February 1, 2008

He Who Cannot Control His Water (and Sodium) Will Not Survive: The Kidney

(Neither Will He Be Allowed in the Pool, i.e. the gene pool)

By Dr. Howard Glicksman

Dear Reader:
This article deals with the kidneys and some of what they do to allow us to live on earth.

In order for you to be better able to understand how important their function is for our survival and their dependence on, and relationship with, other organ systems and mechanisms within the body to accomplish this amazing feat, I have provided you here with a brief overview of some of the basics regarding what is needed for cell and total body integrity, function, and survival.

In my opinion, without at least a limited understanding of these basics of life, it would be impossible to appreciate the overall significance and necessity of kidney function and how it actually relates to our survival capacity within the constraints of the laws of nature. Anyone who is ignorant of this information would be at significant risk of being easily misled into a belief that such a system could actually have come into existence solely by the random forces of nature without the need for intelligent agency. Such is the present situation within society which is daily presented with a naturalistic and materialistic viewpoint through the media, academia, and the culture.

The intelligent design movement does not claim that evolution has not taken place at all.

It admits to it havingplayed a role in the development of life, but with limits. What it does question is the notion that natural selection acting on random variation has been the one and only force at work in this enterprise. This would presuppose that life came into being merely from random chemicals coming together to form biologically significant molecules which then organized themselves into cells with complex structures and then multi-system organisms with complex body plans.

As Dr. Bill Dembski has stated: “Intelligent Design is the study of patterns in nature that are best explained as the result of intelligence”

Just because organisms have similar systems doesn’t automatically mean that they came about at random without a mind at work. Human experience and invention informs us that when something tends to work well one is not inclined to try to “reinvent the wheel” and therefore similar mechanisms to accomplish function and survival capacity must be deemed to either have been intentioned by design or have come into being at random.

However the sciences of forensics and archaeology presume that humankind is capable of determining when something has been caused by intelligent design, that is a “mind at work”, in fact our whole justice system hinges on such a premise. For without this capability how would we be able to determine if a person’s death was natural, suicide, accidental or a murder: or if a fire was caused by nature, accident or was arson?

So I provide this information for you, not in order to try to prove to you that that life was intelligently designed rather than having taken place only by the random forces of nature. No! I provide it to empower you to be able to use your own intellect to better discern what you believe to be more plausible in this matter and to be better able to formulate in your own mind what scientific questions still need to be answered by evolutionary biologists in order to justify their position based on what we know about life and death. Just a cursory examination of this article combined with a deep understanding of what it presents and poses as being left unanswered by Neo-Darwinists should make the humble pause at the realization that certain known aspects of life have been completely ignored in order to be able to present dogmas on others.

The Inconvenient Facts of Human Life: Individual Cells
The body is made up of trillions of cells. There are brain cells, lung cells, blood cells, bone cells, and about 200 other types of cells, each with their own unique function, which together make up the body. Each of these is separate in and of itself and is surrounded by a cell membrane (also called the plasma membrane). One must keep in mind that the human being is a multi-system organism with a complex body plan. This means that in contrast to one celled organisms, which come up directly against the outside world, what most of our cells come up against is the cell membranes of neighboring cells within a given organ or body structure, all of which is bathed in a liquid that is appropriately called the interstitial fluid (fluid between the cells).

The inner substance of the human cell largely consists of water. This fluid, known collectively as the intracellular fluid (ICF) , contains within it dissolved chemicals, such as sodium ions (Na+), potassium ions (K+), chloride ions (Cl-),and various proteins, in specific concentrations, that are necessary for cell survival and proper function.

Floating within the fluid of the cell’s cytosplasm, are various structures, organelles,

In addition to the cell membrane, the cytoplasm and the organelles, the cell also contains a supportive cytoskeleton which is made up of microtubules, microfilaments and intermediate filaments, all of which can change the shape of the cell in response to changes in the environment. See: http://web.jjay.cuny.edu/~acarpi/NSC/13-cells.htm

The Inconvenient Facts of Human Life: Multi-system Organism: Part I

Our cells do not live within a vacuum, nor can they live independently without the help of other cells in the body. Being cells within a multi-system organism, and not being in direct contact with the outside world, they must somehow be able to obtain what they need for survival; things like oxygen and glucose to provide energy to run the processes that take place in the cell and amino acids to build structural proteins and enzymes for various metabolic processes. They must also be able to maintain their internal environment ofwater, with its proper concentration of  chemicals such as Na+, K+ and various proteins while releasing chemicals such as carbon dioxide (CO2) and ammonia (NH3) which are toxic by-products of energy and protein metabolism respectively.

The body accomplishes this task by way of the circulatory system and interstitial fluid surrounding the cells in the tissues. The body takes in oxygen through the lungs, and water, glucose, amino acids, sodium, potassium, and other elements through the gastrointestinal system. These are placed in the plasma within the bloodstream and is propelled through the body by the heart along the arteries. The blood travels along ever decreasing caliber vessels (arterioles) to the capillaries in the tissues where these chemicals are released into the interstitial fluid and then make their way into the cells. The cells are able to release CO2 and NH3 into the interstitial fluid which is picked up in the capillary and sent back through the veins to the heart where they are eventually released from the body through the lungs and the kidney, respectively.

So, although the cell is protected from the outside by its cell membrane, in order to bring in and release what it needs for survival this membrane must be able to allow the passage of these and other chemicals in and out ofthe cell. The problem here being that directly outside the cell membrane of every cell of the body is the interstitial fluid. A fluid that provides life-giving chemicals to the cell, like oxygen, glucose, and amino acids, but also contains vastly different concentrations of Na+ and K+. In opening itself up, through the cell membrane, to the interstitial fluid in order to obtain the necessities of life, the cell is at the same time risking its own integrity and ability to survive because of the laws of nature. Remember as stated above, for cell survival it must maintain its proper concentrations of chemicals in solution, such as Na+ and K+. But the fluid inside the cell (ICF) contains very high concentrations of K+ and low concentrations of Na+ whereas the fluid outside the cell, in the plasma and the interstitial fluid (the extracellular fluid, ECF) contains the opposite, high concentrations of Na+ and low concentrations of K+.

The problem that arises in this setting is that when a membrane, like the one that surrounds each of our cells, is permeable to water and also Na+ and K+, is placed between two fluids containing differentconcentrations of Na+ and K+, like the ICF and the ECF, the natural thing to happen is for the Na+ and K+ to leave the fluid of higher concentration and go into the fluid of lower concentration. In other words, because of this setup, which is necessary for life, there is a natural tendency for K+ to leak out of the cell into the interstitial fluid and for Na+ to leak back into the cell from the interstitial fluid. This movement is described as Na+ and K+diffusing down their respective concentration gradients.

This is such an important concept to understand in order to appreciate how the body works and functions within the constraints of the laws of nature that I will summarize this point again. The cell is protected by the cell membrane but it has to be able to allow water and chemicals to cross in and out for survival. In letting down its guard, so to speak, the cell is able to obtain what it needs for survival at the expense of allowing these chemicals (Na+ and K+)to follow the laws of nature and in effect try to reverse these necessary chemical concentrations which exist inside (ICF) and outside the cell (ECF).

What has to be understood here and considered is that if this activity, of Na+ moving into the cell and K+ moving out of the cell, were allowed to continue to its natural end, then the end of cell life and eventually human life would follow soon afterward. The point here being that this really is how the laws of nature act within the human body. They act not in a way that causes life but that causes death. In order to survive and exist within the natural world and its laws of nature, the cells of the body, and the body itself as a multi-system organism, must have a mechanism by which it can reverse these effects of the laws of nature and thereby stay alive.

