Show the model answerAttempt it first — that is what makes it stick
(a) Physiological factors determining cerebral blood flow 6 marks
What earns the marks6 marks
| Normal value | About 50 mL/100 g/min; 12-15% of cardiac output to an organ that is 2% of body weight |
|---|---|
| The definite equation | CBF = CPP / CVR, and CPP = MAP − ICP (or CVP, whichever is higher) |
| Metabolic | Flow-metabolism coupling: regional flow follows regional metabolic rate |
| Myogenic | Autoregulation: arterioles constrict as pressure rises; lower limit not less than MAP 70 mmHg in most adults |
| Chemical | PaCO₂, 1-2 mL/100 g/min per mmHg; PaO₂ below 8 kPa (60 mmHg) |
| Neurogenic | Sympathetic stimulation raises arterial pressure and CPP; cerebral sympathetic nerves limit the flow response to a surge |
| Other physiological | Temperature through metabolic rate, blood viscosity, cardiac output, venous pressure |
Commonly lost: The examiner critique asked for the physiological factors, not the physical, pharmacological or pathological ones.
1 · Normal value and the governing equation
- Global CBF is about 50 mL/100 g/min. The adult brain weighs about 1350 g, 2% of body weight, yet receives 12-15% of cardiac output, a reflection of its high metabolic rate.
- Oxygen consumption averages about 3.5 mL O₂/100 g/min, roughly 50 mL/min for the whole brain and 20% of the body’s total.
- Flow and metabolic rate are both about four times greater in grey matter than in white matter.
Commonly lost: The examiner critique recorded many answers giving only the generic flow = pressure / resistance. Naming CPP and CVR, then defining CPP from MAP and ICP, is what makes intracranial pressure a determinant.
2 · The determinants, by mechanism
| Determinant | Effect on CBF | Mechanism | Key value |
|---|---|---|---|
| Cerebral metabolic rate | Regional flow rises and falls in proportion to regional metabolism (neurovascular coupling) | No single mechanism. Local by-products of metabolism (K⁺, H⁺, lactate, adenosine, ATP) act directly on vascular tone; glutamate from active synapses drives nitric oxide release; astrocyte glutamate receptors generate vasodilator prostaglandins and epoxyeicosatrienoic acids | CMRO₂ about 3.5 mL O₂/100 g/min |
| Perfusion pressure (autoregulation) | Held relatively constant across the autoregulatory range; pressure-passive below and above it | Myogenic: a rise in pressure depolarises arteriolar smooth muscle, calcium enters through voltage-gated channels, the vessel constricts and cerebrovascular resistance rises. Tone is modulated by endothelial nitric oxide and by innervation | Lower limit not less than MAP 70 mmHg (CPP 60-65 mmHg) in most adults; upper limit conventionally about 150 mmHg |
| PaCO₂ | Varies directly with PaCO₂ across about 3.3-9.3 kPa (25-70 mmHg) | CO₂ diffuses freely across the cerebrovascular endothelium and lowers brain extracellular pH, relaxing arteriolar smooth muscle; nitric oxide, adenosine and arachidonic acid metabolites contribute. Metabolic acidosis has little immediate effect because the barrier excludes H⁺ | 1-2 mL/100 g/min per mmHg |
| PaO₂ | Little effect from 8 to over 40 kPa (60 to over 300 mmHg); rises rapidly below 8 kPa; falls modestly at very high tensions | Below 60 mmHg haemoglobin saturation falls rapidly. Deoxyhaemoglobin releases nitric oxide and ATP, vascular ATP-dependent K⁺ channels open, and the rostral ventrolateral medulla acts as an oxygen sensor | Threshold 8 kPa (60 mmHg) |
| Sympathetic innervation | Restrains flow at rest; limits the rise in flow during an acute pressure surge | Fibres from the superior cervical ganglion act mainly on the larger arteries. Sympathetic activity rising with an acute rise in MAP limits downstream microvascular pressure and flow, protecting against breakthrough of the blood-brain barrier. More effective against rises than falls in pressure | At rest, MAP, PaCO₂ and metabolic rate predominate |
| Temperature | Falls with cooling | Primarily through suppression of metabolic rate: coupling again, not a separate mechanism | CMR falls 6-7% per °C |
| Blood viscosity | Only modest changes across the normal haematocrit range | Haematocrit is the single most important determinant of viscosity. In anaemia resistance falls and flow rises, partly as a response to reduced oxygen delivery rather than to viscosity alone | Haematocrit 33-45% |
| Cardiac output | May contribute to flow independently of MAP | Supported by volunteer studies of preload change; a meta-analysis did not confirm an independent relationship, so it is a contributor rather than an established determinant | One estimate: a 30% fall in cardiac output, about a 10% fall in CBF |
| Venous and intracranial pressure | A rise reduces perfusion pressure | Perfusion pressure is arterial pressure minus the downstream pressure: venous pressure, or within the skull, ICP | Normal CSF pressure 5-10 mmHg |
Commonly lost: The examiner critique recorded that most did not describe sympathetic stimulation raising blood pressure, and thereby cerebral perfusion pressure.
