Cerebral Blood Flow

Describe the distribution of blood volume and flow in the various regional circulations and explain the factors that influence them, including autoregulation. These include, but not limited to, the cerebral and spinal cord, hepatic and splanchnic, coronary, renal and utero-placental circulations

With respect to cerebral blood flow:

• Normal is ~750ml.min^-1 or ~15% of resting cardiac output
  Note that the brain makes up only ~2% of body weight.
  • A relatively high blood flow is required due to the high cerebral metabolic rate for oxygen (CMRO₂) of 50ml.min^-1
• The brain is sensitive to interruptions in flow as it has:
  • A high metabolic rate
  • No capacity to store energy substrates

The factors affecting cerebral blood flow can be classified by the factors in the Hagan-Poiseuille Equation:

$CBF \approx {\Delta P \pi R^4 \over 8 \eta L}$, where:

• $\Delta P$ is the pressure difference driving flow, i.e. CPP
• $R$ is the radius of the blood vessels
• $\eta$ is the blood viscosity
  These are also called rheologic factors.
• $L$ is the length of the tube, a fixed quantity

Factors Affecting Perfusion Pressure{#cpp)

• Cerebral Perfusion Pressure is the difference between mean arterial pressure and intracranial pressure: $CPP = MAP - ICP$
• A normal CPP is ~80mmHg
• In normal individuals, CBF is classically thought to be autoregulated over a CPP range of 60-160mmHg
  • This occurs by myogenic means, similar to the kidney
  • In normal circumstances, this is dependent on MAP (i.e., with a normal ICP < 10mmHg, CBF is regulated over a MAP range of 50-150mmHg).
• Note that more recent evidence would suggest that CBF is autoregulated over a much narrower range of perfusion pressures, and has a greater capacity to buffer an increased rather than decreased perfusion pressure

• At the lower limit, the reduced perfusion pressure means flow cannot be maintained even with maximal vasodilation
• At the upper limit, the high perfusion pressure overcomes maximal vasoconstriction
  • Additionally, the increased CBF may result in damage to the blood-brain barrier
• The curve is left-shifted in neonates and children (due to lower normal MAP)
• The curve is right-shifted in chronic hypertension
• The curve is probably inaccurate in the pathological conditions where it would otherwise be useful, such as malignancy, subarachnoid haemorrhage, CVA, or TBI
  • This may be due to damage to either the feedback mechanisms, or the effectors (vasculature)
  • Flow may become pressure-dependent, and small changes in MAP can have large changes in CBF

Factors Affecting Vessel Radius

Vasodilation and constriction affect both cerebral blood flow and ICP, as vasodilatation increases cerebral blood volume and therefore may increase ICP through the Monroe-Kellie doctrine.

Vessel calibre is affected primarily by four factors:

• Cerebral metabolism
• PaCO₂
• PaO₂
• Neurohormonal factors
• Temperature

Cerebral Metabolism

Cerebral metabolism (typically given by the cerebral metabolic requirement for oxygen, CMRO₂) has a linear association with cerebral blood flow - this is known as flow-metabolism coupling. This is controlled locally through the release of vasoactive mediators, such as H⁺, adenosine, and NO. Determinants of cerebral metabolism include:

• Drugs
  Cerebral metabolism may be decreased by use of drugs such as benzodiazepines, barbiturates, and propofol.
• Temperature
  CMRO₂ decreases linearly by ~7% per degree centigrade, allowing prolonged periods of reduced CBF without ischaemic complications.

PaCO₂

Carbon dioxide acts as a cerebral vasodilator.

• CBF is almost linear between 20mmHg and 80mmHg
  • Above 80mmHg, the circulation is maximally dilated
  • Below 20mmHg, the circulation is maximally constricted
    Additionally, the alkalosis causes a left-shift of the oxyhaemoglobin curve. This reduces offloading of oxygen, causing hypoxia and subsequent vasodilation.
    
  • There is a right-shift in chronic hypercapnea
    The mechanism of action is complex, but involves local increase in H⁺ ions.
  • Changes to CBF with CO₂ are dependent on current arteriolar tone - vasodilatory effects of CO₂ are significantly reduced when the perfusing pressure is low.

PaO₂

• CBF increases rapidly when PaO₂ falls below 60mmHg so that cerebral oxygen delivery is maintained
  Hypoxia causes a release of adenosine and reduced calcium uptake, with subsequent vasodilation

Neurohormonal

• Autonomic control of cerebrovascular tone is limited, though is responsible for the right-shift in the autoregulation curve with sustained hypertension

Factors Affecting Blood Viscosity

• Blood viscosity is dependent on haematocrit
• Reduced haematocrit is associated with increased CBF, but reduced O₂-carrying capacity
  The optimal haematocrit is ~0.3-0.35, which provides the best balance between reduction of viscosity to improve cerebral blood flow, without reducing DO₂.

References

1. Kam P, Power I. Principles of Physiology for the Anaesthetist. 3rd Ed. Hodder Education. 2012.
2. Hill L, Gwinnutt C. Cerebral Blood Flow and Intracranial Pressure. FRCA Website.
3. Willie CK, Tzeng YC, Fisher JA, Ainslie PN. Integrative regulation of human brain blood flow. J Physiol. 2014 Mar 1;592(5):841-59.
4. Muizelaar JP. CBF and management of the head-injured patient. In: Narayan RK, Wilberger JE, Povlishock JT, eds. Neurotrauma. New York: McGraw-Hill, 1996:553–561.