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| Calcium
Control
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All
multicellular organisms (MCOs), like us, have an intracellular and an
extracellular space. The volume of the intracellular fluid (ICF) must be
controlled for cell survival and so must its chemical content which is totally
different than that of the extracellular fluid (ECF).
The
last several articles explained that the concentration of Na+ and K+ ions in the ICF and ECF are exactly opposite: Na+ ions are high in
the ECF and low in the ICF and K+ ions are high in the ICF and low
in the ECF. This difference must be maintained for proper tissue and organ
function, that is, for survival itself.
One
reason for this is that all nerve and muscle function (including the heart) is
dependent on it.
Another
important ion regarding nerve and muscle cell function is calcium (Ca2+).
In particular, the ECF (fluid between the cells and in the circulation) has a
Ca2+ ion concentration that is about 10,000x greater than the ICF and
must be maintained for life.
How
this is accomplished in the body has been explained by physiologists but how
this came to be is never really properly explained by evolutionary biologists,
except to say that “It evolved”.
Here’s
why this is so important!
Cell
Signaling
As
the last article explained, all cells have a negative resting membrane
potential (RMP). Nerve and muscle cells are said to be excitable because upon
adequate stimulation the sodium ion channels open to allow Na+ ions
to flood in from the ECF. This ultimately reverses the polarity of the RMP (from
-ve to +ve = depolarization) allowing them to perform a function. For the nerve
cell the function is the release of a neurohormone and for the muscle cell
(skeletal or cardiac) the function is muscle contraction.
In
the nerve cell, depolarization propagates as an action potential along the axon
where it ultimately makes (voltage gated) calcium ion channels open up to allow
Ca2+ ions to move down their concentration gradient and flood into
the cell. This sudden rise of Ca2+ ion concentration in the nerve
cell then signals it to release its neurohormone.
In
the muscle cell (skeletal or cardiac) depolarization ultimately causes Ca2+ ions to be released and move down their concentration gradient into the
cytoplasm from where they are being stored in the sarcoplasmic reticulum. This
sudden rise of Ca2+ ion concentration in the muscle cell is the signal
for its contractile proteins to interact to cause muscle contraction.
It
is important to note here that to reset the nerve and muscle cell so they can
function again, at the right moment the sodium ion channels close to stop Na+ ions from continuing to enter the cell and the potassium ion channels open to
allow K+ ions to leave. This causes the cell membrane to repolarize (from
+ve back to -ve). Also, to return the intracellular calcium to its extremely
low concentration, calcium pumps in the cell membrane use energy to pump Ca2+ ions out of the cell into the ECF and also, in the muscle cells, back into the
sarcoplasmic reticulum for storage.
In
addition to the above, calcium ions are also involved in maintaining control of
the sodium ion channels to make sure they remain properly responsive to
stimuli. The body must maintain tight control of the concentration of Ca2+ ions in the ECF because low levels can make the sodium ion channels much more
responsive whereas high levels can make them much less responsive. Either of
these situations can lead to nerve and muscle dysfunction, debility and death.
But
maintaining tight control of the ECF’s Ca2+ ion concentration is a
dynamic process because the body is always bringing in new supplies of calcium
through the gastrointestinal system and this must be balanced by how the
function of other organ systems affect the serum Ca2+ as well.
Let’s
take a closer look!
Following
the Rules of MCO (Human) Life
Life
doesn’t happen within a vacuum nor the vivid imaginations of evolutionary
biologists. The reality is that living within the forces of nature, and the
laws that govern them, obligates the body to constantly gain and/or lose
calcium. Here are three reasons why.
1.
About
99% of the body’s total calcium is housed in the bone. And 99% of the calcium
in the bone is in crystalline form, as calcium hydroxyapatite (Ca10(PO4)6(OH)2),
which is not available to the rest of the body. The remaining one percent of the
calcium in the bone is in solution, as calcium phosphate (Ca3(PO4)2),
in the bone tissue fluid that surrounds the bone cells. The bone tissue fluid is
in contact with the capillaries and therefore is in communication with the body
through the circulation. It is from the dissolved calcium in the bone tissue
fluid that bone-building cells take calcium to make the calcium crystals for
bone. And it is into the bone tissue fluid where calcium is deposited by the bone-breakdown
cells (osteoclasts) when the calcium crystals are removed from the bone. By way
of the bone tissue fluid, the bone acts as a reservoir for the body’s calcium needs
and metabolism.
2.
Although the gastrointestinal system readily absorbs
water, salt and sugar, this is not the case for calcium. In fact, on its own,
the gastrointestinal tract can only absorb about 10% of the calcium it
encounters. To improve this, activated Vitamin D (calcitriol) formed within the
body, attaches to specific receptors in the nucleus of the intestinal cells and
signals them to take in more calcium. In a normal diet this can increase the
calcium absorption to 30% and in ones with very low calcium, up to 90%.
3.
Protein metabolism produces ammonia which the liver converts into a
more soluble molecule called urea. The build-up of ammonia and urea in the body
can be toxic. The kidneys continuously filter water, containing calcium, from
the blood. This fluid moves through millions of microtubules becoming more
concentrated with urea as it becomes urine. If none of this calcium could be
reabsorbed the body would lose its total calcium content in about two months.
The
Hard Problem
The
normal range for serum calcium is 8.5-10.0 units (u). In general, a level <
7u or > 15u is thought to be incompatible with life because it interferes
with nerve and muscle (skeletal and cardiac) function. However, being able to
maintain control of the ECF’s Ca2+ ion concentration is a dynamic process and so is a very hard problem because of the constant functional
changes occurring in the bone, kidneys and gastrointestinal system. In general,
it is determined by how much calcium moves in or out of the bone, how much calcium
is lost from the body through the filtering of blood by the kidneys, and how
much calcium is brought into the body through the gastrointestinal system with
the help of calcitriol.
