Human Biochemistry Volume 2 - Murray R. 1993

Biochemistry of Intra- and Intercellular Communication
Hormones Regulating Calcium Metabolism
General Characteristics

The total calcium content in The Human Body is approximately 1 kg. About 99% of this calcium is localized in the bones, where, combined with phosphate, it forms hydroxyapatite crystals that serve as the inorganic structural component of the Skeleton. Bone is a dynamic tissue that undergoes continuous remodeling in response to mechanical load; in a state of dynamic equilibrium, the processes of Bone Formation and resorption are tightly balanced. The vast majority of bone calcium cannot freely exchange with the calcium in the extracellular fluid (ECF). Thus, In addition to providing mechanical support, bones function as a massive calcium reservoir. Approximately 1% of skeletal calcium constitutes a readily exchangeable pool, another 1% resides in the periosteal space, and together these two sources form the mobile (mixed) Ca²⁺ pool. The Hormones discussed in this chapter regulate extracellular calcium levels by modulating Ca²⁺ Transport Across the membrane separating the ECF from the periosteal fluid. Parathyroid hormone exerts a stimulatory effect on this transport, and calcitriol is also involved in its stimulation. Calcitonin (CT), on the other hand, can prevent this effect.

In Blood Plasma, calcium exists in three forms: 1) complexed with organic and inorganic acids, 2) protein-bound, and 3) ionized. Approximately 6% of total calcium is bound in complexes with citrate, phosphate, and other anions. The remaining amount is distributed almost equally between the protein-bound form (primarily albumin) and the ionized (free) form. Ionized calcium (Ca²⁺), whose concentration in most mammals, birds, and freshwater fish is tightly maintained within the range of 1.1–1.3 mmol/L, represents the biologically active fraction. The Organism has a very low tolerance for significant deviations of Ca²⁺ levels from this normal range. When Ca²⁺ levels drop, animals exhibit progressive hyperexcitability, which can escalate to tetanic seizures. Conversely, a marked elevation of plasma Ca²⁺ can lead to death due to Muscle paralysis and coma.

Calcium Ions and their paired phosphate ions are present in blood plasma at concentrations close to the solubility limit of their salts; consequently, the binding of Ca²⁺ to Proteins prevents precipitation and ectopic calcification. Changes in the concentration of Plasma Proteins (primarily albumin, although globulins also bind calcium) are accompanied by corresponding shifts in total plasma calcium. For instance, in hypoalbuminemia, the drop in total plasma calcium is 0.8 mg% for every g% decrease in albumin concentration. Naturally, an increase in plasma albumin produces the opposite effect. The binding of calcium to plasma proteins is pH-dependent: acidosis shifts calcium toward the ionized form, whereas alkalosis enhances protein binding, thereby reducing the concentration of Ca²⁺. This mechanism likely accounts for the tinnitus and paresthesia observed in hyperventilation syndrome, which induces acute respiratory alkalosis.