prevents outcome switching.
Crossover trial = each patient is their own control - reduces variability, requires fewer patients; BUT needs adequate washout period; NOT suitable for acute conditions, irreversible outcomes, or progressive diseases.
Retrospective cohort = uses existing data, follows exposure → outcome - faster and cheaper than prospective; limited by data quality; direction of inquiry (exposure to outcome) distinguishes it from case-control studies (outcome to exposure).
RRR = ARR / control event rate = (CER - EER) / CER - always interpret alongside the ARR and NNT; RRR can be misleading without baseline risk context; a 50% RRR could mean 10% vs 5% (ARR 5%) or 0.2% vs 0.1% (ARR 0.1%).
Case-control study → odds ratio (not relative risk) - the OR approximates the RR only when the disease is rare (<10% prevalence); OR = (a×d)/(b×c) in a 2×2 table; the OR overestimates the RR when the outcome is common.
Stepped-wedge = all clusters get the intervention, but timing is randomised - useful when denying the intervention long-term is unethical; each cluster serves as its own control; must account for time effects in analysis.
Composite endpoints = more events → more power → smaller trials - BUT always examine individual components; the composite may be driven by the least important component; clinically important components (death) may not be significantly affected.
LR+ = sensitivity / (1 - specificity) - tells you how much a positive result increases disease probability; LR+ >10 = conclusive for ruling in; LR- <0.1 = conclusive for ruling out; independent of prevalence.
GRADE = High/Moderate/Low/Very Low certainty - RCTs start high but can be downgraded (5 reasons); observational studies start low but can be upgraded (3 reasons); GRADE is the standard framework used by Cochrane, WHO, and NICE.
Bland-Altman plot = agreement between two measurement methods - plots difference vs mean; shows bias (mean difference) and limits of agreement (±1.96 SD); correlation ≠ agreement; a high correlation does not mean methods are interchangeable.
DSMB = independent safety monitors - can recommend stopping for harm, benefit, or futility; follow pre-specified stopping rules; maintain independence from investigators and sponsors; essential for any trial with mortality or serious morbidity outcomes.
PDSA = Plan-Do-Study-Act - iterative, small-scale testing of changes; the foundation of quality improvement methodology; multiple cycles refine the intervention; different from research (no control group, no randomisation).
Forest plot = visual summary of meta-analysis - squares = individual study effects (size = weight), horizontal lines = CIs, diamond = pooled estimate; check for consistency between studies and whether the diamond crosses the line of no effect.
Multiple comparisons inflate type I error - 20 tests at alpha 0.05 gives ~64% chance of at least one false positive; correct with Bonferroni (conservative) or FDR methods; best approach is pre-specifying a single primary outcome.
Skewed data → median (IQR); normal data → mean (SD) - the mean is distorted by outliers in skewed distributions; always check the distribution before choosing summary statistics.
3+ groups, continuous normal data → ANOVA; 2 groups → t-test; non-normal data → Kruskal-Wallis (3+ groups) or Mann-Whitney (2 groups); categorical data → chi-squared.
Two categorical variables → chi-squared test; expected cells <5 → Fisher's exact test; ordinal categories → chi-squared for trend - ensure each variable is correctly classified as continuous, categorical, or ordinal before selecting a test.
AUC = overall discrimination ability - 0.5 = coin flip, 1.0 = perfect; it represents the probability that a diseased patient scores higher than a non-diseased patient; compare AUCs to determine which test discriminates better.
Non-significant p-value ≠ no difference - the study may be underpowered; check the CI for clinically important values; to prove equivalence, conduct an equivalence trial; 'absence of evidence is not evidence of absence' (Altman).
Linear regression = continuous predictor → continuous outcome - produces a regression coefficient (change in outcome per unit change in predictor); R² = variance explained; check assumptions: linearity, normality of residuals, homoscedasticity.
Sensitivity-specificity trade-off - lowering the threshold increases sensitivity but decreases specificity; choose threshold based on clinical context: ruling out dangerous conditions = prioritise sensitivity; confirming diagnosis = prioritise specificity.
