The brain has an absolute dependence on the blood for its immediate supply of oxygen and energy substrates. Interruption of oxygen or substrate supply by compromise of pulmonary or cardiovascular function or metabolic factors results in encephalopathy and, ultimately, cell death. The brain utilizes approximately 20% of the total oxygen supply of the body. While glucose remains the primary energy substrate for the brain, alternative substrates may be used, under certain circumstances. For example, in the developmental period as well as during fasting in the adult, ketone bodies are generated and blood concentrations may become sufficiently high to afford an alternative energy substrate. The appropriate enzymes required for ketone body utilization are maintained in both developing and adult brain in readiness for an emergency such as prolonged fasting or starvation. In conditions such as hypoglycemia, alternative energy substrates, such as glycogen and amino acids, may be used, but the limited pool size and compartmentation of these substrates limits their ability to support cerebral energy requirements (Chap. 31).

Given the high dependency of cerebral energy production and neurotransmitter synthesis on glucose and oxygen (Fig. 38-1), any limitations in the supply of these substrates can result in metabolic encephalopathy.

Figure 38-1

Simplified schematic diagram of the major metabolic pathways linking glycolysis and tricarboxylic acid (TCA) cycle flux to the synthesis of neurotransmitters: acetylcholine, GABA, glutamate and aspartate. αKGDH, α-ketoglutarate dehydrogenase; (more...)