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Many metabolic disorders such as hypocalcemia, hypomagnesemia, and ketoacidosis alter nervous tissue function, especially electrical transmission, when there are no morphologic lesions. Some cause degeneration of neurons and ultimately necrosis, often in selective areas of the CNS. These include hypoglycemia, hypoxia, and hepatoencephalopathy, the latter producing a striking hypertrophy and hyperplasia of astrocytes. Most are characterized by a lack of inflammation. The perinatal disease referred to as hypoxic and ischemic encephalopathy (Figure 4.10) also fits this category but is likely complex in its specific pathophysiology.

Inherited, neuronal, metabolic disorders are often expressed as abiotrophy with selective, delayed neuroaxonal degeneration, or as lysosomal storage disease with an accumulation of metabolic products in macrophages and neurons. Other metabolic disorders result in hypomyelination or demyelination.