January 15, 2004

Which Came First, the Chicken or the Egg?
(Egg white that is, better known as albumin or protein)

By Dr. Howard Glicksman

What exactly is albumin?  It’s one of the main plasma proteins that is produced in the liver.  The gastrointestinal system breaks down protein, that is contained in the food and drink that we consume, into the amino acids that have formed them, and absorbs them into the bloodstream.  The liver then takes these amino acids and at the direction of various signaling proteins, produces enough of the different plasma proteins that the body needs for survival.  Biomolecules such as albumin, globulins and the clotting factors.

How does the liver know how to do this?  The blueprints for the formation of these protein structures are contained in the DNA within the liver cell’s nucleus.  When the liver cell is stimulated by these various messengers, it simply consults the protein formation library that it possesses and then starts to churn out the needed protein for the body.  Remember, there are 20 different amino acids. For example, the protein, albumin, contains 585 amino acids.  Therefore the chances of these amino acids randomly coming together to form a molecule of human albumin is in the order of 20 to the 585th power.  This equals about one chance in 10 raised to the 760th power: pretty long odds.

Of course, chemical evolution presupposes that with untold zillions of amino acids lying around it is possible that many molecules of human albumin could have formed randomly.  But our current understanding of how life works is that the body requires specific biomolecules, for specific actions, in specific amounts falling within a narrow range, that are controlled by a sensor and signaling system.  The body can’t rely on the random forces of nature to produce enough of the biomolecules it needs in order to function. 

The intelligent agents at work in the body directing it to create enough of these necessary biomolecules is the DNA contained in each cell’s nucleus and the signaling system consisting of hormones and other proteins.  Given the likelihood of albumin forming at random compared to the known fact that it is produced by the liver cell at the direction of DNA and various signaling messengers, isn’t it much more plausible that this system was intelligently designed than coming into being by the random forces of nature? 

Still too hard to accept as the truth?  Well let’s see if macroevolution can explain how these proteins developed one step at a time while together still performing a function that directly impacts the viability of the circulation.  A function so important that without the presence of plasma proteins in the bloodstream we could not survive on Earth.

The plasma proteins that are contained in the bloodstream have various functions within the body.  Albumin, which represents about 60% of total plasma protein, and 25% of the liver’s total output, serves as a transport protein for lipids and steroid hormones.  The globulin portion of plasma proteins is subdivided into alpha, beta and gamma globulins.  The alpha and beta globulins are produced in the liver and they transport lipids and fat-soluble vitamins in the blood.  The gamma globulins, which are also known as antibodies, are made in blood related cells and they help defend the body from infection.  The clotting factors, which are made in the liver, are responsible for preventing the body from bleeding to death.      

But it’s not the specific functions of any given individual protein that I’m concerned about in this month’s column.  I’d like to reveal to you and discuss the importance of the combined effect of the blood’s plasma proteins, of which albumin plays the most important part, in maintaining an adequate blood volume and thereby the body’s circulation.  This effect is based on their biochemical and physical properties and not on their biomolecular functions, which in themselves are also vital for life.  A little anecdote that affected me personally might be helpful at this time.

In 1996 my beloved mother-in-law died from complications of a disease called amyloidosis.  This is a condition in which the body stores useless protein in various organs which impairs their ability to function properly.  The first sign that we had that she was ill was when she developed swollen ankles.  It turned out that the disease had affected her kidneys and they were leaking protein into the urine and out of her body.  The disease eventually affected her liver, the site where most plasma proteins are made, which further reduced her serum protein levels and consequently caused her to swell all over her body.  This swelling occurred because the fluid in her body was preferentially going out of the bloodstream and into the interstitial space (the space between the cells but outside of the circulation).  With most of her body water residing out of the circulation, she began to experience such a significant drop in blood pressure that when she stood up she’d almost immediately pass out.  Not surprisingly, this made her very weak and she spent most of her last days in bed.  Eventually, with chronic swelling of her legs, she developed a skin infection which put her into septic shock and she died soon afterward. The severely reduced protein, or in her case, albumin levels, caused by this disease was ultimately responsible for her death.

But if we were to logically extrapolate from this scenario and try to imagine human life without any plasma proteins at all in our systems, would this even be possible?

The lesson to be learned here, one that every physician knows, is that without the plasma proteins in the bloodstream it would be impossible for a human to maintain an adequate blood volume and pressure in order to be able to live.  In other words, if there weren’t any plasma proteins in the circulation, there’d be no circulation!  Read on to see how the presence of plasma proteins in the circulation plays a major role in keeping us alive.  Along the way, ask yourself; how macroevolution can ever explain its development?

