Principles of General Physiology

Frictional resistance in fluids being proportional to the square of the rate at which the rubbing surfaces glide over one another, we see why there is comparatively little resistance in the capillaries. Owing to the enormous increase of total sectional area, the rate of flow is far less than in the arterioles. Now, the total amount of the friction experienced by the blood obviously depends on that property of liquids known as internal friction, which differs greatly in different cases ; compare water with treacle, for example. It is, therefore, of some importance to find out what are the various conditions on which this property depends.

We have to consider homogeneous liquids, such as pure liquids and true solutions, colloidal solutions and suspensions, such as that of blood corpuscles in plasma. Chemical Composition. — As a rule, the internal friction increases with the molecular weight and, in homologous series, in proportion thereto. The increase of the viscosity of water, due to the formation of polymers of a higher molecular weight, has been discussed above. Temperature. — Rise of temperature causes considerable decrease of viscosity, as is known to every one in the case of such liquids as castor oil, glycerol, etc. Hence also the necessity of using a thick lubricating oil for the cylinder of an aircooled petrol motor ; the high temperature would make another one too thin to serve its purpose. The viscosity of blood diminishes to a large extent as the temperature is raised, so that less work is demanded of the heart in order to drive a given amount of blood through the arterioles ; or the same work will drive the blood at a greater rate. This is an incidental advantage possessed by warm-blooded animals.

Blood. — Changes in the viscosity of blood, other than those produced by differences of temperature, are also of importance. The presence of corpuscles increases the viscosity, which is therefore lower in defibrinated or " laked " blood than in normal blood. Dilution has also the effect of diminishing viscosity, so that a dilute blood passes more rapidly through the renal vessels and the excretion of urine is favoured. Viscosity of Colloidal Solutions. — The internal friction of the blood plasma,

as a colloidal solution, is affected by the same factors as those which act on that of colloidal solutions in general. A brief account only can be given here ; the reader will find more details in the report of the discussion at the Faraday Society on 13th March 1913. As regards suspensoids, the degree of dispersity is the main factor, and it appears that the maximum of viscosity is at medium values of dispersion, being less with very small as well as with

very large particles. It is uncertain whether this is connected with the variable amount of the dispersion medium associated with the particles. Emulsoids show great variety of changes in viscosity, so that the determination of this property is a valuable one in the investigation of such systems (see the paper by Wo. Ostwald, 1913, from which the following statements are chiefly derived). I have already referred to the effects of concentration, temperature and degree

of dispersion. Other factors are solvate formation ; electrolytic dissociation, in which solvate formation is probably involved ; previous thermal treatment, as in the case of gelatine, which also shows an influence of mechanical treatment, even in the liquid state, in that its viscosity diminishes by repeated passage through a narrow tube and gives evidence of some kind of " structure " ; inoculation with Mnall quantities of a more viscous colloid, which produces a much greater

effect than that due to its own viscosity ; time, especially shown by the effect of the rate at which the temperature is changed ; and finally the addition of electrolytes or non-electrolytes, which may raise or depress viscosity in the most varied manner. A particularly striking instance of large changes in viscosity produced by small changes in temperature is shown by such colloids as gelatines which form gels, and also by those which coagulate on heating. As an illustration we may take the change in the viscosity of a dilute albumin sol when heated (Fig. 68, from the paper by Wo. Ostwald). From 50' to 57° the viscosity decreases regularly. At 57° '5, just before the appearance of turbidity, a large increase occurs, which, at 60°, gives place to an equally steep decrease. After that, the curve forms practically a continuation of the direction of the first part below 57°, as if nothing had happened in the meantime.

In the case of agar, the effect of concentration is very marked; from 0 to 1 per cent, the viscosity increases from that of water The general theory of the viscosity of such two-phase systems has been treated by Hatschek (1910-1913). Certain conclusions may be given here. Suppose the particles themselves are undeformable, then the viscosity is independent of their size and is a linear function of the volume of the dispersed phase only. The matter is more complicated in the case of two liquid phases, emulsions or emulsoid colloids, and the change of shape due to the shearing force must be taken into account. With emulsoids above a certain concentration, there is a very rapid rise of viscosity with further increase in concentration. The particular concentration at which this effect begins to show itself varies with different colloids and serves as a measure of their "lyophilic" properties or affinities for the solvent. With caseinogen it begins at 5 per cent., with glycogen at 25 per cent., with india-rubber at 0'4-0-5 per cent. The great swelling of india-rubber in its solvents, before the hydrosol is formed, is a familiar fact. It will be clear that, in the investigation of such systems, the rate of shear is an important factor, since on this depends the degree to which the deformed droplets are able to return to their normal resting shape, spherical or polyhedral, according to the relative volume of the two phases. Hatschek (1913) has improved the apparatus of Couette, in which this rate of shear can be altered at will. It consists essentially of two concentric cylinders, the outer one of which can be rotated at a desired rate, while the inner one is suspended by a wire. The liquid is in the space between the two and the degree of torsion of the wire is measured by the deflection of a beam of light reflected from a mirror attached to the cylinder.

