Principles of General Physiology

hydrogen or hydroxyl ions. A weak acid or a low degree of acidity is such because there are relatively few hydrogen ions present. The different degrees of dissociation enable us to express the strength of acids or bases, with the exception of those which do not obey the law of mass action, in numerical quantities, known as their "dissociation constants" or "affinity constants." To understand the meaning of these, a brief account of the law of mass action is introduced. This law states that the rate of any reaction is proportional to tinmasses of the reacting substances. The meaning of " velocity constant " and of "equilibrium constant," as the ratio of the two velocity constants of the two opposite reactions in a reversible system, is explained.

The " dissociation constant " is the equilibrium constant of the reversible reaction of electrolytic dissociation. Since it presupposes that the law of 111.1-^ action is followed, it can only be given in the case of weak electrolytes. Instances of the activity of hydrogen and hydroxyl ions in cell processes artgiven ; such are the action of enzymes, the character of the heart beat, and so on. Hence accurate methods of determining the hydrogen ion concentration arc indispensable. The methods of the use of indicators, the gas electrode and the hydrolysis of esters or cane-sugar are described.

In connection with the hydrogen electrode, the theory of electrode potentials is discussed and the precautions necessary in the use of the method with blood .unpointed out. In the use of the method of hydrolysis of esters, etc., the peculiar effect of neutral salts in increasing the hydrolytic action of a given concentration of strong acid has to be taken into account. The powerful effect of changes in hydrogen ion concentration on physiological processes requires the existence of mechanisms for the prevention of any considerable changes of this kind.

There are two chief chemical systems in which the reactions occurring on the addition of acid or alkali are of such a nature as to require the addition of comparatively large amounts of acid or alkali in order to produce any marked change in the hydrogen ion concentration. These systems are the bicarbonate-carbondioxide system and that of the acid and alkaline phosphates. The former is the more widely occurring one, although the phosphate system is also of importantin protoplasmic reactions. The proteins also play a subordinate part, owing to their amphoteric nature, but chiefly on account of their comparatively high concentration.

In the reactions referred to in the previous paragraph, the phenomena known as " hydrolytic dissociation " play an important part. This process is shown to occur by the presence of free acid and free base in solutions in water of salts of weak acids or bases. It is due to two facts'; the first is that water itself is a very weak electrolyte, being to a minute extent electrolytically dissociated into hydrogen and hydroxyl ions ; the second is the slight electrolytic dissociation of weak acids and weak bases. By interaction of the four ions thus present, there is an excess of hydroxyl ions when the base is the stronger and of hydrogen ions when the acid is the stronger. A very small degree of hydrolysis of the salts of many organic acids with strong bases is frequently to be met with, even in cases where the acid would be expected to be a weak one.

In the bicarbonate system, the escape of carbon dioxide as gas, when the hydrogen ion concentration of the system rises, is an important factor in the maintenance of neutrality. Numerical results are given in the text, showing the efficiency of the system at hydrogen ion concentrations not very far above or below that of neutrality. Carbon dioxide possesses powers of neutralising alkali of a degree not shared by any other acid, except hydrogen sulphide, a fact which is significant in view of its universal production as the result of oxidations in the organism.

The effect of rise of temperature on the bicarbonate system is to increase the alkalinity, on account of the greater temperature coefficient of electrolytic dissociation of water than of sodium bicarbonate. The hydrogen ion concentration of blood at 38° is 0'4 x 10 ~7 and the hydroxyl ion concentration is 7'2 x 10" 7 molar; that is, it is just on the alkaline side of neutrality. This concentration of hydrogen ions reacts alkaline to methyl orange or litmus, acid to phenolphthalein ; the colour of neutral red in such a solution is yellowish orange.

The method of preparing solutions of known concentrations in hydrogen ions by the use of phosphate mixtures is described in the text. The experiments of Ringer on the heart of the frog have shown that, for an efficient artificial saline solution to replace blood, it is not sufficient to take sodium chloride alone in isotonic concentration, but that the presence of potassium and calcium salts is indispensable in addition. In this action, it is the cation that is the necessary part of the salt.

