November, 2013

CAUTION: HORMONES AT WORK: PART V: CALCIUM


By Dr. Howard Glicksman

We live in a world made from matter. Matter is made up of atoms and molecules that follow the laws of nature. All life is made up of atoms and molecules that are organized into cells. Our body has trillions of them. Calcium is a chemical element that is vital for life. Everyone knows that we must eat food and drink liquids that contain calcium so we can have strong bones. Most people realize that it is the digestive system that brings calcium into the body and puts it into the blood so it can be used to build up the skeleton. Some people even know that the digestive system controls how much calcium enters the body and that the kidneys regulate how much calcium goes out of the body through the urine. But what most people do not understand and appreciate is how, in addition to strengthening the bones, calcium also plays a major role in heart, nerve, gland and muscle function as well. The body must make sure that it has enough calcium, not only in the bones, but also in the blood and the cells too. Having the right amount of calcium in the right places is not as simple as just eating food or drinking liquids that contain calcium. Nor is it as simple as just having properly working digestive and cardiovascular systems, bones and kidneys. In fact, without the bodyís ability to control the amount and location of calcium, life as we know it would be impossible. The proof of this is that when our body loses control of its calcium, we die. In other words, control is the key to life. But how does the body do it? One of the most important sets of molecules which work to give the body control are hormones. Letís first look at what is needed to control something and then weíll see where hormones fit into the scheme to keep us alive.

Control
To be able to control something requires having at least three different parts all working together in harmony. The first thing you need is a sensor to detect what needs to be controlled. If you have no way of being aware of what needs to be controlled how can you control it? The sensor is like the reconnaissance team that an army sends out to check on the whereabouts and activities of its enemy. Without this information the army would be working in the dark. The second thing you need to control something is an integrator which interprets the information from the sensors, makes decisions about what needs to be done, and then sends out orders. If you donít understand the information from the sensors and canít make decisions about what should be done then what use are the sensors in the first place and how can you control something? The integrator is like army headquarters where the information from the reconnaissance team is analyzed, decisions are made about what needs to be done and orders are sent out. Without army headquarters there would be no coordinated action in the field. The third thing you need to control something is an effector which receives the orders from the integrator and does something. If you have a sensor to detect what needs to be controlled and an integrator to know what needs to be done, but not an effector to do it, then whatís the use of having the first two and how can anything be controlled? The effector is like the soldiers, who at the orders received from headquarters, go and do what needs to be done. Without soldiers there is, in effect, no army and the battle is already lost.

Hormones are protein molecules that are sent out by special gland cells into the blood to help regulate specific functions of the body. The hormones are chemical messengers sent out by gland cells just like the orders sent out by army headquarters. The gland cells have sensors on their surface that can detect how much of a specific chemical (like calcium) is present in the blood. So, the gland cells have their own reconnaissance team that can detect a specific chemical which the body must control to survive. The gland cells take the information from their sensors, analyze it, and then send out the right amount of a specific hormone into the blood. The gland cells act as the integrator, just like army headquarters, to send out orders to direct activities in the field. These actions, done at a distance from the gland cells, are designed to achieve a specific goal; the control of a specific chemical (like calcium) so the body can stay alive. The hormones from the different gland cells travel in the blood to specific target organs to pass on their orders. The cells in these organs act as the effector, which, like the soldiers in the field, receive the orders and perform a specific action. This effect, done at the direction of the integrator, helps to control the specific chemical (like calcium) that was sensed by the gland cells which sent out the hormone in the first place.

However, army headquarters must send out different orders to different soldiers telling them to do different things. So too, the bodyís different gland cells must send out different messages to different target cells to get different things done. And just as the soldiers canít take just any message or do whatever they want, the target cells must respond to the right message and do the right thing, otherwise the body wouldnít be able to control anything. The way the body ensures that the right target cells receive the right orders so they can do the right thing is for them to have specific receptors. The receptors in the target cells are proteins with a special shape that allow them to attach to specific molecules when they come in contact with them. Think of it like a key fitting into a lock, or tuning your radio or television to a specific station. When the hormone attaches to its specific receptor this signals the target cell to do something. And what the target cell does directly affects the specific chemical (like calcium) that the gland cell which sent out the hormone detected in the first place. Now weíll look at how the laws of nature affect calcium in the body and how it takes control so it has enough calcium where it needs it to be. Be prepared to exercise your wonder as you never have before!