Independent predictor = significant after adjusting for other variables - reflects the unique contribution of the variable; use clinical knowledge for variable selection; report adjusted OR/HR with CI; be cautious of overfitting (too many variables for the number of events).
Pre-test probability = clinician's disease estimate BEFORE the test - individualised by clinical assessment; modified by likelihood ratios to produce post-test probability; the same test result means different things in different clinical contexts.
Paired t-test = same subjects measured twice (before/after) - assumes normally distributed differences; non-parametric equivalent = Wilcoxon signed-rank test; more powerful than independent t-test because each subject is their own control.
A CI crossing the null value (0 for differences, 1 for ratios) = not statistically significant - but always examine whether the CI includes clinically important values; a non-significant result whose CI includes important effects suggests an underpowered study, not proof of no effect.
SD = variability of individual observations; SEM = precision of the mean (SEM = SD/√n) - SD is used for descriptive statistics; SEM is used for inferential statistics; beware of graphs using SEM bars, which look narrower but don't reflect individual variability.
Post-test odds = pre-test odds × LR - use Fagan's nomogram for quick bedside calculation; LR- of 0.05 is excellent for ruling out (drops 50% pre-test probability to ~5%); LR+ of 20 is excellent for ruling in.
Incidence rate = new cases / person-time at risk - accounts for variable follow-up; different from incidence proportion (cumulative incidence = new cases / population at risk); different from prevalence (existing cases / population at a point in time).
Shapiro-Wilk = test of normality - also use visual methods (histogram, Q-Q plot); formal tests are sensitive in large samples and insensitive in small ones; central limit theorem means parametric tests are robust when n > 30.
Always decompose composite endpoints into individual components - a significant composite can be misleading if driven by the least important component; check that all components move in the same direction and have similar clinical importance.
10 events per variable is the minimum EPV for logistic regression - 80 events with 10 predictors (EPV = 8) risks overfitting; use penalised regression, variable reduction, or internal validation (bootstrapping) when EPV is low.
Discrimination = can the model separate outcomes? (c-statistic/AUC); Calibration = do predicted probabilities match observed rates?
PPV = TP/(TP+FP) = probability of disease given a positive test - depends on prevalence; high prevalence → high PPV; low prevalence → low PPV; the most clinically relevant measure when facing a positive result.
Spearman's rho = non-parametric correlation using ranks - use for ordinal data, non-normal distributions, or non-linear monotonic relationships; robust to outliers; Pearson's r = parametric, for normally distributed continuous linear relationships.
Critical appraisal priorities for RCTs - randomisation, allocation concealment, blinding, ITT analysis are the core methodological concerns; funding source is a contextual factor, not a primary validity criterion; assess the methods, not just who paid for the study.
RCT = random allocation → reduces selection bias + distributes known AND unknown confounders equally; RCTs are the gold standard for assessing treatment effectiveness (Level 1b evidence); systematic reviews of RCTs are Level 1a; key quality features: randomisation, allocation concealment, blinding, ITT analysis; RCTs answer 'does this treatment work?' not 'what causes the disease?'.
Single-blind = participants blinded; double-blind = participants + investigators; triple-blind = participants + investigators + outcome assessors/analysts; prevents performance bias (behaviour change) and detection bias (outcome interpretation); not always feasible (surgery, physiotherapy); blinded outcome assessment helps when full blinding is impossible; CONSORT requires blinding details to be reported.
RRR = (CER - EER)/CER - proportional reduction; can exaggerate benefit when baseline risk is small; ALWAYS report alongside ARR and NNT for clinical interpretation; pharmaceutical industry often reports RRR (more impressive); ARR = CER - EER (absolute difference); NNT = 1/ARR; example: RRR 50% from 2% to 1% → NNT 100 (less impressive); RRR 50% from 40% to 20% → NNT 5 (very impressive).
