MECHANISM OF BRAIN DEATH

Brain injury has a number of sources, such as traumatic or cerebrovascular injury and generalized hypoxia, all of which produce brain edema. Based on the pathologic mechanisms involved, brain edema is classified as vasogenic or cytotoxic.^{[13] [14] [15]} Because it is rare that only one mechanism operates exclusively, the label of vasogenic or cytotoxic is only relative.

Vasogenic edema is induced by an increase in cerebrovascular peremeability after leaking of serum proteins into the brain parenchyma (i.e., after destruction of the blood-brain barrier). Chemical mediators such as histamine, serotonin, angiotensin, bradykinin, and prostaglandins are believed to induce destruction of the blood-brain barrier.^[16] Cytotoxic brain edema occurs in hypoxic and ischemic conditions and results from disturbance of cellular osmoregulation, a process that depends primarily on energy-dependent functioning of ionic pumps. The disturbance of osmoregulation increases entry of water into brain parenchyma. Although in a pure form of cytotoxic edema the blood-brain barrier would remain basically intact, cytotoxic edema would nevertheless disturb blood flow and induce hypoxia and vasogenic edema.

Brain edema may be focal at first, but it then spreads throughout the whole brain in a predictable sequence. Because the brain is covered by a rigid bony skull, its edema is accompanied by an increase in intracranial pressure, which, if sufficiently high, exceeds arterial blood pressure. When cerebral circulation ceases, aseptic necrosis of the brain ensues. Within 3 to 5 days, the brain becomes a liquefied mass, a condition known as respirator brain. ^[17] Such increased intracranial pressure compresses the entire brain, including the brainstem, and total brain infarction follows.^[18]