Calcium
Calcium is a mineral that is present in some of the food and beverages we take into our digestive system. Just as sodium and potassium become positively charged ions when they dissolve in water, so too, calcium becomes a positively charged Ca++ ion when it is in solution. It is then brought into the body through the blood. However, in contrast to sodium and potassium, only a very small amount of the bodyís calcium is present as Ca++ ions in the water that is either inside or outside the cells. In fact, about 99% of the bodyís calcium is located in its over two hundred different bones.

Bone is a specialized connective tissue consisting of mainly two types of cells; the osteoblast (bone-forming cell) and the osteoclast (bone-breakdown cell). The osteoblasts lay down a firm organic mesh and mineralize it with calcium crystals. The osteoclasts reverse this process by removing the calcium from the bone tissue. Although bone is a solid material it nevertheless has a very active metabolism. The bones continually undergo a process called remodeling in which the osteoclasts breakdown bone and release calcium while the osteoblasts deposit calcium to build the bone back up again. The bones provide support and protection for many important organs. The skull protects the brain and the vertebrae protect the spinal cord, and the sternum and ribs protect the heart and the lungs. The bones also house the marrow tissue that produces the blood cells which are necessary for life. Finally, our bones also provide the framework on which our muscles are attached which allows us to move around and do all sorts of things.

About 99% of the calcium in bone is in a solid crystalline form. The remaining 1% is in solution as Ca++ ions in the fluid that surrounds the bone cells. It is from this bone tissue fluid that the osteoblasts take calcium to crystallize the bone and where the osteoclasts place the calcium they remove from the bone. This bone tissue fluid is in contact with the circulation through the capillaries that feed the bone with blood. Through the capillaries the Ca++ ions can move from the bone tissue fluid into the circulation and back again. Once inside the blood the Ca++ ions become available to the rest of the body. Since the calcium that is crystallized in bone goes back and forth to and from the bone tissue fluid, and the bone tissue fluid is in contact with the circulation through the capillaries, this means that the bone can act as a reservoir for the rest of the calcium needs of the body.

Recall, two-thirds of the bodyís water is called the intracellular fluid because it is located inside our trillions of cells. The other one-third is called the extracellular fluid because it is located outside our cells. About 20% of the extracellular fluid is in the blood and is called plasma. The other 80% is located in between the cells and is called the interstitial fluid. The number of Ca++ ions in a given volume of water is called the Ca++ ion concentration. Although 90% of the calcium outside the bone is located in the cells, most of it is not dissolved in its fluid (cytosol) but is stored in its organelles. The cytosol has an extremely low Ca++ ion concentration. In fact, it is about ten thousand times less than what it is in the blood and the interstitial fluid. For human life to survive this difference in the Ca++ ion concentration between the extracellular and intracellular fluid must stay relatively constant. Without this difference there would be no proper heart, nerve, gland or muscle function. However, when it comes to maintaining this relationship the laws of nature present the body with a major problem.

Diffusion refers to the natural law where particles in solution are always in motion. This constant motion makes them spread out evenly within a solvent. For example, when sugar is dissolved in water the sugar molecules spread out evenly within the solution. When two solutions containing different concentrations of the same chemical (solute) are separated by a membrane that allows the solute to pass through it, the particles of solute naturally move from an area of higher concentration to one of lower concentration. Itís just like when they predict the weather on TV, the meteorologist shows you that the air in a high pressure system is expected to move to an area of low pressure. This natural movement of the solute by diffusion ultimately makes the chemical concentration on both sides equal.

