Physiology note 2 : Cerebral Autoregulation
CEREBRAL AUTOREGULATION
Contributed by Lt Col
Purushotham G
DEFINITION
Cerebral autoregulation (CA) is a
homeostatic process defined as the intrinsic ability of brain to maintain a
steady cerebral perfusion matched to cerebral metabolic demand across a range
of blood pressures. It is a protective mechanism critical
to preserving brain function at extremes of arterial blood pressure as brain is
sensitive to both under and over perfusion and
prevents damage from hyperemia, or ischemia. Cerebral autoregulation (CA) is achieved by reflex vasoconstriction or vasodilation of the cerebral arterioles in response to changes in perfusion pressure.
IMPORTANCE
OF CA
The cerebral autoregulation curve also known as the “Lassen
curve”, first described by Lassen in 1959 is a graphical
representation of the relationship between Cerebral blood flow (CBF) and
Cerebral perfusion pressures (CPP). It represents the autoregulatory capacity
of the cerebral vasculature over a range of CPP values. In the classic
representation, Lassen's curve shows a sigmoidal shape, indicating that CBF
remains relatively constant within a certain range of CPP, but begins to
decrease at lower CPP values and plateau at higher CPP values.
The autoregulatory system in the brain can
maintain essentially constant CBF between a MAP of 50 to 60 mm Hg to 150
to 160 mm Hg. When MAP decreases to less than 50 to 60 mm Hg, maximum
vasodilation is reached, and CBF decreases proportionally with the MAP,
resulting in ischemia. On the other extreme, when MAP exceeds 150 to 160 mm Hg,
arteriolar vasoconstriction is exhausted, and hydrostatic pressure increases
continuously, resulting in cerebral edema and breakdown of the blood–brain barrier (ie, hypertensive
encephalopathy or ICH)
Figure 1 a
Figure 1 b
Autoregulation depicting
relationship between cerebral blood flow (CBF) and cerebral perfusion pressure
or mean arterial blood pressure.
a.
Representation
of the autoregulation curve described by Lassen4 in 1959 based on between-subject analysis of
patients during pharmacological interventions and pathologies.
b. Re-conceptualised version of the autoregulation
curve with a smaller plateau region (Willie and colleagues)
FACTORS
REGULATING CEREBRAL AUTOREGULATION
Cerebral oxygen delivery is a function of cerebral blood
flow (CBF) and blood oxygen content, whereby cerebral blood flow (CBF) is
dependent on cerebral perfusion pressure (CPP) and inversely proportional to
cerebrovascular resistance (CVR).
CBF = CPP/CVR = (MAP – ICP)/CVR
Regulation of CBF is mediated by
four main factors which include:
a. Myogenic
mechanisms - The myogenic tone is the response
of vascular smooth muscle cells which constrict or dilate in response to
changes in transmural pressure. These pressure changes involve membrane
depolarisation
and activate voltage-gated calcium channels and proteins in the
vessel wall, triggering various downstream cascades.
b. Neurogenic mechanisms - Neurogenic control of the cerebral
vasculature is suggested to be an important factor in cerebral autoregulation,
particularly in large vessels and contributes to fine-tuning of blood flow
playing a key role in regional variability of CBF. Neurons and other cell types
like astrocytes and microglia regulate smooth muscle function via adrenergic
and cholinergic fibres releasing various neurotransmitters with vasoactive
properties.
c. Endothelial mechanisms - The local endothelial factors which are
released by physical stimuli (shear stress or haemorrhage), neurotransmitters,
or cytokines modulate the vascular tone and thus autoregulation. The
vasoconstrictors thromboxane A2 and endothelin-1 and the
vasodilators like nitric oxide (NO) are important regulators of CBF.
d. Metabolic Mechanism - These involve variations of metabolic
activity and effects of Paco2, Pao2, and pH
in the local environment that adjusts the blood flow. Studies have demonstrated
that each mm Hg increase in Paco2 above normal corresponds
with a 3–6% increase in CBF, while each mm Hg decrease in Paco2
corresponds with a 1–3% reduction in CBF. The cerebral vascular smooth muscle
cells constrict with increased pH and relax with decreased pH. The CBF
increases below a Pao2 of 50 mm Hg as a result of a reduction
of vascular smooth muscle tone via increased activation of membrane potassium
channels and inhibition of transmembrane calcium flux
Methods
to Measure Cerebral Autoregulation
There
are various methods described to measure CBF autoregulation. Static changes are
the changes in MAP or ICP that occur over minutes to hours, while dynamic
changes are transitory fluctuations in CBF in response to MAP changes.
Calculating the cerebral blood flow at 2 different equilibrium states of
arterial blood pressure has been the traditional method used for both static
and dynamic measurements.
a.
Static measurement - In measurement of this the first
pressure measurement is taken at baseline while the second is measured after
manual or pharmacologic intervention of blood pressure.
b.
