Membership of the Royal College of Surgeons (MRCS) Pathology, Microbiology and Pharmacology Flashcards

24 sample cards from the Pathology, Microbiology and Pharmacology deck

Sampled from the end of the deck, so these are different cards from the ones shown on the syllabus page.

1. Compare ulcerative colitis and Crohn's disease pathologically.

   UC: mucosa/submucosa only, continuous from rectum proximally, limited to colon, no granulomas, crypt abscesses, pseudopolyps. Crohn's: transmural inflammation, skip lesions anywhere mouth-to-anus (terminal ileum common), non-caseating granulomas, cobblestoning, fissures, fistulae and strictures.

2. Define the Barrett's oesophagus metaplasia and its malignant significance.

   Barrett's is metaplasia of the lower oesophageal stratified squamous epithelium to columnar (intestinal-type, goblet-cell containing) epithelium due to chronic acid reflux. It is premalignant, predisposing to oesophageal adenocarcinoma via a metaplasia-dysplasia-carcinoma sequence.

3. Outline the adenoma-carcinoma sequence in colorectal cancer with key gene changes.

   Normal mucosa → adenoma → carcinoma, driven by progressive mutations: APC (early adenoma initiation), KRAS (adenoma growth), then loss of TP53 and 18q/DCC/SMAD with carcinoma development. Microsatellite instability (mismatch-repair defects, e.g. Lynch syndrome) is an alternative pathway.

4. List the histological grades of hepatic injury terms: steatosis, hepatitis, cirrhosis.

   Steatosis: reversible fatty change of hepatocytes. Hepatitis: hepatocyte inflammation/injury (with ballooning, Mallory bodies, lobular inflammation). Cirrhosis: irreversible end-stage with diffuse fibrosis and regenerative nodules disrupting the architecture, predisposing to portal hypertension and hepatocellular carcinoma.

5. Differentiate the common benign and malignant breast lesions and the key receptors assessed in breast cancer.

   Benign: fibroadenoma (mobile, young women), fibrocystic change, duct papilloma, phyllodes (can be borderline/malignant). Malignant: invasive ductal (no special type, most common) and invasive lobular carcinoma; DCIS is in situ. Key receptors: oestrogen receptor (ER), progesterone receptor (PR), and HER2 — triple-negative if all absent.

6. Compare follicular adenoma, papillary and medullary thyroid carcinoma.

   Follicular adenoma: benign, encapsulated. Papillary carcinoma: most common thyroid cancer, spreads via lymphatics, Orphan-Annie-eye nuclei and psammoma bodies, good prognosis. Follicular carcinoma: spreads haematogenously, capsular/vascular invasion. Medullary carcinoma: arises from parafollicular C cells, secretes calcitonin, associated with MEN 2.

7. Distinguish the three commonest skin malignancies by behaviour.

   Basal cell carcinoma: commonest, locally invasive, rolled pearly edge, almost never metastasises. Squamous cell carcinoma: can metastasise (low-moderate), arises in sun-damaged skin/scars. Malignant melanoma: most aggressive, metastasises early; prognosis depends on Breslow thickness.

8. State the prognostic significance of Breslow thickness in melanoma.

   Breslow thickness is the vertical depth in millimetres from the granular layer of the epidermis to the deepest tumour cell. It is the single most important prognostic factor: thicker tumours have a worse prognosis and a higher risk of metastasis (it also guides surgical excision margins).

9. Define pharmacokinetics and its four components (ADME).

   Pharmacokinetics is what the body does to the drug. ADME: Absorption (drug entering the bloodstream), Distribution (movement into tissues/compartments), Metabolism (biotransformation, mainly hepatic phase I/II), and Excretion (elimination, mainly renal).

10. Define pharmacodynamics, and the terms efficacy, potency, agonist and antagonist.

    Pharmacodynamics is what the drug does to the body. Efficacy: maximal effect a drug can produce. Potency: amount of drug needed for a given effect (lower dose = more potent). Agonist: binds and activates a receptor. Antagonist: binds but blocks/produces no response (competitive or non-competitive).

11. Give the equations for volume of distribution and drug clearance.

    Volume of distribution: $V_{d} = \dfrac{\text{amount of drug in body}}{\text{plasma concentration}}$. Clearance: $CL = \dfrac{\text{rate of elimination}}{\text{plasma concentration}}$. The elimination half-life links them: $t_{1/2} = \dfrac{0.693 \times V_{d}}{CL}$.

12. Differentiate zero-order from first-order kinetics and give a drug example of zero-order.

    First-order: a constant FRACTION of drug is eliminated per unit time (rate proportional to concentration), giving a constant half-life — most drugs. Zero-order: a constant AMOUNT is eliminated per unit time (saturated enzymes), so half-life rises with dose — e.g. ethanol, phenytoin, high-dose aspirin.

