Principles of General Physiology

Under other conditions, fluid is absorbed from the tissue spaces into the blood. After loss of blood by haemorrhage, for example, water is taken by the blood from the tissue spaces. According to Starling (1896, p. 321) the process depends on the osmotic pressure of the colloids of the blood. Although lymph contains a certain amount of protein, this amount is normally small as compared with that in the blood plasma, so that the osmotic pressure of the latter is higher than that of the lymph. Under normal conditions, this would result in absorption of water by the blood, were it not that the difference of osmotic pressure is balanced by the difference of mechanical pressure in favour of the contents of the blood vessels. If this latter pressure rises above the osmotic pressure of the colloids of the blood, water will be driven into the tissue spaces and the blood will become more concentrated. If it falls, as after loss of blood, water will pass in the other direction, and the volume of the blood will be increased at the expense of the tissue fluids. It is assumed that the walls of the blood vessels are permeable to all the solutes of blood and lymph, with the exception of those in the colloidal state.

It is, perhaps, well to make a few remarks with respect to the view held by some that osmotic pressure only exists in the presence of a semi -permeable membrane. If this is so, we are incorrect in speaking of the osmotic pressure of a solution under any circumstances except those in which it is separated from pure solvent by means of a membrane impermeable to solutes. When, therefore, that property of a solution which would cause it to show osmotic pressure under these special circumstances is determined by some other method, such as freezing point, another name must be used.

It is clear that such a practice, although perhaps in agreement with the original meaning of osmosis as used by Dutrochet, would give rise to much inconvenience, and even confusion. We need a word to express the total concentration of a solution in such elements as act as molecules in the sense of Avogadro's law, since the molar concentration does not afford the information in the case of electrolytes and colloids. It seems to me that we are quite justified, even in theory, in speaking of the osmotic pressure of the blood, for example, without any reference, even in thought, to a semi-permeaDle membrane. We mean to express those properties conferred by the kinetic energy of the molecules, or elements equivalent to them, of the solutes. In the presence of a semi-permeable membrane it would be shown as a definite pressure, capable of measurement by a manometer ; but the phenomenon which causes this pressure is always there and leads to diffusion, amongst other things.

This denying of the existence of osmotic pressure except in relation to a membrane leads to the denial of its existence altogether, since we know of no perfect semi-permeable membrane. No objection is made to the statement that the air in a vessel open to the atmosphere has a pressure of 760 mm. of mercury, although it is not to be detected unless the vessel is closed and provided with a manometer while the outer atmosphere is removed. In the present book I intend to continue to make use of the words "osmotic pressure," meaning thereby that property of solutions conferred upon them by the kinetic energy of the solutes.

The name " tonicity " is sometimes used, especially in reference to blood corpuscles and living cells in general, but it is not necessarily the same as osmotic pressure, unless we admit that the latter may vary according to the membrane used. For example, we say that a solution of sodium chloride is "isotonic" with mammalian blood corpuscles, because it produces no change in their volume. But we might add an equivalent amount of urea to this solution without making it less " isotonic" with the blood corpuscles, because their membrane is permeable to urea. On the other hand, its osmotic pressure is really doubled, as shown by vapour pressure measurements. The word "isotonic" can only be used when the nature of the particular membrane is specified and refers only to those constituents of the solution to which the membrane is impermeable ; osmotic pressure refers to the total concentration, assuming that the membrane is impermeable to all the solutes, permeable to the solvent.

Macallum (1911, p. 617) appears to suggest that the van't Hoff-Arrhenius theory of osmotic pressure does not hold in physiological phenomena. The osmotic pressure of the cellcontents is said not to be given by the total concentration of electrolytes in the cell, because these may be concentrated by surface tension at the cell-membrane. This does not seem to me to be quite the correct way of putting the matter. Osmotic pressure is only shown by free electrolytes. In estimating, therefore, the osmotic pressure due to the potassium salts in a cell, that part of the salts adsorbed on surfaces must be left out of account. Although the actual concentration of potassium may be greater at the cell boundary, it does not follow that its osmotic pressure is any greater here, because it is concentrated on account of its property of lowering surface energy, and, to do this, it must be held in constraint by the surface, adsorbed in fact, and thus unable to possess the kinetic energy necessary for the manifestation of osmotic activity.