Evidence hierarchy (therapy): 1a (SR of RCTs) > 1b (individual RCT) > 2a (SR of cohort) > 2b (cohort) > 3a (SR of case-control) > 3b (case-control) > 4 (case series) > 5 (expert opinion); Cochrane reviews are the gold standard SRs; 'garbage in, garbage out' - SR quality depends on included studies; the hierarchy may vary for different clinical questions (diagnosis, prognosis, harm).
P-value = probability of observing results this extreme (or more) IF null hypothesis is true; p < 0.05 = 'statistically significant' (by convention); p-value is NOT the probability the null hypothesis is true; statistical significance ≠ clinical significance; always report alongside confidence intervals and effect sizes; multiple comparisons increase type I error risk (Bonferroni correction); 'significant' just means unlikely by chance alone, not necessarily important.
Type I error (α) = false positive (reject true null); Type II error (β) = false negative (fail to reject false null); power = 1 - β (target ≥80%); small studies have low power → high Type II error risk; 'absence of evidence ≠ evidence of absence'; non-significant result may mean: (a) truly no difference, (b) difference exists but study was underpowered to detect it; always check the study's power calculation.
CASP = Critical Appraisal Skills Programme - structured checklists for appraising studies; three key domains: (1) Validity (internal validity - was the study well-designed?), (2) Results (how big and how precise?), (3) Applicability (can I apply this to my patients?); different checklists for different study types; freely available at casp-uk.net; widely used in UK medical education and journal clubs.
95% CI = range within which we are 95% confident the true value lies; for OR/RR: if CI crosses 1.0 → not significant (p > 0.05); if CI does NOT cross 1.0 → significant (p < 0.05); narrow CI = precise estimate; wide CI = imprecise (small sample or high variability); CI provides more information than p-value alone (effect size + precision); for mean differences: if CI crosses 0 → not significant.
Audit = measures practice vs standards → quality improvement (audit cycle); Research = generates new knowledge → tests hypotheses; Audit does NOT need REC approval (but may need local registration); Research DOES need REC approval; audit cycle: standard → measure → compare → change → re-audit; service evaluation = describes current practice (no standard comparison); the key question: 'Is this trying to generate new knowledge?' → if yes, it's research.
Composite endpoints = combine outcomes for increased power; concern: components may be unequally important and unequally affected; ALWAYS examine individual component results; a 'positive' composite result driven by the least important component is clinically misleading; good composites have components of similar importance, similar expected treatment effect, and similar frequency; example: MACE = Major Adverse Cardiovascular Events (death + MI + stroke).
LR+ = sensitivity/(1-specificity) - how much a positive test increases disease probability; LR- = (1-sensitivity)/specificity - how much a negative test decreases disease probability; NOT affected by prevalence (unlike PPV/NPV); LR > 10 or < 0.1 = very useful test; LR = 1 → no diagnostic value; use with Fagan's nomogram: pre-test probability → LR → post-test probability; LRs are the best way to communicate test usefulness to clinicians.
Statistical significance = unlikely due to chance (p < 0.05); clinical significance = large enough to matter in practice; large studies can find statistically significant but clinically trivial differences; always consider: effect size (ARR, NNT), confidence intervals, clinical context, patient values, costs; GRADE system integrates evidence quality with clinical applicability; the question should always be 'Is this difference meaningful for my patients?' not just 'Is p < 0.05?'.
Heterogeneity = variability between study results beyond chance; I² measures it: 0% = none, 25% = low, 50% = moderate, 75% = substantial; sources: clinical, methodological, statistical; explore with subgroup analysis/meta-regression; high heterogeneity → use random-effects model or don't pool; visual assessment: if studies point in different directions on the forest plot = heterogeneity; chi-squared test (Q statistic) tests for heterogeneity.
Trials stopped early for benefit tend to OVERESTIMATE effects by ~29% (STOPIT-2); fewer events → greater statistical uncertainty → random fluctuations appear as large effects; requires pre-specified stopping rules + independent DSMB; stringent statistical boundaries (O'Brien-Fleming) reduce false early termination; when reading a study, check if it was stopped early - interpret the results with more caution if so.
