December 15, 2003

Hamlet Meets Modern Medical Science Part II
(Alas, poor Yorick, me thinks he dost protest too much!)

By Dr. Howard Glicksman

Let’s review a few things about the body. Everyone seems to know that we consist of mostly water and other chemicals. The main elements that are necessary to form the structures and perform the functions of the cell are hydrogen, oxygen, nitrogen, carbon, phosphorus and sulfur. But there are other chemical elements that are found in the fluid within (intracellular) and without (extracellular) the cell, that are also important for life. Examples of these are sodium, potassium, magnesium and calcium. The cells in the body have the ability to adjust the concentration of these chemicals so that life-sustaining chemical reactions may continue to occur and we may continue to survive here on Earth.

Having said this, I would now like to discuss the metabolism involving just one of these chemical elements; calcium. But keep in mind that all of the others in their own ways are just as important to sustain life. We know that bone consists of calcium and therefore one of calcium’s main jobs is to structurally support the body through the skeleton. But what most people don’t know is that the presence of small concentrations of calcium in the cells and in the fluid outside of the cells is absolutely necessary for life.

The calcium concentration in cells is of the order of about ten thousand times less than the fluid outside of the cells in the interstitial space. The body’s cells are able to make sure that this relationship stays steady by various mechanisms.

Without elemental calcium in the intracellular and extracellular fluid and the cells’ ability to control its concentration, there would be no proper nerve or muscle function and we would not be able to breathe, our heart would not be able to pump and we would not be able to interact with the environment through our nervous system. Without the presence of this extraskeletal calcium in the body, our blood would cease to have the ability to clot and we would spontaneously bleed to death. And finally, if it weren’t for the existence of properly controlled concentrations of calcium ions in our gland cells, they wouldn’t be able to secrete the hormones or enzymes that they produce and the metabolic processes in the body, each of which is vital for life, would cease to function. Needless to say, all of this would spell doom for humankind!

Not to worry, for the very fact that you can read this paragraph is partially due to the free calcium ions that are contained in your retinal photoreceptor cells which allow them to repetitively transmit neural messages to the visual cortex of your brain. But how do our cells get calcium in the first place? We already know from the last column that calcium is absorbed through the intestinal tract at the “urging” of activated Vitamin D, which itself comes about by enzymatic reactions in both the liver and the kidney. Most of this calcium is deposited in the skeleton as bone. But what happens after that?

About 99% of the body’s calcium is contained in bone. The remaining 1% resides in the other cells of the body and in the extracellular fluid that exists in the circulation or the interstitial space, (see Figure 1). Approximately 99% of bone calcium is in crystalline form i. e. it is fixed in the bone as calcium hydroxyapatite ,Ca5(OH)(PO4)3, and as such is not available to the rest of the body. The remaining 1% of bone calcium is in solution as simple calcium phosphate which allows it to be rapidly exchanged with the interstitial fluid that surrounds the bone cells. It is from this pool of calcium that bone is mineralized and also made available to the rest of the body. This bone tissue fluid, which contains calcium in solution, is not only the supplier of the calcium that is needed to make bone, but is also in direct contact with the body’s circulation and through it the rest of the cells of the body.

Figure 1. The proper allocation of calcium within the body is absolutely necessary for our survival. Macroevolution would appear to be insufficient in explaining how this occurred in a functioning multi-system organism with a complex body plan.

Now let’s go back and consider our bone structure. Remember in the last column we said that there are bone-forming cells and bone breakdown cells which are involved in ongoing bone activity. If you think about what happens when each of these cells is in operation you’ll see that when a bone-forming cell lays down bone, it reduces the amount of calcium in the surrounding tissue fluid by a miniscule amount because it just took some of the calcium away and deposited it in crystalline form. Conversely, when the bone breakdown cell is operational it makes the bone release some calcium into the nearby tissue fluid thereby raising the concentration of calcium in this fluid by a tiny amount. Keep in mind that this pool of calcium in the bone tissue is in constant contact with the circulation and therefore is capable of affecting the supply of calcium in the extracellular space and from there the cells of the body.

So one can readily see that the calcium in the bone effectively acts as a reservoir for all of the intracellular and extracellular calcium needs of the body. Without bones the body would be incapable of providing itself with an adequate supply of calcium when it is needed and therefore many of the biomolecular processes that are vital for life, such as blood clotting, hormone and enzyme secretion by gland cells, and neuromuscular activity, would be nonfunctional and we would not exist.

