July, 2013

CAUTION: HORMONES AT WORK: PART III: SODIUM


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. Sodium is a chemical element that is vital for life. Everybody knows that we get sodium mainly from the salt in the food we eat and the liquids we drink. And many people know that sodium is brought into the body by the digestive system and put into the circulation where it travels to the tissues. There are even some who know that it is the kidneys that regulate the bodyís sodium content. However, what most people do not know, or appreciate, is that in addition to playing a vital role in nerve and muscle function, sodium also is important for keeping water where it is supposed to be in the body. Having the right amount of sodium in the right place in the body is not just as simple being able to swallow things that contain sodium. Nor is it as simple as having properly working digestive and cardiovascular systems and kidneys. Without the body being able to control its supply and whereabouts of sodium, life as we know it would be impossible. The proof of this is that when our body loses control of its sodium, 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.

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 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 sodium) 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 sodium) 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 sodium) 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 sodium) that the gland cell which sent out the hormone detected in the first place. Now weíll look at how the laws of nature affect sodium in the body and how the body takes control so it has enough sodium where it needs it to be. Be prepared to exercise your wonder as you never have before!

Sodium
The chemical name for table salt is sodium chloride and its chemical formula is NaCl. NaCl is an ionic compound because the two atoms that join together to form it each have an electrical charge. Sodium (Na) gives up one of its electrons to chlorine (Cl) and becomes a positively charged sodium ion (Na+). The chlorine gets one extra electron from sodium and becomes a negatively charged chloride ion (Cl-). When table salt is dissolved in water the Na+ and Cl- ions are released from each other. This means that the NaCl that enters the circulation and the cells in our body breaks up into Na+ and Cl- ions.

All the water in our body contains dissolved Na+ ions in solution. This water can only be located in one of two places; either inside our cells or outside our cells. 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 around and in between the cells and is called the interstitial fluid. Water molecules are small enough to freely pass back and forth between the blood and the interstitial fluid and between the interstitial fluid and the cell. In other words, the interstitial fluid acts as a bridge by which water can travel back and forth between the cells and the blood. Na+ ions can also pass through biological membranes as well. The number of Na+ ions in a given volume of water is called the Na+ ion concentration. The Na+ ion concentration outside the cell is normally about ten times more than what it is inside the cell. For life to continue this difference in Na+ ion concentration between the extracellular and intracellular fluid must be maintained. However, when it comes to accomplishing this feat the laws of nature present the body with two major problems.

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 Na+ ions can pass through the plasma membrane this means that diffusion would naturally be expected to make Na+ ions pass from the extracellular fluid (which has a higher concentration) into the cells (which have a lower concentration). If this movement of Na+ ions into the cell were allowed to take place the Na+ ion concentration in the cells would rise, and in the extracellular fluid it would fall. However, as noted above, for life to continue the ten fold difference in Na+ ion concentration between the extracellular and intracellular fluid must be maintained. If the natural law of diffusion were allowed to go unchecked life as we know it would be impossible. But thatís not the only problem the cell would face.

Osmosis refers to the natural law where two solutions containing different concentrations of the same solute are separated by a membrane that only allows water to pass through (but not the solute) then water will go from the area of lower concentration to the area of higher concentration. This natural movement of water, by osmosis, like diffusion, ultimately makes the chemical concentration on both sides equal. But, since the solute cannot pass through the membrane, water (the solvent) goes in the opposite direction instead.

There are many protein molecules present in the cell and the blood that are too large to cross biological membranes. These proteins perform vital functions that support cell life and body function respectively. Therefore the proteins in the cells and the blood are too important to be allowed to wander away from their respective locations. The extracellular fluid contains a much smaller concentration of protein compared to what is inside the cell. This means that if unopposed diffusion allowed Na+ ions to go into the cell and stay there, causing an overall increase in the cellís total chemical concentration, osmosis would naturally make water enter the cell as well to keep the total concentration of chemical particles the same on both sides.

Recall, to live, grow and work properly the laws of nature demand that each cell keep its volume of water and total chemical concentration relatively constant. Without a mechanism in place to prevent Na+ ions from naturally coming into the cells by diffusion, and water by osmosis, human life would be impossible. This is what the random forces of nature, like diffusion and osmosis, do. They cause death, not life. To survive in the world, life must come up with a way to combat these laws of nature.