PRISMA = reporting standard for systematic reviews/meta-analyses; 27-item checklist + 4-phase flow diagram (identification → screening → eligibility → included); related: CONSORT (RCTs), STROBE (observational), STARD (diagnostic), CARE (case reports); PRISMA 2020 is the current version; most journals require PRISMA compliance for systematic reviews; EQUATOR Network coordinates all reporting standards.
Pre-test probability = estimated disease probability BEFORE testing; based on clinical assessment, risk factors, prevalence; profoundly affects post-test probability; Bayesian reasoning: post-test probability depends on pre-test probability × likelihood ratio; low pre-test + positive test → still may be low post-test probability (many false positives); clinical decision rules (Wells score, HEART score) help estimate pre-test probability; this is why 'testing everyone' is wasteful and potentially harmful.
Audit cycle = standard → measure → compare → change → re-audit (ITERATIVE); incomplete without re-audit; standards must be evidence-based and measurable; audit is a quality improvement activity (not research); does not require REC approval (usually needs local registration); common in UK training (foundation and specialty curricula); closing the loop (re-audit) is the most commonly missed step.
Reporting guidelines summary - CONSORT = RCTs; STROBE = observational studies (cohort, case-control, cross-sectional); PRISMA = systematic reviews/meta-analyses; STARD = diagnostic accuracy studies; CARE = case reports; SPIRIT = trial protocols; TRIPOD = prediction models; all hosted by the EQUATOR Network (equator-network.org); STROBE has 22 items covering all sections of an observational study paper.
Sample size determinants - effect size (smaller → larger n), alpha (0.05), power (80-90% → larger n), variability (higher → larger n), event rate; calculated BEFORE the study; underpowered studies → Type II error risk; always check the power calculation when appraising a study; a non-significant result in an underpowered study does NOT prove no effect (absence of evidence ≠ evidence of absence).
Explanatory = 'Can it work?' (efficacy, ideal conditions, selected patients, strict protocols); Pragmatic = 'Does it work?' (effectiveness, real-world, broad patients, usual care); explanatory → high internal validity, low external validity; pragmatic → lower internal validity, high external validity (generalisable); PRECIS-2 tool maps trials on the continuum; most emergency medicine questions need pragmatic evidence (does this work in MY ED with MY patients?).
Cohen's kappa = agreement beyond chance; κ ranges -1 to 1; 0.61-0.80 = substantial, 0.81-1.0 = almost perfect; used for inter-rater reliability, test-retest reliability, diagnostic test agreement; corrects for chance agreement (unlike simple percentage agreement); weighted kappa for ordinal data; affected by prevalence (prevalence paradox); commonly used and tested in MRCEM.
Cross-sectional = snapshot, measures PREVALENCE, no temporal sequence, cannot establish causation; Cohort = follows over time, measures INCIDENCE, establishes temporal sequence, can calculate RR; Cross-sectional answers 'How common is this NOW?'; Cohort answers 'Does this exposure LEAD TO this outcome?'; Case-control answers 'Was this exposure MORE COMMON in people with this disease?'; know these distinctions for MRCEM.
CDR = evidence-based clinical tool for decision-making; three validation phases: derivation → validation → impact analysis; examples: Canadian C-spine Rule, Ottawa Ankle/Knee Rules, Wells score, HEART score; supplement (don't replace) clinical judgement; apply only to the population in which validated; a derived-but-not-validated rule should be used with caution; level of evidence increases with validation stage.
Levels of measurement - nominal (categories, no order), ordinal (ordered categories, unequal intervals), interval (equal intervals, no true zero), ratio (equal intervals, true zero) - determines which statistical tests are appropriate.
Angiogenesis = new vessels from existing vessels, driven by VEGF (released by hypoxia via HIF-1α); essential for granulation tissue and wound healing; also critical for tumour growth; anti-VEGF drugs (bevacizumab) are anti-cancer therapy; vasculogenesis = de novo formation (embryonic).