Here’s
how Steve Laufmann and I explained the situation in our book Your Designed Body.
What
type of innovation do you think would be needed to solve this really hard
problem?
What
sorts of information would be needed to maintain tight control of the serum Ca2+ ion level?
Take
a few minutes to think it through.
The
(Dynamic) Innovative Solution
The
first thing needed to take control is a sensor that can detect what needs to be
controlled. The cells in the four parathyroid glands, that are embedded in the
four corners of the thyroid gland, have sensors that can detect the level of
calcium in the blood.
The
second thing needed to take control is something to integrate the data by
comparing it to a standard (set-point), decide what must be done and send out
orders. The parathyroid cells send out a constant amount of a hormone called
parathyroid hormone (PTH). If they sense that the calcium level is dropping,
they send out more PTH, and if it is rising, they send out less PTH.
It
is important to realize that the metabolic effect of a given amount of PTH,
like it is for almost all other hormones, is usually limited to a few minutes
because of its breakdown by enzymes. This is what allows the body to take
moment to moment control of its metabolic functions.
The
third thing needed to take control is an effector that can respond to the
orders and do something about the situation. PTH travels in the blood, attaches
to specific receptors on the bone cells, and tells them to release more calcium
into the blood. PTH travels to the kidneys and does two things. It attaches to
specific receptors on the cells of the microtubules and tells them to take back
more calcium from the urine that is presently in production. It also attaches
to certain other kidney cells and tells them to activate Vitamin D
(calcitriol). The PTH-induced increase in calcitriol then goes to the
intestinal cells and tells them to bring more calcium into the body.
The
combined effect of PTH is to increase the blood level of calcium by promoting
its release from the bone, reuptake by the kidneys and absorption into the body
by the gastrointestinal system. If the calcium level is rising, the PTH level
drops and reverses these effects. How nice!
Real
Numbers Have Real Consequences
Physicians
and engineers do their work within the real world where real numbers have real
consequences—even death! Here is how we expressed it in Your Designed Body.
“Physicians
don’t get to make stuff up. They don’t have the luxury to merely observe how
life looks or theorize about its superficial qualities. They need to know how
the body really works, how the parts affect each other, and what it takes in
practical terms to keep it all working over a (hopefully) long lifetime. Though
their mistakes sometimes take longer to discover than those of physicians,
engineers also must live in the real world. Engineers design, build, deploy,
and operate complex systems that do real work in the real world. And it takes
yet more work to keep the systems from failing.”
As
opposed to physicians and engineers, the concept of “functional capacity” seems
to be totally absent from the mindset of evolutionary biologists. That’s
because their theoretical constructs always lack the objective criteria needed
to verify that a given biological structure works well enough for survival—in
other words its functional capacity and the control mechanisms needed to
maintain it are good enough
Yet,
no matter how complex the genetics leading to a sophisticated biological
structure, if it can’t control and maintain the functional capacity to combat and/or
use the laws and forces of nature to its advantage, the organism in which it is
housed is as good as dead.
The
same applies to calcium control.
Besides
the fact, as stated above, that the serum concentration of calcium must stay
within a narrow range for proper nerve and muscle (skeletal and cardiac)
function there is another important aspect of calcium metabolism to consider that
relates to its solubility in water.
Consider
how the body deposits solid calcium within the bone. The osteoblasts first lay
down a ground substance (mostly consisting of collagen), called osteoid, within
the extracellular space. Then, using a specified process, these bone-building
cells increase the local concentration of calcium and phosphate in the surrounding
bone tissue fluid which makes them precipitate out of solution as insoluble crystals
of hydroxyapatite. Now, imagine what would happen if this deposition of calcium
crystals occurred in other places of the body—places where fluid flows!
Ca2+ is a cation that interacts with different anions to form calcium salts in
solution. The solubility of a given calcium salt depends on the specific anion,
pH, temperature and presence of other chemicals. For example, calcium chloride
and calcium acetate are very soluble, calcium citrate, calcium lactate and
calcium gluconate are moderately soluble, but calcium phosphate, calcium
carbonate and calcium oxalate are poorly soluble.
Notice,
that despite calcium phosphate being poorly soluble it remains in solution
within bone cell fluid. That is, until the osteoblast using a specified process
increases the local concentration of calcium and phosphate to make them
precipitate out of solution as insoluble hydroxyapatite crystals. This means
that another important factor determining the solubility of a given calcium
salt is the relative concentrations of the calcium cation and the specific
anion.
Since
the kidneys filter calcium from the blood and bring back as much water as the
body needs from the urine in production, the normal concentration of calcium in
the urine can be double what it is in the serum. However, when the serum
calcium level rises far above normal, this makes the kidneys filter out much more
calcium which can result in the urine concentration of calcium being two to
three times normal.
The
increase in urinary calcium concentration allows more Ca2+ ions to
interact with anions, like oxalates and phosphates, to form poorly soluble salts
which then precipitate out of solution. This can result in calcium salts being
deposited within the tissues of the kidneys (nephrocalcinosis) or as stones within
the kidneys (nephrolithiasis) and/or the urinary system (urolithiasis). All of
these conditions can lead to recurrent urinary infections and worsening kidney
function.
So,
one can see that there are a lot of reasons why calcium has to be kept under
control. And it certainly appears that the system in the body that uses sensors
and hormones with their specific receptors to control its calcium really knows
what it’s doing.
“Evolutionary “Explanations”
Questions
Onward!
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