There is evidence that the salt composition of the blood plasma of higher vertebrates is a relic of the composition of the ocean in pre-Cambrian ages. At this period, the blood plasma had the same salt content as the sea water, and when the ancestors of the present land vertebrates left the ocean at the close of the Cambrian epoch, they carried with them an adaptation to this particular concentration of salts. The necessity of salts having "antagonistic" action towards each other's toxic properties applies to protoplasmic action in general.

A number of examples is given showing the intervention of electrolytes in physiological processes ; enzymes, haemoglobin, hsemolysin, secretion, muscular contraction, pigment cells, coagulation of the blood, transmission of excitation from nerve to muscle and from nerve fibre to nerve cell, action of drugs, phagocytosis, narcosis, the respiratory centre, are referred to briefly. The salts of weak acids with weak bases have an importance in that they are much more strongly dissociated electrolytically than either the free acids or the free bases themselves.

Amphoteric electrolytes, of which proteins and amino-acids, next to water itself, are the most important, are capable of forming salts with either acids or bases, provided that these are fairly strong. There is no adequate evidence of combination with neutral salts. There are certain heavy metals which have a very powerful action on living cells, even when in extremely minute concentration. Zinc and manganese greatly favour the normal growth of Aspergillus, while copper, lead, and some other metals have an intensely toxic action on the protoplasm of Spirogyra and animal cells. This latter effect is known as " oligodynamic " action.

THERE is no doubt that if water were as uncommon a liquid as, say, amyl-alcohol or toluene, it would be looked upon as endowed with the most wonderful properties. Common as it is, ancient philosophers like Thales regarded it as the origin of all things, and the development of science has shown how important it is in all the phenomena with which we have to deal. It is chosen to fix standards of density, of heat capacity and so on ; most of the reactions with which chemistry is concerned take place in aqueous solutions. The action of water, in its several forms of ice, liquid or vapour, is the chief factor in geological changes. Finally, all physiological actions have their seat in systems containing water as an essential component.

We have already had occasion to take some account of its intervention in protoplasmic activity, in the production of the colloidal state, in permeability and osmotic pressure, and, in the previous chapter, in the dissociation of electrolytes. We turn now to consider its various physical and chemical properties in turn, together with their importance in vital processes. For many points to which attention is directed, I may acknowledge my indebtedness to the third chapter of L. J. Henderson's "Fitness of the Environment" (1913), to which the reader is referred for more details.

Of all solids and liquids under ordinary conditions of temperature and pressure, water has the highest heat capacity, or specific heat. In other words, it takes more heat to raise the temperature of a given mass of water by a given amount, than it does in the case of any other of these substances. Liquid water is therefore chosen as the unit of specific heat, and in consequence also to define the unit of quantity of heat. The small calorie is that amount of heat required to raise the temperature of one gram of water from 0° to 1° C.

The law of Dulong and Petit, that the specific heat of an element varies inversely as its atomic weight, shows that a substance to have a high heat capacity must consist of elements whose average atomic weight is low. Compounds of hydrogen obviously will have the first place. The most general way in which this fact of the high specific heat of water is important to life is the tendency of the sea, lakes, and rivers to prevent any considerable change of temperature. It also enables vast quantities of heat to be transported from the hotter to the colder parts of the earth by means of ocean currents. Naturally, other properties of water, such as latent heat of evaporation, etc., play a large part in maintaining a constant temperature.

The high specific heat of water is directly favourable to the living organism, composed as it is, in its active parts, of some 80 per cent, of water. The heat produced by muscular activity would otherwise cause a great rise in the temperature of the body before it could be eliminated from the surface by radiation and evaporation. The more highly organised a creature is, the more sensitive are the delicate adjustments of its chemical and physical processes to slight changes in temperature.