Liver produces acute-phase proteins stimulated by IL-6; CRP (rises 6-12h, peaks 48h, t½ 19h) is best for acute monitoring; ESR reflects fibrinogen/Ig (slower to rise/fall); negative APPs decrease (albumin, transferrin); SAA → AA amyloidosis if chronic; fever via PGE₂ on hypothalamus.
Exudate = protein-rich (>30 g/L), increased permeability, inflammation; Transudate = protein-poor (<30 g/L), haemodynamic cause; Light's criteria: protein ratio >0.5, LDH ratio >0.6; heart failure = transudate; infection/malignancy = exudate; diuretics can cause misclassification.
Congo red + apple-green birefringence = amyloid; AA = secondary (SAA from chronic inflammation → kidneys); AL = primary (light chains from plasma cells → heart, kidneys); beta-pleated sheet structure; treat AA by controlling inflammation; RA, TB, bronchiectasis, FMF are common causes.
Labile cells (skin, gut) = continuous division, regenerate well; Stable cells (liver, kidney) = quiescent but can divide; Permanent cells (cardiac, neurons) = cannot divide → heal by fibrosis/scarring; MI → scar, NOT new muscle; repair = scar tissue; regeneration = original tissue restoration.
Caseous = cheese-like, TB hallmark, amorphous granular debris in granuloma centres; Coagulative = preserves architecture, most ischaemic infarcts; Liquefactive = digests tissue, brain infarcts and abscesses; Fat = pancreatitis (saponification); Fibrinoid = vessel walls in hypertension/vasculitis.
Primary intention = clean approximated wound, minimal scar (sutured incision); Secondary intention = tissue loss, granulation fills defect, larger scar; phases: haemostasis → inflammation → proliferation → remodelling; wound reaches ~80% strength at 3 months; never 100%; type III collagen → type I during remodelling.
Infection = most important LOCAL factor impairing healing; diabetes = most common SYSTEMIC cause; vitamin C needed for collagen hydroxylation (scurvy = poor healing); steroids suppress healing; smoking impairs via vasoconstriction + CO; wounds need adequate O₂, nutrition, blood supply.
Macrophages = most important cell in wound healing; replace neutrophils at 24-48h; debride, release growth factors (PDGF, VEGF, TGF-β), coordinate repair; M1 (pro-inflammatory) → M2 (pro-repair) transition is key; macrophage depletion severely impairs healing; neutrophil depletion does not (in sterile wounds).
Hepatic fibrosis = type I and III collagen from activated stellate cells (Ito cells) in space of Disse; TGF-β is the key fibrogenic cytokine; capillarisation of sinusoids impairs hepatocyte function; fibrosis is potentially reversible with early treatment.
Langhans = horseshoe nuclei (TB, sarcoidosis - note spelling, NOT Langerhans); Foreign body = scattered nuclei (sutures, talc); Touton = ring nuclei + foamy cytoplasm (xanthomas); Warthin-Finkeldey = measles; all formed by macrophage fusion driven by IFN-γ.
C5a = most potent chemoattractant + most potent anaphylatoxin; C3b = opsonisation (most important complement function); C5b-9 = MAC (lyses Neisseria - deficiency causes recurrent meningococcal/gonococcal infection); C3a, C4a, C5a = anaphylatoxins.
Crohn's = transmural + skip lesions + granulomas + fissuring ulcers + any GI location + fistulae; UC = continuous + mucosal only + starts at rectum + crypt abscesses + pseudopolyps + colon only; Crohn's cobblestoning + fat wrapping; UC has higher colorectal cancer risk with pancolitis.
Fibroblasts = ECM production (collagen, fibronectin); recruited by PDGF, TGF-β; vitamin C needed for collagen hydroxylation (proline/lysine); lysyl oxidase (copper) for cross-linking; type III → type I collagen during remodelling; myofibroblasts → wound contraction.
Apoptosis = programmed, controlled, no inflammation, apoptotic bodies phagocytosed; Necrosis = uncontrolled, cell swelling, inflammation; intrinsic pathway: cytochrome c → caspase-9; extrinsic pathway: death receptors → caspase-8; both converge on caspase-3 (effector); BCL-2 inhibits apoptosis (anti-apoptotic).
