Control of calcium‐phosphate balance: parathyroid hormone, calcitonin and vitamin D3.
Calcium (Ca2+) and phosphate (PO43−) balance is crucial for various physiological processes, including bone formation, nerve function, muscle contraction, and enzyme activity. Three hormones—parathyroid hormone (PTH), calcitonin, and vitamin D3 (calcitriol)—play key roles in regulating these minerals, working in concert with the small intestine, bone, and kidneys.
Calcium in the Body
The body maintains calcium in 3 main pools:
- Intracellular calcium.
- Calcium in blood & extracellular fluid.
- Bone calcium (99% of total body calcium).
Calcium in the blood exists in two forms:
- Protein-bound calcium, primarily bound to albumin. Changes in blood pH affect this binding. In alkalemia, more Ca2+ binds to albumin, leading to a decrease in free Ca2+ and potential hypocalcemia. In acidemia, H+ ions displace Ca2+ from albumin, increasing free Ca2+ and potentially leading to hypercalcemia.
- Ultrafilterable calcium is not bound to protein and is readily filtered by the kidneys. This includes a small portion complexed to anions like phosphate and the biologically active, free, ionized Ca2+.
Organs Involved in Calcium Control
Three organs are primarily responsible for controlling calcium levels:
- Small intestine: Absorbs dietary calcium, a process enhanced by calcitriol.
- Bone: Serves as a reservoir of calcium and phosphate, which can be mobilized or stored as needed.
- Kidneys: Reabsorb filtered calcium and excrete excess calcium.
Parathyroid Hormone (PTH)
PTH is secreted by the chief cells of the parathyroid glands in response to decreased plasma Ca2+ levels. It acts to increase calcium levels.
Actions
PTH increases plasma Ca2+ through actions on bone, kidneys, and indirectly, the intestine:
- 1. Bone: PTH promotes bone resorption, releasing calcium and phosphate into the ECF. This is a two-step process involving both osteoblasts and osteoclasts.
- Initially, PTH directly stimulates osteoblasts, which are responsible for bone formation.
- However, PTH also indirectly stimulates osteoclasts, which are responsible for bone resorption, via cytokines released by osteoblasts. This resorptive effect overrides the bone-forming effect, leading to a net release of Ca2+ and phosphate from bone.
- 2. Kidneys: PTH has two key actions on the kidneys:
- Inhibits phosphate reabsorption in the proximal convoluted tubule, promoting phosphaturia (increased phosphate excretion). This action is crucial because the phosphate released from bone would otherwise bind to free Ca2+, limiting the increase in plasma ionized Ca2+. By increasing phosphate excretion, PTH ensures that more Ca2+ remains free in the plasma.
- Stimulates Ca2+ reabsorption in the distal convoluted tubule, further increasing plasma calcium levels.