Commonly lost: The examiner critique recorded answers stating that autoregulation against a rising pressure is vasodilatation. It is vasoconstriction: if flow is to stay constant while pressure rises, resistance must rise.
3 · Hagen-Poiseuille, used properly
Q = πΔPr⁴ / 8ηl
- Q volume flow (m³/s) · ΔP pressure drop along the vessel (Pa) · r radius (m) · η viscosity (Pa·s) · l length (m).
- Its use here is the fourth power of the radius: small changes in arteriolar calibre produce large changes in resistance, which is how the metabolic, myogenic, chemical and neurogenic mechanisms above all act.
Commonly lost: The examiner critique recorded candidates quoting it without using it to explain the corrections that maintain flow, and some using it to argue for haemodilution: in normal healthy individuals, changes in haematocrit and viscosity have minimal effects on CBF.
(b) The four diagrams 4 marks
What earns the marks4 marks
| (i) Metabolic control | CBF against CMRO₂: a straight line through the normal point |
|---|---|
| (ii) Autoregulation | CBF against MAP: a gently sloped plateau between two labelled limits, pressure-passive at each end |
| (iii) PaCO₂ | A sigmoid: steep across the physiological range, plateaux at the extremes |
| (iv) PaO₂ | Flat through the normal range, rising steeply below 8 kPa (60 mmHg) |
| Every graph | Both axes named with units, the correct shape, and the values that define it |
Commonly lost: The examiner critique required proper complete graphs with the axes properly labelled and relevant values included. A line that is neither clearly straight nor clearly curved was not accepted.
(i) Metabolic control: CBF against CMRO₂
Cerebral blood flow against cerebral metabolic rate — flow-metabolism coupling
- Shape: a straight line with a positive slope.
- Axes: Y = CBF (mL/100 g/min), X = CMRO₂ (mL O₂/100 g/min).
- Mark: the normal point, CBF 50 at a CMRO₂ of about 3.3-3.5.
- Why: flow follows demand. Anaesthetic suppression of metabolism and hypothermia lower both; seizures raise both, metabolism by as much as 400%.
(ii) Autoregulation: CBF against mean arterial pressure
Cerebral blood flow against mean arterial pressure: autoregulation
- Shape: a plateau with a pressure-passive limb at each end.
- Axes: Y = CBF (mL/100 g/min), X = mean arterial pressure (mmHg).
- Mark: label both limits: the lower limit at a MAP of 70 mmHg (CPP 60-65 mmHg) and the upper at about 150 mmHg, with flow near 50 across a gently sloped plateau.
- Outside the limits: below, flow falls with pressure and ischaemia threatens; above, flow rises passively and the blood-brain barrier is at risk of breakthrough.
- Shifts: the dashed curve is chronic hypertension, with both limits moved to the right. The curve lies further left in neonates. Hypercapnia blunts the response to a rising pressure; hypocapnia extends autoregulation over a wider pressure range.
(iii) CBF against PaCO₂
Cerebral blood flow against arterial carbon dioxide tension
- Shape: a sigmoid: lower plateau, steep near-linear middle, upper plateau.
- Axes: Y = CBF (mL/100 g/min), X = PaCO₂ (kPa or mmHg).
- Mark: the normal point, CBF 50 at 5 kPa (38 mmHg); a slope of 1-2 mL/100 g/min per mmHg across the physiological range; the response attenuated below about 3.3 kPa (25 mmHg) and above about 10-10.7 kPa (75-80 mmHg).
- Why it plateaus: the cerebral arteries are already maximally constricted at the low end and maximally dilated at the high end.
- Qualifications: moderate hypotension (MAP reduced by less than a third) attenuates CO₂ responsiveness and severe hypotension (MAP reduced by about two thirds) abolishes it. The response is not sustained: CBF returns toward normal over 6-8 hours as CSF pH normalises, so abruptly restoring a normal PaCO₂ after prolonged hyperventilation raises CBF and ICP. The dashed curve is chronic hypercapnia, reset to the right.
Commonly lost: The examiner critique recorded candidates who drew the autoregulation curve instead. Against PaCO₂ the middle is steep and the plateaux are at the extremes; a CO₂ graph that is flat in the middle is the autoregulation curve.
(iv) CBF against PaO₂
Cerebral blood flow against arterial oxygen tension
- Shape: flat, with a sharp upturn at the left.
- Axes: Y = CBF (mL/100 g/min), X = PaO₂ (kPa or mmHg).
- Mark: flat at about 50 from 8 kPa (60 mmHg) upward; rising steeply below that knee, to double normal or more with severe hypoxaemia.
- At high tensions: little change up to over 40 kPa (300 mmHg); at 1 atmosphere of oxygen flow falls by about 18%.
- Why the knee sits there: below 60 mmHg haemoglobin saturation falls rapidly, and flow rises in inverse linear relation to saturation. Hypercapnia augments the response; hypocapnia limits it.
Commonly lost: The examiner critique recorded candidates describing a decrease in CBF once PaO₂ fell below 50-60 mmHg. Severe hypoxia increases cerebral blood flow.