Na+ and K+ Diffusion: SO WHAT?
First we will look why the cell would die if Na+ and K+ were allowed to reverse their concentrations in the cell: this is based on known human physiology and death. Then we will look at how this would ultimately result in total body death. Only by understanding and appreciating these processes will you be able to formulate in your mind questions needed to be answered by evolutionary biology in order to justify their position that all life came solely from the random forces of nature without intelligent design.

Osmosis and its Power to Destroy Life
The first thing that has to be considered is the law of nature regarding the movement of water when two solutions are separated by a semi-permeable membrane. What this refers to is a membrane that allows water to freely pass but not the chemical in solution. So for example, if you had two fluids, one containing pure water and the other water with sugar in solution, separated by a membrane that allowed water to pass but not the sugar, the natural thing to happen is for the water to move from the less concentrated solution to the more concentrated solution. In other words, since the chemical itself, in this case, sugar, can’t move down its concentration gradient, like Na+ and K+ across the cell membrane, the water goes in the opposite direction. This process is called osmosis and in this setting the sugar exerts an osmotic pressure, or tendency for the movement of water across the membrane. (see Figure 1)

Inside and outside the cells of the body, water is the solvent for which other chemical particles, like Na+, K+ and proteins are in solution. The cell membrane is effectively semi-permeable in that it allows water to freely pass in and out and to some degree Na+ and K+ and other ions through their specific ion channels as well, but it doesn’t allow proteins to cross in and out like Na+ and K+ can. One can see this would be important since these proteins have vital functions within the cell and if they were allowed to cross the cell membrane and leave en masse, then the cell would dysfunction and die.

Cell function and survival are very dependent on cell volume. In particular, the cells of the brain are very sensitive to changes in size. Any significant shrinkage or expansion usually results in confusion, lethargy, somnolence, coma, and eventually death. This is a medical and scientific fact.

Since the cell membrane allows water to freely cross over to either side, in order for the cell to maintain its proper volume of fluid, the concentration of chemical particles in solution on either side of the membrane must be equal. It doesn’t matter what the specific chemicals are, it’s the total number in solution that matters. There are numerous different particles involved but the main chemical outside the cell is Na+ and its counterpart inside the cell is K+. However since these ions are able to pass through the cell membrane and diffuse down their concentration gradients their importance with regard to water movement is much less in comparison to the proteins within the cell that must remain and by necessity are unable to cross the barrier.

As Na+ and K+ cross the cell membrane, trying to equalize their concentrations on either side, the protein inside the cell that can’t pass over, like the sugar in the above example, begins to exert an osmotic pressure. This osmotic pressure is the force that moves water from outside to inside the cell because the protein inside can’t cross the membrane, just like the sugar in the above example. Another way of putting it is that, just like the sugar, the protein is considered to be osmotically effective because it can’t move across the cell membrane and therefore it must remain inside the cell as part of the particles in solution within the intracellular fluid. So when the other chemical particles cross over to try to equalize their concentrations, especially Na+ and K+, the presence of more particles within the cell as compared to outside the cell results in water moving from outside to inside the cell causing dangerous volume expansion.

Since cell function and survival is dependent on it being able to maintain its proper volume one can immediately see that the same laws of nature that make the Na+ and K+ move across the cell membrane to equalize their concentrations are also responsible for water entering the cell. But the cell has a mechanism to prevent what by the laws of nature should take place and result in cell death.

Now I just want you to pause at this point and review what’s just been expressed here.

The motion of Na+ and K+ across the cell membrane down their concentration gradients, causing them to go into and out of the cell respectively, combined with the osmotic pressure exerted by the protein inside the cell that can’t go across the membrane, is what the random forces of nature do to life. They cause disorder and destruction unless life is able to come up with a way, a mechanism, of reversing them and maybe even using them to its advantage.

In this setting, where the laws of nature just take their random course, the cell would have a natural tendency to not only equalize the concentrations of Na+ and K+ inside and outside the cell, but also let water in causing volume expansion. This is something that all scientists know would result in instant death for the cell and the body as a whole.

People must be aware of this important fact of life in order to just begin to appreciate the complexity of how the cell, and the body as a whole, is capable of survival within the framework of the random forces of nature.

We are not talking here about just random genetic mutation or cell transformation resulting in the information within the cell being capable of producing innovative tissues and organs. We are talking here of the most basic level of cell and total body survival capacity, as well.

To look at life forms and convince oneself that they all came from nothing or the same progenitor, without a mind at work, without taking into account these most basic factors of life is like looking at the development of different air planes without taking into consideration jet propulsion, aerodynamics, and electronics. For the mere presence of parts should not assume function and the mere presence of function should not assume survival capacity. So let us now see how the cell is able to manage to stay alive given the random forces of nature that are exerting pressures on it to dysfunction and die.  

Pumping for Life
To combat this tendency for cell expansion and certain death, the cell has a sodium pump, also known as a Na+/K+ ATPase, which pushes Na+ out of cell while bringing K+ back in. Actually the cell membrane of each cell contains in the order of a million of  these pumps, each working diligently to keep the cell alive by pumping Na+ out of the cell to prevent water from entering. In this way, although the cell membrane is somewhat permeable to Na+, effectively it becomes impermeable because the sodium pump sends the Na+ back out again thereby allowing water to stay out of the cell and keeping its volume where it needs to be.

For an animated demonstration of a sodium pump please see: http://www.brookscole.com/chemistry_d/templates/student_resources/shared_resources/animations/ion_pump/ionpump.html

The presence of the sodium pump in all of the cells of the body, pumping Na+ out of the cell and keeping it in the ECF is why Na+ is known to be the major osmotically effective particle in the ECF. This means that in general, wherever Na+ ion is in the ECF, it tends to keep water with it, preventing it from going back into the cell. In other words, if there wasn’t any Na+ in the blood, there wouldn’t be enough fluid in the blood to allow for human survival.

Whew! It’s Hard Work
The job of the sodium pump, pushing chemicals like Na+ and K+ against their concentration gradients, in the direction they naturally do not want to go, is like having to walk against a strong driving wind. This survival effort requires a lot of energy. So much so that it has been estimated that at rest, over half of the energy needs of the body are taken up by all of the sodium pumps in the trillions of cells of the body constantly maintaining the proper balance of water inside and outside of the cell.

As mentioned above, the cells of the body do not live within a vacuum. They make up the multi-system organism called the human body. Each of these cells must be able to obtain oxygen and glucose and release carbon dioxide for its energy needs in order to survive.

There are cells located in the lungs which help to bring in oxygen and get rid of carbon dioxide, and cells in the intestines which help to bring in glucose for this purpose. There are cells in the heart muscle, the blood, and along the blood vessels that help the oxygen and glucose to get to the cells in the tissues by way of the interstitial fluid where they in turn release carbon dioxide which goes along other blood vessels back to the heart and lungs where it is released from the body through the air we breathe. All of these cells need energy to be able to do this.

Energy: SO WHAT?
We have just said that the sodium pump is absolutely necessary for cell survival. We said this because of the phenomenon of osmosis which naturally takes place between two fluids separated by a semi-permeable membrane, like the cell and the interstitial fluid. Osmosis in this setting allows water to enter the cell causing its volume to increase uncontrollably resulting in death. So the sodium pump constantly works to prevent this from happening by pushingNa+ out of the cell and bringingK+ back in. But this requires a lot of energy to keep our cells alive and functioning properly. So much energy in fact that as mentioned above, about one half of our energy requirement for survival is taken up by the millions of sodium pumps in the trillions of cells in our bodies constantly and diligently pumping out sodium to prevent cell death.

