Calcitonin and Calcium Homeostasis: Bone and Kidney Roles in Blood Calcium Regulation

Short summary

Osmosis explains how calcium levels are kept stable by three hormones, parathyroid hormone, vitamin D, and calcitonin. The video details calcitonin's origin in thyroid C cells, its actions on bone and kidney, and why its exact physiological role remains partly mysterious.

Overview of calcium homeostasis

The video begins by describing extracellular calcium distribution, splitting calcium into diffusible and non-diffusible pools. Diffusible calcium is further categorized into free ionized calcium, which participates in essential cellular processes, and complexed calcium, which is bound to small anions and is not readily usable by cells. Non-diffusible calcium is bound to large proteins like albumin and cannot cross membranes. This sets the stage for understanding how hormonal signals regulate these pools to maintain blood calcium within a narrow range, typically 8.5 to 10 mg/dL.

Calcitonin: origin and production

Calcitonin is introduced as a polypeptide hormone involved in regulating blood calcium levels. It is produced by parafollicular cells, or C cells, of the thyroid gland. The thyroid is described as a neck gland with follicles lined by follicular cells, with C cells situated in the connective tissue between follicles. The protein precursor pathway is outlined: preprocalcitonin (141 amino acids) is cleaved to procalcitonin (with 116 amino acids remaining after the removal of a peptide), then to the 33 amino acid immature calcitonin, and finally to mature calcitonin (32 amino acids). Mature calcitonin is stored in secretory granules in C cells and released when needed.

Calcitonin versus other regulators

Calcitonin is contrasted with parathyroid hormone (PTH) and vitamin D. Unlike PTH and vitamin D, calcitonin does not regulate minute-to-minute calcium levels in a critical way, and removing the thyroid or lacking calcitonin does not drastically disrupt calcium homeostasis. Nevertheless, calcitonin can be used pharmacologically at high doses to treat hypercalcemia, indicating a functional role in calcium balance, particularly under pathological conditions.

Mechanisms: bone and kidney effects

The video explains two principal mechanisms by which calcitonin lowers extracellular calcium. In bone, calcitonin binds to its receptor on osteoclasts, activating a G protein and adenylate cyclase, which raises cyclic AMP. Elevated cAMP reduces osteoclast activity, diminishes the ruffled border, and decreases bone resorption, thereby limiting the release of calcium and phosphate from bone into the blood. In the kidney, calcitonin receptors in the distal convoluted tubule (the segment with calcium reabsorption via apical calcium channels) reduce calcium and phosphate reabsorption by principal cells, increasing urinary excretion of calcium and phosphate (calciuria and phosphaturia). Together, these actions lower circulating calcium levels and help maintain homeostasis within the normal range.

Clinical context and recap

Normal calcium is detected by calcium-sensing receptors on C cells, which trigger calcitonin release when extracellular calcium rises. The video emphasizes that this regulatory axis is not a tight, day-to-day control loop like PTH and vitamin D, and that the precise physiological role of calcitonin remains somewhat mysterious, as experimental removal of calcitonin does not severely disrupt calcium regulation. Nevertheless, in clinical settings, calcitonin can be used to manage hypercalcemia, illustrating its contributory, if not essential, role in calcium balance. The discussion concludes with a quick recap: calcitonin is released in response to high extracellular calcium, it inhibits bone resorption and promotes renal loss of calcium and phosphate, and it helps keep total blood calcium within the 8.5 to 10 mg/dL window.