Calcium homeostasis: How is it regulated?
Calcium is important for many bodily functions.
It’s mainly required for forming biomaterial for bones and teeth, existing primarily as bound calcium.
For all other physiological functions, calcium is required in its free, ionic form.
Ionic calcium is involved, for example, in forming action potentials, in the crossbridge cycle in
muscle contraction, in cell division, as factor IV in secondary hemostasis, and as a neurotransmitter
and second messenger in cell communication.
Because of its many roles, the total amount and distribution of calcium in the body is strongly regulated.
Let’s look at this in further detail.
Under physiological conditions, calcium is absorbed from the intestine and excreted
via the kidneys.
The majority of calcium, approximately 99%, is stored in the body as calcium phosphate in bones and teeth.
Around one percent of total body calcium is extracellular, whereas approximately 0.01% is intracellular.
In cells, calcium is stored in cell organelles, such as the mitochondria and the endoplasmic reticulum,
keeping the cell cytoplasm basically free of calcium.
Extracellular calcium is transported throughout the body via the blood vessels.
Two primary factors are responsible for stabilizing blood calcium levels:
the parathyroid hormone, in short PTH, which forms in the parathyroid glands, and vitamin D,
which is synthesized in the liver and skin and converted into its active form,
calcitriol, in the kidney.
A third regulator is calcitonin, which forms in the thyroid gland, though its physiological significance in regulating
calcium homeostasis is likely relatively low.
This assumption derives from the fact that calcitonin doesn’t need to be substituted in an underactive thyroid to maintain calcium levels.
However, later on in this episode, we’ll see that it still plays a role in regulating blood calcium levels.
Vitamin D facilitates the absorption of calcium and phosphate from food in the gastrointestinal
tract, maintaining their blood levels.
This activates osteoblasts and, consequently, mineralization as well as bone remodeling.
In the kidney, vitamin D ensures the resorption of calcium and phosphate; however, for the latter, only in the presence of PTH.
Now, PTH also stabilizes blood calcium levels, primarily by activating osteoclasts and,
therefore, bone demineralization.
Consequently, this causes the release of calcium and phosphate.
Since phosphate is an alkaline anion, an increased release needs to be compensated for by increasing
the excretion of alkaline anions, such as phosphate and bicarbonate, via the kidneys.
Accordingly, PTH decreases phosphate resorption.
At the same time, it facilitates calcium resorption in the kidneys.
As a result, differing amounts of calcium and phosphate are resorbed.
If both amounts were equal, phosphate would bind directly to the calcium ions,
thereby preventing an increase in free ionic calcium.
PTH only indirectly affects absorption in the gastrointestinal tract by facilitating the production of active vitamin D.
So in summary: Vitamin D elevates the amount of calcium and phosphate in the blood, while PTH also increases
calcium levels but decreases those of phosphate.
The body registers whether the right amount of extracellular calcium is present using calcium-sensitive receptors.
These are located primarily in renal tubular cells and the parathyroid gland.
If there’s an increase in serum calcium, for example, in hypercalcemia, this inhibits PTH secretion but stimulates the
release of calcitonin.
In turn, calcitonin ensures that less calcium is absorbed from food.
Also, it inhibits osteoclast activity and, therefore, the release of calcium and phosphate from the bones, and facilitates their excretion via the kidneys.
Therefore, calcitonin can lower calcium and phosphate blood levels.
This is why it’s also used as a therapeutic agent in hypercalcemia.
In contrast, if there’s a decrease in serum calcium, for example, in hypocalcemia,
this stimulates PTH secretion.
In addition, vitamin D then facilitates osteoclast activity, which, in turn, increases the release of calcium and phosphate from the bones.
Consequently, blood calcium levels increase again. Needless to say, despite these regulatory
mechanisms, calcium imbalances can occur.
Now, let’s check out the quiz on the next slide.