Hypocalcemia

Hypocalcemia occurs commonly in both inpatients and outpatients. This laboratory abnormality has multiple causes and may occasionally occur in patients without symptoms but more commonly causes tingling paresthesias or muscle cramps in those with mild-to-moderate hypocalcemia. More severe hypocalcemia is associated with tetany, seizures, bronchospasm, laryngospasm, cardiac dysrhythmias, or sudden death. These variable symptoms are attributed to the fact that ionized calcium plays a critical role in many tissues, with roles as varied as regulation of cellular secretion, muscle contraction, nerve function, and blood clotting. About 50% of serum calcium is found in the ionized form, unbound to proteins or anions, whereas 45-50% is bound to proteins, largely to albumin, and the remaining less than 5% bound to anions. Although serum ionized calcium is the biologically active form of calcium, measurement of this form of calcium is more difficult and often not routinely available. Because most laboratories report serum total calcium, this is often the only form of serum calcium available to clinicians trying to assess calcium homeostasis. Several factors affect measurement of serum total and ionized calcium. Alterations in serum albumin increase or decrease serum calcium without affecting ionized calcium. Decreases in serum albumin below 4.0 g/dL decrease total calcium by 0.8 mg/dL for each 1.0 g/dL decrease in serum albumin. Correspondingly, increases in serum albumin above 4.0 g/dL increase total calcium by 0.8 mg/dL for each 1.0 g/dL increase. Albumin-corrected serum calcium is a more accurate representation of serum calcium than total calcium. Dehydration increases serum total calcium due to hemoconcentration. Acidemia increases serum ionized calcium, and alkalemia decreases ionized calcium, without affecting total calcium levels. Circulating citrate or phosphate decreases serum total calcium, whereas monoclonal proteins may increase serum total calcium. Because variations in intravascular volume and calcium-binding proteins affect serum total calcium, ionized calcium should preferentially be measured in complex clinical situations associated with changes in volume status, albumin concentration, and/or blood pH. Under normal circumstances, serum total calcium corrected for serum albumin should be adequate. Hypocalcemia is present when serum total calcium, albumin-corrected total calcium, or ionized calcium is below the lower limit of normal. Serum total calcium below 8.5 mg/dL (2.13 mmol/L), or ionized calcium below 4.80 mg/dL (1.20 mmol/L), is considered below normal in most assays. Before launching into an exhaustive investigation of hypocalcemia, calculation of albumin-corrected serum calcium should be performed, and serum ionized calcium should be checked, if possible, to verify that it is decreased. Situations in which serum total or albumin-corrected calcium are decreased, but ionized calcium is normal, are often due to the presence of binding protein abnormalities. This chapter reviews key points to the diagnosis of hypocalcemia, signs and symptoms, the differential diagnosis, laboratory tests and interpretation, and present and future therapies of hypocalcemia. Three clinical cases will illustrate issues in the assessment and management of hypocalcemia.