436 
WATURE 
[Marcu 31, 1923 

considered is outside the limits of any reasonable 
diagram : occasions, in physiology, where this occurs 
will be comparatively rare. 
The hydrogen ion concentration of a solution can be 
measured in a variety of ways: (a) by calculation from 
the laws of mass action, with a knowledge of the com- 
ponents of the solution and the proper constants ; (6) 
by the use of a so-called hydrogen electrode: if a 
platinum wire, coated with platinum black and satur- 
ated with hydrogen gas, be dipped into a solution, it 
acts like a metallic electrode of pure hydrogen, and its 
electrode potential can be measured and made to give 
the c.H of the solution; (c) by the use of so-called 
“ indicators,’’ that is, dyes which change colour as the 
hydrogen ion concentration is altered, owing pre- 
sumably to changes in their degree of electrolytic 
dissociation: the colour is used to measure the value 
of c.H. The study and measurement of the hydrogen 
jon concentration is becoming to-day almost a complete 
science in itself, and progress in physiology, and in 
some branches of colloid chemistry, still waits on 
further improvements in the accuracy and adapt- 
ability of its technique. 
The importance of the hydrogen ion concentration 
in biology is bound up with the phenomena attending 
the dissociation of weak acids and of the so-called 
amphoteric electrolytes, and with the theory of 
“buffers.” A weak acid, for example, carbonic acid 
H,CO,, is one which is only slightly dissociated into 
its ions: the reaction H,CO,2=H’ + HCO’, goes almost 
entirely <: similarly with a weak base. The salt of 
a weak acid is a very effective regulator of the hydrogen 
ion concentration ; it acts as a ‘‘ buffer ”’ to resist the 
effect of adding a strong acid. Let the salt of the 
weak acid be XY, dissociated into its ions X* and Y’. 
Let us add to this a strong acid HZ, dissociated into 
H’ and Z’: we might expect the c.H to be largely 
increased. In our solution now are all the ions X*, Y’, 
H’, and Z’: H* and Y’, however, cannot exist side by 
side in solution in appreciable amount, since (by 
hypothesis) the acid HY is a weak one, that is, the 
reaction H*+ Y’==HY goes almost entirely ~. Hence 
the hydrogen ions are eliminated to form the un- 
dissociated weak acid HY, and we are left (i.) with 
the ions X° and Z’ of the salt XZ of the strong acid, 
and (ii.) with the undissociated weak acid HY. 
The expected increases in c.H can, in this way, be 
reduced almost to an insignificant amount, and in 
physiology (where an exact constancy of c.H appears 
to be necessary for the maintenance of the normal 
physico-chemical structure and behaviour of the living 
cell) the presence of very effective “ buffers ” in every 
organ, tissue, and cell has been shown in recent years 
to be of ultimate importance. Phosphates, carbonates, 
and the salts of proteins, such as hemoglobin, are the 
chemical agents by which this regulation is effected. 
In addition to these we have what we may call “ living 
buffers,” the cells of the respiratory centre and the 
kidney for example, which by their activity maintain, 
in an amazingly accurate manner, the constant c.H 
required in the “internal environment” of all the 
other cells of the body ; that is, in the blood and tissue 
fluids which bathe them. In the body, the important 
buffers are those absorbing the effects of added acid, 
especially carbonic and lactic acids, which are pro- 
NO. 2787, VOL. 111] 



duced with great rapidity and amount during muscular 
exercise. The salts of weak bases, however, are equally 
effective buffers, from the physico-chemical point of 
view, in their capacity of neutralising the effect of 
strong alkalies. Some bodies, moreover, the so-called 
‘amphoteric electrolytes,” of which amino acids and 
proteins are the most notable, are capable of function- 
ing both as weak acids and as weak bases : hence their 
salts (for example, sodium ‘‘ hemoglobinate,” or 
hemoglobin chloride) may act, under suitable con- 
ditions, as buffers of either type. 
The importance of the hydrogen ion concentration 
in physiology is almost certainly concerned—at least 
in part—with the electrical properties of the proteins 
which constitute the formed constituents of living cells. 
It may also be concerned with the processes of oxida- 
tion and reduction occurring in metabolism, but with 
these we will not deal further now. Proteins are 
complex compounds of amino acids, and each amino 
acid possesses the latent possibility of acting either 
as a weak base (in virtue of its— NH, group) or as a 
weak acid (by reason of its —COOH group). Hence 
proteins are capable, at a suitable c.H, of forming salts 
at many and varied points in their enormous molecules. 
These salts are largely dissociated into their ions, so 
that the protein of the living cell may be regarded as 
a large electrified molecule, surrounded by a shell of 
attendant positive (or negative) ions. 
The electrical phenomena accompanying any form 
of activity in a living tissue demonstrate the import- 
ance of this electrification of the fundamental chemical 
basis of protoplasm, and it is well known that the 
existence and properties of colloidal solutions are 
intimately dependent upon the electrical charges on 
the surfaces of the colloidal particles. Now-the degree 
of dissociation of a weak acid HZ, into its ions H* and 
Z’', depends upon the hydrogen ion concentration : 
according to the laws of chemical mass action the ratio 
of the dissociated to the undissociated part is inversely 
proportional to c.H. Hence, if the protein be acting 
as a weak acid, the degree of electrification of the 
protein molecule will be decreased by an increase of 
c.H, and if the behaviour of a living cell depend upon 
the electrical characters of its protein constituents we 
should expect it to be largely modified by an appreciable 
change in c.H. 
This actually occurs : the most violent and extensive 
physiological response is produced, both in single cells 
and in larger complex animals, by quite small changes 
in ¢.H, and all animals possess the power of reacting, 
in a sudden and vigorous manner, to any alteration in 
the c.H of the fluid immediately in contact with their 
cells, in such a sense that the change is diminished, or 
neutralised, and the physico-chemical characters of 
the protein molecules of their protoplasm are main- 
tained in their normal state. We know, at present, 
very little about the molecular structure of living 
protoplasm: we cannot, however, be far wrong in 
supposing that the ionic and electrical phenomena 
displayed by the protein molecules which constitute 
it are among its most fundamental properties, and that 
these are modified, to a high degree, in accordance with 
purely physico-chemical laws, by the hydrogen ion 
concentration of the fluid in which it is suspended or 
dissolved. 
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