Principles of Cerebral Metabolism and Blood Flow

Introduction

The brain’s survival and function depend on its ability to maintain a constant supply of oxygen and energy-rich substrate. To accomplish this feat the complex architecture of the brain that accounts for approximately 2% of total body mass demands approximately 20% of the total cardiac output, and consumes roughly one quarter of resting total body oxygen consumption.

Cerebral Hemodynamics

An understanding of the complex cerebral circulation first requires an understanding of basic physical principles about flow. Ohm’s law predicts that flow (Q) is proportional to the pressure gradient between inflow and outflow (ΔP) divided by the resistance to flow (R).

Q=ΔP/RQ=ΔP/R
Q = Δ P / R

Analogously in the brain, cerebral perfusion pressure (CPP), the difference between arterial inflow and venous outflow pressure, represents the driving pressure for cerebral blood flow (CBF). CPP is the difference between mean arterial pressure (MAP) and the pressure in the thin-walled veins. Venous pressure changes with changes in intracranial pressure (ICP) and is typically 2 to 5 mm Hg higher than the central venous pressure. CPP, therefore, can be described as:

CPP=MAP−ICPCPP=MAP−ICP
CPP = MAP − ICP

Poiseuille’s law demonstrates that in addition to CPP (ΔP), blood viscosity (η) and vessel radius (r) are key determinants of CBF (Q). Vessel length (L) is generally not measured in physiologic systems.

Q=(πr4ΔP)/8ηL)Q=(πr4ΔP)/8ηL)
Q = ( π r 4 Δ P ) / 8 η L )

Viscosity, the internal friction of blood flow, is frequently overlooked because direct measurement is difficult. Importantly, however, viscosity is felt to vary directly with changes in hematocrit and any other process that alters blood’s cellular composition. Blood viscosity also varies inversely with vessel diameter. This is a consequence of the increased velocity gradient of laminar flow as vessel size decreases, a parameter known as the shear rate. Thus for a given blood velocity, shear rates are greater in smaller vessels and apparent viscosity is consequently lower in the microcirculation. This effect is known as the Fahraeus-Lindquist effect.

The most powerful factor in Poiseuille’s law that can influence CBF is vessel radius. For example, the maximum constriction that can be obtained by hyperventilation is approximately 20% from baseline. This, however, leads to a decrease in CBF of approximately 60%. From a practical standpoint, all of this diameter regulation takes place in the microcirculation.

With knowledge about how much blood flows to the brain and how much oxygen the brain extracts from this blood (arteriovenous difference in oxygen, AVDO ₂), one can calculate cerebral metabolic rate of oxygen (CMRO ₂) consumption.

CMRO2=CBF×AVDO2CMRO2=CBF×AVDO2
CMRO 2 = CBF × AVDO 2

Physiology of Cerebral Blood Flow and Cerebral Blood Volume

Normal CBF is approximately 50 mL/100 g brain tissue/min. Flow is normally greater in gray matter than white matter. Under normal conditions there are critical thresholds for CBF in the brain to maintain tissue health and cellular integrity. When CBF is reduced to 25 mL/100 g/min there is electroencephalographic slowing, and at 20 mL/100 g/min loss of consciousness occurs. When CBF is less than 18 mL/100 g/min, cellular homeostasis becomes jeopardized and neurons convert to anaerobic metabolism. At a CBF of 10 mL/100 g/min, membrane integrity is compromised and irreversible brain damage is inevitable ( Table 1.1 ). Tissue infarction, however, is related not only to CBF, but to time as well.

Table 1.1

Cerebral Blood Flow Thresholds

Cerebral Blood Flow (mL/100 g/min)	Threshold	Consequences
40-60	—	Normal
20-30	Neurologic function	Start of neurologic symptoms
		Altered mental status
16-20	Electrical failure	Isoelectric electroencephalogram
		Loss of evoked potentials
10-12	Ionic pump failure	Na ⁺and K ⁺pump failure
		Cytotoxic edema
<10	Metabolic failure	Complete metabolic failure with gross disturbance of cellular energy homeostasis

From Doberstein C, Martin NA. Cerebral blood flow in clinical neurosurgery. In Youmans R, editor. Neurological surgery: a comprehensive reference guide to the diagnosis and management of neurosurgical problems. Philadelphia: WB Saunders; 1996. p. 521, Table 21-4.

Many different factors are postulated to maintain adequate CBF, but it is believed that local metabolic factors are of primary importance. Under normal circumstances, in areas of increased cerebral activity, vasoactive substances are released, which alters vascular tone and local perfusion. The compensatory increase in perfusion then creates a local washout effect, which leads to a reduction in perfusion. Key local metabolites include, but are not limited to, carbon dioxide (CO ₂), potassium, adenosine, nitric oxide, histamine, and prostaglandins.

Cerebral blood volume (CBV) is determined by CBF and capacitance vessel diameter. CBV thus increases with vasodilation and decreases with vasoconstriction. The relationship between CBF and CBV, however, is complex and under both normal and pathologic situations these variables may be inversely related. Furthermore, blood volume is not equally distributed throughout the brain, with greater volume per unit weight in gray matter than white matter. The central volume principle relates the volume that intravascular blood occupies within the brain (CBV in mL) and the volume of blood, which moves through the brain per unit time (CBF in mL/min).

CBF=CBV/τCBF=CBV/τ
CBF = CBV / τ

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