Let’s review our understanding of how the human body works.  The body consists of billions of individual cells each of which require nutrients, oxygen and water to survive and function.  The cells obtain these vital necessities from the blood in the circulation. The effectiveness of the circulation is dependent on three basic components, namely the blood volume, the pumping action of the heart, and the vascular system, which consists of the arteries, the veins and the microcirculation.  The microcirculation in turn is made up of the arterioles, the venules, and the capillaries.    

The cells are able to indirectly pick-up nutrients and oxygen and allow for any needed exchange of water and certain chemicals with the bloodstream at the level of the capillary.  The capillary is a very thin walled tube, often with extremely small pores, that allows for the transfer of water and some chemicals to the surrounding interstitial fluid.  The interstitial fluid is in direct contact with the cells with which a similar exchange can take place.  Therefore, the capillary is the true “organ of the circulation.” i.e. this is where the action takes place and without which the rest of the vasculature would be useless.  The heart is the pump, the blood vessels are the conduits, and finally the capillary performs the ultimate function of the circulation.  All three components are necessary.

But if water is able to move in and out of the capillary, then what stops most or all of it from going out of the circulation into the interstitial space?  For if this were to happen there would be a catastrophic reduction in the body’s effective blood volume and we would cease to exist.  What happened to my mother-in-law demonstrates that under the right set of circumstances, this can definitely occur. 

Or alternatively, if water is able to freely travel from the cell to the interstitial space and then into the circulation at the level of the capillary, then what stops most of the water from leaving the cells and going into the bloodstream?  In this scenario we would have a high blood volume but our cells would effectively be dehydrated without enough water in them. 

The answer to these questions lies in our knowledge of the two competing forces that are always acting on the blood in the capillary.  These forces directly affect the flow of water either in or out of it.  This “pushing out”  (filtration)  and “pulling in” (absorption), results in a critical exchange of fluid across the capillary membrane.  An exchange that is vital for life. 

The physical force that ultimately results in a net pushing out of fluid (filtration) from the capillary to the interstitial space is called hydrostatic pressure.  Remember that the heart pumps the blood out of the left ventricle into the aorta and from there it travels down ever-decreasing caliber arteries until it enters the small arterioles on its way to the capillary.  This requires a certain back pressure that continues to diminish as the blood travels through the arterial system. 

But as the blood enters the capillary, the pressure left over that has propelled it thus far begins to be applied against the capillary wall, thereby tending to push fluid into the interstitial space.  It’s sort of like squeezing out a sponge.  The pressure applied by your making a tight fist around it pushes the fluid out just like how the hydrostatic pressure that is responsible for propelling the blood from the heart to the capillary starts to squeeze the water out of the capillary through its pores. 

As the blood continues along the capillary and begins to enter the venule, the initial force that propelled it into the arterial side gradually diminishes.  Although capillaries in different tissues can act differently, the average hydrostatic pressure tending to push fluid out of the capillary at the arterial end is about 35 mmHg and at the venous side it is about 20 mmHg. (Fig. 1)  The lesson to remember here is that hydrostatic pressure tends to push water out of the capillary and into the interstitial space thereby reducing the amount of water in the circulation. 

The second physical force which ultimately tries to pull the water back into the capillary (absorption) is called osmotic pressure.  This term refers to the physical pressure that exists between two aqueous solutions with different concentrations of a particular solute which are separated by a membrane that allows water to pass freely through it but not what is in solution. i.e. what is dissolved in the water on both sides of the membrane is not able to pass through it but water can.  For example, if you had a solution of water mixed with sugar and you put it in contact with plain water, with a membrane between them that only allowed the water to pass through it, but not the sugar, then there would be a measurable osmotic pressure that moves the water from the plain solution across the membrane into the sugar solution. (Fig. 2)   

The capillary membrane which separates plasma and the interstitial fluid is exactly this type of membrane in that it allows water to pass through it but not the plasma proteins.  The interstitial fluid has much less plasma protein in solution than the blood, so there is an osmotic pressure exerted as water from the interstitial space is pushed back into the capillary.  The net osmotic pressure that ultimately tries to pull the water from the interstitial space back into the capillary remains relatively constant along the length of the capillary and is about  24 mmHg. (Fig 3).  The lesson to remember here is that the current understanding of capillary physiology holds that the plasma proteins, in particular, albumin, are wholly  responsible for the osmotic pressure that exists in the capillary system.  In fact this protein plasma induced osmotic pressure is known as oncotic pressure, which alludes to its ability to prevent swelling.  In other words, it is the plasma proteins by virtue of their inability to cross the capillary membrane, that are totally responsible for the ability of the capillary to grab back the water that is squeezed out of it by hydrostatic pressure.