But how do the bones know how much calcium to keep and how much to give to the circulation in order to provide for the calcium needs of the body? Notwithstanding the concept that without any extraskeletal calcium in the cells and the circulation we would not exist, we also know that if the calcium level in the blood does not stay within a very narrow range, this will result in death. Through medical research we have come to know that the body does have a mechanism for controlling the amount of calcium in the bloodstream. As I detail for you one of the main components of the mechanism for the control of serum calcium levels in the body, I’d like you to consider whether it is indeed plausible that all of this could have come into being by random variation one step at a time? By the way, we’re getting closer to solving the puzzle of poor Yorick!

In order to maintain the proper serum concentration of calcium and prevent it from going too low, the body contains four little glands that are embedded in the four outer corners of the thyroid gland. They are called the parathyroid glands and they are able to produce and secrete parathyroid hormone (PTH). Each of these gland cells has a calcium sensor on its cell membrane that is constantly monitoring the level of calcium in the serum. When there are upward or downward deflections of the concentration of calcium in the serum, the parathyroid glands will adjust their production and output of parathyroid hormone downwards or upwards respectively. i. e. in an inverse relationship.

But that isn’t the end of the story. The hormone that is released by the parathyroid gland contains 84 amino acids (all proteins consist of individual amino acids chemically bonded together) and it needs to travel to the liver where it is enzymatically converted into an activated hormone that has 34 amino acids. This, now activated parathyroid hormone remnant, travels to the bone and the kidney where it locks onto specific parathyroid hormone receptors and causes the desired effects. What exactly are these effects?

Normal levels of parathyroid hormone are vital for the maintenance of bone. It promotes the production and function of the bone-forming cell. But if a major drop in serum calcium occurs, resulting in an increase of production and secretion of parathyroid hormone, this has been observed to result in the resorption of bone and the release of calcium into the nearby bone tissue fluid. There is some controversy as to the exact biomolecular mechanism behind this activity. However, it is known that when high amounts of activated parathyroid hormone lock onto the bone-forming cell it tends to inhibit its activity thereby prevent it from pulling calcium out of the bone tissue fluid.

In contrast to this, high levels of parathyroid hormone stimulate the activity of the bone breakdown cell thereby allowing it to cause a release of calcium from the bone into the surrounding tissue fluid. No matter the exact mechanism, it is evident that some of the bone cells must contain parathyroid hormone receptors in order that when high levels of activated parathyroid hormone are present, it results in the net resorption of bone and the release of calcium into the surrounding bone tissue fluid which then allows it to be readily available to the body.

There are two different kidney tubule cells, each in the possession of parathyroid hormone receptors, where activated parathyroid hormone can exert its effect. The tubule cell that is responsible for reabsorbing calcium from the urine will be stimulated to hold on to even more. And the tubule cell that is capable of activating Vitamin-D will be prompted to increase its production as well. The former activity will directly result in more calcium being brought back into the body from the kidney, and the latter activity will increase the absorption of calcium by the cells in the intestine.

In review, when the calcium level drops, the parathyroid glands produce and secrete more parathyroid hormone which directly causes the increased release of calcium from the bones and an increase in reabsorption of calcium from the current urine in production. In addition, by way of Vitamin-D activation, it indirectly results in an increase of calcium absorption from the intestine. The overall net effect of all of these actions is to raise the level of calcium in the bloodstream. And just to be sure that everything is kept in proper check, the actual activity of a given amount of parathyroid hormone is limited to about six minutes because most of it is made inactive and is excreted by the combined effects of the liver and kidney. In effect, the calcium sensor’s activity in the parathyroid gland cell turns the switch on and the combined actions of the liver and kidney turn it off in order that the body may maintain a close control of its serum calcium concentration. (Figure 2)

Figure 2. The presence and control of calcium in our bodies is absolutely vital for life. Macroevolution's step by step mechanics would appear to be too simplistic to explain the origins of this irreducibly complex metabolic system.

Now just think about all of this for a while:

The first item absolutely requires the presence of calcium in proper concentrations within and without the cells or else we would not survive. The remaining items must all be present and work properly or else the narrow range of serum calcium will be breached and likewise, death will occur.