Since Ca++ ions can pass through the plasma membrane this means that diffusion would naturally be expected to make Ca++ ions pass from the fluid outside the cells (which has a much higher concentration) into the intracellular fluid (which has a much lower concentration). If the constant movement of Ca++ ions into the cell were allowed to continue, the Ca++ ion concentration in the cells would markedly increase and the Ca++ ion concentration in the extracellular fluid would markedly decrease. However, as noted above, for human life to continue the ten thousand fold difference between the Ca++ ion concentration in the extracellular and intracellular fluid must be maintained. So, if the natural law of diffusion were allowed to go unchecked, life as we know it would be impossible.

The body indeed does have an answer to this dilemma of diffusion otherwise you wouldnít be sitting there reading these words. Just like the sodium-potassium pumps (see the last two articles), the work of the calcium pumps in the plasma membrane allows the cell to combat the constant inward movement of Ca++ ions by diffusion. Recall, from the last two columns (on sodium and potassium), that as diffusion naturally moves Na+ ions into the cell and K+ ions out of it, the sodium-potassium pumps use a lot of energy to send them back where they came from. This activity allows the body to maintain the proper Na+ and K+ ion concentrations inside and outside the cells. The calcium pumps also use energy to do the same thing for Ca++ ions. As the Ca++ ions naturally move into the cell by diffusion, the calcium pumps push them back out so the Ca++ ion concentration in the intracellular fluid can remain very low. Without the calcium pump, heart, nerve, gland and muscle function would be impossible.

It is the controlled and massive movement of Ca++ ions into the heart muscle cells at the right time that allows them to perform coordinated contraction and enables the heart to pump blood to the lungs and throughout the body. It is the controlled and massive movement of Ca++ ions into the nerve cells at the right time that signals them to release their neurotransmitters so they can stimulate muscle cells, gland cells, and other nerve cells. It is the controlled and massive movement of Ca++ ions into gland cells at the right time that allows them to release their hormones which enter the blood to have their specific metabolic effects throughout the body. And it is the controlled and massive movement of Ca++ ions from within the sarcoplasmic reticulum in muscle cells at the right time that allows their proteins to interact to bring about coordinated muscle contraction. If it werenít for the calcium pumps keeping the Ca++ ion concentration in the cells very low in comparison to the blood, there would be no heart, nerve, gland, or muscle function, and there would be no human life.

No matter how much calcium is in the body, the calcium pumps continue to pump Ca++ ions out of the cells to keep the Ca++ ion concentration within them extremely low. In effect, the calcium pump is blind to the overall calcium needs of the body. However, clinical experience teaches that if the Ca++ ion concentration in the blood rises too high above, or falls too far below, the normal range of 8-10 units, then severe weakness, coma and death are the result. One can therefore see that being able to control the bodyís total calcium content and the Ca++ ion concentration in the blood is vital for life. The ability to do this involves three main organs; the digestive system, the bones and the kidneys.

One of the main jobs of the kidneys is to filter water, and the chemicals dissolved within it, from the blood and place it in small tubules. This means that chemicals like glucose, sodium, potassium, calcium, and others, are all filtered out of the blood with water. The cells lining the tubules in the kidneys then take back what the body needs in the way of water, and other chemicals, based on the instructions they receive from different hormones. The total amount of water in the extracellular fluid is about 14 liters and the amount of water the kidneys normally filter out of the blood is about 7.5 liters per hour. This means that if the kidneys could not take back anything of what they filter, all of the extracellular fluid, and the chemicals within it, would be removed from the body in just under two hours. The kidneys usually take back about 99% of the calcium they filter. One can therefore see that one way to help control the total calcium content and the Ca++ ion concentration in the blood would be through adjusting how much calcium is either brought back in, or is allowed to go out, of the body through the kidneys.