In this connection, some observations by Arisz (1913) are of interest. These experiments were made to determine the fluidity, that is, the inverse or reciprocal of viscosity, as a function of temperature in the case of the sol and gel of gelatine. It was found that a continuous curve is given, so that there is no break at any point and the process is a uniform one. The intensity of the Faraday effect and the elasticity were found to show similar continuity. The method used in the case of the gel was to determine the viscosity by the rate of change of shape under the action of a constant force.

Water, of all substances known to us, is endowed with the most remarkable combination of properties, all of which play a part in contributing to the importance of its association with living processes. Ordinates — logarithms of the time of flow through the capillary Among these properties, we may note its high specific heat, its great latent heats of solidification and of vaporisation, its good conduction of heat, which is unusually high for a non-metal, its point of maximum density at 4° above its freezing point, its high surface tension, its transparency to radiant energy, its solvent powers, and, as a solvent, its chemical inertness is important, and its large dielectric constant. In the majority of these, it stands higher than any other substance, and where it is exceeded, it is only by one or two very exceptional liquids, such as ammonia and prussic acid. While some of these are dependent on each other, others appear to be independent. The manner in which each of these characteristics intervenes in relation to living organisms is given in the text.

Many of these properties find a satisfactory explanation in the nature of water as a polymerised compound, consisting of three degrees of aggregates — trihydrol, a compound of three molecules of H2O, and apparently identical with ice ; dihydrol, of two molecules, present in largest proportion in ordinary liquid water ; and finally monohydrol, or steam, of single molecules. The relative proportion of these to one another changes as the temperature varies, so that passing upwards the concentration of the polymers decreases regularly.

The application of heat, therefore, has to do three things : decompose the polymers, heat the polymers and heat the single molecules ; the anomalies connected with the specific heat of water are thus explained. The point of maximum density at 4° can be explained on the assumption that ice, or trihydrol, exists in liquid water, since ice at 0° has a lower density than water at Oc ; and, as water is heated from 0° upwards, there are two opposite processes going on, dilatation of the molecules, according to rule, and contraction, due to change of ice to water. Since the latter process is preponderant at the lower temperatures and nearly absent at the higher, there must be a point where the difference between them is least.

The unusual increase both of viscosity and of compressibility as the temperature falls is also explained by the existence of polymers. Certain other properties of water are to be explained by the fact of its being, of all liquids, that one containing the greatest number of molecules per unit volume. The proof of the existence of single molecules, monohydrol, in liquid water is given by consideration of solution volumes and will be found in the text.

Many solutes, both electrolytes, ions and non-electrolytes, take up a certain number of molecules of water, forming "hydrates." Whether this is to be regarded as chemical combination appears to be rather a matter of opinion. It is shown that the theory of osmotic pressure, as given in Chapter VI., is not affected by the hydration of solutes nor by the polymerisation of solvent. Water, to a very small extent, is electrolytically dissociated. The value of the dissociation constant, obtained by four independent methods, is practically identical, a satisfactory proof of the correctness of the assumption.

This electrolytic dissociation of water is the cause of the " hydrolytic dissociation " of salts of weak acids and bases dissolved therein. The properties of water as a catalyst are, in many cases, of importance. The concentration of water in reversible reactions of hydrolysis and synthesis is a potent factor in the regulation of reactions in protoplasmic systems. There are, no doubt, mechanisms of a colloidal nature present in such systems and effective in bringing about changes in the active concentration of water. Diminution of water favours synthesis, increase favours hydrolysis.

There is evidence that certain bacteria can be completely deprived of water without causing their death. When organisms become encysted, it appears that they do not become completely dried, but that the membrane of the cyst is practically impermeable to water. When dry, both organisms and complex organic compounds, such as enzymes, can withstand, without destruction, a much higher temperature than in the presence of water. The molecules of liquids in their movements .past one another experience friction ; this is known as their internal friction and gives rise to their viscosity.

The part played by the viscosity of the blood in causing the "peripheral resistance " of the arterial system is pointed out, and it is shown that this factor, on which depends, with a given heart beat, the height of the arterial pressure, is due to the internal friction of the blood and not to its friction against the walls of the blood vessels. The viscosity of colloidal systems depends, in the main, on the degree of dispersion of the internal phase. In the case of suspensoids, the maximum of viscosity is at a medium degree of dispersion. In the case of emulsoids, where the internal phase is deformable, there are more factors to be taken into account, especially the rate of shear.