So now that we know one of the reasons why our cells can die, sodium pump failure. So let’s consider this question:

What must happen for the body to die, no matter the insult; whether it be a heart attack, a stroke, cancer, pneumonia, or trauma? In other words; what is the final common pathway to human death?

At the multi-system organism level the human must usually experience a cardio-pulmonary arrest in order to die. What this means is the breathing stops, or the heart stops, or they both stop simultaneously.

When asked why cardiopulmonary arrest results in death, most people will say that without immediate and efficient resuscitation, lack of oxygen to the brain will result in death. What they also mean to say is that in order to breathe, maintain our circulation, and be conscious, we need a properly functioning brainstem, and with prolonged lack of oxygen to this region, as occurs in cardiopulmonary arrest, these cells die and so do we.

For more a picture and information on the brainstem see: http://www.waiting.com/brainstem.html

So we now have to go a little deeper and ask ourselves why this lack of oxygen would result in cell death, and more specifically, brainstem cell death?

The answer lies in considering what every cell must be able to do in order to survive the laws of nature as they apply to membranes, like the human cell‘s, that allows some chemicals to diffuse down their concentration gradients and water to enter the cell by osmosis due to it having impermeable chemicals such as protein within it.

As noted above, about half of the energy we use at rest is needed to keep the sodium pumps going in the cells of our bodies. This includes the sodium pumps in our brainstem cells as well, which by the way are estimated to take up over 70% of their energy usage.

What happens when the body doesn’t have enough oxygen for its energy needs?

Especially for the cells which, although they don’t do any physical work, like the heart and muscles, they nevertheless have the highest metabolic needs in the body. ?Well what happens when a car runs out of gas or the electricity doesn’t flow through a light bulb?

The brainstem is constantly receiving, processing, integrating, and sending messages all over the body. What happens when there isn‘t enough oxygen (or glucose) to meet the energy needs of the brainstem cells?The sodium pumps fail, water leaks in, and the cell volume rises. Medical science knows that brain cells are exquisitely sensitive to these changes in cell volume. Brain cell expansion results in confusion, lethargy, somnolence, coma, and eventually death.

So when we suffer a cardiopulmonary arrest resulting in prolonged lack of oxygen to the brainstem cells, which tell us to breathe, control our circulation, and keep us conscious; they die: and so do we, and it’s all because of the random forces of nature.

The Inconvenient Facts of Human Life: Multi-system Organism Part II

When One Cell Suffers: They All Suffer
Now that we have looked at how the cells are able to receive a continuous supply of energy while being able to rid themselves of metabolic toxic waste we must address another very serious issue. Since our cells exist within a multi-system organism and are dependent on such organs as the lungs, the gastrointestinal tract, and the circulation to receive what they need for energy and toxic waste disposal, they are therefore also at risk and are likely to be affected by ongoing processes elsewhere in the body.

What do I mean by this? Well, we just said that our cells need to strictly maintain their internal chemical environment in order to survive and function properly. Letting oxygen and glucose in and carbon dioxide out of the cell is absolutely necessary for life. But there is a trade-off here. In helping all of the cells of the body to be able to do this, the organ systems involved in this need for life-giving energypay a price.

Without the ability to breathe in oxygen and release carbon dioxide we would not be alive. But every time we exhale we release water vapor and lose water into the air.

Without the gastrointestinal system we would have no way of taking in food to be converted to glucose for energy use and we would die. But this system loses water, sodium, and potassium through the feces.

The body also loses a certain amount of water through the skin by transpiration since it is not a perfect barrier to water loss. Another problem for us is that release of energy in the cells of the body gives off heat and if this builds up too much it can result in hyperthermia and eventually death. The body is able to perspire through the sweat glands and in doing so is continuously losing, yep, you guessed it, water, sodium, and potassium.

Finally, as will be noted in this column, the metabolism of the body produces a certain amount of toxic waste that must be excreted through the kidney. Since the kidney has a limit to how concentrated it can make the urine but must also be able to excrete this toxic waste, there is a certain amount of obligatory water loss, with a variable amount of Na+ as well, that must be released from the body in order for us to survive.

So we can see that the body does not have a closed system for water and sodium. They are always being lost from the body in one way or another in processes that are needed for survival: respiration, gastrointestinal function, transpiration, kidney function, and perspiration.

Control: That’s the Key
Remember we said above that the chemical composition of the fluid in each of the cells of our body must stay relatively stable in order for survival and proper function. To a large extent, for water, Na+ and K+, at the cellular level, this is accomplished by the millions of sodium pumps in the cell membranes of each cell which while at rest uses up about half of the energy needs of the body. But it is important to be aware of the fact that the same can be said about the chemical composition of the fluid outside of the cells as well, the extracellular fluid or ECF which consists of the fluid between the cells (interstitial fluid) and inside the circulation (plasma).

It is a medical fact that thewater content and the concentration of Na+ in the ECF must stay within very narrow ranges in order for body survival. Having too low an amount of water in the body results in low blood pressure, poor tissue perfusion, and eventuallydehydration, as water comes out of the cells, which can result in death. And having too much water in the body, something called fluid overload, often results in disability and depending on the cause and the ability for the body to compensate, can also result in death as well

Having too little or too much Na+ with respect to water in the ECF usually results in the cells responding by either moving more fluid into, or out of, the cell due to osmosis. This takes place because when the Na+ concentration in the ECF is too low it usually means that the concentration of total particles in solution outside the cells is lower than inside the cells so there is a tendency (osmotic pressure) for water to move from the ECF into the ICF causing expansion of cell volume. When the Na+ level outside the cells is too high, meaning that the total concentration of particles outside the cell is higher than inside the cell,the opposite takes place and water tends to move out of the cells making them dehydrated. This phenomenon is usually related to the total water content of the body.

As already noted, the brain cells in particular are extremely sensitive to these volume changes and this often results in confusion, lethargy, somnolence, coma, and eventually death. So maintaining the Na+ level in the ECF within certain narrow limits is vital for life.

But one must keep in mind that the concentration of Na+ in the ECF is related not only to the total amount of Na+ but also the total amount of water in the body since the Na+ level represents how much Na+ there is within a given amount of fluid. So if the total amount of Na+ is normal but the water content is too high or too low, then the Na+ concentration in the ECF will be too low or too high respectively. So in order for the body to be able to continue to survive while up against the random forces of nature it is imperative that it be able to control both its water and Na+ balance, not just either one alone.

 The Inconvenient Facts of Human Life: Multi-system Organism Part III

Water and Sodium: What’s a Body To Do?
The total water in the body consists of about 60% body weight, which means for a 70 Kg man, his total body fluid is about 42 liters. This can be divided into the ICF and the ECF.

The ICF which is the intracellular fluid, or all of the fluid in the cells of the body, represents about 40% of body weight which is about 28 liters. The ECF, which is the extracellular fluid, the fluid outside the cells, is the remaining 20% of body weight which is about 14 liters. The ECF is further divided into the fluid between the cells, the interstitial fluid (ISF) which is about 15% or 10.5 liters, and the plasma volume in the circulation (PV) which contains the remaining 5% or 3.5 liters. The rest of the 40% body weight is made up of solids and fats.

See: http://www.lib.mcg.edu/edu/eshuphysio/program/section7/7ch01/7ch01p03.htm

When the body perspires it loses not only water but also certain amounts of Na+as well. If you were to find yourself in a very humid environment, sweating profusely, it is likely that you would release about 2 liters of fluid per hour in order to maintain a proper core temperature. If all of that water came out from the circulation, which contains only 3.5 liters of plasma, without the body being able to compensate for its losses, it is readily apparent that you would have a precipitous drop in your blood pressure, would faint dead away, and probably die.

