As is true for hyponatremia, the degree of CNS disturbance in hypernatremia is generally related to the rate at which the serum Na rises. Slowly rising values, to levels as high as 170 mEq/L, may be surprisingly well tolerated. Rapid elevations of sodium shrink the brain, especially in infants. Extremely high levels cause impairment of consciousness with asterixis, myoclonus, seizures, and choreiform movements. In addition, muscular weakness, rhabdomyolysis, and myoglobinuria have been reported.
In hypernatremia with hyperosmolality, the brain retains its volume more effectively than do other organs by a compensatory mechanism that has been attributed to the presence of “idiogenic osmoles,” possibly glucose, glucose metabolites, and amino acids. The impairment of neuronal function in this state is not understood. Theoretically one would expect neuronal shrinkage and possibly alteration of the synaptic surface of the cell.
The main clinical effect of hypokalemia (≤2.0 mEq/L) is generalized muscular weakness (see Chap. 45). A mild confusional state had been alluded to in the literature but must be very infrequent. The electrolyte condition is readily corrected by adding K to intravenous fluid and infusing it at no more than 4 to 6 mEq/h. Hyperkalemia (>7 mEq/L) also may manifest itself by generalized muscle weakness, although the main effects are changes in the electrocardiogram (ECG), possibly leading to cardiac arrest.
Limitation of space permits only brief reference to other metabolic disturbances that may present as episodic confusion, stupor, or coma. The most important members of this group are summarized below.
Hypercalcemia This is defined as an elevation of the serum calcium concentration greater than 10.5 mg/dL. If the serum protein content is normal, Ca levels greater than 12 mg/dL are required to produce neurologic symptoms. However, with low-serum albumin levels, an increased proportion of the serum Ca is in the unbound or ionized form (upon which the clinical effects depend), and symptoms may occur with total serum Ca levels as low as 10 mg/dL.
In young persons, the most common cause of hypercalcemia is hyperparathyroidism (either primary or secondary); in older persons, osteolytic bone tumors, particularly meta-static carcinoma and multiple myeloma, are often causative. Less common causes are vitamin D intoxication, prolonged immobilization, hyperthyroidism, sarcoidosis, and decreased calcium excretion (renal failure).
Anorexia, nausea and vomiting, fatigue, and headache are usually the initial symptoms, followed by confusion (rarely a delirium) and drowsiness, progressing to stupor or coma in untreated patients. A history of recent constipation is common. Diffuse myoclonus and rigidity occur occasionally, as do elevations of spinal fluid protein (up to 175 mg/100 mL). Convulsions are uncommon.
Hypocalcemia The usual manifestations are paresthesias, tetany, and seizures. With severe and persistent hypocalcemia, altered mental status in the form of depression, confusion, dementia, or personality change can occur. Anxiety to the point of panic attack is also known. Even coma may result, in which case there may be papilledema as a result of increased intracranial pressure. Aside from the raised pressure, the CSF shows no consistent abnormality. This increase in intracranial pressure may be manifest by headache and papilledema without altered mentation or with visual obscurations. Hypoparathyroidism is discussed again further on, under “Acquired Metabolic Diseases Presenting as Progressive Extrapyramidal Syndromes.”