Fat necrosis in pancreatitis: lipase → free fatty acids + calcium → calcium soaps (chalky white saponification); causes hypocalcaemia; lipase is the most specific enzyme marker; Grey-Turner (flanks) and Cullen (periumbilical) signs = haemorrhagic pancreatitis.
Fever = PGE₂ raises hypothalamic set point; pyrogens (LPS) → macrophage cytokines (IL-1, IL-6, TNF) → PGE₂ via COX-2 → EP3 receptors; NSAIDs/paracetamol block COX → antipyretic; fever ≠ hyperthermia (set point is normal in hyperthermia).
MMPs = zinc-dependent enzymes that DEGRADE ECM (collagen, elastin, fibronectin); essential for remodelling, migration, angiogenesis; regulated by TIMPs; excessive MMPs → non-healing wounds; insufficient MMPs → fibrosis/keloids; MMP:TIMP balance determines net ECM turnover.
Chronic inflammation = lymphocytes + macrophages + plasma cells (not neutrophils); can arise from persistent acute inflammation or de novo; simultaneous destruction + repair + ongoing inflammation; complications: fibrosis, AA amyloidosis, increased cancer risk.
AA amyloidosis primarily affects KIDNEYS (nephrotic syndrome → renal failure); cardiac involvement rare (unlike AL where heart is main target); treat underlying inflammation to reduce SAA; RA, TB, FMF are common causes; liver, spleen, GI also affected; colchicine for FMF-associated AA.
Regeneration = identical tissue restoration (requires intact scaffold + labile/stable cells); Repair = fibrous scar (when scaffold destroyed or cells are permanent); liver regeneration is the classic example; most wounds heal with BOTH; scaffold preservation determines outcome.
Dysplasia = pre-malignant disordered growth; nuclear pleomorphism, hyperchromasia, increased mitoses, loss of maturation/polarity; graded mild (CIN 1), moderate (CIN 2), severe/CIS (CIN 3); does NOT breach basement membrane; cervical dysplasia caused by HPV 16/18 (E6→p53, E7→Rb).
Hypertrophy = bigger cells (cardiac muscle in hypertension, athletes); Hyperplasia = more cells (BPH, endometrial); permanent cells can only hypertrophy (not hyperplase); often occur together; both reversible; pathological hypertrophy can lead to heart failure if sustained.
Bradykinin = pain + vasodilation + increased permeability; generated by kallikrein from HMWK; inactivated by ACE (kininase II); ACE inhibitor side effects (cough, angioedema) are due to bradykinin accumulation; hereditary angioedema = C1 esterase inhibitor deficiency → excess bradykinin.
5-Lipoxygenase → leukotrienes; LTB₄ = neutrophil chemoattractant; LTC₄/D₄/E₄ (SRS-A) = bronchoconstriction (asthma); montelukast blocks CysLT₁; NSAIDs do NOT block leukotrienes (may worsen asthma); leukotrienes 100-1000× more potent bronchoconstrictors than histamine.
Haemostasis (min-hrs) → Inflammation (hrs-days) → Proliferation (days-wks) → Remodelling (wks-yrs); phases OVERLAP; platelets initiate repair via growth factors; macrophages bridge inflammation to proliferation; type III → type I collagen in remodelling; max wound strength ~80% of original.
Red infarcts = dual supply/loose tissue (lung, liver, intestine); White infarcts = end-arterial/solid organs (heart, kidney, spleen); brain = liquefactive necrosis; reperfusion can convert white → red; venous occlusion causes red infarcts; all infarcts pale initially.
Metastatic calcification = calcium deposits in NORMAL tissues due to hypercalcaemia/hyperphosphataemia (CKD, hyperparathyroidism); Dystrophic calcification = calcium in DAMAGED tissues with normal serum calcium (atherosclerosis, TB); key distinction: tissue status vs calcium status.
