Table 25-1 Causes of metabolic encephalopathy*

1. Deprivation of oxygen, substrate, or metabolic cofactors
1. Hypoxia (interference with oxygen supply to the entire brain - cerebral blood flow [CBF] normal)
1. Decreased oxygen tension and content of blood
• Pulmonary disease/ Alveolar hypoventilation
• Decreased atmospheric oxygen tension
2. Decreased oxygen content of blood, normal tension
• Anemia
• Carbon monoxide poisoning
• Methemoglobinemia
2. Ischemia (diffuse or widespread multifocal interference with blood supply to brain)
1. Decreased CBF resulting from decreased cardiac output Stokes-Adams, cardiac arrest, cardiac arrhythmias
• Myocardial infarction
• Congestive heart failure
• Aortic stenosis
• Pulmonary infarction
2. Decreased CBF resulting from decreased peripheral resistance in systemic circulation
• Syncope: orthostatic, vasovagal
• Carotid sinus hypersensitivity
• Low blood volume
3. Decreased CBF due to generalized or multifocal increased vascular resistance
• Hypertensive encephalopathy
• Hyperventilation syndrome
• Hyperviscosity (polycythemia, cryoglobulinemia, paraproteinemia, macroglobulinemia, sickle cell anemia, thallassemia)
4. Decreased CBF due to widespread small-vessel occlusions
• Disseminated intravascular coagulation
• Systemic lupus erythematosus
• Subacute bacterial endocarditis
• Fat embolism
• Cerebral malaria
• Cardiopulmonary bypass
• Sickle cell crisis
3. Hypoglycemia
• Resulting from exogenous insulin
• Spontaneous (endogenous insulin, liver disease, etc.)
• Alcohol consumption, prolonged with no carbohydrate intake
4. Cofactor deficiency
• Thiamine (Wernicke's encephalopathy), niacin, pyridoxine, cyanocobalamin
2. Diseases of organs other than brain
1. Diseases of non-endocrine organs
• Liver (hepatic coma)
• Kidney (uremic coma)
• Lung (CO₂ Narcosis)
2. Hyperfunction and/or hypofunction of endocrine organs
• Pituitary
• Thyroid (myxedema-thyrotoxicosis)
• Parathyroid (hypoparathyroidism and hyperparathyroidism)
• Adrenal (Addison's disease, Cushing's disease, pheochromocytoma)
• Pancreas (diabetes, hypoglycemia)
3. Other systemic diseases
• Cancer (remote effects), porphyria
3. Exogenous poisons
1. Sedative drugs
• Barbiturates, nonbarbiturate hypnotics, tranquilizers, bromides, ethanol, anticholinergics, opiates
2. Acid poisons or poisons with acidic breakdown products
• Paraldehyde, methyl alcohol, ethylene glycol, ammonium chloride, salicylates
3. Enzyme inhibitors
• Heavy metals, organic phosphates, cyanide, salicylates
4. Abnormalities of ionic or acid-base environment of CNS
• Water and sodium (hypernatremia and hyponatremia)
• Acidosis (metabolic and respiratory)
• Alkalosis (metabolic and respiratory)
• Postassium (hyperkalemia and hypokalemia)
• Magnesium (hypermagnesemia and hypomagnesemia)
• Calcium (hypercalcemia and hypocalcemia)
5. Diseases producing toxins or enzyme inhibition in CNS
• Meningitis, encephalitis, subarachnoid hemorrhage
6. Disordered temperature regulation
• Hypothermia, heat stroke
7. Postepileptic (postictal) depression
8. Traumatic dysfunction without histologic structural change (concussion)

*After Plum and Posner