Free fatty acids alter calcium binding: a cause for misinterpretation of serum calcium values and hypocalcemia in critical illness.

FFAs are bound with calcium on the albumin molecule. We hypothesized that changes in circulating FFA levels during critical illness altered calcium-albumin binding. We found that serum from both normal subjects and critically ill patients contained an ether-extractable factor which lowered ionized calcium concentrations and increased albumin-calcium binding. This factor was found in higher concentrations in serum from ill patients. Oleic acid and palmitic acid increased albumin-calcium binding from 2-28% in a dose-dependent manner when added in vitro to calcium-albumin solutions. Scatchard analysis demonstrated that 0.1 mM oleic acid increased the number of calcium-binding sites on the albumin molecule (from three to five sites per molecule) without altering binding affinity. A similar effect was found when we performed Scatchard analyses of ether extracts in serum from three critically ill patients (number of calcium-binding sites increased from three to six). We also found that lipid infusions (during parenteral nutrition) lowered mean serum ionized calcium values in six critically ill patients [4.6 +/- 0.2 (+/- SEM) to 4.1 +/- 0.2 mg/dL; P less than 0.05]. These data support the concept that FFAs increase calcium binding to the albumin molecule. Alterations in FFA concentrations during critical illness may contribute to the poor correlation between corrected total serum calcium and ionized calcium concentrations in critically ill patients. In addition, acute elevations in circulating FFA concentrations may contribute to hypocalcemia in patients with defects in bone calcium mobilization.