As L. J. Henderson points out (p. 91), the most striking change in modern laboratories is the universal introduction of thermostats for carrying on investigations at a constant temperature. In fact, looking round my own laboratory recently, I noticed that there were five of these adjusted to various constant temperatures. Finally, we note that the only other liquid exceeding water in specific heat is liquefied ammonia. Latent heat is the quantity of heat required to change the state of a solid to a liquid, or that of a liquid to a gas, at the same temperature ; or that given out when the reverse change takes place.

In the case of water, 80 calories are necessary to convert 1 g. of ice at 0° into 1 g. of liquid water at the same temperature. This means that as much heat is required for this purpose as to raise the temperature of the resulting 1 g. of liquid from 0° to 80°. To convert 1 g. of water at 100° to 1 g. of vapour at the same temperature, even more is wanted, viz., 536 calories ; so that to vaporise 1 g. requires as much heat as to raise 536 g. by 1°.

A diphasic system of ice and water is therefore an extremely delicate thermostat. As heat is added or removed, no change of temperature takes place, merely ice is melted or water frozen. In this way, the temperature of large bodies of water never falls below their freezing points, and cannot do so, until the whole mass is frozen through. The freezing point of water is not by any means a low one, compared with that of other liquids, and most chemical reactions can take place at this temperature. The latent heat of melting of ice, moreover, is greater than that of any other liquid except ammonia.

The latent heat of evaporation is more important still in the regulation of temperature. Unlike freezing, evaporation takes place at all temperatures, even below 0°. It is naturally greater at higher temperatures, and this fact, in itself, conduces to moderate a rise of temperature when it is already high, while having less effect when the temperature is low. After what has already been said, it will not surprise the reader to find that the latent heat of evaporation of water is absolutely the greatest of all substances known, not even excepting ammonia.

It is to be noted that the large amount of solar heat absorbed in the vaporisation of water from the ocean is recovered again when condensation takes place as rain, and serves not only to warm the cooler places where condensation occurs, but as the source of all the water power of the earth. No other liquid could do this with the same economy of material. The importance of evaporation in getting rid of the excess of heat produced in animal metabolism has been referred to above. If the surrounding temperature is the same as that of the organism, no loss can take place by radiation or conduction, so that evaporation is the only means available, but, at the same time, it is the most effective one.

Here again, water, although a poor conductor compared with metals, takes the highest place among other liquids and even non-metallic solids. The relative values in the following list will illustrate this point : — Thus there is more difference between silver and lead than between lead and water. This fact has its importance in respect of the transference of heat between cells or parts of the same cell where structure prevents convection currents.

The fact that water has its maximum density at a temperature of 4° above its freezing point is familiar to all. Unlike most common substances, when cooled from 4" to 0°, instead of contracting, it expands. At the moment of solidification, there is a further expansion, but this is not uncommon. The two phenomena together account for the fact that large bodies of fresh water, when cooled, freeze only on the surface. Since water at 4° is denser than at a lower temperature, it will sink and no ice will be formed in the depths until it has reached them by growth from the top. In salt water, of course, the ice that separates is free from salts and is therefore still lighter than the sea water.

If ice were formed in the winter at the bottom of lakes and streams, it would never get melted in summer, since the process of diffusion of the warmer and lighter water from the surface is so slow. An old experiment of Rumford's shows that a test-tube of water frozen at the bottom can be boiled at the top without melting the ice. In the lakes, the ice would become thicker every year, until ultimately the whole, or nearly the whole, of the water would be turned to ice.

So far for the thermal properties of water. The only other liquid which approximates to it in the merely thermal properties, necessary for life as we know it, is ammonia, and even this lacks the anomalous expansion before freezing. L. J. Henderson (1913) makes use of these characteristics of water, and there are other exceptional ones, as we shall see, in order to illustrate his point of view that we must consider, not only the adaptation of the organism to the environment, but also the fitness of the environment to the organism. Of course, in one sense, the adaptation of the organism to a particular condition implies also that this condition is fitted for the organism, but there is an obvious distinction to be made, since the organism is capable of change in response to changes in the environment, while the converse does not occur. None the less, it is a remarkable fact that the properties of the substances everywhere present, such as water and carbon dioxide as also those of carbon itself, are just such as to allow the most varied and complex chemical and physical systems with which we are acquainted, and call by the name "vital," to be evolved. No doubt, the mix of the question lies in the words "call by the name vital." In a world in which liquid ammonia took the place of water, another kind of complex organisation might have been developed ; although, it must be admitted, it seems impossible that the complexities and endowments of the "organisms" formed could ever reach the perfection of those whk-h we know under the present conditions (see also the remarks on adaptation on page 201 above).