TLRs = pattern recognition receptors on innate immune cells; recognise PAMPs (TLR4→LPS, TLR3→dsRNA, TLR9→CpG DNA); signal via MyD88→NF-κB→cytokines; surface TLRs (extracellular pathogens) vs endosomal TLRs (nucleic acids); bridge innate to adaptive immunity via DC maturation.
Classical pathway = antibody (IgG/IgM) + antigen → C1q → C4b2a (C3 convertase); Lectin = MBL + mannose; Alternative = spontaneous C3 tick-over; all converge on C3 → C3a (anaphylatoxin) + C3b (opsonin); terminal pathway → MAC (C5b-C9) → lysis.
Autoimmunity = breakdown of self-tolerance; central tolerance (thymic deletion, AIRE) + peripheral tolerance (Tregs/FOXP3, anergy, Fas/FasL); genetic (HLA associations) + environmental (molecular mimicry) + hormonal (female predominance); organ-specific vs systemic.
Acute cellular rejection = days to weeks post-transplant; T-cell mediated (CD4+CD8+); tubulitis + intimal arteritis (Banff); direct and indirect allorecognition; treat: pulse methylprednisolone, ATG if steroid-resistant; prevent: calcineurin inhibitor + mycophenolate + steroid.
NK cells = innate lymphocytes (CD56+CD3-); 'missing self' - kill cells lacking MHC-I; KIR inhibitory receptors; perforin/granzyme killing; ADCC via CD16 (FcγRIII); produce IFN-γ; target virus-infected cells + tumour cells; deficiency → herpesvirus susceptibility.
Dendritic cells = most potent APCs; bridge innate → adaptive; capture antigen peripherally → mature → migrate to lymph nodes → present on MHC-I (CD8+ T) and MHC-II (CD4+ T); Langerhans cells in skin; pDCs produce IFN-α/β (antiviral); determine T-cell polarisation.
Mycophenolate inhibits IMPDH → blocks de novo purine synthesis → selectively antiproliferative for lymphocytes (dependent on de novo pathway); largely replaced azathioprine; teratogenic; side effects: GI, myelosuppression, CMV; azathioprine: check TPMT before starting.
Chronic rejection = IFTA + transplant glomerulopathy + arteriopathy (intimal fibrosis); leading cause of late graft loss; antibody (DSA) + T-cell mediated; largely irreversible; risk: prior acute rejection, non-adherence, HLA mismatch; prevention > treatment; median graft survival 10-20 years.
CRP = pentraxin acute phase protein; hepatocytes produce in response to IL-6; binds phosphocholine → complement activation (C1q) + opsonisation; rises 6-8h, peaks 24-48h; >100 mg/L suggests bacterial infection; short t½ (19h); NOT elevated in SLE (IFN suppression); hs-CRP for CV risk.
HAE diagnosis: C4 low (screening >95% sensitive) → C1-INH level + function; Type I = low level + low function; Type II = normal level + low function; C3 normal; bradykinin-mediated (not histamine); adrenaline/antihistamines INEFFECTIVE; ACE inhibitor angioedema = normal C1-INH/C4.
HLA-DQ2 in 90-95% of coeliac (DQ8 in remainder); tTG deamidates gliadin → DQ2 presents to CD4+ T cells → villous atrophy; screen: anti-tTG IgA (+ total IgA); confirm: biopsy (Marsh 3); treat: lifelong GFD; IgA deficiency 10-15× more common; EATL risk.
Terminal complement (C5-C9) deficiency → recurrent Neisseria (meningitidis + gonorrhoeae); MAC-dependent killing; C1q/C2/C4 → SLE; C3 → pyogenic infections; screen with CH50 (classical+terminal); vaccinate but reduced efficacy; C2 = most common complement deficiency overall.
Basiliximab = anti-CD25 (IL-2Rα) monoclonal antibody; blocks IL-2 signalling on activated T cells; induction therapy at transplantation (day 0 + day 4); well-tolerated; maintenance: tacrolimus + mycophenolate + prednisolone; ATG for high-risk induction or steroid-resistant rejection.
