Show the model answerAttempt it first — that is what makes it stick
(a) Special features of cerebral metabolism 4 marks
What earns the marks4 marks
| Disproportionate metabolic rate | 2% of body weight, 12-15% of cardiac output, 20% of body oxygen |
|---|---|
| Glucose, aerobically | Effectively the sole substrate; oxidative phosphorylation; no useful anaerobic capacity |
| Flow-metabolism coupling | With examples of factors that raise and lower it |
| Almost no reserve | Consequences of oxygen and glucose deprivation |
Commonly lost: The question asks about metabolism, not cerebral blood flow. Graphs of flow against oxygen, carbon dioxide or mean arterial pressure were not required and earned nothing.
1 · A metabolic rate disproportionate to its mass
| Quantity | Value | Comment |
|---|---|---|
| Mass | About 1350 g — roughly 2% of body weight | The comparison is the point |
| Share of cardiac output | 12-15% | Vital-organ priority |
| Share of total body oxygen consumption | About 20% — some 50 mL O₂/min | Ten times its mass share |
| Cerebral blood flow | About 50 mL/100 g/min | About four times greater in grey matter than white |
| CMRO₂ | About 3.5 mL O₂/100 g/min | Same grey/white ratio |
2 · Reliance on glucose, metabolised aerobically
- Glucose is effectively the sole substrate under normal conditions, crossing the barrier by facilitated diffusion on GLUT1, independently of insulin.
- Metabolised by oxidative phosphorylation. Anaerobic glycolysis yields 2 ATP per glucose against 38 for complete aerobic breakdown — which cannot sustain the Na⁺/K⁺-ATPase, so the brain has no useful anaerobic capacity. (38 is the figure the standard anaesthetic physiology text gives; more recent estimates put the true yield nearer 30-32. Either is accepted — the point is the order-of-magnitude gap.)
- Free fatty acids are largely excluded by the barrier, so it cannot switch to fat. Ketone bodies can substitute substantially, but only after several days of starvation upregulates their transporters.
3 · Coupling of blood flow to metabolism
| Element | Detail |
|---|---|
| The relationship | Regional cerebral blood flow varies in proportion to regional cerebral metabolic rate |
| Mediators | Nitric oxide, K⁺ and H⁺, adenosine, lactate, and prostaglandins and epoxyeicosatrienoic acids from astrocytic arachidonic acid metabolism |
| Raises both | Arousal, sensory stimulation, seizures, hyperthermia |
| Lowers both | Anaesthetic agents, hypothermia, sleep, coma |
| Anaesthetics — the limit | Suppress only the electrophysiological component, about 60% of the total, reaching a floor once the EEG is suppressed |
| Hypothermia — the difference | Reduces that AND the 40% housekeeping component, by 6-7% per °C — which is why it keeps working below the isoelectric point |
4 · Almost no reserve
- Cerebral glycogen is negligible.
- Consciousness is lost about ten seconds after circulatory arrest; irreversible injury begins within minutes at normothermia.
- Oxygen deprivation stops oxidative phosphorylation; glucose deprivation removes the only substrate that feeds it.
(b) Cellular changes below 10 mL/100 g/min 1 mark
Commonly lost: The majority answered only “reduced flow, reduced oxygen delivery, anaerobic metabolism, ischaemia”. That is the context. The mark is for cellular events, starting at the pump.
- ATP production fails.
- The cell membrane Na⁺/K⁺-ATPase fails.
- The membrane depolarises as Na⁺ enters and K⁺ leaves; membrane integrity is lost.
- Sodium, water and calcium move intracellularly.
- The cell swells.
- It dies — by necrosis where the insult is severe, or apoptosis where it is milder and delayed.
(c) Physiological basis of cerebral protection 4.5 marks
What earns the marks4.5 marks
| The organising principle | Balance energy supply against demand, and maintain CPP, to prevent a secondary insult |
|---|---|
| The equation | CPP = MAP − ICP |
| Increasing supply | Perfusion pressure, oxygen delivery, normocapnia, normoglycaemia, lowering ICP |
| Reducing demand | Depth of anaesthesia, seizure control, temperature |
| Pair each with its physiology | A list of manoeuvres without the mechanism does not score |
Commonly lost: Answers were disorganised, strategies were not matched to their physiological basis, and the basis was often vague — for example “keep MAP 50-150 mmHg because that is the autoregulatory range”.
| Strategy | Physiological basis |
|---|---|
| Cerebral perfusion pressure: CPP 60-70 mmHg in traumatic brain injury, in practice MAP above 80 mmHg | CPP = MAP − ICP. After an insult the lower autoregulatory limit is higher and autoregulation may be impaired, so a target of “MAP 50-150” is the wrong target |
| Oxygen delivery, not oxygen tension | Delivery is flow × arterial oxygen content, so haemoglobin, saturation and cardiac output all matter. Avoid hypoxaemia; no benefit in hyperoxia |
| Normocapnia | Hypocapnia constricts cerebral vessels and reduces flow; hypercapnia raises cerebral blood volume and ICP. Hyperventilation is a short-term rescue for herniation, not a treatment |
| Normoglycaemia | No substrate reserve, so hypoglycaemia is directly injurious; hyperglycaemia worsens ischaemic tissue through anaerobic lactate production and intracellular acidosis |
| Lowering intracranial pressure | Raises CPP for a given MAP: head-up 30°, neutral neck and unobstructed venous drainage, avoiding coughing and straining, osmotherapy, CSF drainage |
| Strategy | Physiological basis |
|---|---|
| Adequate depth of anaesthesia or sedation | Suppresses the electrophysiological component of CMRO₂ — about 60% of the total. Beyond EEG suppression there is no further metabolic benefit, only haemodynamic cost |
| Seizure control | Seizure activity can raise cerebral metabolic rate by as much as 400%, and a paralysed patient can be in status without visible movement |
| Avoiding hyperthermia, treating fever | CMRO₂ changes 6-7% per °C; hyperthermia also worsens excitotoxicity and barrier disruption |
| Targeted temperature management where indicated | Hypothermia reduces both the functional and the basal components, which is why it continues to reduce demand below the temperature at which the EEG becomes isoelectric |
| Preventing shivering | Raises whole-body oxygen consumption and undoes the benefit of cooling |
(d) Autoregulation after cardiac arrest, if intact 0.5 marks
- The curve is shifted to the right — both the lower and the upper limit move upward.
- Practically: the lower limit is higher than normal, so a MAP that would previously have been adequate may now sit below it. This is the reason for the higher perfusion target in part (c).
Commonly lost: The question says autoregulation remains intact. “Autoregulation fails” is a different statement and does not answer it.