Show the model answerAttempt it first — that is what makes it stick
(a) Functions of the blood-brain barrier 2 marks
What earns the marks2 marks
| Stable microenvironment | So neuronal function is not disturbed by plasma composition |
|---|---|
| Protection | Against potentially harmful circulating substances |
| Traffic control | Prevents uncontrolled passage of neurotransmitters and hormones, either way |
| Function | Detail |
|---|---|
| Maintains a stable microenvironment | Brain extracellular fluid composition is held constant, so excitability is protected from swings in plasma |
| Protects against harmful substances | Excludes large, polar and lipid-insoluble circulating toxins while admitting metabolic substrates |
| Prevents uncontrolled neurotransmitter and hormone passage | In either direction — circulating ones into the brain, centrally released ones into the systemic circulation |
| Enzymatic degradation | Monoamine oxidase and dopa decarboxylase in the endothelium |
| Barrier to microorganisms | And restriction of peripheral immune access — signalling molecules, antibodies, immune cells |
(b) Transport mechanisms 4 marks
What earns the marks4 marks · 5 mechanisms
| Name it | Each mechanism by name |
|---|---|
| Explain it briefly | One clause on how it works |
| Give an example | One appropriate example each — all three were expected |
| Mechanism | How it works | ATP | Example |
|---|---|---|---|
| Simple diffusion | Directly through the endothelial cell membrane, down a concentration gradient | No | O₂, CO₂, water, volatile agents, unionised lipid-soluble drugs |
| Facilitated diffusion | Carrier-mediated, down a gradient, saturable and stereospecific | No | Glucose on GLUT1 (insulin-independent); amino acids on the large neutral amino acid transporter |
| Primary active transport | Against a gradient, hydrolysing ATP directly | Yes | Na⁺/K⁺-ATPase; P-glycoprotein efflux returning lipid-soluble drugs to blood |
| Secondary active transport | Uses the sodium gradient rather than ATP directly | Indirectly | Calcium, magnesium and chloride — how their concentrations are held independent of plasma |
| Vesicular transport | Pinocytosis and receptor-mediated transcytosis. Cerebral endothelium has far fewer vesicles than systemic, so this route is limited | Yes | Insulin, transferrin |
Commonly lost: Fewer candidates mentioned pinocytosis at all. And two classifications were reversed: GLUT-mediated glucose transport is facilitated diffusion, not active; ATPase transporters are active transport, not facilitated diffusion.
(c) Effect of a rising PaCO₂ on the brain interstitium 1 mark
What earns the marks1 mark · two halves
| CO₂ crosses and lowers pH | Hydrated by carbonic anhydrase to H⁺ and HCO₃⁻ |
|---|---|
| The change is large | Because CSF is poorly buffered — the half most often omitted |
- CO₂ is small, uncharged and lipid-soluble, so it diffuses readily across the barrier into brain interstitium and CSF.
- There it is hydrated to carbonic acid, catalysed by carbonic anhydrase, dissociating to H⁺ and HCO₃⁻ — so interstitial and CSF pH falls.
- The fall is large because CSF has limited buffering capacity: CSF protein is about 0.5% of the plasma concentration — roughly 0.26 g/L in the ventricles rising to 0.42 g/L in the lumbar sac, against about 70 g/L in plasma — so there is almost no non-bicarbonate buffer.
- H⁺ and HCO₃⁻ themselves cross only slowly, so interstitial pH tracks arterial CO₂ rather than arterial pH.
Commonly lost: A complete answer needed the limited buffering capacity from the low CSF protein — not just that CO₂ crosses and lowers pH.
(d) PaCO₂ and cerebral blood flow, with a graph 3 marks
What earns the marks3 marks
| Axes with units | CBF (mL/100 g/min) against PaCO₂ (kPa or mmHg) |
|---|---|
| Linear physiological range | Approximately linear across it |
| Plateaux at the extremes | Maximal constriction low, maximal dilatation high |
| Mechanism | Perivascular H⁺ acting on arteriolar smooth muscle |
Commonly lost: The common error was confusion with the autoregulation curve — several drew cerebral blood flow against mean arterial pressure, which answers a different question.
Cerebral blood flow against arterial carbon dioxide tension
- Mark the normal point: flow about 50 at a PaCO₂ of about 5 kPa (38 mmHg) — the point the source figure marks.
- Near-linear across the physiological range, about 3.3-9.3 kPa (25-70 mmHg).
- Lower plateau below about 3.3 kPa (25 mmHg): further vasoconstriction is limited.
- Upper plateau above about 10-10.7 kPa (75-80 mmHg): the vessels are maximally dilated.
- Slope: roughly 1-2 mL/100 g/min per mmHg around the normal value.
| Point | Detail |
|---|---|
| The actual stimulus | Perivascular and interstitial H⁺ concentration around arteriolar smooth muscle — not CO₂ itself |
| Mediators | Nitric oxide, adenosine, arachidonic acid metabolites and reactive oxygen species |
| Effect of hypotension | Moderate hypotension significantly attenuates the rise with hypercapnia; with severe hypotension no response is seen |
| Not sustained | Bicarbonate is extruded from the CSF over 6-8 hours, pH returns toward normal, and the effect is lost, which is why sustained hyperventilation does not keep working |