March 15, 2004

Why Blood is Red and other Bedtime Stories (Count Dracula would have been so disappointed!)

By Dr. Howard Glicksman

Remember that the body consists of hundreds of trillions of cells.  It doesn’t matter if a particular cell is located in the part of your brain that is formulating a plan for world peace or the cure for cancer, or if it has the mundane task of helping its surrounding mates hold up the entire spine by being located in the fifth lumbar vertebra; they all need three basic things for survival.  i.e. water, nutrients and oxygen. 

If you recall from last month’s column, we learned that water and the nutrients we need for life are brought into the body through the gastrointestinal system at the urging of the thirst and hunger centers respectively, both of which are in the hypothalamus of the brain.  We also learned that oxygen is brought in and carbon dioxide is released by the lungs at the urging of the respiratory center which is located in the medulla of the brain. 

You may also recall that in the previous columns we learned that water is able to freely pass into the circulation once it is absorbed by the gastrointestinal system and is redistributed throughout the body wherever it is needed.  The many nutrients that we need for our survival, by various mechanisms, are absorbed by the gastrointestinal system and then make their way in the bloodstream to where they are needed, some of them requiring the help of transport proteins made in the liver.  But what about oxygen?  How do we get the right amount of it to where it’s needed?

At rest the body requires 250 cc/min of oxygen to meet its energy needs.  Moreover, during vigorous exercise, such as when primitive man would have been pursuing prey, the body needs upwards of 3,500 cc/min of oxygen to be able to perform this activity.  Oxygen dissolves very poorly in plasma, only 3 cc per liter.  At rest the heart pumps out about 5 liters/min of blood and with vigorous exercise upwards of 25 liters/min.  A quick calculation shows that because of the plasma’s limited ability to carry oxygen in solution, there would be a major shortfall in the body’s ability to meet its energy needs if this were the only way that the body could transport oxygen from the lungs to the tissues.  At most, only 15 cc/min of oxygen (3 cc/liter x 5 liters/min) would be delivered to the cells when the body in fact needs 250 cc/min, only 6% of what is required.  And during exercise this amount would be an abysmal 75 cc/min (3 cc/liter x 25 liters/min) instead of the necessary 3,500 cc/min, or just a paltry 2% of what is required.  Clearly primitive man would not be able to survive in this situation.

So how does the body do it?  Evidently having an efficient respiratory system to bring in as much oxygen as possible from the air and a powerful cardiovascular system to propel the acquired oxygen toward the tissues is not enough to meet the energy needs of the body.  The missing link is hemoglobin.  Hemoglobin is a complex globular molecule that consists of four smaller units each made up of an iron-containing heme group and a protein part called globin

Each molecule of hemoglobin is capable of combining with four molecules of oxygen.  In fact, one gram of hemoglobin is able to bind to 1.34 cc of oxygen and therefore has the potential to increase the blood’s oxygen carrying capacity significantly.  When oxygen combines with the iron in the hemoglobin molecule it forms oxyhemoglobin, which when fully saturated is bright red.  When oxyhemoglobin releases some of its oxygen into the tissues it becomes darker in appearance.  This explains why arterial blood, which is well oxygenated, is bright red and venous blood, which has just released some oxygen into the tissues, is darker, sometimes approaching the color purple or even blue. 

Let’s go back to the initial problem that we encountered when we considered the body’s inefficiency in transporting oxygen in the blood without the help of hemoglobin.  Remember, we said that at rest the body needs about 250 cc/min of oxygen to meet its metabolic needs.  Only 3 cc of oxygen can dissolve in each liter of plasma and the heart at rest pumps out about 5 liters of blood/min.  Therefore dissolved oxygen in the blood can only provide for 15 cc or only 6% of the body’s energy needs.

Each gram of hemoglobin is able to bind 1.34 cc of oxygen and this increases the capacity for the blood to transport what is needed to the tissues for its energy needs.  The usual amount of hemoglobin in the average adult male is about 15 gm/dl or 150 gm/liter.  This would mean that a liter of blood from an average adult male could carry about 150 x 1.34 =  200 cc of oxygen.  And since the heart usually pumps about 5 liters/min of blood around the body at rest, this would mean that the hemoglobin in an average male would allow for about 1,000 cc/min of oxygen to be available to the body.  With room to spare, there is easily enough oxygen for the 250 cc/min needs of the body at rest.

