Autoregulation and the control of cerebral perfusion
- Brain requires around 14% of cardiac output
- Ischaemia of
- 1 min: unconsciousnes
- 4 min: Irreversible neuronal tissue damage
- Although surgically much longer vascular occlusion times may be tolerated due to collateral pathways
- Autoregulation of cerebral blood flow
- Define: is the ability of the brain to regulate its blood flow despite changes in systemic blood pressure
- Cerebral perfusion pressure (CPP) is classically defined as:
- CPP = MAP— (ICP + CVP)
- MAP mean arterial pressure
- ICP intracranial pressure
- Early studies with baboons demonstrated that ICP represented the effective cerebral venous outflow pressure and importantly the sagittal sinus pressure did not change within a range of ICP, reflecting the rigid nature of dural sinuses compared to parenchymal veins.
- CVP central venous pressure
- CVP is normally low, approximately 2– 5 mmHg.
- Clinically, CVP is therefore often omitted from the equation, giving:
- CPP=MAP−ICP.
- Monro-Kellie hypothesis
- When the intracranial volume rises, compensatory mechanisms can initially maintain ICP at normal or near normal levels (ICP <20 mmHg)
- CSF volume is reduced through movement of CSF into the spinal canal and increased absorption into the venous circulation.
- Partial compression of venous sinuses.
- If compensatory mechanisms are overwhelmed
- A small change in intracranial volume → a significant rise in ICP → a reduction in CPP + cerebral blood flow.
Cerebral blood flow (CBF)
- Approximately 700 ml per minute (50 ml per 100 g per minute).
Grey matter | White matter |
70 ml per 100 g per min | 20 ml per 100 g per min. |
- < 20 ml per 100 g per minute
- Electroencephalographic changes are noted
- < 10 ml per 100 g per minute
- Irreversible cerebral infarction below
- An autoregulatory range exists within which a relatively constant CBF is maintained over a range of mean arterial pressure, between approximately 50 and 150 mmHg (Fig. A).
- The autoregulatory range is increased in hypertensive individuals.
- At low or high mean arterial pressures outside this range, CBF increases passively with rising arterial pressure.
- Mechanisms of cerebral blood flow regulation
- Certain methodologies exist for the measurement and study of CBF.
- Total blood flow measurement
- The Fick principle can be applied following the inhalation of an inert gas (e.g. N20)
- Regional blood flow measurement
- Detection of radioactive 133- xenon
- Positron emission tomography
- Functional magnetic resonance imaging
- Doppler probes
- 3 principle theories have been proposed to describe the mechanism of autoregulation;
- The maintenance of a relatively constant CBF across a range of CPP is thought to involve the myogenic response of cerebral smooth muscle in vessel walls, particularly at higher pressures within the autoregulatory part of the curve.
- Constrict in response to raised pressure
- Dilate in response to reduced pressure.
- The calibre of vessels that mediate autoregulation may span the range of 40– 300 µm but typically less than 100 µm.
- Metabolic regulation is thought to be most influential at low perfusion pressures. When CBF falls to levels outside the autoregulatory range, there is a compensatory rise in oxygen extraction from blood. Regional increases in neuronal activity are associated with corresponding regional increases in cerebral metabolic rate. Mechanisms are likely to involve hypoxia, intrinsic neural pathways, and associated release of metabolic factors. Arterial PCO2
- And PO2 can affect CBF (Figs. B and C), through changes in cerebral vessel diameter. CO2 has a marked and
- Reversible effect on CBF. Hypercapnia causes significant dilation of cerebral arteries and arterioles, with a resulting increase in CBF, while hypocapnia causes the reverse. Following hypocapnia, detectable changes in pial artery diameter and CBF occur after 30 seconds. Due to the curvilinear relationship, outside the physiological range of PCO2, reductions cause a marked reduction in CBF. After a period
- Of 24– 48 h, due to physiological buffering, hypocapnic reduction in CBF may not be maintained. At values beyond 10 kPa, near maximal vasodilation is achieved therefore increases in PCO2 have a modest
- Effect on CBF. The mechanism of hypercapnic vasodilation is not fully understood but is thought to involve the direct effect of H+ on cerebral vascular muscle (Kontos et al., 1977). Finally, hypocapnia is known to improve cerebral pressure regulation while hypercapnia impairs it. Hypoxia is also a profound vasodilator to ensure adequate oxygenation of brain tissue. At levels above 8k Pa, changes in PO2 have a very minimal effect on CBF, with CBF near constant. Below 6.7 kPa, CBF increases rapidly with increasing hypoxia. Again, the mechanism of hypoxic related cerebral vasodilation is not fully understood. Mechanisms are thought to include reduction in adenosine triphosphate (ATP) levels opening potassium channels on cerebral smooth muscle and local changes in nitric oxide and adenosine production.
- Extrinsic and intrinsic control
- Sympathetic innervation from the superior cervical ganglion
- Main control
- Autonomic nervous system
- Regulates extraparenchymal vessels
- Does not play major role in intraparenchymal vessel tone
- Largely due to evidence from denervation studies
- However, it may play a role when blood pressure rises above the normal limits of autoregulation through resetting or modulation of the normal autoregulatory curve.
- This represents an important physiological mechanism that prevents significant rises in CBF and any associated breakdown in the blood- brain barrier that would otherwise be expected from acute surges in blood pressure.
- Parasympathetic supply,
- Little role under normal physiological conditions.
- Some evidence from chronic denervation studies suggests a potential role in maintaining CBF during periods of low perfusion pressure and thereby reducing ischaemia and infarction.
- Intrinsic or central neural regulatory pathways have also been investigated to establish their autoregulatory role, with
- Neuronal nitric oxide implicated and so- called neurovascular units, comprised of neurons separated from microvessels by perivascular ganglia and basement membrane
Myogenic
Metabolic
Neurogenic regulation.
Controversy: Mannitol and cerebral blood flow
- The blood haemocrit level and therefore viscosity of blood can affect CBF.
- Increases in CBF due to reduced haematocrit and viscosity may be counterbalanced by reduced and suboptimal oxygen delivery.
- At haematocrit levels below 30%, increases in CBF can be attributed to low arterial PO2 → cerebral ischaemia.
- Mannitol is known to reduce ICP,
- Mechanism
- Reduce ICP through a direct osmotic action and subsequent reductions in cerebral oedema
- Traditionally
- However due to evidence including its speed of action people doubted this
- Autoregulatory cerebral vasoconstriction and reduction in intravascular volume
- Due to mannitol causing a rapid increase in peripheral intravascular volume and hence cerebral perfusion
- Reduction in blood viscosity (due to changing red blood cell rheology)
- Perfusion and autoregulatory cerebral vasoconstriction occurs
- However, more recent studies in headinjured subjects have not demonstrated a fall in cerebral blood flow following mannitol administration (Diringer et al., 2012)
- Free radicle scavenger.
- Studies have also suggested that prolonged usage may be detrimental through subsequent increases in ICP and recent studies have focused on hypertonic saline which may similarly lower ICP but without such rebound rises (Castillo et al., 2009; Rickard et al., 2014).
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