When any substance is dissolved in a solvent, the solution, as compared with the pure solvent, behaves as if the solute were exercising pressure. This pressure is known as " osmotic pressure," because, when the solution is separated from pure solvent by a membrane which is impermeable to the solute, but permeable to the solvent, it is found that the solvent passes to the solution, - increasing its volume, by the process known for many years as "osmosis."

The existence of the pressure can be shown by connecting the vessel, containing the solution as above, to a manometer, so that increase of volume is prevented, and the manometer indicates the rise of pressure. Indirectly, the effect of the solute on the vapour pressure of the solvent, and the various phenomena dependent upon this, show the pressure exerted by the solute. The amount of this pressure was shown by van't Hoff, on the basis of the experiments of Pfeffer and De Vries, to be identical with that which would be exercised by the solute if converted into gas and compressed to the same volume which it occupied in the solution.

Since the simple gas law only applies, even to gases, under limited conditions, it is not to be expected that it would apply to solutions, especially to concentrated ones, without correcting factors. Such factors are present in van der Waals' " equation of state " as applied to gases and to pure liquids. They result from the considerations of the actual space occupied by the molecules themselves, so that the space left free for movement is diminished, and of the mutual attraction exercised by the molecules upon each other, by which the pressure due to their kinetic energy is reduced.

If similar additional correcting factors are introduced into the van der Waals equation to take account of the interaction between the molecules of the solvent and of the solute, an equation can be formed which expresses the osmotic pressure of solutions in general. The kinetic theory of the origin of osmotic pressure satisfies physiological requirements better than other theories do. Hydration of solute, or imbibition of solvent by it, has a negligible effect, except in the case of very concentrated solutions, owing to the enormous preponderance in number of the free molecules of the solvent in comparison with those fixed by the solute.

In practice, osmotic pressure is measured either directly or by methods depending on changes in vapour pressure, of which the depression of the freezing point of the solvent is that most frequently used. In the case of water, this value is called A- In whatever way the osmotic pressure of a solution is raised by removal of solvent, the same amount of work must be done to produce the same amount of change. The mathematical expression is identical with that for the isothermal compression of a gas.

It follows that, by appropriate means, a solution can be made to do work by dilution ; the capacity factor of this work is the volume of the solution undergoing dilution. Solutions, then, like gases, possess volume energy. According to the kinetic theory, substances in solution must diffuse from places of higher concentration to those of lower concentration, until the same concentration is attained in both. Unlike gases, however, the process is extremely slow, owing to the great resistance met with.

Since the kinetic energy of a molecule, an ion, or a colloidal particle is the " same, these elements are mutually equivalent as regards the production of osmotic pressure, which depends only on the molar concentration of the elements active. Colloidal solutions, therefore, must possess a true osmotic pressure, which is usually small, on account of the low molar concentration of such solutions in active elements. Diffusible impurities play no part in the osmotic pressure of colloids, except in so far as they may affect the degree of dispersion of the particles of the colloidal state.

The osmotic pressure of electrolytically dissociated salts, of which one ion only is colloidal, requires special consideration. It is shown that the diffusible ions, .although the membrane is permeable to them, play their full part in the production of osmotic pressure. Certain special phenomena, of which explanation is given in the text, are present in such cases. A salt of which both ions are diffusible through the membrane, if added to the system, is found, when equilibrium is attained, to have distributed itself in such a way as to. have a lower concentration in the presence of the colloidal salt. This happens whether the two salts have an ion in common or not. There is also a considerable potential difference between the two sides of the membrane, owing to the presence of a permanent " electrical double layer " in that situation. In fact, the system is precisely analogous to a metallic electrode in a solution of one of its salts and the amount of the potential difference is found to be expressed by a similar formula, in which the concentration of the diffusible ions inside the membrane takes the place of the "electrolytic solution tension " of the metal in the formula of Nernst.

Osmotic pressure, as such, plays a part in various physiological phenomena. The volume of animal cells, the turgor of vegetable cells, the reaction of smooth muscle to drugs, the rate of intracellular reactions, the process of secretion, root pressure, the rate of blood flow, the production of lymph, and the absorption of liquid from tissue spaces are discussed briefly in the text. Certain cells possess the power of regulating the osmotic pressure of their contents, while the higher animals have developed mechanisms for maintaining that of their blood and body fluids at a constant value.

