CLINICAL CHEMISTRY
Electrolytes and Blood Gases (Ionized Calcium) Mary F. Burritt Diuision of Clinical Biochemistry, Mayo Clinic, 200 First Street SW,Rochester, Minnesota 55905 Calcium is the most abundant mineral and one of the most plentiful elements in the human body. Approximately 99% of the calcium found in the adult human body is present in the skeleton. The remaining 1%is found in extracellular fluids and in the cells. Bone is metabolically active and serves as a reservoir of calcium. A small percentage is readily available and can be mobilized to maintain circulating blood levels in the normal or reference range (11). In whole blood or serum, calcium exists in three fractions: ionized or free calcium (Ca2+),which accounts for approximately 50% of the total; protein-hound (primarily to albumin), which accounts for approximately40% of totakand asmall fraction that iscomplexedwithanionssuchasphosphate, bicarbonate, citrate. and lactate and accounts for 10% of the total (12). It has been known since 1935. and substantiated in numerous repom, that the ionized fraction in hlwd is the biologically active fractionand isregulated by theparathyroid (13-16). Parathyrin glands,viathe actionofparathyrin (?I") acts to raise serum Ca2+levels by (1)enhancement of calcium reabsorption in the distal convoluted tubule, (2) mobilization of calcium from the skeleton by acting in conjunction with 1,25-dihydroxyvitamin D3 to release Ca from bone, and (3) increasing activity of the renal enzyme la-hydroxylase that synthesizes 1,25-dihydroxyvitamin D3 (11). The development of ion-selective electrode technology, which made the measurement of Ca2+ both precise and reliable, was recently reviewed (17). Highly reliable instrumentation is available from a number of manufacturers and has allowed clinical laboratories to offer the determination on both a routine and emergency basis (18). Some authors have stressed the need to replace determinations of total calcium with those of ionized calcium (19). The clinical uses of ionized calcium determinations include patients with the following conditions: primary hyperthyroidism, renal failure, preterm infants, critically ill neonates and adults, and surgery where rapid transfusion of blood occurs. Recent developments in some of the clinical situations related to hypocalcemia, as well as analytical considerations, will be reviewed in this paper. This review generally covers the time period 1986-1992 but older papers are cited when relevant.
IONIZED CALCIUM IN NEONATES Transient hypocalcemia of short duration may be present during the first week of life. Neonatal hypocalcemia has been reported to occur in 40% of preterm infants, infanta with birth asphyxia, and infants of insulin-dependent mothers (110).
In any discussion of the disturbances of Ca2+in neonatal life and the decision to treat the hypocalcemia, the question of what is "normal" becomes vitally important. In 1987, a well-controlled study reported reference values for Ca2+for days 1,3,and 5 oflife forfull-term infants ( I l l). The reference intervals reported were 1.05-1.37, 1.11F1.42, and 1.2lF1.48 mmol/L, respectively. Adult reference range is l.lS1.33 mmol/L. The mean Ca2+ on day 1 was significantly lower than on days 3 and 5. The authors emphasized that it is impossible to calculate Ca2+from total calcium or vice versa in this patient population. These same authors later studied preterm infants to document the incidence and course of neonatal hypocalcemia (112,113). In one study ( I I Z ) , they evaluated 68 preterm infants (gestational age 53*38 weeks; birth weight