13. Define first-pass metabolism and bioavailability.

    First-pass metabolism is the metabolism of an orally absorbed drug by gut wall and liver (via the portal vein) before reaching the systemic circulation, reducing the amount available. Bioavailability ($F$) is the fraction of an administered dose reaching the systemic circulation unchanged; IV $F = 1$ (100%).

14. Describe the WHO analgesic ladder.

    Step 1: non-opioid (paracetamol $\pm$ NSAID). Step 2: weak opioid (e.g. codeine, tramadol) $\pm$ non-opioid. Step 3: strong opioid (e.g. morphine) $\pm$ non-opioid. Adjuvants (e.g. gabapentinoids, antidepressants, steroids) can be added at any step.

15. Outline the mechanism, key side effects and reversal of opioids.

    Opioids act as agonists at $\mu$ (mu), $\kappa$ and $\delta$ receptors (G-protein coupled), giving analgesia. Side effects: respiratory depression, sedation, miosis, constipation, nausea, pruritus, tolerance/dependence. Reversal: naloxone (a competitive opioid antagonist).

16. Differentiate the mechanisms of local anaesthetics, and why infected/acidic tissue reduces their effect.

    Local anaesthetics reversibly block voltage-gated sodium channels on the internal axonal membrane, preventing depolarisation/action potential propagation. They must cross the membrane in unionised form; in acidic (infected) tissue more drug is ionised, so less crosses and efficacy falls. Max lidocaine dose: 3 mg/kg plain, 7 mg/kg with adrenaline.

17. State the features of the triad of general anaesthesia and an example agent for induction and maintenance.

    The triad is hypnosis (unconsciousness), analgesia, and muscle relaxation (areflexia). Induction commonly with IV propofol (or thiopentone); maintenance with a volatile agent (e.g. sevoflurane, isoflurane) or IV propofol (TIVA); muscle relaxation with neuromuscular blockers (e.g. rocuronium, suxamethonium).

18. Compare depolarising and non-depolarising neuromuscular blockers.

    Depolarising (e.g. suxamethonium): ACh receptor agonist causing persistent depolarisation, rapid onset/short duration, initial fasciculations, NOT reversed by neostigmine (can trigger malignant hyperthermia, hyperkalaemia). Non-depolarising (e.g. rocuronium, atracurium): competitive antagonists, reversed by anticholinesterases (neostigmine) or sugammadex (for rocuronium).

19. Compare the mechanism, monitoring and reversal of heparin (unfractionated and LMWH) and warfarin.

    Unfractionated heparin: potentiates antithrombin III (inhibits thrombin/IIa and Xa), monitored by APTT, reversed by protamine sulfate. LMWH: mainly anti-Xa, monitored by anti-Xa levels if needed, partially reversed by protamine. Warfarin: vitamin K epoxide reductase inhibitor (reduces factors II, VII, IX, X), monitored by INR, reversed by vitamin K $\pm$ prothrombin complex concentrate/FFP.

20. Describe the mechanisms of the common antiplatelet agents aspirin and clopidogrel.

    Aspirin irreversibly inhibits cyclo-oxygenase (COX-1), reducing thromboxane $\text{A}_2$ and platelet aggregation for the platelet's lifespan (~7-10 days). Clopidogrel (and prasugrel/ticagrelor) irreversibly block the platelet ADP receptor $\text{P2Y}_{12}$, reducing aggregation.

21. Name the main classes of direct oral anticoagulants (DOACs) and their targets/reversal agents.

    Direct factor Xa inhibitors: apixaban, rivaroxaban, edoxaban — reversed by andexanet alfa (or PCC). Direct thrombin (factor IIa) inhibitor: dabigatran — reversed by idarucizumab. DOACs need no routine monitoring.

22. List the major antihypertensive drug classes with one mechanism each.

    ACE inhibitors (block angiotensin I→II conversion), ARBs (block AT1 receptor), calcium channel blockers (reduce vascular smooth muscle/cardiac calcium entry), thiazide diuretics (reduce Na+ reabsorption in distal tubule), beta-blockers (reduce heart rate/contractility and renin), and alpha-blockers (vasodilation).

23. Match these antibiotic classes to their mechanism of action: beta-lactams, aminoglycosides, fluoroquinolones, macrolides, metronidazole.

    Beta-lactams (penicillins/cephalosporins): inhibit cell wall peptidoglycan synthesis. Aminoglycosides (gentamicin): bind 30S ribosome, inhibit protein synthesis. Fluoroquinolones (ciprofloxacin): inhibit DNA gyrase/topoisomerase. Macrolides (erythromycin): bind 50S ribosome, inhibit protein synthesis. Metronidazole: produces free radicals damaging DNA (anaerobes).

24. Outline the mechanisms of bacterial antibiotic resistance.

    Enzymatic drug inactivation (e.g. beta-lactamases/ESBLs), modification of the target site (e.g. altered penicillin-binding proteins in MRSA), reduced drug uptake/altered permeability, increased efflux pumps, and development of alternative metabolic pathways. Resistance genes spread via plasmids, transposons and conjugation.

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