The concentration of Na+ in perspiration is lower than the amount in the plasma and interstitial fluid. Therefore, if you were to sweat profusely the excessive loss of water with respect to Na+ makes the concentration of Na+ rise in the fluid outside the cells. As mentioned above, when the Na+ level rises in the ECF this usually means that the total concentration of particles in solution also rises. This rise of total particle concentration outside the cells results in water coming out of them due to osmosis.

Therefore, by water coming out of the cells and into the interstitial space and circulation, due to the osmotic pressure exerted on them by the rise in Na+ concentration brought on by perspiration, the body is able to make a short term correction for this loss of fluid and is able to shore up its blood pressure and circulatory capacity to feed the tissues.

Although the body is able to make some quick compensatory moves with regard to water shifting to prevent a severe drop in blood pressure and death, it is evident that the only long-term solution for these continuous losses is for the body to take in not only water, but also sodium to replenish its stores. The only problem is; given the need to maintain a strict chemical composition and water content not only inside the cells but also outside the cells in the circulation and interstitial fluid, how much water and sodium should the body take in and how often?

So how does the body manage this feat of allowing its cells to have enough water inside them with a high concentration of K+ and a low concentration of Na+ while making sure that there’s enough water between the cells and in the circulation with the proper low concentration of K+ and high concentration of Na+ while we go about our merry lives ?

The former is accomplished as we said by the sodium pumps located throughout the cell membrane of each cell. The latter problem of maintaining the right amount of water in the ECF (the fluid outside the cells in the circulation and the interstitial space), with the proper concentrations of Na+ is managed, not only by the sodium pump at the cellular level, but more importantly, at the total body level, by the kidneys which as we’ll soon see, through various mechanisms are given ongoing information about the moment to moment water and Na+needs of the body in order to accomplish this incredibly complex and vital task.

Get ready for a wild ride of wonder. If after reading this you can still believe that the human body came about totally by the random forces of nature, without a mind at work, without an intelligence directing this magnificent work of art and science, then I’m sorry to say that you can’t say you don’t believe in nothing, it’s safe to say that you can believe in anything. (G. K. Chesterton)

The Kidney: What it Does
The kidney performs several functions in the body. It is involved in the regulation and formation of red blood cells by secreting an hormone called erythropoietin which attaches to erythropoietin receptors on the stem cells in the bone marrow and tells them to differentiate into erythrocytes, also called, red blood cells. These  erythrocytes make hemoglobin which is needed for oxygen transport in the body. People with kidney disease usually make less erythropoietin and are prone to being anemic, which means having low amounts of red blood cells and hemoglobin in the blood.

The kidney also is involved in the process of converting Vitamin D into its active form so it can play its important role in calcium absorption, bone formation, and calcium metabolism. People with kidney disease are prone to calcium and bone related problems.

The kidney conserves important nutrients such as glucose and protein, the loss of which would have a negative impact on the energy needs of the body. People with diabetes who lose sugar through the urine or who have various other kidney ailments that result in protein loss through the urine suffer from these problems as well.

The kidney also excretes foreign substances and in particular the toxic metabolic waste products from protein metabolism. Ammonia molecules are acted upon in the liver to produce the water soluble chemical called urea which can leave the body through the kidney. If either ammonia or urea is allowed to build up in the body to toxic levels they can cause death through nervous system dysfunction.

The kidney is involved in regulation of other chemicals besides sodium, chemicals such as potassium, calcium, phosphate, chloride, magnesium, bicarbonate, and hydrogen ion, all of which must stay within very narrow ranges in the body in order for us to survive.

For the purposes of this column we will focus on the main function of the kidney, which is to maintain the proper balance of sodium and water within the ECF. It must be kept at a proper volume to allow the tissues to have adequate perfusion so that they may receive enough oxygen, glucose, water and other nutrients while being able to take away toxic metabolic waste. But the concentration of Na+ must be kept within certain narrow limits to prevent the excessive expansion or contraction of the cells, particularly the brain cells, which can lead to death. So how do the kidneys do it?

The Kidney: How It’s Set Up
We’ll begin by quickly reviewing the mechanisms by which the kidney functions and then consider what information it would need to “know” in order to be able to make changes in function to preserve the balance of water and Na+ in the body to allow for continued survival.

The basic functioning unit of the kidney is called the nephron of which there are just over a million per kidney. The nephron acts simply by being able to filter out fluid from the blood into microtubules within its tissues by way of a specialized capillary system called the glomerulus. This fluid then follows a circuitous route which includes the proximal tubule, the loop of Henle, the distal convoluted and collecting tubules, and finally, the collecting duct, where it joins with the fluid from other million or so nephrons and is excreted as urine from the body first through the ureter, then housed in the bladder and finally released through the urethra at an opportune time.

For a diagram of the nephron see: http://www.lib.mcg.edu/edu/eshuphysio/program/section7/7ch03/7ch03p11.htm

For a diagram of the glomerulus see: http://www.lib.mcg.edu/edu/eshuphysio/program/section7/7ch03/7ch03p12.htm

Along the way, the nephron  is able to reabsorb what it has filtered out and secrete other substances into this fluid on its way to leaving the body. By certain nerve and hormone messages the kidney is able to make changes in the amount of water and Na+ it lets out or brings back in, thereby being able to maintain the proper balance of the amount of water and Na+ in the ECF to allow for survival. Let’s consider what the kidney does in practical terms and see what information it would need and how it is accomplished.

The Kidney: A Whole lot of Filtering Going On
The kidneys filter about 180 liters of fluid daily. This amounts to about 7. 5 liters/hr. Remember that the body contains about 42 liters of fluid of which about 3. 5 liters are in the circulation as plasma. This means that if the kidneys were not capable to reabsorb any of the fluid that they filter the bodywould lose its total plasma volume in a ½hour and its total body volume in less than 6 hours.

The kidney tubules mentioned above largely are involved in reabsorbing most of the water and Na+ that enters them. In fact about 99% reabsorption takes place since by our own experience we know that from the original 180 liters filtered the body usually produces only about 1-2 liters of urine daily.

But don’t forget, that since the body is obligated to get rid of toxic metabolic waste, like urea, which is produced in the liver, the kidneys are therefore also obligated to produce a certain amount of urine to be able to accomplish this important task. Given the maximum concentrating ability of the kidney this usually amounts to about a ½ liter of urine daily.

If you’ve ever perspired a lot without taking in any fluid, such as working out in the sun or playing a football, you’ve probably noticed that the urine you produce soon afterward is very concentrated and scant in amount. This is because the kidneys somehow know that they need to preserve water and Na+ in order to maintain the proper balance in the body.

But of course, the kidneys themselves can only conserve water and Na+. They can’t produce them on their own. The body must replenish itself with these when it can and so the body tells you to drink by activating the thirst center to make you feel thirsty.

Now if you’ve ever drank several glasses of water you’ve probably noticed that the urine you produce soon afterward is very dilute and in large amounts. This is because the kidneys somehow know that your body now has taken in an excessive amount of water and must excrete this excess to maintain its proper balance of water and Na+. Once you drink a lot of fluid, the distension of your stomach and the excessive amount of water in the body tells your thirst center to turn off and you’re no longer thirsty.

If today your kidneys failed there are numerous reasons why you would die very quickly.

First, your body would lose the ability to balance its Na+ and water which would result in fluid overload. This would cause swelling of the tissues, elevation of blood pressure, and if not relieved, fluid congestion in the lungs, and brain cell volume expansion, soon to followed by death. It would also result in elevation of the K+ level in the body resulting in cardiac dysrhythmia and death. Finally, it would result in the build-up of urea in the bloodstream which would cause not only nausea and vomiting but would be toxic to the brain causing confusion, lethargy, somnolence, coma, and eventually death.

