One aspect of blood chemistry often overlooked is the properties and chemical reactions of some of the more important components in blood fluid. Knowledge of them can increase the understanding of certain diseases and treatments.
Active transport – Is the movement of a chemical substance across a cell membrane against a concentration gradient in a direction opposite to that of diffusion. It requires energy use by the cells of the cell membrane the substance crosses.
Buffer – A substance in a solution that stabilizes the pH of the solution. It does so by combining with hydrogen ions (H+) when H+ concentration [H+] increases and by breaking up and releasing H+ when [H+] decreases. It is a mixture of an acid and the base it transforms into after it loses a proton (H+).
Carbonic-acid bicarbonate buffer system – Is the most important chemical buffer system in the blood. It hinges on the reversible chemical reaction between carbon dioxide (CO2) and water (H2O) and the reaction between the products of that reaction. The chemical equation for the reactions is as follows.
H2CO3 is the symbol for carbonic acid – a weak acid. HCO3– is bicarbonate – a weak base. H+ is a hydrogen ion. The system is one of chemical equilibrium. Therefore, any disturbance in the H+ or CO2 concentration in the blood will cause a net shift in the direction of the reactions to the left or to the right, depending upon the disturbance.
For example, an increase in the concentration of H+ will cause more H+ to bind more HCO3-and thus more carbonic acid (H2CO3) to form. The breakdown of increased amounts of H2CO3 will in turn lead to increased CO2 production. When the reactants and the products reach new steady-state concentrations the rate of formation equals the rate of breakdown and no further net change in the concentrations on either side of the double arrows occurs. At this point the system has reestablished chemical equilibrium. A decrease in CO2 concentration will also drive the reactions to the left. An increase in CO2 concentration or a decrease in H+ will drive the reactions to the right until a new steady-state occurs.
Carbon dioxide must be in its gaseous form (CO2) to freely cross cell membranes. Otherwise, it is difficult for it to enter or leave cells. The reason is CO2 is lipid soluble and can thus pass through cell membranes which are lipid-filled.
On the other hand, bicarbonate (HCO3-) is the form in which most of the carbon dioxide travels through blood and other body fluids. The reason is it is water-soluble and CO2 as a gas is not. Movement of HCO3- in and out of red blood cells does occur in the kidneys and lungs respectively, but not freely. The cost is active transport. The reabsorption of HCO3 that occurs in the renal tubule also requires the use of energy. In the proximal tubule it also requires the action of CA in the tubular cells near the lumen. There, it catalyzes the formation of bicarbonate from a reaction between CO2 and hydroxide ions (OH-). The latter form from the reaction: H2O → H+ and OH-.
Carbonic anhydrase (CA) – Is a family of enzymes that speeds up the chemical reaction between carbon dioxide and water. It is present in many tissues throughout the body. Thus, it plays a role in various chemical reactions involving CO2. It speeds up the chemical reaction in both directions at the point shown below.
CO2 + H2O ↔ H2CO3 ↔ HCO3 + H+
In the kidney it helps remove excess CO2 that kidney and other cells produce during metabolism by speeding up the conversion of CO2 + H2O to H2CO3 which breaks up into HCO3 + H+. The net shift in the reaction is from left to right because of the CO2 concentration gradient caused by the increased CO2 production. As H2CO3 breaks apart into HCO3 and H+ the H+ is secreted into the respective parts of the renal tubule and excreted in the urine. This prevents H+ concentration from increasing – the equivalent of keeping the pH from dropping.
In the lungs CA speeds up the reaction in the opposite direction from right to left. In doing so, it promotes the movement of CO2 from blood into alveolar cells which expel it during expiration. The predominant right to left direction of the bicarbonate buffer system chemical reaction in this setting is due to increased H+ generation from metabolism and the CO2 concentration gradient between blood and alveoli. Exhalation of CO2 is what maintains the latter gradient.
In the absence of dysfunction of the buffer system other factors which tend to raise or decrease CO2 or H+ will also drive the chemical reaction to the left or right so as to keep the pH steady.
Comprehensive metabolic panel (CMP blood test) – Is a group of blood tests which reflects the general state of metabolism and chemical balance of the body. Tests it includes are common electrolytes, markers of liver and kidney function, glucose and total cholesterol. Many laboratories will also calculate a GFR based on the creatinine, age, race and gender.
