One of the interesting relationships among the ash constituents of foods is that between the acid-forming and the base-forming elements, since this has a direct bearing upon the important problem of the maintenance of neutrality in the body.

Although the reaction of normal human blood is alkaline to litmus, the actual excess of hydroxyl over hydrogen ions is found by modern methods to be so slight that blood as well as protoplasm is commonly spoken of as neutral. Thus Henderson writes: "Neutrality is a definite, fundamental, and important characteristic of the organism."

The normal processes of metabolism, however, involve a continual production of acid (chiefly carbonic, phosphoric, and sulphuric) which must be disposed of in order to maintain this neutrality. The factors generally recognized as concerned in the main-tenance of neutrality are: (1) carbonates, (2) phosphates, (3) ammonia, (4) proteins.

As preliminary to even a brief mention of the function of these different mechanisms for maintaining neutrality, it may be well to recur for a moment to the fundamental conceptions which have recently been so well summarized by Henderson as follows: *

"First, the product of the concentrations of hydrogen and hydroxyl ions (at constant temperature) is approximately constant.

(H+) - (OH-) = c.

* Science., Vol. 46, page 78 (July 27, 1917).

Therefore the concentrations of these two ions always vary inversely

(H+) = c.

(OH-).

"Secondly, if for convenience, just as the histologist uses microns instead of meters, we adopt as unit concentrations of hydrogen and hydroxyl ions a very small quantity, viz. the concentration of these ions in neutral solutions, the value of this constant becomes unity.*

(H+) . (OH-) = 1,

(H+) = 1.

(OH-).

It may be noted that, using this unit of concentration, an ordinary decinormal solution of hydrochloric acid has a concentration of hydrogen ions of nearly 1,000,000; and a decinormal solution of sodium hydroxide, a corresponding concentration of hydroxyl ions.

"Thirdly, upon this basis the definitions of neutrality, acidity, and alkalinity are as follows:

For neutrality,

(H+) = 1 = (OH-)

For acidity,

(H+) > 1 > (OH-)

For alkalinity,

(H+) < 1 < (OH-)

"Finally, in any solution containing a weak acid and its salts with one or more bases, regardless of the other components of the solution, the concentration of hydrogen ions is approximately proportional to the ratio of free acid to combined acid.

HA.

( H+) = k ¾

BA.

* The more usual method of expressing hydrogen ion concentration has been referred to in an earlier chapter (page 77).

This relation, however, holds only when the ratio of acid to salt is neither very large nor very small.

"It is therefore evident that in the solution of any weak add, when the quantities of free and combined acid are equal, the value of (H+) is k; if the ratio of acid to salt be 10: 1, (H+) is 10 k, if the ratio be 1:10, (H+) is 0.1 k"

In the case of carbonic acid and of acid phosphates the value of k is near enough to unity so that solutions containing acid carbonate or a mixture of primary and secondary phosphates must always remain nearly neutral.

Carbonic acid produced in metabolism is chiefly disposed of by elimination as carbon dioxide through the lungs. For description of the mechanism and regulation of carbon dioxide elimination the reader must be referred to discussions of the physiology of respiration. Its bearing upon the problem of neutrality is summarized by Henderson as follows:

"This substance is the chief excretory product of the organism. As such it must be eliminated promptly and completely. Moreover, in that it leaves the body not in aqueous solution and as an acid, but almost exclusively in the form of gaseous carbon dioxide, there is no possibility of any variation of the permanent effect produced upon the reaction of the body by the elimination of a definite amount of it. In the final regulation by excretion it is not, therefore, concerned. And yet it has, in the process of excretion, a very important role in regulating the reaction of the body. This depends upon the fact that carbonic acid is not only a waste product, but also a normal constituent of the blood, and, as such, a principal factor in the physico-chemical regulation. Thus, if the ratio of carbonic acid to bicarbonates in a normal individual were 1:15, a large production of acid might cause a destruction of a third part of all the bicarbonates, producing in its place an equivalent amount of free carbonic acid. This, if nothing else occurred, would reduce the relative amount of bicarbonates from 15 to 10, and simultaneously increase the free carbonic acid from 1 to 6. The ratio would now be 6:10, and since the hydrogen ion concentration is proportional to this ratio, this ion would suffer a nearly tenfold increase of concentration. But at this point, or, more strictly speaking, continuously during the process, the excretory function intervenes. There is a tendency for the respiratory process to hold the tension of carbon dioxide in the blood nearly constant. This is the reason why carbonic acid has sometimes been thought the respiratory hormone. Assuming that the exact quantity of carbonic acid set free by the reaction of neutralization were thus eliminated, the ratio would be reduced to 1:10, and the hydrogen ion concentration would rise but one third above its original value. More recent investigations, however, have shown that a tendency to acidity is accomplished by a lowering of the tension of carbon dioxide. Let us suppose that in this case the tension was lowered one third. The free carbonic acid of the blood would then become 0.67 instead of 1.00, and the ratio of acid to salt 0.67:10, which is exactly equal to 1:15, the original ratio. Accordingly, the hydrogen ion concentration would be restored exactly to its original value, and the regulation by excretion would be quite perfect. Now there is abundant evidence to show that something very much like this is always occurring in the body, and, on the whole, I believe that the most delicate of all means to regulate the reaction of the body is to be found in this variation of the tension of carbonic acid during its excretion. Such considerations have strengthened the hypothesis that the hydrogen ion is the true respiratory hormone." (Henderson, loc. cit.)