The brain is a major energy-consuming organ in the body. An adult human brain weighs about 1500 g, which represents about 2% of the body weight, yet it consumes approximately 20% of the total body oxygen. In children up to age 4, the brain utilizes about 50% of the total body oxygen. Cerebral metabolic rate (CMR) is expressed in terms of oxygen consumption (CMRO2), which in a normal conscious adult is approximately 3.5 mL/100 g/min or about 50 mL O2/min in the resting state. In the absence of pathology, CMR is coupled with cerebral blood flow (CBF) at 50 mL/100 g/min.
Cerebral metabolism is directly related to the number and frequency neuronal depolarizations. About 60% of CMRO2 is used to generate adenosine triphosphate (ATP) to maintain neuronal electrical activity as seen by EEG; thus, producing complete electrical silence on EEG with anesthetic agents will decrease CMRO2 by about 60%. The remaining 40% of CMRO2 is used for cellular integrity, which is minimally affected by anesthetic agents.
Oxygen consumption varies throughout the brain, with gray matter utilizing twice the O2 utilized by white matter. Increase in CMR following neuronal activity also results in increase in CBF. The mechanism of CBF coupling to CMR is not well known, but is thought to correlate with metabolic byproducts, possibly due to accumulation of adenosine, nitric oxide, cyclooxygenase, and potassium.
Due to relatively high oxygen consumption, interruption of cerebral perfusion will usually result in unconsciousness within 10 seconds. Under most conditions, if cerebral perfusion is not restored within 3–8 minutes, neuronal ATP stores will become depleted, and irreversible cellular injury will occur. Deep brain structures, such as hippocampus and cerebellum, are most sensitive to hypoxic injury.
SUBSTRATES FOR CEREBRAL METABOLISM
Cerebral function is dependent on a continuous supply of glucose. Under aerobic conditions, glucose is the main substrate for energy production during normal neuronal activity. At rest, brain glucose consumption is 5 mg/100 g tissue/min, of which more than 90% is metabolized aerobically. Insulin is not required for uptake of glucose by cerebral tissue as glucose can easily cross the blood–brain barrier (BBB) via facilitated diffusion.
Although glucose is the preferred substrate for cerebral metabolism during rest, lactate also supplements brain metabolism as an energy source. Lactate contribution to brain metabolism is less than 10% at rest. However, this can increase to 60% during stress or elevated plasma lactate levels (e.g., exercise, hypoglycemia, and hypoxia).
During an episode of prolonged hypoglycemia or starvation, brain glucose stores are rapidly exhausted and cerebral metabolism occurs primarily from lactate and ketone bodies. The three ketone bodies are beta-hydroxybutyric acid, acetoacetic acid, and acetone. Ketone bodies are derived from incomplete oxidation of fatty acids in ...