Primary alterations in cerebral blood flow (CBF) have been postulated to play a role in the genesis of cerebral edema and elevation of intracranial pressure (ICP). The determinants of ICP are described by the Monroe-Kellie doctrine: Within the fixed space of the cranium, an increase in any of the three compartments of brain, cerebrospinal fluid (CSF), or blood will cause an increase in pressure. Under normal conditions, CBF is under autoregulatory control; meaning that blood flow remains relatively constant over a wide range of mean arterial pressure (MAP). Whether CBF changes are primary or secondary to cerebral edema is not clear. Cerebral blood flow studies in both animals and humans have provided conflicting information.14 In experimental studies of acute liver failure in rats, it has been shown that a linear decrease in cerebral blood flow precedes a rise in ICP.11 This has been presumed to occur via auto-regulatory changes responding to diminished metabolic activity.11 It has also been speculated that primary loss of auto-regulation may occur in acute liver failure, resulting in increased blood flow to the brain compared to the cerebral metabolic demands.15 This phenomenon of cerebral hyperemia has been termed "cerebral luxury perfusion" and is felt to primarily contribute to cerebral edema formation.16 Alternatively, loss of auto-regulation could result in cerebral hypoperfusion and hypoxemia, which could also contribute to edema.17
By whatever mechanism, even a small amount of edema may compromise tissue oxygenation through an increase in the diffusion distance from brain capillaries to cells. A vicious cycle of edema and ischemia may then occur. Neuronal function is likely affected by both alterations in extracellular electrolyte composition and ischemic compromise. Astrocytes also play a key role in brain volume regulation and, as we shall see, appear to play a large part in both edema formation and neuronal dysfunction.
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