The body indeed does have an answer to this dilemma of diffusion and osmosis otherwise you wouldnít be sitting there reading these words. The work of about a million sodium pumps in the plasma membrane allows the cell to combat the constant inward movement of Na+ ions by diffusion and water by osmosis. As Na+ ions enter the cell the sodium pumps push them back out. Since extra Na+ ions are not allowed to stay in the cell to increase its total chemical concentration, water is prevented from entering the cell by osmosis as well. This activity requires a lot of energy because the Na+ ions must be pumped out against their natural tendency to move into the cell. It is estimated that at rest, all of the sodium pumps in our trillions of cells take up about one-quarter to one-half of the bodyís total energy needs. This is part of the reason why you die when there isnít enough oxygen or glucose to provide enough energy; malfunction of your cellsí sodium pumps allowing them to become victims of the laws of nature (diffusion and osmosis).

But letís consider what else would happen without the sodium pump. If Na+ ions and water were allowed to move into the cells by diffusion and osmosis what do you think would happen to the extracellular fluid? After all, thatís where the cells would be getting the Na+ ions and water from in the first place. Without the sodium pump the 2/3:1/3 relationship between the intracellular and extracellular fluid would be lost. Without the sodium pump the cells would literally suck Na+ ions (and water) out of the extracellular fluid. This would greatly reduce the amount of fluid in the circulation, compromise blood flow and lead to multi-organ failure and death.

So, the effects of the natural laws of diffusion and osmosis pack a one-two death dealing punch to the body. First, they cause the cells to lose control of their volume and total chemical composition causing their death. And second, by reducing the amount of Na+ ions and water outside the cells they compromise the perfusion of the tissues resulting in total body death as well.

From the above, it is evident that the Na+ ion is one of the most important chemicals in the extracellular fluid. The sodium pumps not only allow the cells to maintain control of their volume and total chemical concentration, but they also do the same thing for the extracellular fluid as well. In fact, it is an axiom of modern medicine that wherever Na+ ions go in the body, so go water molecules as well. With the help of the sodium pump, and being able to control its Na+ ion content, the body makes sure that the right amount of water stays inside the circulation and isnít sucked into the cells. If it werenít for Na+ ions being in the extracellular fluid there would be no circulation and no life.

No matter how many Na+ ions the body has, the sodium pumps keep pushing them out of the cells and back into the extracellular fluid for life to continue. The sodium pumps only know what the cells need and are blind to the sodium needs of the body as a whole. Recall, two-thirds of the bodyís water is inside the cells and one-third is outside the cells in the interstitial fluid and the blood. Since water can move freely across biological membranes by osmosis this means that it naturally shifts from the intracellular to the extracellular space and back again depending on the situation. However, due to the sodium pumps, this is not the case for Na+ ions. As noted above, the sodium pumps work to keep extra Na+ ions from staying inside the cells by pushing them back out again. This activity keeps the Na+ ion concentration in the fluid outside the cells at a level that is about ten times more than it is in the intracellular fluid. The extracellular fluid contains about 90% of the bodyís total sodium while the intracellular fluid contains the remaining 10%. As noted above, this relationship between the extracellular and intracellular fluid must be maintained for human life to continue.

The body is always losing sodium from its digestive system, perspiration and urine output. One way to help the body maintain enough Na+ ions is to take in new supplies by eating food and drinking liquids that contain sodium. But how much is enough? The digestive system absorbs all of the sodium it receives without taking into account what the body actually needs. So, taking in too little sodium, or too much sodium, may not be the right amount for survival. The daily recommended intake of sodium is about 1,500 - 2,300 grams but most people take in over double that amount. Do you know how much sodium is in everything you eat and how much your body actually needs at any given moment? Do you think our ancestors, who were fighting for survival, were able to make these decisions and do what was right for them?

Itís the kidneys that control the bodyís total sodium content. Every hour they filter about 7.5 liters of fluid from the bloodstream. In that hour they also filter out about one half of the bodyís total sodium as well. The last column stated that if the kidneys could not take back any of the water they filter, life would last for only about ninety minutes. Well if the kidneys couldnít take back any of the sodium they filter we would die in about thirty minutes. Normally the kidneys recover about 99.5% of the sodium they filter from the blood. This is very important since wherever sodium goes in the body water generally follows. So, keeping enough water in the body, especially in the blood, is dependent on keeping enough sodium in it as well.

The normal range for the Na+ ion concentration in the blood is about 135-145 units. Death usually takes place if this level drops below 110 units or rises over 170 units. It is important to keep in mind that the sodium concentration of the blood is directly related to the water content of the body. If the water content drops too much then the Na+ ion concentration in the blood will rise (independent of how much sodium is in the body) and if the water content of the body rises too much, then the Na+ ion concentration in the blood will fall (independent of how much sodium is in the body). This means that the body could have an increase in total sodium but if it has gained too much water then the Na+ ion concentration in the blood will actually drop. Likewise, the body could have a decrease in total sodium but if the body has lost too much water then the Na+ ion concentration in the blood will rise.