I think you’ve got the picture and it’s not a pretty one. Without your kidneys and their ability to control various chemicals in your body, like, water, Na+, K+ and urea, just to name a few, the random forces of nature would result in death, death, death.

But How Does the Kidney Know What to Do and When?
The kidney must either have the internal ability to know the body’s needs for water and Na+, or the body must be able to determine these needs and inform the kidney. But this in itself is not enough for after knowing the water and Na+ needs of the body the  kidney must be able to make adjustments within its function of filtration, reabsorption, and secretion, to be able to maintain the body’s proper balance.

The System
It turns out that there are several mechanisms involved in detection, integration, and messaging that take place both within and outside the kidney to allow for the kidney to maintain the body’s proper level of water and Na+. Any system that regulates a parameter of life, like the one involving the kidney maintaining the right amounts of water and Na+ in the ECF, requires basically three components in order to function.

The first component must be a sensor that is able to detect the parameter being controlled, such as in this case, the water and Na+ levels in the body. If there were no way for the body to be able to become aware of its water and Na+ content, then how would it be able to maintain the proper balance necessary for life?

The second component of the system is one that is capable of receiving the information from the sensor and must act as an integrator, or comparator, having some sort of inherent knowledge of the necessary level of the parameter in question, something often referred to as a set-point. If the body is able to detect its own water and Na+ levelbut it doesn’t have the inherent knowledge of what that level should be in order to survive, then what use would it be to be able to detect it in the first place?

This integrator must be able to take the information from the sensor and establish if an adjustment should be made to the parameter in question, such as in this case, the water and Na+ balance in the body. It must be able to send a message to something that can effect a change in the parameter in question. What good would it do if the body could detect its own water and Na+ level and even know what these levels should be in order for survival, but not be able to send a message elsewhere in the body where adjustments can be made?

The third component of the system is called the effector. The effector is the part of the system that is capable of doing something in order to bring the parameter, like the water and Na+ content of the body, into the proper range in order to allow for survival. In this case, for water and Na+,the effector is the kidney.  It does this by adjustment of its ability to filter water and Na+  from the blood and then take back what the body needs, based on the messages from the integrators which have been informed by the sensors.

Car Analogy
Let’s consider a common example of how this ability to regulate an important component of function is used by most of us every day while driving the car. The car requires adequate amounts of gas, oil, and anti-freeze in order to function properly. Any situation resulting in no gas coming through to the cylinders, too little oil for the lubrication of the moving metal parts, or too little anti-freeze for cooling the engine, will result in the car either having no energy for locomotion, seizing, or overheating. All of which will result in the car no longer functioning: or as is commonly said: the car will die.

Let’s see how automotive engineers have provided the same three components in the carthat are needed to prevent the car from dying from no gas for energy, seizing or overheating, and compare that with how the body, with the help of the kidney, is able to maintain the proper balance of water and Na+ for survival.

Part 1: The Sensing must be Sensitive Enough
Remember we said that the first component of a regulatory system for a given parameter is the sensor. In order for the car to be informed about its level of gas, oil, and anti-freeze it must be able to detect its level. The car has a floating sensor in the gas tank to detect the gas level, a pressure sensor in the oil system to monitor the effective oil level, and a temperature gauge to measure the effects of anti-freeze on properly cooling the engine.

In order to talk about how the body is able to detect its own level of water and Na+, it is important to keep in mind that it is Na+ that is the particle that is osmotically effective in the ECF which consists mainly ofthe arterial and venous circulation connected to the interstitial fluid by way of the capillaries. What this means is that since Na+ keeps water inside the ECF, the ability to measure the fluid pressure against a vessel wall would be one way of determining, not only how much water is in the system, but also indirectly, the Na+ content as well, since the fluid wouldn’t be there unless Na+ were there too.

Of course, this requires us to understand that the pressure of fluid against the walls of a compartment, such as a blood vessel, a chamber of the heart, or even the stomach, can indirectly provide information about volume since less volume will cause less distention and more volume more distention which can be detected by sensors within the wall called stretch receptors.

So like the car’s ability to be able to detect its level of gas, oil and anti-freeze, the body has at least five important sensory systems involved in the control of its water and Na+ content. One exists right in the kidney, one in the major arteries just outside the heart (the aorta and carotid arteries), one in the atria of the heart, one in the adrenal gland, and one in the hypothalamus in the brain.

The one in the kidney is called the juxtaglomerular apparatus (JGA), which is a fancy word simply meaning that this sensor exists right next to the glomerulus. It is located in a position that puts it up against not only the blood vessels supplying the nephron with blood, but also as part of one of the loops of the tubule carrying what has been filtered originally by the glomerulus and is to be worked on as it becomes urine.

For a diagram of the JGA with further commentary please see: http://www.lib.mcg.edu/edu/eshuphysio/program/section7/7ch03/7ch03p17.htm

At present it is thought that the cells in the JGA are either capable of sensing the pressure against, and distention of, the walls of the blood vessels nearby, which would be a function of volume and, as noted above, water and Na+ content, or they can directly measure the Na+ within the tubule (see link above).

The sensors in the major arteries, the aorta and the carotid arteries, are the high pressure baroreceptors which monitor the blood pressure. It is important to keep in mind that the total blood volume is about 8% of the body weight which is about 5. 6 liters, of which about 60% of that is plasma (the fluid component of blood, not including the cells). Most of the blood in the body, about 85% of it, resides in the low pressure venous system while the high pressure arterial system contains the other 15%. However it is this 15% that feeds the tissues and is therefore known as the effective blood volume, since it effects what is needed in the tissues, namely perfusion.

The ability of the body to perfuse the tissues is dependent on the high pressure arterial system which depends not only on the volume of blood, but also the force of heart contraction, and the peripheral vascular resistance (PVR). It is easy to see that if the heart were to weaken, such as occurs after a heart attack, its ability to efficiently pump blood with adequate pressure to reverse the effects of gravity and friction would be affected. Likewise, if the volume of blood were to suddenly drop, say due to internal bleeding from a stomach ulcer, then the ability of the body to maintain adequate blood pressure would be compromised as well.

The third and very important component that affects arterial blood pressure is the peripheral vascular resistance. The blood travels from the heart, through ever decreasing caliber vessels to the capillaries where nutrients are given to the tissues and toxic waste products are taken back in to be removed from the body. The downstream arterioles are surrounded by muscle which they are able to contract in order to control the amount of blood entering the capillaries. If too much comes in at once it may overwhelm capillary function, causing too much fluid to leak out of the circulation into the interstitial space which would drop the effective blood volume and pressure resulting in hypotension, shock, and sometimes even death. This is what happens when people die from septic shock (bacterial blood infection).

The low pressure baroreceptors, are sensors located in the atria of the heart which monitor the flow of blood coming back to the heart from the veins after having given the tissues oxygen and nutrients.

The adrenal gland is capable of detecting the level of Na+ and K+ directly and acts accordingly as we’ll soon see. Therefore, as opposed to the high and low pressure baroreceptors, and possibly even the JGA, instead of receiving indirect evidence of Na+ content by assessing the pressure of fluid against a compartment wall, the adrenal seems to be able to directly measure Na+ in addition to K+ as well.

The fifth and final sensory system which we will talk about here is affected by the water and Na+ content of the body and resides in the hypothalamus. The other four sensors largely are concerned with the Na+ content of the body which ultimately affects the water content of the ECF. Remember that this is because although Na+ does leak into the cell it is sent out directly by the sodium pump to prevent cell swelling and therefore it is the major osmotically effective positive ion in the ECF, meaning that at some level, that wherever Na+ is, water should be there too.