The body contains about 1,000 gms of calcium, and 99% of it is in its bones. Also, 99% (990 gm) of the calcium in bone is in a solid form. The remaining 1% (10 gm) of the calcium in bone is present as Ca++ ions dissolved in the tissue fluid that surrounds the bone cells. Recall, it is from this bone tissue fluid that the osteoblasts take calcium to crystallize the bone and the osteoclasts place the calcium they remove from the bone. Also, the bone tissue fluid is in contact with the circulation through the capillaries by which the Ca++ ions can move into the circulation and back again. Of the remaining 1% of calcium outside the bone (10 gm), 90% of it (9 gm) is inside the cells. This means that there is only about 1 gm of calcium dissolved in the extracellular fluid (plasma and interstitial fluid). One can see that the bone tissue fluid (10 gm) contains about ten times more calcium than the extracellular fluid (1 gm). So, as noted above, since the calcium that is crystallized in bone goes back and forth, to and from the bone tissue fluid, and the bone tissue fluid is in contact with the circulation through the capillaries, this means that even a very small change in bone cell activity could alter the total amount of calcium in the circulation. An increase in osteoclastic activity (releasing calcium from the bone) with a decrease in osteoblastic activity (depositing calcium in the bone) would increase the amount of calcium in the bone tissue fluid and make more calcium available to the circulation. And an increase in osteoblastic activity with a decrease in osteoclastic activity would lower the amount of calcium in the bone tissue fluid and make less calcium available to the circulation. One can see that another way to control the total calcium content and Ca++ ion concentration in the blood would be by adjusting the activity of the bone cells.

Unlike water and glucose, calcium is not easily absorbed from the digestive system. In fact, the intestine naturally absorbs only about 10% of the calcium it receives. The body needs activated Vitamin D (calcitriol) to improve the efficiency of calcium absorption by the intestine. Calcitriol exerts its effect on the intestinal cell by attaching to a specific Vitamin D receptor inside the nucleus which improves its ability to absorb calcium. With the actions of calcitriol, calcium absorption from the digestive system usually rises to about 30% in a normal diet, and to 90% in a diet that is very poor in calcium.

It is important to realize that, by itself, Vitamin D is inactive in the body. It must be transported, on a special protein (made in the liver), to the liver, where an hydroxyl group (OH) is added to the 25th carbon. However, at this point it is still inactive. It then has to be transported to the kidney where another OH group is added to the 1st carbon to create calcitriol, the active form of Vitamin D . But when the Vitamin D with the OH group on the 25th carbon is transported to the kidney from the liver, it can follow an alternate pathway instead. Depending on the situation, the kidney can put the second OH group on the 24th carbon instead of the 1st carbon, producing a Vitamin D which is still relatively inactive. This relatively inactive Vitamin D would not be able to help the digestive system be efficient enough in absorbing calcium. One can then see that another way to control the total calcium content and the Ca++ ion concentration in the blood would be to control how much Vitamin D becomes activated to calcitriol to help the intestine bring enough calcium into the body.

In summary, it is the calcium pumps that make sure the cells have a very low Ca++ ion concentration in the cytosol to allow for proper heart, nerve, gland and muscle function. And the three main organs that affect the bodyís total calcium content, and the Ca++ ion concentration in the blood, are the digestive system, the bones and the kidneys. Now, letís look at one of the main ways our body takes control of its calcium so we can live.

Recall, the first thing you need to take control is to have a sensor that can detect what needs to be controlled. The cells of the four parathyroid glands, which are located in the four corners of the thyroid gland, have sensors that can detect the Ca++ ion concentration in the blood.

Recall, the second thing you need to take control is something to integrate the data by comparing it with a standard and then decide what must be done. If the Ca++ ion concentration drops, then the parathyroid glands send out more of the hormone they produce called parathyroid hormone (PTH) and if the Ca++ ion concentration rises, then they send out less PTH.

Recall, the third and final thing you need to take control is an effector that can do something about the situation. PTH travels in the blood and attaches to specific receptors in the target tissues having mainly three effects. PTH tells the kidney tubules to reabsorb more calcium from the urine that is presently in production thereby releasing less calcium in the urine. PTH favors osteoclastic activity and causes an increased release of calcium into the bone tissue fluid which can then enter the circulation. And PTH stimulates the cells in the kidneys to put the second OH group on the 1st carbon of Vitamin D (rather than the 24th carbon) thereby producing more calcitriol. An increase in calcitriol causes the intestine to absorb more calcium. One can see that the combined effects of these three actions causes the body to increase its total calcium content and the Ca++ ion concentration in the blood.