In reality, a sodium level that is high enough to threaten life (> 170 units) is usually due to not having enough water in the body, a condition called dehydration, where the cells donít have enough water inside them. At the same time there usually isnít enough water in the bloodstream as well which causes low blood pressure and blood flow leading to poor tissue perfusion and death. In contrast, a sodium level that is low enough to threaten life (< 110 units) is usually due to having too much water relative to sodium in the body. In this setting water will naturally move from the extracellular fluid into the cells due to osmosis. When this happens, particularly in the brain, it causes confusion, coma and even death. So, one can see that being able to control the bodyís sodium and water content is vital for life. Last monthís column looked at how the body instructs the kidneys to keep the right amount of water inside. Now letís see how it does the same thing for sodium.

Recall, the first thing you need to take control is to have a sensor that can detect what needs to be controlled. In order to understand how the body can detect its own sodium content it is important to keep in mind that it is the presence of enough Na+ ions that keeps enough water in the circulation. Remember, water generally goes wherever Na+ ions go in the body. If youíve ever pumped air into a flat tire and felt the pressure within it rise as it becomes firmer then you can understand how the body accomplishes this task. As blood flows through a vessel, or enters a chamber, the force it applies against the walls causes them to stretch out, just like when air is pumped into a tire. Some of this stretch takes place due to the volume of blood, which is a reflection of its water content. However, we just said that wherever Na+ ions go in the body, water generally follows. Therefore, the water content of blood is directly related to how much sodium is in the body. So, the amount of stretch that takes place as blood flows through a vessel or chamber is in some way related to the amount of sodium in the body.

One system that helps the body manage its sodium content is located in the kidneys where special cells make up what is called the juxtaglomerular apparatus (JGA). The JGA cells are positioned where blood flows into the kidney to be filtered. They have sensors that detect the stretching of the vessel wall which is directly related to the pressure of the blood as it flows past. The blood pressure is dependent on there being enough blood in the circulation. And, as noted above, having enough blood in the circulation is dependent on there being enough Na+ ions in the extracellular fluid. Therefore, as blood enters the kidneys and stretches the vessel walls this provides information on the amount of sodium in the body. The other system consists of cells located in the atrial walls of the heart. They have sensors that detect the stretching of the chambers as blood flows into them. As noted above, the amount of blood in the circulation is dependent on having enough Na+ ions in the extracellular fluid. Therefore, as blood enters the heart and stretches the walls of the atria this provides information about the amount of sodium in the body.

Recall, the second thing you need to take control is something to integrate the data by comparing it with a standard and then deciding what must be done. The JGA cells receive information from their sensors on the amount of stretch being applied by the blood against the vessel wall as it enters the kidneys. If the blood pressure drops then the JGA cells send out more of the hormone they make called renin. And if the blood pressure rises then the JGA cells send out less renin. In contrast, the cells in the atrium respond to a drop in chamber pressure by sending out less of an hormone called atrial natriuretic peptide (ANP). And if the pressure in the atrium rises then the cells send out more ANP. A diuretic is a chemical that causes the excretion of water. A natriuretic is a chemical that causes the excretion of sodium (L. natrium = sodium).

Recall, the third and final thing you need to take control is an effector that can do something about the situation. Renin is an enzyme that acts on angiotensinogen, a protein made in the liver, to form an inactive protein called angiotensin I. Angiotensin I is acted upon by an enzyme in the lungs to produce angiotensin II. Angiotensin II not only stimulates the thirst center but also our appetite for salt as well. Angiotensin II also attaches to specific receptors in the adrenal glands and tells them to release a hormone called aldosterone. Aldosterone attaches to specific receptors on the cells lining some of the tubules in the kidneys and tells them to bring more sodium back into the body. So, one can see that the final effect of renin is to make the body increase its sodium content by eating more salt and reabsorbing more Na+ ions from the urine in production. In contrast, ANP reduces our desire for salt and blocks the release of renin and aldosterone. It also attaches to specific receptors on the tubules in the kidney and tells them to release more sodium into the urine. As you can see, the ANP released from the atria in the heart acts as a perfect counterbalance to renin which is released by the JGA cells in the kidney.