IN the researches of De Vries on plasmolysis (1884, 1885, 1888), it was found that, if sugar in a certain molar concentration was just sufficient to produce a result, a number of other substances, such as mannitol, etc., in the same molar concentration also produced the same effect. On the other hand, another group, sodium chloride, potassium nitrate, etc., produced the effect in a molar concentration which was lower than that of sugar. The relative concentrations of the various substances of the latter group which were plasmolytically, i.e., osmotically, equivalent to that of the former group, were expressed in a series of numerical values, the isotonic coefficients.

Raoult (1878, etc.) found similar facts in his investigation of the freezing points of the different solutions in question, and they were also expressed in terms of osmotic pressure by van't Hoff (1885). The symbol i will often be met with as expressing the number by which the osmotic pressure of a substance such as cane-sugar must be multiplied in order to obtain that of an equimolar solution of the particular substance in question to which the given value of i refers. The following table given by Philips (1910, p. 132), from the data in the paper by van't Hoff arid Reicher (1889), gives a few values of i calculated (I.) from the depression of the freezing point, (II.) from the plasmolytic experiments of De Vries, and (III.) from electrical conductivity. The meaning of the third column will be seen later.

Now, when we remember that the osmotic pressure of a solution is in direct proportion to the number of molecules of the solute present in unit volume, we see that, apparently, a smaller number of molecules of the second group of substances produces the same effect as a larger number of the first group. If we make a solution by adding 1 gram-molecule of potassium chloride to 10 litres of water, we find that its osmotic pressure is about 1'8 times that of a solution made with 1 gram-molecule of cane-sugar.

It is quite clear, therefore, that there are more osmotically active elements in the first solution (potassium chloride) than in that of cane-sugar. Since that of the latter solution corresponds to the number of molecules taken, it follows that, in the former case, the number of active " molecules " has somehow increased. In other words, the molecules must have been split up so as to make a larger number. When the molecules of gases, such as chlorine at a high temperature, are found to be split up into atoms, so that they no longer appear to obey

Avogadro's law, they are said to be " dissociated." In the same way we may speak of the molecules in our solutions with anomalous osmotic pressures as being "dissociated." But what sort of dissociation are we to suppose that such a salt as potassium chloride undergoes in water? It is plain that hydrolysis into hydrochloric acid and potassium hydroxide is not to be thought of ; these cannot exist together in solution. Moreover, such a hypothesis would not explain the phenomena in the case of acids or bases, which behave in the same way as salts. Again, it cannot be potassium and chlorine in their ordinary state, since potassium is immediately converted by water into its hydroxide, and chlorine would be easily detected if present. Looking at the lists of substances in the two classes referred to, we are at once struck by the fact that those substances which give an abnormally high osmotic pressure and are, as we have seen, " dissociated " in solution in water, are all good conductors of electricity, whereas the " normal " ones are non-conductors. Further, it is found that if a substance which gives an anomalous osmotic pressure in water and is a good conductor is dissolved in a solvent in which it no longer conducts electricity, as, for example, hydrochloric acid in benzene, its osmotic pressure is normal, or, at any rate, not greater than normal.

Suppose that we take a solution of hydrochloric acid in water and pass an electric current through it, we find free chlorine is separated at the anode, where the current enters, and free hydrogen at the cathode, where the current leaves the solution. One of the constituents of the solute, which is called an " electrolyte " when it conducts electricity, " wanders " in one direction, the other in the other direction. Faraday was the first to use the name "electrolyte," and he showed that this is actually the way in which the electric current is carried through the solution of a substance which is capable of conducting it. Each constituent of the electrolyte carries a definite quantity of electricity ; in our case, the hydrogen carries positive electricity from the anode to the cathode, and the chlorine carries negative electricity from the cathode to the anode. The name used by Faraday (1834, pp. 78 and 79, and 1839, I. pp. 197, 198) for these electrically charged atoms, or molecules, was " ions " (iwv, participle of tipi, "going"), those carrying a positive charge, which they give up at the cathode, being "cations" (Kara — down), and those with a negative charge "anions" (ai'a = up), in accordance with the direction in which they move in relation to the current, regarded as of positive electricity. The electrodes are " anode " and "cathode" (68ds = way). A portrait of Faraday will be found in Fig. 51. In order to conduct a current, then, the solute must be decomposed into positively and negatively charged parts, that is, " electrolytically dissociated."

