Fellowship of the Royal College of Anaesthetists (FRCA) Physiology and Biochemistry Syllabus

Name the three forms in which $CO_2$ is carried in blood and their approximate proportions.

As bicarbonate $\approx 70\%$ (via carbonic anhydrase, $\ce{CO2 + H2O <=> H2CO3 <=> H+ + HCO3-}$), as carbamino compounds $\approx 23\%$, and dissolved $\approx 7\%$.

What is the Bohr effect and what is the Haldane effect?

Bohr effect: increased $CO_2$/$H^+$ reduces haemoglobin's $O_2$ affinity (right shift), aiding $O_2$ release in tissues. Haldane effect: deoxygenated haemoglobin carries more $CO_2$, aiding $CO_2$ loading in tissues and unloading in lungs.

Which receptors control ventilation and what are their primary stimuli?

Central chemoreceptors (medulla) respond to CSF $H^+$/$P_aCO_2$ (dominant drive). Peripheral chemoreceptors (carotid and aortic bodies) respond to low $P_aO_2$ (mainly <8 kPa), raised $P_aCO_2$ and $H^+$.

Define oxygen toxicity and the relevant pulmonary and CNS effects.

Prolonged high $P_iO_2$ generates reactive oxygen species. Pulmonary: tracheobronchitis and diffuse alveolar damage (Lorraine-Smith effect). CNS: at hyperbaric pressures, seizures (Paul Bert effect). Retinopathy of prematurity in neonates.

Write the equation for glomerular filtration rate using clearance and its normal value.

$GFR = \dfrac{U_x \times \dot{V}}{P_x}$, ideally with $x = $ inulin or creatinine. Normal $\approx 120\ \text{mL·min}^{-1}$. Filtration fraction $= GFR/RPF \approx 0.2$.

State the determinants of net glomerular filtration pressure.

$NFP = P_{GC} - P_{BC} - \pi_{GC}$, i.e. glomerular capillary hydrostatic pressure minus Bowman's capsule hydrostatic pressure minus glomerular oncotic pressure; $GFR = K_f \times NFP$.

Explain how the counter-current multiplier concentrates urine.

The loop of Henle's thick ascending limb actively pumps $\ce{NaCl}$ out (impermeable to water) while the descending limb is water-permeable, building a hyperosmotic medullary gradient (up to ~1200 mOsm·kg⁻¹). ADH then makes the collecting duct water-permeable, allowing water reabsorption.

Give the body fluid compartment volumes for a 70 kg adult (60% water).

Total body water $\approx 42\ \text{L}$; intracellular $\approx 28\ \text{L}$ (2/3); extracellular $\approx 14\ \text{L}$ (1/3), of which interstitial $\approx 10.5\ \text{L}$ and plasma $\approx 3.5\ \text{L}$.

How is plasma osmolality calculated and what is its normal range?

$Osm = 2[Na^+] + [glucose] + [urea]$ (mmol·L⁻¹). Normal $\approx 275\text{–}295\ \text{mOsm·kg}^{-1}$. An osmolar gap >10 suggests unmeasured solutes (e.g. ethanol, methanol).

Write the Henderson-Hasselbalch equation for the bicarbonate buffer system.

$pH = pK_a + \log_{10}\dfrac{[HCO_3^-]}{0.03 \times P_aCO_2}$, with $pK_a = 6.1$. Normal arterial $pH = 7.35\text{–}7.45$.

Classify the four primary acid-base disturbances by $pH$, $P_aCO_2$ and $HCO_3^-$.

Respiratory acidosis: low pH, high $P_aCO_2$. Respiratory alkalosis: high pH, low $P_aCO_2$. Metabolic acidosis: low pH, low $HCO_3^-$. Metabolic alkalosis: high pH, high $HCO_3^-$. Compensation moves the other variable in the same direction.

Define the anion gap and give causes of a raised anion gap metabolic acidosis.

$AG = [Na^+] - ([Cl^-] + [HCO_3^-])$, normal $8\text{–}12\ \text{mmol·L}^{-1}$. Raised AG causes (MUDPILES): methanol, uraemia, DKA, propylene glycol, isoniazid, lactate, ethylene glycol, salicylates.

State the Nernst equation and the equilibrium potential for $K^+$.

$E_{ion} = \dfrac{RT}{zF}\ln\dfrac{[ion]_o}{[ion]_i} \approx 61\log_{10}\dfrac{[ion]_o}{[ion]_i}\ \text{mV at 37°C}$. For $K^+$, $E_K \approx -90\ \text{mV}$; resting membrane potential $\approx -70\ \text{mV}$ (nerve).

Describe the ionic phases of a neuronal action potential.

Depolarisation: voltage-gated $Na^+$ channels open ($Na^+$ influx). Repolarisation: $Na^+$ channels inactivate, voltage-gated $K^+$ channels open ($K^+$ efflux). Hyperpolarisation: slow $K^+$ closure. Absolute then relative refractory periods follow.

Outline the sequence of events in chemical synaptic transmission.

Action potential depolarises terminal → voltage-gated $Ca^{2+}$ entry → vesicle fusion and neurotransmitter release → diffusion across cleft → postsynaptic receptor binding → EPSP/IPSP. Transmitter removed by reuptake, enzymatic breakdown or diffusion.

State the determinants of cerebral perfusion pressure and the autoregulation range.

$CPP = MAP - ICP$ (or CVP if higher). Cerebral autoregulation keeps CBF (~50 mL·100g⁻¹·min⁻¹) constant over MAP $\approx 50\text{–}150\ \text{mmHg}$. CBF rises with $P_aCO_2$ and falls with hypocapnia.