IDA = most common anaemia; microcytic hypochromic + pencil cells; ferritin <15 = diagnostic (but acute phase reactant); low iron, high TIBC, low transferrin saturation; investigate cause: GI in men/postmenopausal; treat: oral iron 3 months post-normalisation; IV if intolerant/malabsorption.
TTP = ADAMTS13 deficiency → ultra-large VWF multimers → platelet microthrombi; pentad: thrombocytopenia + MAHA (schistocytes) + neuro + renal + fever; NORMAL coagulation (vs DIC); >90% mortality untreated; Rx: plasma exchange + steroids + caplacizumab; do NOT give platelets.
Grading = degree of differentiation (microscopic - how it looks); Staging = anatomical extent of spread (macroscopic - how far); staging is generally the stronger prognostic factor; G1=well-differentiated, G3/4=poorly differentiated/anaplastic; TNM: T=tumour, N=nodes, M=metastasis; Gleason (prostate), Nottingham (breast).
INR >8 + non-life-threatening bleeding → stop warfarin + IV vitamin K 1-5 mg; life-threatening → stop warfarin + IV vitamin K 5 mg + PCC (25-50 IU/kg); vitamin K takes 6-12h; PCC acts immediately; PCC preferred over FFP (faster, concentrated, less volume); warfarin inhibits factors II, VII, IX, X.
Warburg effect = aerobic glycolysis in cancer; glucose → lactate even with O₂; advantages: fast ATP + biosynthetic precursors + NADPH + acidic microenvironment; basis of FDG-PET/CT (increased glucose uptake); emerging hallmark of cancer; seemingly inefficient but provides growth advantages.
HIT type II = IgG anti-heparin/PF4 → platelet activation via FcγRIIa → thrombocytopenia + THROMBOSIS (prothrombotic!); 5-10 days; 4Ts score; STOP all heparin; start argatroban/fondaparinux; NO warfarin until platelets >150; NO platelet transfusions; UFH > LMWH risk.
CML = Philadelphia chromosome t(9;22)/BCR-ABL; full myeloid maturation spectrum + basophilia + massive splenomegaly + very high WCC; low LAP score (vs high in leukaemoid reaction); 3 phases: chronic → accelerated → blast crisis; treat: TKIs (imatinib first-line); >90% 5-year survival on TKIs.
Multiple myeloma = clonal plasma cells + M-protein + CRAB (Calcium, Renal, Anaemia, Bone); Bence Jones protein = urinary free light chains; BM plasma cells ≥10%; IgG most common paraprotein; MGUS → myeloma ~1%/year; treat: VRd + auto-SCT if eligible + bisphosphonates; lytic lesions (NOT blastic).
Dysplasia = pre-malignant disordered growth; increased N:C ratio + hyperchromasia + pleomorphism + disorganisation + increased mitoses; reversible if cause removed; graded mild/moderate/severe (CIS); CIS = full-thickness WITHOUT basement membrane invasion; invasion through BM = carcinoma; cervical (HPV), colorectal (adenoma-carcinoma sequence).
Protein S LOW in pregnancy (C4BP increases, binds free protein S) → unreliable testing; defer thrombophilia testing to 6-12 weeks postpartum; also affected by: acute VTE, warfarin (protein C/S are vitamin K-dependent), liver disease, OCP; genetic tests (FVL, prothrombin) unaffected by clinical state.
Rouleaux = RBC stacking ('coins') from elevated plasma proteins (fibrinogen, immunoglobulins) reducing zeta potential; consider myeloma (paraprotein) in elderly with rouleaux + bone pain + renal impairment; raised ESR mechanism; also in inflammation, infection, pregnancy; investigate with SPEP + free light chains.
Rivaroxaban/apixaban/edoxaban = direct Factor Xa inhibitors; dabigatran = direct thrombin (IIa) inhibitor; predictable PK, no routine monitoring; renal-dependent clearance; reversal: idarucizumab (dabigatran), andexanet alfa (Xa inhibitors); PCC if specific reversal unavailable; Xa at convergence of intrinsic/extrinsic pathways.