To summarize, when the sensors in the JGA cells detect a drop in pressure and blood flow they release more renin. More renin ultimately tells the body to drink more water and eat more salt, and the kidneys to hold onto more sodium. At the same time the atria in the heart send out less ANP. Less ANP reduces the inhibition of salt intake and the release of renin and aldosterone, and allows the kidneys to bring back more sodium into the body. The final result of an increase in renin and decrease in ANP causes more sodium to enter and remain in the body. When the JGA cells detect a rise in pressure and blood flow they release less renin. Less renin ultimately limits the desire for water and salt and allows the kidneys to release more sodium. At the same time the atria in the heart send out more ANP. More ANP reduces the desire for salt, inhibits the release of renin and aldosterone, and tells the kidneys to release more sodium. The final result of a decrease in renin and an increase in ANP causes less sodium to enter and remain in the body. These are two of the main mechanisms by which the body controls its sodium content. Recall, it is the sodium pump, which pushes sodium out of the cell, and makes sure that there is enough water in the circulation. In other words, it is the sodium pump that makes sure that water stays where itís supposed to stay in the body. It is responsible for maintaining the 2/3:1/3 ratio between the intracellular and extracellular fluid.

Points to Ponder
The way our body makes sure it has enough sodium where it is supposed to be is not just as simple as eating and drinking things with salt in them. Neither is it just as simple as having properly working digestive and cardiovascular systems and kidneys. To control its sodium content and its whereabouts the body needs, not only millions of sodium pumps in the plasma membrane of its cells, but also (1) the JGA cells in the kidneys with stretch receptors that are able to produce (2) renin, which converts (3) the inactive protein angiotensinogen (made in the liver) into angiotensin I that is then converted by (4) a specific enzyme in the lungs, into the active protein, angiotensin II which attaches to (5) specific receptors on (6) certain adrenal cells that produce aldosterone which attaches to (7) specific receptors on (8) specific cells in the kidneys, and (9) atrial cells with stretch receptors that produce (10) ANP which attaches to (11) specific receptors in the adrenals and kidneys. If any one of these eleven parts is missing or not working properly the whole system fails and the body dies because it loses control of its sodium content. 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 its sodium content 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 or water content, or this one for sodium? Remember, without any one of these systems working properly we die. In addition to these there are many other irreducibly complex systems each of which is absolutely vital for life. There are control systems in the body for potassium, calcium, 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 thatís beyond irreducible complexity, to enable these systems to keep us alive within the laws of nature.

If you were running a public swimming pool and were unable to control the concentration of chlorine in the water, do you think it would be safe for use? Having too low a concentration would result in bacterial overgrowth leading to serious illness for swimmers. And having too high a concentration would lead to chemical irritation and damage to the skin and mucous membranes of swimmers. Real numbers have real consequences when it comes to dealing with the laws of nature. A swimming pool must have the right amount of chlorine, at a level that kills off bacteria without injuring swimmers. The same applies to the body and how it functions. Not just any amount of sodium 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 sodium in the right place. The sodium had to be distributed in such a way that 90% of it was dissolved in the water that is outside the cells supporting blood pressure and blood flow. And the remaining 10% had to be dissolved within the water inside their cells supporting cell function. Their kidneys had to be able to take back most of the sodium they filtered out, about 99.5% of it. But if they had taken in too much salt, their kidneys had to be able to get rid of the extra sodium as well. And their bodies had to balance their sodium and water content so that the sodium level in their blood was not too high or too low. For, when it comes to human life there are clear objective numbers that must be maintained to stay alive. In general, a sodium level above 170 units, or below 110 units, is incompatible with life. For our ancestors to have survived and reproduced they would have needed to produce the right amount of urine with right amount of sodium for the right situation. But what if the system that uses renin and ANP to control the bodyís sodium content were set differently so that the kidneys either didnít let go of enough sodium or held on to too much? 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. For, not just any amount of sodium 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 ďnatural survival capacityĒ. 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 systems that use renin and ANP to control the bodyís sodium content seem to inherently know how much sodium the kidneys must release to keep the blood level of sodium where it should be and they do it naturally. The same can be said for each of the other control systems that manage oxygen, glucose, potassium, calcium, 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 by random chemicals coming together to form cells, then simple organisms, and then complex ones like us? The sodium pumps in the plasma membrane provide our cells with their own desalination plant, getting rid of extra sodium to control its total chemical content and volume. Do you think that desalination, a process that uses lots of energy to apply reverse osmosis on sea water to remove its salt and produce fresh water could have come about without a mind at work (human ingenuity and invention)? 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.