Concentration gradient – Is the gradual change in the density of a substance dissolved in a solution. The difference is manifest in space. It might be from top to bottom, bottom to top, right to left, or left to right.
Dehydration – Is the excessive loss of water from within cells and the space between cells. It differs from hypovolemia in that the loss is not from the intravascular space. Because there is a net loss of free water it results in hypertonicity. – Dehydrated – adj. – Dehydrate – v.
Hyperkalemia – Higher than normal serum potassium.
Hypervolemia – Is a state of too much fluid in the intravascular space. It is also termed volume overload. –
Metabolic acidosis – Is a disruption in the body’s balance between the amount of acid and base such that the pH is below normal. It might be the result of overproduction of acid by the body; the kidneys not removing enough of it; or excessive loss of sodium bicarbonate from diarrhea or through the kidneys, so there is not enough to neutralize the acid, even if there was not an overproduction of acid.
There are different types of the disorder depending on the type of acid in excess. Diabetic ketoacidosis is but one form.
Lactic acidosis is another type. It is the result of the overproduction of lactic acid. Causes of it include:
- Excessive alcohol intake
- Certain forms of cancer
- Liver failure
- Certain medications such as excessive aspirin
- Decreased tissue perfusion for various reasons, particularly if it is of a magnitude consistent with shock
Osmole – Is a standard unit of osmotic pressure. It is the osmotic pressure resulting from the amount of solute that dissociates in solution to form a quantity of molecules, ions, or both equal to a mole.
Osmosis – Is the passage of the liquid portion of a solution through a semipermeable membrane from a region of greater concentration to one of lesser concentration. The process continues until the concentration of dissolved particles in both areas is the same.
Perfusion – Is the flow of blood through the arteries and capillaries of an organ or its tissues. Normal perfusion is that which is sufficient for cells to survive and perform their functions. – Perfuse – v. – To cause perfusion.
Shock – Is a state of under perfusion of several organs of the body which is life-threatening. The mechanism can be loss of blood volume; poor heart pump function; or circulatory collapse. There are a number of causes of each.
Tonicity – Is the effective osmolality of a solution. It differs from osmolality in that it is not just the concentration of solute particles in a solution. It is the concentration of those that are capable of exerting osmotic pressure across a specified membrane. Thus, it is membrane specific. The two terms might be synonymous if none of the solutes in a solution cross a membrane separating it from another solution. But in humans this is not the case. Most of the solute in blood is salt (sodium and chloride ions) which cannot passively cross cell membranes. But a fraction of other particles can. Therefore they are not osmotically active (cause osmosis). In this case the concentration of the total number of particles in solution is slightly greater than those that can cause osmosis. Hence, the tonicity of such a solution is slightly less than the osmolality.
The primary use of the term tonicity is for comparing solutions. There are three common references to it. In field of health care the use of either term refers to the tonicity of a solution in comparison to that of blood. The three designations are the following:
- Isotonic – the sum of the concentration of solutes capable of causing osmosis is the same and both compared solutions.
- Hypertonic – the sum of the concentration of solutes capable of causing osmosis is greater in a solution than in a compared one.
- Hypotonic – the sum of the concentration of solutes capable of causing osmosis is less in a solution than in a compared one.
Observing the effect of saline (sodium chloride) – table salt in solution – on red blood cells highlights the differences in the terms. The result is based on the fact that sodium and chloride ions don’t passively cross the cell membrane of red blood cells. Therefore, when submerged in a salt solution of a different concentration than blood the flow of water across the cell membranes of the red blood cells is the primary means by which the salt concentration becomes equal within the cells and in the surrounding fluid. In other words, osmosis occurs.
In the above test, there would be no flow of water across the cells’ membranes if the test solution is isotonic because there is no significant difference in the salt concentration and thus no need for a water shift. A hypotonic solution would cause water to flow from the solution into the cells. Depending on the amount of water that enters, cells might burst. A hypertonic solution on the other hand, would cause water to flow from the cells into the solution. This would cause the cells to shrink.
Volume contraction – Is a decrease in the volume of fluid from the vascular tree. It includes the loss of liquid and solutes.
– Volume contracted – adj.