Hypoxia-ischemia edema

A number of toxic conditions beside hypoosmotic stress and hypoxia/ischemia produce brain edema and the causes may be related to regulation of the aquaporins (see Ch. 34). AQP1 and AQP4 are intensely upregulated in reactive astrocytes in subarachnoid hemorrhage [69], in human glioma and astrocytoma [70] and AQP4 in endothelia and reactive astrocytes in metastatic carcinoma [71,72]. 

Alteration in mental status occurring in patients with systanic sepsis always carries a serious prognosis. The mechanisms of impaired brain function are poorly understood and are probably multifactorial. Considerations include hypoxia, ischemia, mitochondrial dysfunction and anaerobic cerebral energy metabolism, blood-brain barrier dysfunction or impaired transporter function, cerebral edema, toxins like ammonia or endotoxins, and last but not least, clinical use of cerebral depressants and sedatives in severely ill patients. In patients with multi-organ failure, clearance of common short-acting sedatives can become prolonged, resulting in severe and protracted alteration of mentation. 

Cerebral edema occurs in response to a wide variety of insults, including ischemia, hypoxia, infection, and noninfectious inflammation. Shifts in brain water, which is the basis of the cellular swelling, are due to osmotic forces, and result in increases in intra- and extracellular spaces. A reasonable amount of tissue swelling can be tolerated in most parts of the body, however, the restrictions imposed by the rigid tentorium and bony skull cause life-threatening herniation with relatively small increases in the brain compartments. Two early anatomists, Monroe (1733-1817) and Kellie (1758-1829), recognized that increased intracranial pressure due to swelling in the cerebrospinal fluid (CSF), blood, or brain tissue compartments could increase intracranial pressure the concept of limited expansion capacity of the intracranial contents is called the Monroe-Kellie doctrine. 

The forces driving water flow to form cytotoxic edema are osmotic, generated in brain injury conditions (ischemia, trauma, hypoxia) by disturbances in ionic homeostasis due to failure of the Na /K+ ATPase and/or dramatic influx of Na" and Ca " via ionotropic glutamate receptors (excitotoxicity) and other ionic channels. These pathological alterations in cellular ionic homeostasis result in Na" " and water flow from the intravascular and extracellular space into the intracellular compartment. 

In contrast to ischemia-reperfusion, relatively few studies examined the effect of hypoxia on microvas-cular function, despite clinical evidence of a microvascular inflammatory response in this setting. For example, systemic hypoxia occurs in people at high altitudes and may result in high-altitude cerebral edema (HACE). Although the underlying cause of this serious condition is not yet known, microcirculatory alterations were proposed to play a major role. For example, increased leukocyte-endothelial interactions are frequently associated with the pathological features of environmental hypoxia." " ... 

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