Which of the following can decrease ionized calcium concentration?

• A. Alkalosis (uncovers albumin binding sites)
• B. Citrate binds ionized calcium (from blood products)
• C. Acidosis increases ionized calcium
• D. Albumin binds ionized calcium (decreases availability)

Answer: (B)

Ionized calcium is the active form of calcium in the blood, and its free concentration can be reduced either by chelation or by shifting calcium to the protein-bound pool depending on pH. Citrate used as an anticoagulant in stored blood products binds calcium to form calcium–citrate complexes, pulling calcium out of the ionized pool. This directly lowers the amount of free calcium available in circulation, which is why transfusion with citrate-containing products can cause hypocalcemia in the recipient. In contrast, acidosis tends to increase ionized calcium because hydrogen ions compete with calcium for albumin binding, displacing calcium into the free form, while alkalosis promotes more calcium binding to albumin and decreases the ionized fraction. Albumin binding itself means calcium is not ionized, so greater albumin-bound calcium reduces the ionized portion, but the clearest, most immediate decrease from a clinical standpoint during transfusion is citrate chelation.