If one takes into account the hydrostatic pressure at the arterial end of the capillary that is pushing the water out of the capillary and applies the osmotic pressure being applied by the protein in the blood trying to pull the water from the interstitial space into the capillary, one will see that the net effect of these two opposing forces is 35 mmHg -24 mmHg = +11 mmHg.  This means that the net force at the arterial end of the capillary is +11 mmHg which results in a net filtering of water out of the capillary and into the interstitial space.  (Fig. 4)

If one does the same calculation for the venous side of the capillary, one will see that the net effect of these two opposing forces is 20 mmHg – 24 mmHg = - 4 mmHg. This means that the net force at the venous end of the capillary is -4 mmHg which results in water being absorbed back into the capillary. (Fig. 4)

Total filtering of water from the capillary is also dependent on many other factors, for example, capillary membrane permeability, surface area of the capillary membrane and the velocity of blood flow through the capillary.  Actually, with the above forces at play in the capillaries of the body, only 0.5% of the water passing through the capillaries is ultimately filtered out into the interstitial fluid.  However, given the fact that 4,000 liters of plasma passes through the body’s capillaries daily, this means that almost 20 liters of water is removed from the capillaries into the interstitial space every day.  This represents one half of the total water in the body!  But 80% of this water is reabsorbed at the venous end of the capillary because of the inherent osmotic pressure that is applied by the plasma proteins of which albumin carries the lion’s share.  The other 20% eventually makes its way back into the circulation through a low pressure system called the lymphatics.

The key thing to notice here is that at the arterial end of the capillary, water is filtered out of the capillary, and at the venous end it is reabsorbed back into the circulation.  Of course changes in plasma protein concentration will alter the osmotic pressure which may affect the capillaries’ ability to reabsorb all of the water that was filtered out.  The body may be able to make some adjustments for these changes in protein levels so that one does not notice any fluid collection in the tissues.  But as the case of my mother-in-law clearly demonstrates, there is ample clinical evidence to show that when serum protein levels drop too low, as occurs in many diseases of the body, the compensatory mechanisms of the body are overwhelmed and water tends to go out of the circulation causing significant drops in blood pressure, severe debility, and death. 

Ask any physician to tell you about conditions, such as

So what are we supposed to make of this?  Well, what would have happened if there were no plasma proteins in the bloodstream at some time or other i.e. with no attendant oncotic pressure being applied at the level of the capillary?  Which came first, the capillary and its ability to provide nutrients and water to the cell; or plasma proteins, particularly albumin, in the bloodstream in order to preserve the water content of the circulation? 

If the capillary with its physiological function came first, how did the body maintain its intravascular volume without the necessary oncotic pressure applied by the plasma proteins?  If the plasma proteins came first but without the capillary, then how did the body properly transfer water and other nutrients to the interstitial space and then on to the cell?  And what about the body’s sophisticated mechanism for controlling the amount of albumin in the bloodstream through various signaling proteins?  How did this come about step by step and when exactly did it develop, before or after the existence of capillaries or the plasma proteins? 

Seems to me that in order for this system to work properly, all three components must be in place and be in proper working order or else the human body would not be able to survive.  If all of this developed one step at time then somewhere along the way one of these vital parts must have been absent; or if present in a rudimentary form, didn’t function exactly as it does now.  Macroevolutionists must be able to show us how a simple organism could develop into a functioning entity with a complex body plan and multiple interdependent biomolecular systems.  The cells in many of these entities need a “capillary-type” system to receive the necessities of life, and based on our current understanding of how this “capillary-type” system functions, it is readily apparent that the absence of an adequate amount of plasma proteins would render the organism as non-functional and therefore would not be able to survive and propagate.          

It would seem to me that these are some of the logical questions that have to be answered by the people who embrace the step by step mechanics of macroevolution.  Comparing similar gene structures between similar or distantly related organisms is all well and good. But eventually those genes have to ultimately produce a biomolecule that works within an irreducibly complex system that provides a vital function for the body. 

Modern medical science and what it knows about human biomolecular and physiological  function; and more importantly, the pathophysiology behind biomolecular dysfunction, should give macroevolutionists pause and make them realize that the bar has definitely been raised.  Just saying that “It evolved over time” should not be acceptable anymore.  What specifically needs to be asked is: “Given our understanding of the complex interdependence and narrow range of biomolecular function for viability, how could this system have evolved over time and still have stayed functional, thereby allowing the organism to survive and propagate?”          

Next month we’ll be looking at whether or not it would have been good for humankind to never have had to experience shortness of breath, thirst or hunger. 

What do you think? Compare your answers to next month’s analysis of the problem as we then apply it to the theory of macroevolution.  

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: 1.15.04