Here are some questions that need to be answered by those who espouse the validity of the step-by-step development of such a system as macroevolution predicts.

What is the order of how each of these components came into place and how did the system as we know it function each step along the way?

I’m sure that many of you can come up with more questions that would need to be answered before anyone should consider that macroevolution can explain all of this. If you have scientific evidence that can answer these questions and thereby lend some credence to the theory of macroevolution, I’d really like to hear from you. You can contact me at drhglicksman@yahoo. com.

But what of poor Yorick and his bones? Animal studies have shown that complete removal of the parathyroid glands results in a prompt and profound drop in serum calcium and death. But just imagine if the parathyroid glands ran amok and caused an elevation of serum calcium. Modern medicine is familiar with a condition known as primary hyperparathyroidism. Usually this is caused by the overgrowth of one or more of the parathyroid glands and they secrete too much parathyroid hormone despite what the calcium sensors try to tell them.

If you review what we just have said about how the parathyroid hormone affects the bone cells, you’ll immediately see that too much parathyroid hormone activity could cause an imbalance within the bone resulting in an increase in bone breakdown activity. Many bone irregularities and defects could result and this is probably what Hamlet saw when he looked at Yorick’s skull and other bones. But Hamlet seemed to be talking about much more than just bone pains. Could chronically elevated calcium levels have affected Yorick in other ways as well?

Just consider this list of symptoms that can occur if someone has primary hyperparathyroidism. Elevated levels of calcium in the bloodstream can cause kidney stones, kidney infections and ultimately kidney failure. It can make the blood pressure rise and cause palpitations as well. People with this condition often have severe fatigue, muscle weakness, nausea, constipation, weight loss, peptic ulcers and nonspecific abdominal pains. And if all that weren’t enough, besides the aches and pains that they suffer from bone and joint problems, because calcium is involved in stimulating and transmitting nerve and muscle impulses, it is not uncommon for people with primary hyperparathyroidism to have a variety of mental health disturbances ranging from the apathy of depression to delusional agitation and everything in between. Hard to believe that just by looking at poor Yorick’s skull, Hamlet could deduce so much, isn’t it? But of course, Hamlet had the advantage of having known poor Yorick.

So now you can see how important calcium is for the body. It seems to me that those who support macroevolution’s step-by-step mechanics must scientifically demonstrate how it is that calcium is present in proper concentration within the cell, and outside of the cell, and in bone, in order that all of the calcium-dependent biomolecular processes in the body may properly function and thereby allow us to live. But even that is not enough! For they must also demonstrate how the body was able to develop, step-by-step, the mechanisms that it uses to control its calcium metabolism while at the same time accounting for how the system actually functioned absent each successive innovation along the way. A conundrum if I ever saw one.

So far in these monthly columns, I have tried to show you how these biomolecular systems can be considered irreducibly complex because of the absolute need of each component in order for them to be able to function and allow us to survive. But by reviewing what I’ve said so far about calcium metabolism, you may have deduced for yourself another level of irreducible complexity. For remember, a gland cell’s ability to secrete enzymes or hormones is itself dependent on the body’s ability to control its calcium metabolism and provide gland cells with an adequate intracellular concentration of calcium. Yet the mechanism in the body for accomplishing this calcium control is provided by glandular tissue, namely the parathyroid glands. Therefore, the parathyroid gland cells also require an adequate amount of calcium in their intracellular fluid in order for them to be able to release parathyroid hormone. Hence, one can readily see that, in effect, the gland cells largely responsible for calcium metabolism in the body are themselves dependent on their own function in order to be able to function in the first place. Now, how can this be reconciled? I don’t think it can!

Next month I’ll be answering the proverbial question: Which came first the chicken or the egg? Stay tuned for more wonder to come!

Dr. G.

Howard Glicksman M. D. graduated from the University of Toronto in 1978. He practiced primary care medicine for almost 25 yrs in Oakville, Ontario and Spring Hill, Florida. He recently left his private practice and has started to practice palliative medicine for a Hospice organization in his community. He has a special interest in how the ethos of our culture has been influenced by modern science’s understanding and promotion of what it means to be a human being.

Copyright 2003 Dr. Howard Glicksman. All rights reserved. International copyright secured.
File Date: 12.15.03