State the Monro-Kellie doctrine.

The skull is a rigid box containing brain (~80%), blood (~10%) and CSF (~10%). An increase in one component must be offset by a decrease in another, or ICP rises. Initial compensation buffers volume, then ICP rises steeply.

Compare first (fast) and second (slow) pain fibres.

Fast/first pain: $A\delta$ fibres, myelinated, sharp/well-localised, fast conduction. Slow/second pain: C fibres, unmyelinated, dull/burning/poorly localised. Both synapse in dorsal horn and ascend mainly via the spinothalamic tract.

Explain the gate control theory of pain.

Activity in large $A\beta$ (touch) fibres excites inhibitory interneurons in the dorsal horn substantia gelatinosa, 'closing the gate' and reducing transmission of nociceptive ($A\delta$/C) input to projection neurons. Descending pathways also modulate the gate.

Contrast sympathetic and parasympathetic preganglionic/postganglionic transmitters and receptors.

Both: preganglionic release ACh acting on nicotinic receptors. Parasympathetic postganglionic: ACh on muscarinic receptors. Sympathetic postganglionic: noradrenaline on adrenoceptors (exception: sweat glands use ACh/muscarinic; adrenal medulla releases adrenaline).

List the steps of excitation-contraction coupling in skeletal muscle.

Action potential travels down T-tubule → dihydropyridine receptor activates ryanodine receptor → $Ca^{2+}$ released from sarcoplasmic reticulum → $Ca^{2+}$ binds troponin C → tropomyosin moves → actin-myosin cross-bridge cycling (ATP-dependent) → contraction; $Ca^{2+}$ reuptake causes relaxation.

Describe neuromuscular transmission at the motor end-plate.

Action potential → presynaptic $Ca^{2+}$ entry → ACh vesicle release → ACh binds postjunctional nicotinic receptors → $Na^+$ influx → end-plate potential → muscle action potential. ACh is hydrolysed by acetylcholinesterase. A large safety margin exists (~70% receptor block before failure).

Name the anterior pituitary hormones and a key target/action of each.

GH (growth/IGF-1), ACTH (adrenal cortisol), TSH (thyroid hormone), LH and FSH (gonads), prolactin (lactation). Posterior pituitary (stored, not made there): ADH (water reabsorption) and oxytocin.

Compare the actions of insulin and glucagon on glucose metabolism.

Insulin (β-cells): lowers blood glucose—promotes glucose uptake (GLUT4), glycogenesis, lipogenesis, protein synthesis; inhibits gluconeogenesis. Glucagon (α-cells): raises blood glucose—promotes glycogenolysis and gluconeogenesis.

Describe the hormonal control of plasma calcium.

PTH (low $Ca^{2+}$): raises $Ca^{2+}$ via bone resorption, renal reabsorption and activation of vitamin D ($1\alpha$-hydroxylase), increasing gut absorption; lowers phosphate. Calcitonin lowers $Ca^{2+}$. Vitamin D (calcitriol) increases gut $Ca^{2+}$ and phosphate absorption.

Match key gastrointestinal secretions to their source cells.

Parietal cells: HCl and intrinsic factor. Chief cells: pepsinogen. G cells: gastrin. Mucous/neck cells: mucus and $HCO_3^-$. Pancreas: bicarbonate (ductal) and enzymes (acinar). I cells: CCK; S cells: secretin.

Summarise the synthetic and metabolic functions of the liver.

Synthesis of albumin, clotting factors (except VIII and vWF) and bile; glucose homeostasis (glycogen storage, gluconeogenesis); lipid and protein metabolism; urea cycle (ammonia detox); bilirubin conjugation; drug metabolism (phase I CYP450 and phase II conjugation); storage of vitamins and iron.

State the basal metabolic rate value and the equation linking $\dot{V}O_2$ to energy expenditure.

BMR $\approx 1\ \text{kcal·kg}^{-1}\text{·h}^{-1}$ (~70 kcal·h⁻¹, oxygen consumption ~250 mL·min⁻¹). Respiratory quotient $RQ = \dfrac{\dot{V}CO_2}{\dot{V}O_2}$: 1.0 for carbohydrate, ~0.7 for fat, ~0.8 mixed diet.

Describe red cell physiology: lifespan, production control and key features.

Erythrocytes are biconcave, anucleate; lifespan ~120 days; produced in marrow under erythropoietin (renal, hypoxia-driven); rely on anaerobic glycolysis and the pentose phosphate pathway; broken down in the spleen with iron recycling and bilirubin formation.

Outline the coagulation cascade pathways and their common convergence.

Intrinsic pathway (XII→XI→IX→VIII, monitored by APTT) and extrinsic pathway (tissue factor + VII, monitored by PT) converge at factor X activation (common pathway): $X\to Xa$ converts prothrombin (II) to thrombin, which converts fibrinogen (I) to fibrin, stabilised by XIII.

State the ABO and Rh blood group compatibility rules for red cell transfusion.

Group O = universal red cell donor (no A/B antigens); group AB = universal recipient. Anti-A/anti-B are naturally occurring IgM. RhD-negative recipients (especially females of childbearing age) should receive RhD-negative blood to avoid anti-D sensitisation.

List the major cardiovascular and respiratory changes of normal pregnancy at term.

Cardiac output rises ~40% (↑HR and SV), plasma volume rises ~50% (dilutional anaemia), SVR and BP fall in mid-pregnancy. Minute ventilation rises ~50% (↑tidal volume) causing a compensated respiratory alkalosis ($P_aCO_2 \approx 4.1\ \text{kPa}$); FRC falls ~20%.