But what about the concentration of Na+ in the ECF and the water content within the cells themselves, the intracellular fluid? Just because there’s enough Na+ and water in the ECF doesn’t automatically mean that it’s in proper balance and there’s enough water in the cells too. Remember, that the main osmotically active positive ion in the cell is K+, not Na+, and that usually the cell is working hard through the sodium pump to keep Na+, and with it, water, out of the cell. So what mechanism exists to make sure that the cells represented by the ICF have enough fluid and that the concentration of Na+ in the ECF is correct?

You may recall that the law of nature played out in the body between the fluid inside the cell and outside the cell is called osmosis. Remember that by this is meant that when two solutions of fluid containing different concentrations of particles within them are separated by a membrane that allows water to freely pass through but not the particles, then water will go into the solution that has more particles.

Therefore, the flow of water into or out of the cell is directly dependent on, not the concentration of any individual particle, such as Na+, K+ or protein, but the total concentration of all particles in the cell as compared to outside of the cell. The side that has more particles, by definition, has more osmotic pressure, and is able to pull water from the other side into it.

Consequently if there were a way for the body to be able to detect the osmotic pressure across the cell membrane, the tendency for water to flow into or out of the cell, then it would be able to regulate its water and Na+ balance. And surprisingly enough, this is exactly what the sensor in the hypothalamus detects; osmotic pressure or osmotic effectiveness across the cell membrane in either direction, and it is therefore called an osmoreceptor.

Sensor Recap
So in summary, while the car has a sensor in the gas tank, and something to measure the oil pressure and determine the engine temperature reflecting the effect of the anti-freeze, the body’s equivalent sensory devices for controlling its water and Na+ content and balance are the juxtaglomerular apparatus in the kidney (JGA), the high and low pressure baroreceptors in the major arteries and atria of the heart respectively, the adrenal glands, and the osmoreceptors in the hypothalamus.

Part II: Integration is Integral
Now that it is established that the body has the capability of sensing its water and Na+ content, in order to be able to maintain these levels in the ranges for survival it must now have the second component of the system, the integrator; something that inherently knows what these levels should be and is able to inform the kidney.

For the car and its monitoring of gas, oil, and anti-freeze, this second component consists of the gas gauge, the oil pressure gauge, and engine coolant temperature gauge on the dashboard which send the driver a message about their status.

In the kidney, the JGA within each nephron monitoring the local blood volume/pressure or actual Na+ level in the tubule fluid, is always secreting an hormone called renin.   If the JGA detects a decline in the blood volume/pressure or Na+ level it begins to send out more renin, and if these parameters increase, the renin level decreases in response.  In other words, the JGA and its release of renin is inversely proportional to changes in the parameter it is monitoring and its ability to adjust represents the second component of the maintenance system needed for control of the body’s water and Na+.

Renin is an enzyme that acts on an inactive protein called angiotensinogen which is produced in the liver. The product of this activity is called angiotensin I which is acted upon by an enzyme in the lungs to produce angiotensin II . What does angiotensin II do to bring about a change in these parameters? We’ll have to wait until we discuss the third and final component, the effector. (see Figure 2)

The high pressure baroreceptors located in the aorta and carotid arteries respond to drops in arterial blood pressure, which usually reflects loss of water and Na+ from the effective blood volume, by stimulating the sympathetic nervous system to release more norepinephrine within the region of the kidney. Like the JGA monitoring system, the high pressure baroreceptor response through sympathetic nerve stimulation is inversely proportional to changes in the arterial blood pressure. If the blood pressure drops the message to the sympathetic nervous system is strengthened and if the blood pressure rises, the message is lessened again.

The low pressure baroreceptors, located in the atria of the heart, respond to the capacity of the venous system as blood returns from all over the body at low pressure. They do this by way of sensing the distention of the atrial walls as the blood returns.

The low pressure baroreceptors in the atrial walls react to changes in distention by sending two different types of messages. If there’s less distention because theblood volume has dropped, the atria walls harboring sympathetic nerves will be stimulated to send out more norepinephrine into the kidney region. This is similar to what happens with the high pressure baroreceptors mentioned above, and this represents an inverse relationship because less distention results inmore release of norepinephrine.

But the low pressure receptors in the atria are also capable of releasing another hormone called atrial natriuretic peptide (ANP). The name itself, natriuretic, means, to excreteNa+, which tells you how its going to work on the kidney. Therefore when the walls of the atria have increased distention due to an increase in blood volume they respond by increasing their release of ANP and when the distention is less they release less ANP, so this is a directly proportional response to the changes in the parameter being assessed.

The adrenal gland is able to measure the Na+ and K+ levels directly. It responds to drops in Na+ by releasing more of a hormone called aldosterone, an inverse relationship.

Finally, the osmoreceptor in the hypothalamus reacts to increases or decreases in the concentration of particles in the ECF (increases or decreases in ECF osmotic pressure), the force to pull water out of, or into, the cells, by increasing or decreasing its release of a protein called anti-diuretic hormone (ADH)  also known as vasopressin. This is a directly proportional  relationship since when the osmotic pressure in the ECF increases or decreases, the release of ADH increases and decreases, respectively.

Integrator Recap
So in summary, the second component for regulating parameters like gas, oil, and anti-freeze levels in the car is accomplished through notifying the driver by way of the gas, oil pressure, and temperature gauges on the dashboard.

Similarly, for regulation of water and Na+ balance and content, the body uses the hormones; angiotensin II, norepinephrine, atrial natriuretic protein (ANP), aldosterone, and anti-diuretic hormone (ADH) as messengers produced in reaction to the information provided by the sensors in the JGA, the high and low pressure baroreceptors, the adrenal gland, and the osmoreceptors in the hypothalamus.  

Part III: The Effector must be Effective
You may have figured out by now that every component of the system needs to be present and in working order for the entire mechanism to be effective. Being able to monitor the levels or function of gas, oil, and anti-freeze in the car isn’t going to accomplish much if after you notify the driver about what’s wrong they can’t do something about it.

The same can be said for the body and its need to control its content and balance of water and Na+. It may be able detect these parameters and send out messages notifying the body of the problem but unless these messages can have an effect somewhere it would be totally useless to the entire enterprise.

The third component of the regulatory system in the car regarding gas, oil, and anti-freeze is the human component, the driver and then the mechanic. Once the driver is made aware of the gas, oil, or anti-freeze problem by way of observing the gauges on the dashboard, she must take corrective action. This would involve not only replacing the needed gas, oil, or anti-freeze to their respective compartments, but also giving consideration to having these systems checked for leaks and dysfunction by a mechanic.

The third component, or effector, of the regulatory system in the body for water and Na+ control, the part where the messages from the JGA, the high and low pressure baroreceptors, the adrenals, and the osmoreceptors in the hypothalamus, must have an effect, are the kidneys. The kidneys where 180 liters/d of fluid is filtered from the blood and then is reabsorbed as the needs of the body regarding water and Na+ are made known through these messengers. Here’s how it works!!

Recall that the JGA senses either Na+or blood volume as it enters the glomerulus and with a drop in this parameter will send out more renin which enzymatically becomes angiotensin II. This hormone, by attaching to angiotensin II receptors in the muscles surrounding the downstream arterioles, causes them to contract and increases the peripheral vascular resistance thereby elevating the blood pressure.

In fact, angiotensin II is the most powerful vasoconstrictor in the body, being five times more powerful than adrenaline. By causing this vasoconstriction, not only does the overall body blood pressure rise but it reduces the flow of blood into the nephrons of the kidney thereby reducing the amount of fluid being filtered which results in the body being able to retain more water and Na+.