Now let’s consider the body during exercise.  Remember we calculated that without hemoglobin the body could only provide about 2% of its energy needs by way of oxygen in solution.  Obviously, without hemoglobin, or some other way to efficiently transport oxygen from the lungs to the tissues, primitive man could not have survived.  But when we factor in the 200 cc of oxygen/liter that 150 gm/liter of hemoglobin in blood provides for the body, and then apply the 25 liter/min cardiac output during exercise, we see that the body can provide almost 5,000 cc/min of oxygen during maximal exercise.  This would seem to allow for the 3,500 cc/min needs of the body during this activity.

Keep in mind that there are many other factors involved in exercise physiology which I have not addressed here.  I only want you to get a sense of the problems that the body faces in order to be able to survive, given the laws of nature.  So, based on our knowledge of human physiology, it is evident that without hemoglobin, or some other mechanism allowing for the efficient transport of oxygen in the circulation, a multi-system organism with a complex body plan would not be able to live on the Earth.

But where does hemoglobin come from?  Enter: the red blood cell (erythrocyte). 

The red blood cell’s main purpose in the body is not only to produce hemoglobin, but also to house it in order that the body may have an efficient way of transporting oxygen from the lungs to the tissues.  Clinical experience tells us that if hemoglobin is left floating free in the circulation, it will promptly be filtered out of the blood by the kidneys. 

Red blood cells originate from stem cells in the bone marrow.  These primitive cells are influenced by chemical messengers derived from surrounding support tissue in the bone marrow.  These messengers affect the stem cell by attaching to receptors on the cell membrane to make it develop along the red blood cell line. 

Red blood cells generally live about 120 days at which time they are destroyed by the actions of either the spleen the liver or the lymph nodes.  Most of the red blood cell’s components are recycled by the body and stored for further usage.  But since the red blood cell has a definite limited lifespan, in order for the body to be able to maintain the oxygen carrying capacity of the blood, it needs to be able to detect any decrease in red cell mass in order to make the proper corrections.  But the body must also be careful to not form too many red blood cells either.  Don’t forget that red blood cells float in the blood and too many of them may alter the flow mechanics of the circulation.  This can result in blockage of small blood vessels which can lead to tissue damage and even organ injury and death.  A condition known as polycythemia rubra vera often results in an overproduction of red blood cells which can cause these effects.

 So, what’s a body to do?  I’d like to introduce you to the hormone; erythropoietin.

Erythropoietin is produced in the kidney, probably from the cells that line the capillaries near the tubules.  These cells are capable of monitoring the amount of oxygen in the blood.  When there is a drop in the oxygen content, which may reflect a drop in total red cell mass within the body, these cells secrete erythropoietin. The erythropoietin travels in the bloodstream to the partially matured stem cells in the bone marrow and attaches to an erythropoietin receptor on the cell membrane.  This stimulates the primitive red blood cell to mature into an  erythroblast which is capable of producing hemoglobin based on the blueprints contained in its DNA.  These red blood cells, that now contain hemoglobin, undergo further changes and are then released into the bloodstream to replenish the ones that have been lost through various means. 

The above mechanism for control of red blood cell, and consequently, hemoglobin production, explains two very commonly observed phenomena in clinical practice.  People with severe emphysema have difficulty bringing in adequate amounts of oxygen to the circulation because of poor lung function.  These people have frequently been observed to have above-normal  levels of hemoglobin.  The fact that the kidney cell senses total oxygen content rather than total red cell mass explains this quite elegantly. 

The overall poor oxygenation of the blood afforded by emphysematous lungs makes the kidney cell realize that there’s not enough oxygen in the body.  So it secretes more erythropoietin in order to produce more red blood cells which, although they may not be fully saturated with oxygen, will try to compensate for this lack in the tissues.  Clinical evidence shows that there is a limit to how well this will compensate for various activities, but it does make a difference nonetheless.  If the kidney cell were only somehow able to detect total red cell mass this wouldn’t happen.  Evidently, oxygen content in the blood acts as an indirect indicator of total red cell mass. 