Dynamic autoregulation - It refers to short-term, fast blood
flow responses to changes in systemic pressure. The input signal is blood
pressure or volume change and the resulting change in the intracranial
compartment acts as the output signal. Pressure changes are inducible using stimuli
such as body tilt, thigh-cuff release, or lower body negative pressure and
measured by transcranial Doppler which allows for the visualization of
real-time blood-flow velocities (with a temporal resolution of approximately 5
msec).
There
are more than 20 different types of cerebral autoregulation indices based on
device used to measure CBF or surrogate each having their own merits and
limitations.
Transfer
Function Analysis
Transfer
function analysis (TFA) is based on linear, stationary modeling and a fast
Fourier transform algorithm to compute spectral estimates of blood pressure and
cerebral blood flow.
Time
Domain Analysis
This
approach measures the degree of correlation between blood pressure and various
cerebral output signals. A rolling Pearson correlation coefficient is
calculated between 30 consecutive, time-averaged (10 sec) values of
arterial blood pressure and cerebral blood flow (or its surrogates). The
resulting coefficient provides an estimate of the autoregulatory function of
each variable.
Wavelet
Analysis
This
approach also known as multimodal pressure-flow analysis, considers both the
time and frequency content of the signal. The wavelet analysis produces maps of
phase shift and coherence between blood pressure and cerebral blood flow
velocity over various frequencies and time points.
Projection
Pursuit Regression
Projection
pursuit regression (PPR) is a non-parametric method in which a linear
transfer function between input (blood pressure) and output (brain blood flow)
is analysed.
Pressure reactivity index (PRx)
The
pressure reactivity index (PRx) is a valuable tool in neurocritical care that
provides information on the dynamic relationship between intracranial pressure
(ICP) and CPP. This approach is considered as a hybrid pseudodynamic
measurement of CBF autoregulation as it measures both static and dynamic
changes and is based on analysis of naturally occurring ICP waves (i.e.
Lundberg ‘B waves’) that occur at a frequency of 0.5–2 per min. In
neurocritical care, PRx serves as a surrogate marker for CA, allowing clinicians
to assess the brain's ability to maintain stable CBF during a range of BP
fluctuations.
In
addition to blood flow velocity, other intracranial signals are frequently
helpful in dynamic vasoregulatory investigation. Examples include near-infrared
spectroscopy (NIRS), local brain tissue oxygenation (PbtO2), and ICP
monitoring from cerebrospinal fluid draining systems.
Use
of cerebral near infrared spectroscopy is a validated and practical method of
CBF autoregulation monitoring. When processed regional cerebral oxygenation
(%rSO2) signals are utilised as a surrogate of CBF, the
autoregulation index is termed the cerebral oximetry index (COx) or tissue
oxygenation index (TOx).
CLINICAL RELEVANCE OF CA
Understanding
the principles of CA is essential for the management of various neurological
conditions, including TBI, stroke, and neurodegenerative diseases. Impairments
in autoregulatory function can predispose individuals to cerebral ischemia or
edema, exacerbating neurological injury.
Cerebral autoregulation is one of the
compensatory mechanisms in acute ischemic stroke to preserve CBF and the brain tissue viability. Also, CA affects outcome of revascularization therapies since an impaired cerebral
autoregulation causes reperfusion injury manifested as brain edema or hemorrhage Therefore studying
cerebral autoregulation could improve outcome in ischemic stroke following thrombolytic or EVT administration.
Recent
studies have demonstrated significant regional differences between the anterior
and posterior circulatory territories which are driven by the distinct
functional specializations of these brain regions and their corresponding
metabolic demands. PRES characterized by headache, encephalopathy, visual
impairment, and seizures predominantly affects the posterior circulation of the
brain, particularly the parieto-occipital regions and is closely related to
failure of CA leading to hyperperfusion and vasogenic edema especially in the
posterior circulation.
Conclusion
Cerebral
blood flow (CBF) autoregulation is the physiologic process whereby blood supply
to the brain is kept constant over a range of cerebral perfusion pressures
ensuring a constant supply of metabolic substrate.
In
contrast to the traditional teaching that 50 mm Hg is the autoregulation
threshold, recent investigations have found wide inter-individual variability
of the lower limit of autoregulation ranging from 40 to 90 mm Hg in adults and
20–55 mm Hg in children
For
progressively faster changes in BP (minutes, seconds), CBF becomes
incrementally more unstable and may show large fluctuations leading to adverse
outcomes in patients with traumatic brain injury, ischaemic stroke,
subarachnoid haemorrhage, intracerebral haemorrhage, and in surgical patients.
Recent
studies have shown significant differences in the autoregulatory mechanisms
between the anterior and posterior circulatory territories of the brain.
References
- Monitoring of cerebral blood
flow autoregulation: physiologic basis, measurement, and clinical
implications Vu, Eric L. et al. British
Journal of Anaesthesia, Volume 132, Issue 6, 1260 - 1273
b.
Silverman
A, Petersen NH. Physiology, Cerebral Autoregulation. [Updated 2023 Mar 15]. In:
StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2025 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK553183/
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