Homeostasis of calcium and phosphate

Homoestasis can be defined as an ability of the organism to maintain its equilibrium through adjustment of physiological processes.  

Calcium and phosphate are usually considered together due to their deposition in bone in form of the hydroxyapatite crystals and common hormones that regulate their levels. Moreover, the same organs play key role in regulation of plasma levels of both elements: kidneys, bone and intestines. Here, calcium and phosphate are considered separately for clarity.

Above is a schematic representation of Ca²⁺ and P homeostasis showing immediate net actions of PTH and active form of vitamin D.

Homeostasis of calcium

Calcium is an important element that is required for functioning of an organism. It is utilised in many ways, ranging from intracellular signalling to bone-building component.  The most obvious physiological processes depending on Ca²⁺ is muscle contraction, hormone secretion, nerve conduction, exocytosis and control of enzyme activity. Therefore, body tightly controls its plasma levels.

Table below gives specific numbers about calcium in human body.

Top half of the table is oriented around balancing calcium on daily basis. Bottom half depicts distribution of calcium.

It is important to note that most important form of calcium in the plasma is ionized calcium, which is a target for hormonal control.

Action of hormones

When cells of the parathyroid gland sense decreased blood calcium levels, parathyroid hormone (PTH) is secreted and its synthesis begins. PTH promotes Ca²⁺ reabsorption and phosphate excretion in kidneys, bone resorption and stimulates synthesis of active form of vitamin D. Bone resorption allows for relatively quick release of calcium from body internal stores. This process is discussed in more detail in the bone section. PTH stimulates the final step of 1,25-Dihydroxyvitamin D synthesis in the proximal tubule of the kidney. This active form of vitamin D causes increased absorption of Ca²⁺ in the intestine as well as increased bone resorption, providing positive feedback. The same is true for action of vitamin D on the kidney reabsorption of calcium. In the effect of synergistic action of PTH and vitamin D, calcium levels are restored to normal range. Both, normal calcium blood level and active form vitamin D provide a negative feedback on parathyroid gland, inihibiting PTH secretion and synthesis.

In case of elevated calcium levels, hormone calcitonin comes into play. Synthesised and secreted by cells in the thyroid gland, its main function is to increase bone mineralization and prevent its resorption. However, its action on human organism is limited as explained in section on hormones. Therefore, main tool for countering elevated levels of calcium is inhibition of PTH. This proves to be sufficient if the underlying cause of altered calcium levels is not a disease.

Homeostasis of phosphate

ATP is a molecule that is widely utilized in the organism. It is a source of energy and is often used as a source of phosphate in phosphorylation processes, which are extremely important. Phosphorylation is used by cells for protein trafficking and enzyme activation – an example of phosphate importance for human body. Moreover, phosphoproteins, phospholipids, nucleic acids and nucleotides (referred together as soft tissues) consist of phosphate.

Table below presents phosphate in numbers. Those are averages for a 70 kg person in good health and under proper diet.

Top half of the table shows how phosphate is balanced on daily basis. Bottom half represents the distribution of phosphate in human body.

Blood plasma levels of phosphate are not tightly controlled by the organism. Hormones acting on calcium homeostasis exert secondary effects on phosphate levels, altering it.

Action of hormones

When PTH acts on kidneys it causes phosphate excretion. This prevents elevation of phosphate levels which could result from bone resorption (effect of the same hormone). 1,25-Dihydroxyvitamin D causes increased phosphate absorption in the intestine and promotes reabsorption of phosphate by kidneys, which is opposite to PTH action. It has to be noted that PTH is much more potent in exerting its action on kidneys. Calcitonin lowers phosphate levels, but it has to be recalled that this hormone is not of high physiological importance.