Pathophysiology
Clinical meaning
Calcium (Ca2+, normal total 8.5-10.5 mg/dL, ionized 4.5-5.5 mg/dL) is essential for muscle contraction, cardiac conduction, blood clotting, and nerve impulse transmission. Only ionized (free) calcium is physiologically active; approximately 40% is bound to albumin. The calcium-phosphate-PTH axis maintains homeostasis: when calcium drops, parathyroid hormone (PTH) is released, which (1) increases osteoclastic bone resorption (releases Ca2+ and PO4 from bone), (2) increases renal calcium reabsorption and phosphate excretion, and (3) activates vitamin D (calcitriol) in the kidneys, increasing intestinal calcium absorption. Calcium and phosphate have an inverse relationship: when one rises, the other falls. Hypocalcemia (<8.5 mg/dL) increases neuromuscular excitability because low extracellular Ca2+ lowers the threshold for nerve depolarization, causing tetany, paresthesias, and Chvostek/Trousseau signs. Hypercalcemia (>10.5 mg/dL) decreases neuromuscular excitability, causing muscle weakness, constipation, and cardiac conduction abnormalities (shortened QT). Severe hypercalcemia (>14 mg/dL) is a medical emergency with risk of cardiac arrest. Always correct calcium for albumin level: corrected Ca = measured Ca + 0.8 x (4.0 - albumin).