The parathyroid glands control the level of calcium and phosphates in the blood.
- Phosphate levels can vary up to 2-3x the normal level without causing major problems
- Calcium levels have to be much more tightly controlled
- Contraction of skeletal, cardiac and smooth muscle
- Blood clotting
- Control of nerve impulses
- Increases in the level of calcium cause depression of the nervous system
- Decreases in the level of calcium causes excitation of the nervous system
- There are 4 parathyroid glands in humans – one behind each of the poles of the two lobes of the thyroid gland.
- The glands are about 6x3x3mm
- They have the appearance of dark brown fat. They can often be hard to distinguish from just another lobule of the thyroid gland – and in the past in total thyroidectomise, they were often removed by mistake.
- You can lose the function of half of the parathyroid glands before there will be any physiological degradation. Even if you lose more than this, the remaining tissue is often able to hypertrophy, so that over time you may regain normal parathyroid function.
- PTH causes an decreased excretion of calcium by the kidneys.
- PTH causes an increase in the rate of calcium and phosphate absorption from bone. This effect is caused by PTH action on osteocytes. Osteocytes are osteoblasts that have become trapped in the matrix they secrete and are found throughout the bone. Generally osteoblasts are found on the surface and osteoclasts are found in the bone matrix. Osteoclast activity is not altered by PTH.
The osteoblasts and osteocytes are all connected to one another by thin filmy extensions. These extensions cover the whole bone, and are known as the osteocytic membrane system. This membrane separates the bone surface from the extracellular fluid. The cells that make up this membrane, pump calcium ions out of the bone side and into the extracellular fluid, meaning that the concentration of calcium ions in the fluid surrounding the bone is only 1/3 of that in the extracellular fluid. So, when stimulated by PTH, these cells increase the rate at which they pump calcium, and thus increase the concentration of calcium in the serum. When the pumps reduce their activity, levels of calcium increase in the bone fluid, and these extra ions are deposited in the bone matrix.
- If PTH is raised for long enough, then it will also cause proliferation of osteoclasts and greater activation of the osteoclasts already present. This will increase the amount of breakdown of bone, and increase serum concentrations of calcium and phosphates. It is thought that his mechanism is not directly mediated by PTH, but that osteoblasts and osteocytes release a second, unknown messenger that acts on osteoclasts.
Levels of calcium in the blood will begin to rise within minutes of PTH being secreted.
Extended activation of the parathyroid glands can thus lead to weakened bones, and this will cause secondary stimulation of osteoblasts. However, this is not great enough to prevent the increased action of osteoclasts, and overall bone degradation will still occur.
PTH also has one other effect: increasing calcium and phosphate absorption from the gut.
PTH and phosphate
- Phosphate excretion from the kidney is ↑
- Phosphate absorption from the gut and from bone is also ↑
- The net effect is a fall in serum phosphate concentration
Excretion by kidneys
Absorption from gut
Absorption from bone
Net Serum concentration
- Decreased absorption of bone by osteoclasts
- Decreased formation of new osteoclasts – however, a longer-term result of this will be a decrease in the number of osteoblasts and so long-term there will be little effect on calcium concentrations.
Vitamin D is also closely associated with calcium metabolism. Vitamin D causes:
- Increase absorption of calcium from the guy
- Decreased excretion of calcium from the kidney
- It may also increase calcium release from bone into blood (debated)
In disorders of calcium metabolism (i.e. secondary hyperparathyroidism), assessing vitamin D status, and treating any deficiency is often the first line treatment
Conditions involving the parathyroid gland
Hyperparathyroidism is mostly clinically significant in cases of Chronic Kidney Disease.
Tumour of the parathyroid gland (rare)
Basically occurs after years of secondary hyperparathyroidism, after the secondary cause has resolved. The parathyroid gland has been used to producing such high levels of PTH for so long, it basically just broken, and secretes high levels of PTH even though levels of Ca2+ are now responsive to PTH. There is hyperplasia of the glands, and loss of response to Ca2+.