We may note here that, according to Nernst (1911, p. 356), the word " ionisation," sometimes used, is better reserved for the case of the gas ions, which are produced by X-rays, ultra-violet light, etc., and consist of a number of molecules of the gas grouped around a single electron. It is obvious from the facts of electrolytic conduction that hydrogen and chlorine are capable of existence in forms which have quite different properties from those which they possess in their ordinary familiar forms. While they are engaged in carrying electric charges through the solution in which a current passes, they cannot be recognised as hydrogen and chlorine.

The actual amount of electricity carried by a univalent ion is, as was shown by Faraday's work, a definite quantity, and is now known by the name suggested by Johnstone Stoney as an " electron." A bivalent ion carries two electrons and so on. Helmholtz (1881) put forward the view that electricity itself has an atomistic structure, so that, in a certain sense, we may look upon positive and negative electrons as two new univalent elements. Thus a positive electron may be said to replace Cl in HC1, forming hydrogen ion instead of hydrogen chloride (Nernst, 1911, p. 395). If this be so, it is not surprising that hydrogen ion is completely different from hydrogen itself, since it is a new chemical compound, and the essence of chemical combination consists in the manifestation of properties unlike those of the constituents.

The modern development of the science of electrons does not belong to the subject of this book; those interested may consult the short work by Ramsay (1912) on "Elements and Electrons." It is well, however, to refer to one point. The existence of two kinds of electrons, positive and negative, has been assumed above. The question is not yet definitely decided as to whether there is only one kind, the negative, and whether an apparent positive charge is really only the absence of a negative one. This does not affect the argument, and there is evidence in favour of the existence of positive electricity.

Since a hydrogen atom is a very different thing from a hydrogen ion it is not permissible to use the same symbol for both. It is generally agreed to use a dot for a single positive charge and a dash for a single negative one, repeating them as many times as the valency of the ion requires. Thus, H', Ca", NH4' are positive ions, and Cl', SO4", PO4'" are negative ions. The signs + and - , used at one time, are no doubt more expressive, but cause difficulties to the printer, when added to the top of a symbol and, in other positions, would be liable to cause confusion.

Although it is most convenient to speak of the possession of positive and negative charges, it should be remembered that it is possible that the apparent presence of a positive charge may mean simply the absence of a negative one, so that, for example, H' means that the hydrogen ion has one less negative electron than an "uncharged" atom and two less than OH'. So far we have spoken only of the ions present in a solution through which an electrical current is actually passing. Now Clausius (1857) pointed out that, in order to explain the phenomena of electrolysis, a part of the molecules of the electrolyte must be assumed to be already dissociated into ions, which possess movements independent of one another. In the case of

the solutions with anomalous osmotic pressures we notice, in the table given on page 169 above, that the "isotonic coefficient," or van't Hoff's factor i, that is the ratio between the actual osmotic pressure of a solution of an electrolyte, and that which it would have if it contained only non-dissociated molecules, is not a whole number^ although in dilute solutions of strong acids and bases it is very near being so. In dilute hydrochloric acid it is practically 2, but in. sodium chloride of O'l per cent, it is only 1 -9. Measurements of electrical conductivity show the same ratio between the part of the solute that carries the current, i.e., the ions, and the non-dissociated fraction which takes no part in the process, as the table referred to shows.

Arrhenius (1887), on considering these various facts, was led to see that the anomalous osmotic pressures of solutions of electrolytes could be very simply explained by the assumption that the dissociation into ions is not merely the state during the passage of a current, but is the normal condition of the solution of an electrolyte under any circumstances. Evidence that this is so will be given presently. The theory is that known as the "electrolytic dissociation theory,"

which plays so large apart in science at the present day. A portrait of Arrhenius is given in Fig. 52. Arrhenius had already suggested naming those molecules which take part in the passage of an electrical current, and whose ions are independent of one another in their movements, "active," and those whose ions are firmly combined together " inactive," and in his classical paper, " Ueber die Dissociation der im Wasser geloster Stoffe" (1887, p. 637), he gives the evidence for the acceptance of two hypotheses, which are : —

" 1. The Law of van't Hoff applies not only to the greater number of substances, but to all, including those which had been considered to be exceptions (electrolytes in watery solution)." This law of van't Hoff, which is a generalisation of Avogadro's law, has already been quoted (page 148 above), but, for reference, it may berepeated here : — " The pressure which a gas possesses at a given temperature, when a definite number of molecules are present in a definite volume, is of the same value as the osmotic pressure which is exerted, . under the same conditions, by the greater number of substances, when they are dissolved in any kind of liquid."