Parathyroid Function

Calcium regulation

Why is calcium important in the body and why does it have its own gland system to tightly control the levels in the body? The blood calcium levels are kept within a very narrow range of 2.1-2.6 millimoles per litre. Calcium ions are of vital importance for the human body, playing key roles in numerous crucial physiological processes.

The vast majority (99%) of the body's calcium is actually contained within the skeleton as calcium salts, making up the inorganic parts of the bone. The remaining 1% is found in several forms in the blood and most extracellular calcium is derived from dietary sources. If there is insufficient dietary calcium then it is mobilised from the skeletal stores to maintain appropriate serum levels.

The serum calcium is tightly controlled because calcium provides the electrical signal for the nervous and muscular systems, explaining why so many of the symptoms of a high calcium are related to these systems. 

The movement of calcium ions across cell membranes affects many fundamental processes such as:

  • intracellular cell signalling, secretion and proliferation
  • enzymatic reactions
  • muscle cell contraction
  • nerve cell activity
  • blood clotting

Maintenance of the calcium concentration within this narrow physiological range is achieved by a complex series of processes involving several organ systems (parathyroid, kidney, gut, bone and skin) and the interaction of a variety of hormones (PTH, vitamin D and calcitonin) with calcium and phosphorus ions.

The calcium sensing receptor (CaR) was first cloned in 1993 and is found not only on the surface of parathyroid cells, but also renal cells and thyroid C-cells (responsible for production of calcitonin) and a variety of gastrointestinal cells.

As the calcium levels become normal, the rising calcium then acts to inhibit further PTH release in a feedback loop (Fig. 1).

Fig.1: The intricate regulation system of body calcium, involving a complex web of hormone control and feedback in various parts of the bodyThe other main hormone involved in calcium regulation is calcitonin which is produced by the C cells of the thyroid (parafollicular cells). Calcitonin  is released in response to a rise in blood calcium and acts to reduce it by inhibiting the osteoclast mediated resorption of bone and decreasing calcium reabsorption by the kidney. The role of calcitonin in calcium control however, is still not well understood.

How parathyroid hormone works

Like in the thyroid, the parathyroids have receptors (in this case calcium receptors) that detect the level of calcium in the body. Parathyroid hormone (PTH) is released when these calcium receptors (CaR) on the surface of the parathyroid glands detect low blood calcium levels. The release of PTH is therefore inversely proportional to the calcium levels in the blood.

PTH is an 84 amino acid peptide hormone, with a half-life of 4 minutes in the circulation, which acts to raise blood calcium levels. It acts via PTH receptors, which are found on its target tissues, raising blood calcium in three main ways:

  1. It indirectly activates osteoclasts - these are bone cells that promote the resorption (destruction) of bone, thus releasing some of the calcium stored there to the serum in times of hypocalcaemia (low blood calcium).
  2. It promotes the reabsorption of calcium from the urine - PTH stimulates the distal tubule cells of the kidney to reabsorb calcium (and excrete phosphate) from the urine, reducing the loss of calcium in hypocalcaemia.
  3. It promotes the activation of vitamin D precursors in the kidney – PTH increases the production of active vitamin D (1,25-dihydroxycholecalciferol) which increases the uptake of calcium from digested food in the small intestine.

Tiny alterations of blood calcium levels upset this delicate balance of calcium movement and can lead to a wide range of problems, particularly related to the muscular and nervous systems, reflecting calcium's vital role in these areas.

High blood calcium (hypercalcaemia) effects:

When excess calcium accumulates in the blood, the following serious effects are possible (further details can be found on the webpage Hyperparathyroidism):

  • Formation of stones - the excess calcium can form stones (calculi) in organs such as the kidneys.
  • Fractures - hypercalcaemia often indicates excessive resorption (degradation) of bones making them prone to break after only minor trauma (pathological fractures).
  • Proximal myopathy - weakness in the proximal muscles (the muscles of the upper limbs) due to insufficient calcium for efficient muscle contraction.
  • Pancreatitis - calcium deposits in the pancreas can result in inflammation of the pancreas causing pain, nausea and vomiting.
  • Mental changes - alterations in brain activity due to abnormal nerve function can lead to  depression, confusion, memory loss and parkinsonism-type symptoms.

Low blood calcium (hypocalcaemia):

When blood calcium becomes too low the following can occur:

  • Paraesthesia - this is a sensation of numbness and 'pins and needles', particularly in the  fingers and toes, due to impaired activity of sensory nerves.
  • Cramps - altered calcium levels cause abnormalities of muscle contraction resulting in cramps around the body. In particular it can cause laryngospasm (spasm of the muscles of the larynx).
  • Tetany - this is prolonged sustained involuntary contraction of muscles due to muscle nerve conduction problems.
  • Agitation and seizures - abnormal levels of brain activity can cause seizures and agitation.