But angiotensin II has another way of affecting Na+ in the body. It goes to the adrenal gland and tells it to release more aldosterone. This hormone then goes back to the kidney and tells the collecting duct in the nephron to reabsorb more Na+ in exchange for K+.

So in summary, when the JGA senses a drop in pressure or low Na+ it sends out more renin which eventually is converted into angiotensin II. The angiotensin IIattaches onto its receptor in the adrenal gland causing the release of aldosterone which tells the kidney to reabsorb more Na+. The angiotensin II also attaches onto its receptor in the muscle cells surrounding the arterioles and thereby causes vasoconstriction which generally elevates the body’s blood pressure and specifically reduces the amount of fluid filtered by the nephron, resulting in an overall retention of water and Na+ in the body.

The high pressure baroreceptors, on detecting a drop in blood pressure will increase the messages being sent along the sympathetic nervous system and cause the release of norepinephrine generally throughout the body and specifically in the kidney region. Once this neurotransmitter attaches to the receptors in the smooth muscle surrounding the arterioles it will have a similar vasoconstricting effect as does angiotensin II with the resulting elevation of blood pressure, reduction in filtration, and improvement in Na+ and water retention.

However the increased release of norepinephrine by the sympathetic system in response to this drop in blood pressure has three other direct effects as well. It stimulates the JGA to release renin which increases the amount of angiotensin II resulting in more vasoconstriction and also Na+ reabsorption due to angiotensin II’s effect on aldosterone secretion from the adrenal gland. Norepinephrine also directly stimulates the kidney tubules to reabsorb more Na+ and tells the hypothalamus to release anti-diuretic hormone (ADH or vaspressin) which we’ll soon see tells the kidney to hold onto more water.

The low pressure baroreceptors in the walls of the atria of the heart, in response to a drop in pressure, stimulate the sympathetic nervous system to release more norepinephrine throughout the body and in the region of the kidney which causes the same effects as listed above. If they detect a rise in pressure, meaning more fluid in the circulation they diminish their message which lessens the release of norepinephrine causing the opposite result of vasodilation, increased filtration, and less water and Na+ reabsorption.

In addition to affecting the sympathetic nervous system the atria will increase their secretion of ANP when the atrial pressure is rising and lower its secretion when the atrial pressure is dropping. ANP acts to cause the arteriolar muscle to relax resulting in vasodilation and a drop in peripheral vascular resistance and blood pressure while allowing more blood to be filtered through the kidneys resulting in an increase loss of water and Na+. It also inhibits the release of renin from the JGA resulting in a decrease in angiotensin II (the vasoconstrictor) and aldosterone secretion (promotes reabsorption of Na+). Finally, ANP also directly acts in the collecting duct of the nephron to block Na+ reabsorption. All of these actions result in a net decrease in water and Na+ reabsorption which allows it to leave the body through the urine.

The aldosterone released from the adrenal gland in response to either stimulation by angiotensin II or drops in Na+ and rises in K+ go to the kidney and tell the collecting duct to reabsorb more Na+ and release more K+.

The osmoreceptor in the hypothalamus is sensitive to the total concentration of particles in the extracellular fluid, not just the Na+. So in effect it is measuring the tendency of water to cross the cell membrane, either into, or out of, the cell. When water is forced to come out of the cell, this means that the osmolarity, or concentration of particles in the ECF is higher than that of the cell. The underlying reason for this situation usually relates to an overall loss of water in comparison to Na+ from the ECF, such as occurs with severe perspiration. As the osmolarity in the ECF rises, the osmoreceptor sends messages for the neurons nearby to make sure that more ADH is released.

ADH acts by telling the collecting duct to reabsorb more water (not Na+) and in doing so tries to correct the situation. ADH, like ANP, inhibits the release of renin from the JGA thereby resulting in more Na+ loss through the urine. Remember, the stimulation of ADH results from there being too much of a concentration of particles in the ECF, of which Na+ is the most prominent. So the way to solve this problem is to either increase the supply of water or decrease the amount of Na+. This is exactly what ADH tries to accomplish through the kidney: directly telling it to reabsorb more water in the collecting duct and by inhibiting the release of renin, telling it to let more Na+ out in the urine.

Effector Recap
So in summary, the human component is the effector for making sure that the car has enough gas, oil, and anti-freeze after being properly informed by the gauges on the dashboard. Likewise, the kidney is the body’s effector for controlling its water and Na+ content and balance after being properly informed by the JGA, the high and low baroreceptors, the adrenal glands and the hypothalamus.

And oh! By the way! Just in case you were wondering! When your blood pressure drops and you’re losing Na+  and water, the body has mechanisms through the osmoreceptors, angiotensin II and the low and high pressure baroreceptors to tell you to drink water and take in salt. Thought you might like to know this very important information as well. Looks like the body’s really got it covered doesn’t it?

One More Thing to Think About
One must also keep in mind that when considering how such a complex and interrelated system could have come about solely by the random forces of nature, given what we now know about what Na+ and water will naturally do, it is important to be aware of two other necessary components to allow for proper function.

They consist of the specific hormone receptor on the cell membrane of the cells in the kidney, and the specific proteins,known as enzymes, which chemically react with the hormones to make them inactive and limit their effects.

How’s That Again?
The JGA senses Na+ or the local arterial pressure and sends out renin which eventually becomes angiotensin II, the high pressure baroreceptors detect the arterial blood pressure and affect the release of norepinephrine, the low pressure baroreceptors sense the blood volume in the venous system and do likewise, but also send out ANP, the adrenal gland senses the level of Na+ and K+ and sends out aldosterone, and the osmoreceptors in the hypothalamus sense the tendency for water to go into or out of the cells, and thereby modulates the release of ADH.

These messengers all travel to the kidney and “tell” it to do something to correct the situation regarding the water and Na+ content of the body as determined by these specific sensors and monitors. The problem now is to consider how the kidney recognizes all of these different messages and how much the kidney should react and for how long?

The car again provides a useful analogy here. If you were running out of gas it would be important for you to be sure that the gas sensor in the tank is directly connected to the gas gauge on the dashboard which has been properly calibrated. This may sound stupid but if the technicians accidentally connected the wires of the gas sensor to the oil pressure gauge instead, then you would be misinformed about how much gas you have in the tank.

And just as important, if the gas sensor is connected properly to the gas gauge but what the indicator on the dashboard told you did not accurately reflect how much gas there is in the gas tank because it wasn‘t set right, then again you would be misinformed and be at risk of allowing your car to run out of gas and die.

After all you don’t usually look at the oil pressure or temperature gauge to determine what your gas status is do you? Well the same can be said for the body’s ability to control its water and Na+. The kidney cells can’t just react to any random protein that happens to be floating by and hope that this will solve the body’s water and Na+ problems, can it?

Each of the hormones mentioned above, angiotensin II, norepinephrine, ANP, aldosterone, and ADH directly affect the target tissue, in this case the cells in the kidney, by locking onto specific receptors on the cell membrane. Only by angiotensin II and norepinephrine connecting up, like a key in a lock, with their specific receptors on the cell membranes of the arteriolar muscle cells, do they know then to contract. And only by aldosterone and ADH connecting up, like a key in a lock, with their specific receptors on the kidney tubular cell membranes, do they know then to bring in more Na+ and water respectively.

The other question that has to pondered is this one. Once these messenger hormones are sent out on a mission to the kidney to inform it of the water and Na+ needs of the body, what happens then after the kidney responds and corrects the situation?

