Cerebral blood flow in fulminant hepatitis

Fulminant hepatic failure (FHF) is often complicated with cerebral edema, intracranial hypertension, and coma. Cytotoxic and vasogenic factors have been recognized in the etiology of cerebral edema. One of the main causes seems to be the accumulation of glutamine in astrocytes, which is produced from ammonia and the excitatory neurotransmitter glutamate. Ammonia is detoxified within the brain in astrocytes, where it increases the osmotic pressure for water. Ammonia-induced astrocytic water accumulation seems to act as an integrative trigger for the development of intracranial hypertension. While cerebral blood flow is sometimes reduced in the first stage of FHF, as compensatory cerebral vasoconstriction to reduce mean arterial pressure, it later increases as hyperammonemia decreases cerebral arteriolar tone. Despite vasodilation in the systemic and splanchnic beds at early stages of the disease, cerebral vessel resistance may increase, so that cerebral perfusion pressure may be preserved. When cerebral vascular tone is no longer effective in the course of illness, vasodilation gradually develops and rapidly becomes poorly responsive to carbon dioxide stimulation, which signifies loss of autoregulatory tone and cerebral hyperemia develops. Prolonged excessive flow may lead to brain swelling, vasogenic edema, and intracerebral hemorrhage. Brain edema further aggravates the critically reduced cerebral perfusion and is responsible for the high mortality.