In summary, when the parathyroid glands detect a drop in the Ca++ ion level in the blood they send out more parathyroid hormone (PTH). More PTH tells the kidneys to hold onto more calcium, the bone cells to release more calcium into the blood, and activates more Vitamin D which tells the intestine to bring more calcium into the body. When the parathyroid glands detect a rise in the Ca++ ion level in the blood they send out less PTH. Less PTH tells the kidneys to let more calcium go out of the body through the urine, the bones to release less calcium into the blood, and activates less Vitamin D which reduces how much calcium is brought into the body by the digestive system. It is also important to note here that the absence of PTH is incompatible with life.

Points to Ponder
The way our body makes sure it has enough calcium where it is supposed to be is not just as simple as eating and drinking things with calcium in them. Neither is it just as simple as having properly working digestive and cardiovascular systems, bones and kidneys. To control its calcium content and its whereabouts the body needs, not only calcium pumps in the plasma membrane of its cells, but also (1) parathyroid gland cells that can detect the Ca++ ion level in the blood, (2) the ability of these cells to produce and correctly adjust the release of parathyroid hormone (PTH) based on the changes in the level of Ca++ ions, (3) the presence of specific PTH receptors on the cells in the kidneys and the bone cells, (4) the osteoblasts and (5) the osteoclasts, (6) the transport protein produced in the liver to carry Vitamin D in the blood, (7) the ability of the liver to add the OH group to the 25th carbon of Vitamin D, (8) the ability of the kidneys, at the direction of PTH, to apply the second OH group to the 1st carbon of Vitamin D and (9) the vitamin D receptor in the nucleus of intestinal cell. If any one of these nine parts were to be missing, or not working properly, the whole system would fail and the body would die because of the loss of calcium control. Each part that contributes to the sensor, the integrator, and the effector is needed to perform its vital function for body survival. Dr. Michael Behe has called a system where the absence of any one part renders it useless as being irreducibly complex. The system our body uses to control calcium demonstrates irreducible complexity.

One must then wonder how an irreducibly complex system with so many vital parts could have come into existence? Does it make sense that this system could have come about one step at a time? First the sensor, with no integrator or effector, or the integrator with no sensor or effector, or the effector with no sensor or integrator? The idea is totally absurd. They must have all come together as a system to perform a function to keep the body alive. And which system came first? The ones mentioned previously to control oxygen transport, blood glucose, water content, sodium and potassium, or this one for calcium? Remember, without any one of these systems working properly, we die. In addition to these there are other irreducibly complex systems each of which is absolutely vital for life. There are control systems in the body for blood pressure and temperature just to name a few more. Each of these systems has its own sensor(s), integrator(s) and effector(s). And if just one of these parts is missing the whole system fails and the body dies. But if a system is irreducibly complex does that make it automatically capable of supporting life? If you think about it youíll realize that thereís one more piece of the puzzle thatís needed, a piece that goes beyond irreducible complexity, to enable these systems to keep us alive within the laws of nature.

Visit a natural history museum and you are likely to see one or more human skeletons displayed next to the bones of other animals. Often this will be used to convince the observer of how macroevolution explains the origin of life. But trying to figure out how life came about by just looking at its various parts is like trying to figure out how the airplane came about by just looking at the fuselage, the wings and the tail section without taking into account things like jet propulsion, aerodynamics, electronics and modern metallurgy. The origin of life involves not just how life “looks” but how it actually “works” to stay alive. This article has clearly shown that when it comes to calcium and bone, and their effect on human survival, thereís much more than just what meets the eye.