The answer is that these systems are always sending out a certain amount of hormone based on the present water and Na+ balance and content of the body since this is an ongoing, never ending process that requires moment to moment attention for our survival. After all, we are always losing water and Na+ by various degrees just by being alive and we must take in water and Na+ every day, which must be properly managed.

The changes in hormone release from any one system is a reflection of the changes that its sensors detect regarding the water and Na+ content of the body. However, not only is it necessary for specific receptors to be present on the specific kidney cell membranes to receive the message and then to know what to do, in order to maintain close control, it is important that these hormones not overstay their welcome and continue to stimulate the kidney when in fact the situation has changed.

This is where the enzymes come into play. They are always roaming around looking for these hormones to deactivate them so they don’t have a prolonged effect on kidney function so that once a change has occurred, the kidney can respond to the new messages.

Once again the car analogy can be used here. Once the gas tank is noted to be empty, one only needs to put enough gas into it until it is filled. As the agent, or effector, who reacts to the message of the gas sensor through the gas gauge on the dashboard, you the driver, stop yourself from overfilling the tank when you see it has come up to the brim. A reassessment of the gas gauge will now verify that your tank is full and that you can get back in the car and drive away reassured that it won’t run out of gas, at least for the next several hundred miles, that is, unless you have a leak in your gas tank.

Questions for Mr. Darwin
So when considering how such a system could have come about solely by the random forces of nature, without a mind at work, one must keep in mind that each and every component must not only exist, but also function properly in order to give the human being the capacity to survive on earth within the random forces of nature. What is needed are the specific cell’s ability to produce a specific hormone that connects up with a specific receptor on the kidney cell which then effects a specific change that correlates perfectly with what the specific cell is capable of sensing, while at the same time being limited in its activity by a specific enzyme that deactivates it.

All of the information to produce these components is contained in the DNA. In addition, not only must each and every one of these components be present and in working order, they must also cause an effect that adequately allows for a change in the water and Na+ balance and content that allows for survival. In other words, the combined effects of these five mechanisms through the kidney must result in the maintenance of the proper level of water and Na+ in the ECF and ICF otherwise the effects of osmosis will cause cell death and eventually total body death.

Evolutionary biologists would have us believe that life as we know it has come about solely by the random forces of nature. But what this exercise has demonstrated is that when the random forces of nature; such as chemicals in solutions separated by a permeable membrane diffusing down their concentration gradients; and chemicals in solution separated by a semi-permeable membrane causing water to move across by osmotic pressure, are unleashed on living cells, that these natural forces, if not counteracted, will result in cell death. This is what the random forces of nature are capable of doing; causing death: not life.

So the mammalian cell is capable of life at least partly because of its ability to move Na+ out the cell and bring K+ back in by way of the sodium pump. The sodium pump is absolutely necessary because of the tendency for the random forces of nature to cause Na+ and K+ to diffuse down their concentration gradients which allows water to enter the cell because of the impermeable proteins contained within it. By the sodium pump being able to accomplish this task it is able to preserve the  proper cell volume and allow for survival. A natural question from a student would have to be for evolutionary biologists to explain in detail, not only where the sodium pump came from but also how it knew exactly what to do and to what degree in order to allow for mammalian cell survival?

Somehow just saying that “it evolved over time” and “ if it hadn’t evolved we wouldn’t be here to be ask that question” is intellectually unsatisfying, evasive, and ultimately represents circular reasoning. Saying “we really can‘t be certain” and “isn’t it providential for us that it did come about ?” seems more truthful and shows humility.

But explaining how the energy dependent sodium pump came about and knew exactly what to do in order to maintain the cell volume of the cells in the brainstem, the cells that make you conscious and aware, the cells that tell you to breathe, and the cells that control your circulatory system, is only the beginning. For this only answers the question at the cellular level. What about at the multi-system organism level?

The brainstem cells are themselves dependent on the lungs to bring in oxygen and release carbon dioxide, the gastrointestinal tract to bring in glucose, amino acids, vitamins, minerals, sodium, potassium, and water etc, and the circulatory system to bring these vital elements to their doorstep and take away the toxic metabolic waste products. Medical science knows that in order for these systems to continue to be able to do this that a multi-system organism must be able to control its water and Na+ balance and content otherwise the brainstem cells will either shrink or expand too much, which will cause dysfunction manifesting as lethargy, confusion, somnolence, coma, and eventually death.  

This exercise has demonstrated not only the complexity of each of the systems involved in the task of water and Na+ control in the body but also their interdependence and finally, their inherent capacity and knowledge, to act in a way that allows for survival.

I leave it to you the reader to be able to put together specific questions that a reasonable person who is knowledgeable about the human physiology regarding water and Na+ balance within the body, would need answered in order to believe that such a system could have come about by the random forces of nature.

I would also point out here that merely comparing the genetics behind the development of this or that hormone and its specific receptor without taking into account its overall function within a given organism and then its capacity for survival within the laws of nature, is wholly inadequate to explain the development of life.

To use the car analogy again. It is possible to construct a car with the usual parts but inadvertently put in an electrical system with the capacity of a drill gun. This system would never have the ability to maintain the electrical needs of the car, and therefore although this car would have parts that can function, it would not have the capacity to start and provide the energy needs for proper car function. This is somewhat akin to what happens to people who develop chronic neurodegenerative conditions like, Multiple Sclerosis, Parkinson’s Disease, Amyotrophic Lateral Sclerosis (Lou Gehrig’s Disease). They have parts that can function but the nervous system is not working properly which would directly impact our hominid ancestor’s survival capacity. Just because you have a neuromuscular system in place doesn’t mean that it is necessarily going to work well enough to allow for survival.

The same car could have its electrical system upgraded but at the same time if a lawn mower engine were to replace the V8 engine presently in place, once again, the car would be able to start but it wouldn’t be able to move fast enough due to the limited capacity of the engine. This is what happens with people who have heart failure, emphysema and anemia. Their bodies are functioning but not at the capacity that would allow for survival because these systems are unable to provide enough energy to the muscles because of organ dysfunction. Just because you have a heart, lungs and red blood cells to carry oxygen to the tissues doesn’t necessarily mean that they will be working adequately to allow for survival.

Finally, if the car had its V8 engine replaced but instead of motor oil, vegetable oil was put into the system, then it would have the tendency to seize up because of the metal parts not being properly lubricated to prevent the build of friction. This is what happens to people who have severe arthritis involving their joints. The body is functioning but because of this problem their survival capacity has been rendered limited. Just because you have bones and joints doesn’t necessarily mean that they will work properly to allow for survival.

Evolutionary biologists’ viewpoint seems to me to be only one dimensional. They only try to show how individualparts may have come into existence but never talk about function or survival capacity both of which involve taking into accountthe random forces of nature. But I’ll leave this to you the reader to consider.

P. S.: Remember we said that the kidney is involved in controlling not only the water and sodium balance and content of the body through the extracellular fluid, especially the blood volume, and its osmolarity, which ultimately affects cell volume, but it also regulates the body’s content of potassium, magnesium, hydrogen ion, bicarbonate, phosphate, and calcium; is involved in retaining glucose and amino acids, excreting metabolic toxic waste, and finally, affecting red blood cell formation and activation of Vitamin D which is important in calcium metabolism.

Each of these separate functions is vital for life, without which we would not be able to survive, and each of them have their own layer of complexity that must still be explained above and beyond the dogma of “it evolved over time”. With what we know about how life works and how easy it is for it to die, to lose the capacity for survival, specifically because of the random forces of nature, this meager answer should no longer be acceptable to students of science.

See you next time!!

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 2008 Dr. Howard Glicksman. All rights reserved. International copyright secured.
File Date: 2.01.08