# pH (not ph, not PH, not Ph)

The pH scale was devised to give a simple way to express the concentration of hydrogen ions (H+) in a solution. I am not quite sure that it was successful. Before we describe pH, let's first try and understand why we care about the concentration of H+.

You should know that water has a molecular formula of H2O. However, a very small percentage of water undergoes the following reaction:

### H2O <------------> OH- + H+

You should understand that in "pure" water, the amount of H+ will equal the amount of OH-. However, this relationship hardly ever is true in the real world since there is practically no such thing as "pure" water. So what is the relationship between H+ and OH- in ordinary solutions? It has been found that the product of the concentration of H+ and the concentration of OH- is a constant (Kw) as shown in the following equation:

### Kw = [H+] x [OH-] = 1 x 10-14

The value of Kw is 1 x 10-14. By knowing this relationship, it is then possible to determine the concentration of OH- if one knows the concentration of H+ (or vice versa) by dividing 1 x 10-14 by [H+]. Practically, what this relationship means is that as the [H+] is increased in a solution, the [OH-] must decrease (and of course, the opposite is true as well). Adding acid to pure water will push Reaction 1 to the left. Thus, if one takes a solution of pure water and adds some H+ to it, the [H+] will increase and the [OH-] will decrease. Now, you might be wondering why this occurs. Bypassing all the physical chemistry details, let's take a look.

First, understand that H+ and OH- are attracted to one another due to their respective charges. Also, they "want" to react with one another to form water. It just happens to be that there is always a very small portion of the water molecules that form these ions (1 out of 553,500,000 water molecules to be exact). It is actually more correct to say that they can react with one another to form water it just that it takes so long for the H+ and OH- to find one another, another water molecule will break up to form new H+ and OH-. Thus the constant formation of water is balanced by the constant break up of water and there is always a small amount of water in the ionized form (H+ and OH-). Imagine, then, that in a glass of pure water the few H+ and OH- are looking for one another but since they are so rare, they cannot find each other easily. By the time they do find each other, another H2O breaks up so that the actual number of H+ and OH- will remain constant. Let's now add some H+ to our glass. Initially, there will be a lot more H+ around searching for the free OH-. Thus it is more easy (and quicker) for the H+ to find the OH- and react with them to form water. This will occur faster than the breakup of water so there is a net reaction removing OH- and forming water. As the OH- disappear, it will be harder (and longer) for the H+ to find them. Eventually, a steady state condition will occur (when the net formation of water is exactly balanced by the break up of water) and the system will be in equilibrium again. When this occurs, you would intuitively guess that the concentration of H+ would be higher than in pure water (because you added more H+) and that the concentration of OH- would be less than in pure water because more of it would be able to "find" a H+ partner since an excess of H+ was added.

A couple definitions to remember: a solution that has equal amounts of H+ and OH- is said to be a neutral solution. One that has a greater concentration of H+ than OH- is an acidic solution. One that has a greater concentration of OH- than H+ is a basic (or alkaline) solution. Any substance that increases [H+] (and therefore decreases [OH-]) of water is an acid, one that increases [OH-] (and therefore decreases [H+]) is a base.

The concentration of H+ in pure water is 0.0000001 (1 x 10-7) moles/liter. Since this is pure water, the concentration of OH- must be the same. A long time ago in Denmark, the Danish biochemist S.P.L. Sorensen decided that he did not like such numbers and developed the pH scale to express the H+ concentration of a solution. Sorensen define pH as follows:

### pH = -log[ H+]

Thus to determine the pH of pure water, simply put 0.0000001 into your calculator, press the log button and take the negative of the result. If you did this, then the pH of pure water would be 7. Remember, an acidic solution is one that contains a greater concentration of H+ than pure water, thus the concentration would have to be greater than 0.0000001 moles/liter. If you were to calculate the pH of any acidic solution, you would find that the pH would be less than 7. Conversely, a basic solution would have a pH greater than 7. Ever since Sorensen developed the pH scale, students have been confused by this inverse relationship (this is why I think he really developed pH - to confuse students!). An acidic solution is one with a greater concentration of H+ and a lower pH. Be sure that you understand the relationship between pH, acidity and alkalinity.

Now that you know what pH is, why is it important to physiology? A superficial answer would be to explain that changes in the pH of an organism can lead to death. Since animals are constantly producing a variety of metabolic acids, uncorrected changes in pH would lead to physiological problems. In humans, for example, plasma pH levels higher than 8 or lower than 7 result in death (the "perfect" pH is 7.4). While this is true, it does not answer the basic question, why is pH important?

To understand the reason why pH is important (at least in a general sense), we must understand something about weak acids and bases. Generally, if the word acid is mentioned, one often thinks about a strong acid (such as hydrochloric acid, HCl). A strong acid is one that completely dissociates to give a lot of H+. However, the vast majority of acids found in the body are weak acids. Weak acids are ones that do not completely dissociate when dissolved in water. (Similar statements could be said for strong and weak bases, however, there are few instances where the body produces bases in excess so that generally having high pH is not usually a physiological problem.) Let's look at a typical weak acid. We will use acetic acid as an example. The dissociation of acetic acid is shown below: As you can see, the acetic acid is an acid as it increases the amount of H+ in a solution. Notice that some of the acetic acid is in the undissociated (and unionized) form. Not all of the acetic acid dissociates thus acetic acid is a weak acid. Note that the reaction described in below is similar to that for the dissociation of water shown above. So again, you can think of the dissociated forms of acetic acid (CH3COO- and H+) as wanting to get together but cannot because it takes too long for them to find each other. Thus the dissociation of acetic acid, like that of water, is an equilibrium reaction with both forms of acetic acid found in solution.

### CH3COOH <------------> CH3COO- + H+

Now imagine we have a solution of acetic acid in which the amount of dissociated acid is equal to the amount undissociated ([CH3COOH] = [CH3COO-]). Suppose some H+ is added to the solution. How would this affect the dissociation of acetic acid? Since there are more H+ around, it is easier for H+ and CH3COO- to find each other and form CH3COOH. Therefore, there would be a net production of the undissociated (and unionized) form of acetic acid and a net reduction in the ionized form. We would now say that this reaction was shifted to the left (as CH3COOH is being formed from CH3COO-, see the above equation)

Now suppose that we add some base (OH-) to our acetic acid solution. This has one more step, so follow carefully. Increasing [OH-] makes it easier for OH- and H+ to find each other and form water. Thus, there will be a decrease in the amount of H+ as more of it is used to form water. This decrease in the [H+] makes it harder for the CH3COO- to find any H+ since there are fewer of them. As a result, more CH3COOH will be able to dissociate pushing the reaction in the above equation to the right. Therefore, there would be a net production of the dissociated (and ionized) form of acetic acid and a net reduction in the unionized form.

So, the addition of H+ pushes the equilibrium of the equation to the left (producing more CH3COOH) while the addition of OH- pushes the reaction to the right (producing more CH3COO-). The same arguments are valid for any weak acid (or weak base). Thus the amount of ionized or unionized form of a weak acid (or base) is determined by the pH of the solution.

How does this affect physiology? As you will soon see, the structure and function of a major category of biochemicals (the proteins) is partially determined by the presence of specific ionized (or, for that matter, unionized) chemical groups. Since these molecules are acids or bases, the proportion of each that is ionized is determined by the pH of the solution. Therefore, changes in the pH will cause changes in the ionization of these groups that will then alter the structure of these molecules. This, in turn, affects the function of the molecules, often inactivating them and possibly resulting in death. We will deal with this later when we discuss proteins.