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Calcium Physiology

Parathyroids || Kidney || Vitamin D || Related Articles

Calcium has many unique roles in the body. It serves as a trigger for neurotransmitter release. It plays a vital role in cellular messaging. It is involved in blood clot formation. And it is a crucial component of bone. As such, calcium concentrations must be kept in close check by the body. Calcium homeostasis is a unique mix of kidney, bone, parathyroid, and gut interactions. This article will discuss normal calcium physiology.

The Parathyroids

There are four parathyroid glands that sit adjacent to the thyroid gland in the neck. They are roughly pea sized, but play an important role in calcium physiology. Each parathyroid gland has cells known as Chief cells (aka: principal cells). These cells secrete a hormone known as parathyroid hormone (PTH).

Parathyorid hormone is released in response to two stimuli: decreased blood calcium concentrations or increased blood phosphate concentrations.

PTH's main role is to increase the amount of calcium and decrease the amount of phosphate in the blood stream. It does this by increasing the amount of active vitamin D produced by the kidney, increasing the kidneys ability to re-absorb calcium from urine, Parathyroidsincreasing intestinal absorption of calcium, and increasing the release of calcium from bone.

Review - the main roles of parathyroid hormone on calcium are:

(1) Increase the hydroxylation reaction of vitamin D by the kidney.
(2) Increase the kidneys ability to resorb calcium from urine.
(3) Increase the guts ability to absorb calcium from the diet.
(4) Increase the release of calcium from bone.



The kidneys perform two important functions with regards to calcium: activating vitamin D and filtering/re-absorbing calcium.

There is an enzyme in the proximal convoluted tubules of the kidney known as 25-hydroxyvitamin D 1-alpha hydroxylase (I know, its a mouthful). Its role is to hydroxylate (ie: attach an -OH group) the first carbon of vitamin D. When vitamin D is in its 1,25 hydroxylated form it is "active" (for more on vitamin D see below).

Interestingly, patients with long standing kidney disease have a decreased ability to make active vitamin D. This is due to an increased level of phosphate (phosphate is normally excreted by the kidneys, but rises in kidney failure) in the blood. Higher than normal levels of phosphate inhibit the hydroxylation reaction that occurs in the kidney.


Vitamin D

Most people know they need vitamin D, but few no why or understand how it works. There are two ways to get vitamin D: diet and sunlight. The two types of dietary vitamin D are ergocalciferol (aka: vitamin D2) and cholecalciferol (aka: vitamin D3). Ergocalciferol is a form of vitamin D found in plants; cholecalciferol is the form of vitamin D found in meat. They have subtle differences in their chemical make up that does not affect function.

The other form of vitamin D is synthesized in the skin. An intermediate molecule known as 7-dehydrocholesterol (an intermediate in cholesterol biosynthesis) is converted to cholecalciferol in the dermis upon exposure to sunlight.

Vitamin D forms

Ergo and cholecalciferol are not "active" forms of vitamin D. In order to become active they must first undergo two separate hydroxylation reactions. The first hydroxylation, occuring at the 25th carbon, occurs in the liver. The second hydroxylation, occuring at the 1st carbon, occurs in the kidney. Once both hydroxylations are complete the vitamin is in its active form. At this point it is known as "1,25-OH-Vitamin D" or "calcitriol".

Once in its active form it can partake in calcium homeostasis. Active vitamin D diffuses into various cells where it binds to proteins in the nucleus known as nuclear receptors. When bound to vitamin D these proteins either increase gene expression or repress it depending on the cell and/or protein. The main roles of active vitamin D are as follows:

(1) Increased calcium absorption from the gut. This occurs via increased translation of various genes involved in calcium transport.

(2) Increased release of calcium from bone.


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