Integrated Calcium and Phosphate Regulation

  • As mentioned previously, even slight variations in extracellular concentration of calcium can lead to significant clinical consequences whereas large swings in phosphate concentration are of relatively little significance. Consequently, calcium and phosphate regulatory mechanisms of the body are primarily designed to maintain near-constant levels of blood calcium more than anything else. Calcium homeostasis requires processes which can buffer both short-term and long-term changes in extracellular calcium concentration. As discussed below, short-term and long-term homeostasis of extracellular calcium concentration appear to occur with distinct regulatory mechanisms.
Short-term Regulation
  • The total amount of calcium dissolved in the extracellular fluid is relatively small and ingestion of large amounts of calcium or a massive bout of diarrhea could lead to gain or loss, respectively, of nearly a third of the total extracellular calcium. Such short-term gains and losses of extracellular calcium are buffered by calcium regulatory mechanism which operate on the timescales of seconds to minutes. These mechanism appear to act independently of endocrine systems and involve rapid addition or resorption of bone salts which are deposited throughout the body. Amorphous bone salts appear to be in chemical equilibrium with calcium and phosphate dissolved in the extracellular fluid. Consequently, even slight changes in extracellular calcium concentration result in rapid deposition and resorption from bone salts, thus maintaining a near-constant calcium concentration on a second-to-second timescale.
Long-term Regulation
  • Long-term deficiencies or dietary calcium are quite common, although given modern diets long-term excesses may be possible as well. Consequently, regulatory mechanisms must exist which prevent slow declines or rises in extracellular calcium concentration over weeks to months. Parathyroid Hormone (PTH) appears to be the major long-term regulator of calcium homeostasis
  • The regulatory actions of (PTH) are discussed in Parathyroid Hormone Physiology although it should be pointed out that some of its actions occur indirectly via modulation of Vitamin D synthesis as discussed in Vitamin D Physiology. In scenarios of long-term calcium deficiency, PTH in conjunction with Vitamin D, act to progressively liberate crystalline calcium in the form of hydroxyapatite from bones and boost as much as possible GI calcium absorption. In scenarios of long-term calcium excess, PTH in conjunction with Vitamin D, act to deposit calcium in the form of hydroxyapatite in bones and reduce GI calcium absorption.