Real numbers have real consequences when it comes to dealing with the laws of nature. If an airplane doesnít have enough power to take off against gravity or isnít built strong enough to resist the power of the wind and breaks apart, then itís as good as dead. The same applies to the body and how it works to survive against the forces of nature. Not just any amount of calcium in the bone, the blood, or the cells will do. Based on what we know about how the body actually works our ancestorsí ability to survive and reproduce depended on them having the right amount of calcium in the right places. About 99% of their calcium had to have been in their bones and had to be strong enough to not easily break from a simple injury or the pulling of muscles. Of the remaining 1% of body calcium that is outside the bones, about 90% of it had to have been stored in their cells with only a very tiny amount in the cytosol to allow for proper heart, nerve, gland and muscle function. The last 0.1% of their body calcium had to have been dissolved in their blood and interstitial fluid at the right level of concentration to prevent severe weakness, coma and death (8-10 units). To achieve this their kidneys had to have been able to take back the right amount of calcium after filtering it out of the blood. Their bones had to have had enough calcium in the tissue fluid to serve the calcium needs of the rest of their body. And their digestive system had to have had enough calcitriol (active Vitamin D) to absorb enough calcium from what they took into their bodies. But what if the system that uses parathyroid hormone (PTH) to control the bodyís calcium content and concentration in the blood had been set differently? What if their kidneys had let go of too much calcium or held on to too much. What if their bones had put too much calcium into the tissue fluid or not enough? And what if their digestive system had absorbed too much calcium because of high levels of calcitriol, or not enough due to low levels of calcitriol? Clinical experience teaches that our ancestors could never have survived and reproduced.

Real numbers have real consequences when it comes to dealing with the laws of nature. Not just any amount of calcium is enough to keep the body alive. It has to be the right amount and it has to be in the right place. Just because a system is irreducibly complex does not automatically mean that it will be able to function well enough to allow for life. Besides being irreducibly complex, systems that allow for life must also have a “natural survival capacity”. By this I mean that each system must give the organism the capacity to survive by taking into account the laws of nature. This usually involves having a knowledge of what is needed to keep the organism alive within the laws of nature and then being able to do what needs to be done. The system that uses parathyroid hormone seems to inherently know how much calcium the kidneys should release, how much calcium should be in the bone tissue fluid, and how much active Vitamin D is needed to absorb enough calcium from the digestive system to keep the calcium content and blood level where it should be, and it does it naturally. The same can be said for each of the other control systems that manage oxygen transport, glucose, sodium, potassium, blood pressure and temperature as well. Not only are each of these systems irreducibly complex with a natural survival capacity, but without any one of them the body dies.

The laws of nature have put up many obstacles to prevent life from existing. Just as a car can die from not having enough gas for energy, or oil for seizing parts, or anti-freeze for engine overheating, so too, all physicians know that there are many different pathways to death. If you really want to begin to understand how life came into existence, you first have to understand how easily it can become non-existent. Did life really come about solely by random chemicals coming together to form cells, then simple organisms, and then complex ones like us? In other words, without “a mind at work” to make it happen?

If an archaeologist were digging and found a bronze helmet would she be likely to think that it had come about by the random forces of nature? Of course not! She would know that bronze is a manmade alloy made from copper and tin. And further, the shape and other features of the helmet would tell her that its function was to protect the human head.

The combination of these facts would make her come to the conclusion that the bronze helmet would be a human artifact worthy of further study and display. The human skull is made up of many different bones that together protect the brain and other features of the head. The calcium compound that makes up the skull is produced by bone cells in conformity with the calcium metabolism of the body and does not occur naturally in non-living things. The skull not only has openings for the eyes, ears, nose and mouth, but also for the spinal cord and the nerves that supply motor and sensory function to the head and neck as well. Many present-day scientists would have no difficulty in asserting that it took “a mind at work” to bring the bronze helmet into existence. However, believing that life has come about solely by the random forces of nature, they would also paradoxically assert that the human skull and what lies within it did not require “a mind at work”. No, when it comes to the origin of life it seems to me that Science still has a lot of explaining to do!

Dr. G.
drhglicksman@yahoo.com

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 now practices 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. Comments and questions about this column or any of the previous ones are welcome at drhglicksman@yahoo.com

Copyright 2013 Dr. Howard Glicksman. All rights reserved. International copyright secured.