We pass on to consider some other of the physical properties of water. As we have seen, its surface tension, 75 dynes, is higher than that of any other liquid except mercury, although glycerol, 65 dynes, is not far below it. We have also seen, in Chapter III., the importance of this in relation to the phenomena of adsorption, which play so large a part in physiological processes, owing to the heterogeneous nature of the systems concerned. The supply of water from the soil to plants is greatly influenced by the large surface tension of water, since it is thus enabled to reach the roots from a considerable distance. It is said that, under ordinary circumstances, water may rise in the soil as much as 4 or 5 feet. See the monograph by Russell (1912, pp. 102-105).

Water in the liquid state is practically transparent to all the rays of the visible spectrum. In very deep layers it appears blue, which means that it absorbs more of the rays of longer wave length than of the shorter. The rays of still longer wave length, heat rays, are comparatively more absorbed, so that a vessel of water is a fairly efficient method of absorbing the heat from an arc lamp, used for purposes of microscopic observation or photography. Ultraviolet rays are absorbed to a very small extent.

This relatively small absorption of the energy of radiation is probably of some importance in allowing the access of this form of energy to substances in solution in water. Especially in the case of the green leaf, the light energy must not be degraded to heat before reaching the photo-chemical system of the chloroplast. When it is said that chemistry has been built up almost entirely on aqueous solutions, it is not to be understood that water has been used as a solvent merely because of its cheapness and accessibility, but that it has unique properties in this respect. In fact, there is no other liquid capable of dissolving so great a variety of substances. As regards inorganic salts, very few are soluble in any other liquid. Of organic substances, more are to be found which require alcohol, ether, and so on for solution, but, even here, the majority can be dissolved in water.

Geological facts are, perhaps, the most striking evidence of the efficiency of water as a solvent, but details are out of place here. It is sufficient to recall the fact (L. J. Henderson, 1913, p. 113) that the total amount of dissolved matter carried by the rivers of the world to the sea amounts to five thousand million tons per annum. Turning to the living organism itself, a list of the substances found in urine, which were practically all previously in solution in the blood, illustrates the variety of chemical compounds soluble in water. These are : — urea, carbamic acid, creatinine, creatine, uric acid, xanthine, guanine, hypoxanthine, adenine, oxalic acid, allantoin, hippuric acid, phenaceturic acid, benzorc acid, phenolsulphuric acid, indoxylsulphuric acid, paraoxyphenylacetic acid, urobilin, urochrome, uroerythrin. hsematoporphyrin, glucose, lactose (when the mammary glands are active), glycuronic acid, glycine, alanine, leucine, tyrosine, various enzymes, putrescine, cadaverine, chlorides, bromides, iodides, phosphates, sulphates, salts of potassium, sodium, ammonia, calcium, magnesium, iron, carbonic acid, nitrogen, argon and other substances. In pathological conditions : proteins, oxybutyric and acetoacetic acids, acetone and, in some abnormalities of metabolism, cystine and homogentisic acid. Only a few of these are soluble in other liquids to any extent, even in alcohol.

Chemical Stability. — With the exception of hydrolytic and electrolytic dissociation, the action of water upon solutes is practically nil. This depends upon its chemical inertness and stability. Substances can therefore be recovered, by evaporation of the solvent, in their original state. This applies also to substances which undergo electrolytic dissociation, since the ions reunite on concentration ; and even to some extent to hydrolytically dissociated solutes, when the products are nonvolatile.