A large number of diseases and exogenous agents interfere with the metabolic activities of the nerve cells in the cerebral cortex and the central nuclei of the brain. The better known examples are hypoxia, global ischemia, hypoglycemia, hyperand hypoosmolar states, acidosis, alkalosis, hypokalemia, hyperammonemia, hypercalcemia, hypercarbia, drug intoxication, and severe vitamin deficiencies (see Chap. 39). In general, the loss of consciousness in these conditions parallels a reduction in cerebral metabolism. For example, in the case of global ischemia, in which oxygen and glucose are removed from the brain, an acute drop in cerebral blood flow (CBF) to 25 mL/min/100 g brain tissue from its normal 55 mL/min/100 g causes slowing of the EEG and syncope or impaired consciousness; a drop in CBF below 12 to 15 mL/min/100 g causes electrocerebral silence, coma, and cessation of most neuronal metabolic and synaptic functions. Even lower levels of ischemia are tolerated if they arise more slowly, but neurons cannot survive when flow is reduced below 8 to 10 mL/min/100 g. Oxygen consumption of 2 mg/min/100 g (approximately half of normal) is incompatible with an alert state. In other types of metabolic encephalopathy, cerebral blood flow may stay near normal while metabolism is greatly reduced. An exception is the coma that arises from seizures, in which metabolism and blood flow are greatly increased. Extremes of body temperature (above 41°C [105.8°F] or below 30°C [86°F]) also induce coma through a nonspecific effect on the metabolic activity of neurons. Some of these metabolic changes are probably epiphenomena, reflecting in each encephalopathy a specific type of dysfunction in neurons and their supporting cells. Again, in reference to reducing the level of consciousness, for most metabolic alterations, the rate of change of the underlying derangement is as important as its absolute level.
The endogenous metabolic toxins that are responsible for coma in many common medical conditions cannot always be identified. In diabetes, for example, acetone bodies (acetoacetic acid, β-hydroxybutyric acid, and acetone) are present in high concentration but which causes coma is not entirely clear; similarly in uremia, there is probably an accumulation of dialyzable small molecular toxins, notably phenolic derivatives of the aromatic amino acids but these are not clearly the proximate cause of coma. In hepatic coma, elevation of blood NH3 (ammonia) to five to six times normal levels corresponds roughly to the level of coma but the direct effect on ammonia on neurons is not fully characterized. Lactic acidosis may affect the brain by lowering arterial blood pH to less than 7.0 and this alone may suffice to alter neuronal metabolism globally. The impairment of consciousness that accompanies pulmonary insufficiency is related mainly to hypercapnia. Restated, the toxic effects of these molecules has not been confirmed or well understood, as further on. In acute hyponatremia (Na <120 mEq/L) of whatever cause, neuronal dysfunction is probably a result of the intracellular movement of water, leading to neuronal swelling and loss of potassium chloride from the cells. The mode of action of bacterial toxins and cytokines released during the systemic inflammatory response of sepsis is likewise incompletely understood.