Another phenomenon which has been noted for many years is that people with various levels of kidney failure also have commensurate degrees of red cell and hemoglobin reduction (anemia).  This is now easily explained by the fact that since kidney failure is a reflection of fewer kidney cells functioning properly, there also would be less and less amounts of erythropoietin available to stimulate the bone marrow, resulting in anemia.

One can readily see why a person with kidney failure might be so tired and short of breath.  Not only would they have the metabolic problems from kidney failure to deal with, but also the anemia that is associated with them.  Nowadays, most patients who are on dialysis for kidney failure receive erythropoietin injections to help keep their hemoglobin levels elevated.

There are many reasons why people may have difficulty providing their bodies with enough hemoglobin to efficiently carry oxygen to the tissues.  I’ve just mentioned a few here to let you see the complexity of the problems that are faced by physicians when they encounter a patient with anemia. 

Clinical evidence shows that if any one of the following components were to be missing, adequate amounts of red blood cells and hemoglobin would not be provided to the body and it would suffer debility, manifesting primarily as severe weakness and shortness of breath, and often death because it would be unable to transport enough oxygen to the tissues to support its energy needs.

This list is by no means exhaustive.  There are a whole host of other factors that are necessary in order that enough hemoglobin may be produced in the body to meet its oxygen carrying needs.  But I think you get the picture. 

Macroevolutionists seem to think that just by showing us that similar systems exist within similar or more primitive organisms, we should believe that each component came into being one step at a time based on the forces of nature.  That random mutation, or incidental change, acting on natural selection, somehow explains how these intricate, interdependent systems, which provide functions adequate for survival, somehow explains the origin of life.  But I beg to differ.  I think that this position is only scratching the surface of what needs to be demonstrated.

Many people point to the fact that this system is irreducibly complex, i.e., if any one part is missing the whole system will breakdown, to claim that it must have been intelligently designed.  For how could the system have developed, one step at a time and still have remained functional?  A valid point. 

Critics have suggested, if I’ve interpreted them correctly, that many of the components of each irreducibly complex system in the body may have existed in different organisms, either doing nothing or something else, and then came together in a higher organism where each of the parts now took on a new function.  But then, they claim, since these organisms no longer exist, it’s impossible to determine what these other functions may have been.  In response to this claim, one writer in the discussion forum cleverly stated that: “Dr Glicksman asks me to exercise my wonder, but you ask me to exercise my credulity.”  But I think that irreducible complexity is not enough.  It’s only part of the answer.

Many people point to the specified complexity that is contained within these systems.  By this is meant that there is an inherent function, message or meaning to a particular part or combination of parts that can only point to intelligent design since the likelihood of this occurring at random is so astronomical as to approach zero.  I agree.  Within the system that I’ve described there is specified complexity in that every component working together results in giving the body the ability to transport enough oxygen to the tissues so that the body may meet its energy needs. 

But also, the DNA that provides the blueprints for the production of hemoglobin, the cells in the kidney that can sense oxygen content, and the receptors on the stem cells and the primitive red blood cells, all demonstrate specified complexity in that for them there is meaning in mere chemicals. 

Critics that I’ve encountered never even discuss this aspect of intelligent design.  They never try to explain how a cell can develop the ability to detect a chemical or cellular change.  And that coincidentally that same cell has the ability to produce and secrete a chemical messenger that can impact a distant organ’s function which directly impacts the chemical or cellular change that was detected by it. 

But to me, even that’s not enough.  It too is only part of the answer.  The combination of both irreducible and specified complexity does make a compelling case for intelligent design.  But I still think that these two markers of intelligent design point to an even higher level of function that needs to be addressed.

Let’s return to the problem that the body had before hemoglobin came on the scene.  Remember, the body requires 250 cc/min of oxygen in order to meet its energy needs at rest.  The laws of nature provide us with  the solubility of oxygen in plasma from room air at  body temperature as being about 3 cc/liter.  The cardiac output at rest is 5 liter/min.  Therefore, without hemoglobin, the body can only provide itself with 15 cc/min of oxygen, which would make survival impossible.  The corollary to this being that at rest, the heart would have to be able to pump out over 80 liters/min of fluid in order to make up the difference.  But that would require a bigger and stronger heart which would need even more oxygen!

 Now along comes hemoglobin with its ability to carry 1.34 cc of oxygen per gram.  You may recall that the average male has 150 gm/liter of hemoglobin in his blood which will allow him to carry 200 cc of oxygen per liter.  Since the cardiac output of the heart at rest is about 5 liters/min, this would allow the body to carry about 1,000 cc of oxygen to the tissues at rest, more than adequate for survival. 

But what if this system were to be set to produce only 15 gm/liter of hemoglobin instead of 150 gm/liter?  What then?  This would result in only 100 cc/min of oxygen being available to the tissues at rest, and the body would malfunction and eventually die.  The system as it stands would still demonstrate irreducible and specified complexity, but it still wouldn’t be sufficient to allow for life.  What would have gone wrong here and what does this point us to?

For lack of a better term I call this; the complexity of survival capacity.  Clearly, it is the cells in the kidney that have, not only the ability to detect the oxygen content of the blood, but also an inherent knowledge of what that oxygen content should be!  It is based on this inexplicable knowledge, that they send out enough erythropoietin for the purpose of raising the red blood cell mass in order to keep the oxygen content at a level that they deem to be appropriate.  Is there anyone reading this who knows exactly how much oxygen, or any other chemical in the body, should be in their blood at any given moment and is personally able to detect it and correct it if necessary by their own efforts?    

But even that’s not enough for biological survival!  For not only must the kidney cells be able to have the combined capacity to send out enough erythropoietin to effect an adequate response, the bone marrow must also have the capacity to respond in kind.  And don’t forget that even if there’s enough hemoglobin in the blood, you still need proper lung function to bring in enough oxygen and an efficient heart to pump enough blood to the tissues in order to be able to meet their demand for energy.  We must also remember that the bone marrow, the lungs, and the heart are themselves dependent on this oxygen for their own survival! 

No, the final overarching questions for Macroevolution have to be: How is the body able to determine what its optimal level of anything should be?  And then how does it know how to go about  maintaining it?  It’s hard enough to know how a cell that produces a chemical messenger developed that ability and also the ability to monitor a given metabolic parameter.  Never mind that it also seems to know what the optimal level of that metabolic parameter should be.  But that’s not the end of the analysis, for once the messenger cell sends the message throughout the body, there have to be cells that can interpret the message and have the capacity to effect the necessary adjustment of the metabolic parameter in question to maintain adequate function for survival.  Finally, over and above this is the realization that many times the cells in question are dependent upon their own function in order to survive.

When these questions can be answered, we may then be just starting to truly understand the origin of life.  Macroevolution, with its step by step mechanism for development, buttressed only by the observation of similar systems existing within more primitive organisms, to my mind is not sufficient to explain the irreducible and specified nature of the complexity that is required for biological existence.  The fact that these systems exist within multi-system organisms with complicated body plans may explain to some degree why they have been able to win the battle of natural selection up until this point in time.  But macroevolution certainly does not explain how they came into existence in the first place.  To blur this distinction discredits science and does a disservice to the public.

Concluding that life has been intelligently designed is not a cop-out.  It’s not a giving up on scientific investigation.  It is simply an acceptance of what appears to be the truth given our fullest understanding of how life actually works.  Advances in science and technology have indeed made our lives immensely better than in the past.  I am always amazed when the people who support macroevolution point to this fact to justify their position.  For just because we know how something works, and more importantly, how it can be fixed when it breaks down, has nothing to do with where it came from.  These have nothing to do with each other in principle and in consequence.  Operation science is distinct from origin science, and it is indeed unfortunate that many scientists do not recognize this fact to the detriment of society and the culture. 

Next month we’ll explore how the body is able to prevent itself from bleeding to death, in: You’re hurt and bleeding, quick, how do you spell relief? H-E-M-O-S-T-A-S-I-S.

Dr. G.

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

Copyright 2004 Dr. Howard Glicksman. All rights reserved. International copyright secured.
File Date: 3.15.04