Discussion by the Faraday Society, 1910 (Transactions of the Faraday Society, 6, Parti., July 1910). FOOD may be defined as any substance taken in by an organism and made use of for any purpose. The uses of food may be said to be threefold. When an organism is increasing in size, it is clear that the additional matter laid on must be obtained from without. In the adult organism, the main part of the food is used to afford energy for muscular movement, production of heat, etc. But there is also a small but essential part required for the repair of wear and tear on the part of the tissues themselves, even in the adult. This may be thought to be identical with growth, but we shall see later that there is evidence to show that certain things may be necessary for growth, although not so for maintenance. It is as if, after a machine has been constructed, certain working parts only require repair.

Perhaps an illustration may help to make these differences clear. A petrol motor in process of construction needs the supply of iron, steel, brass, copper, porcelain, insulation material, asbestos, and so on. Some of these cannot be replaced by any other ; insulating material, for example, cannot be replaced by metal. We shall find analogous conditions in the growth of living things. When the engine is completed, fuel must be given in order that work may be done by it. This fuel does not enter as a constituent of the fabric, and corresponds to that part of our food which is utilised for the giving of energy. If the motor is kept at work, certain parts require replacement from time to time, owing to their wearing out : such are piston rings, linings of bearings, etc. These are the analogous parts to that fraction of our food which is needed for repair of tissue waste, or maintenance. We may note that certain parts practically never require renewal, such as the fly-wheel or the framework. The reader will probably ask, what does the lubricating oil represent1? We must not, of course, expect to be able to push our simile to all details and it seems to fail here. The agents known as enzymes in some ways correspond to the lubricating oil, but these are formed by the organism itself. On the whole, water and salts are the nearest food constituents representing the function of the lubricant ; they afford no energy, but are indispensable to the working of the living machine. We may also compare the waste products in the two cases. The products of combustion of petrol escape in the exhaust gases as carbon dioxide and water vapour, just as the same substances are given out in the gases expired from the lungs.

The waste lubricating oil carries with it fine particles of metal, worn from the cylinder and bearings ; in a similar way, the water excreted by the kidneys removes the products formed in the wear and tear of the tissues, in addition to other things, whose meaning will become plainer presently. For the present, attention may be called to our nitrogen food, the proteins, of which a part only is used for the giving of energy, the nitrogenous part being excreted as a waste product, urea, by the kidneys. We can imagine something of this kind in the case of the petrol motor; suppose that there were an incombustible impurity in the fuel, and that it were converted by the heat of the explosion into something very soluble in the lubricating oil of the cylinder, it would then pass out with the waste oil, which represents the urine.

From the three different purposes to which food is applied, it will be obvious that substances necessary for one object may not be so for another. There are, however, some food-stuffs which are indispensable for all purposes, such as oxygen, hydrogen, nitrogen, and carbon. Oxygen. — This, although not commonly regarded as a food, is actually the most important of all. Life, except in rare cases of a special nature, is impossible without it for more than a very short time. As already pointed out (page 29) the energy of the animal body is derived from the oxidation of food. It is important to note that there is, in the animal, no formation of substances which endow the organism with more energy than that supplied to it in the food. Energy given out in one reaction may, however, be used to raise energy potential in another reaction, as we shall see exemplified in the case of muscle. In the green plant, on the contrary, energy derived from the sun is made use of to raise the energy of carbon dioxide and water to that of carbohydrate.

Water and Salts. — Although these substances afford no energy, their supply is essential for the numerous purposes made plain in the preceding chapters of this book. A continued supply is needed, since the kidney must excrete water in order to dissolve the waste products, and salts from the blood pass throug*h the glomerular filter along with the water. Consideration of the osmotic pressure of these salts as they exist in the blood, about 3'5 atmospheres, shows that a large amount of work would be required to separate them from the water in which they are dissolved.

The value of Carbon and Hydrogen as giving energy by oxidation is obvious. Their heats of combustion are sufficient to show this. They are, of course, always in various forms of combination in food-stuffs, so that the whole of their energy is not available. It might appear that, for purposes of giving energy, hydrogen alone might serve, but it is unnecessary to state that it would be useless as gas and no chemical compounds except those with carbon are available. Similar remarks apply to carbon itself. These two elements are then always taken in combination and in fact partially oxidised, since the hydrocarbons are too inert chemically to admit of reaction under the conditions compatible with the existence of the protoplasmic system. The special value of carbon, with respect to the great variety of compounds which its peculiarities enable it to form, has been pointed out on page 41 above.

The position of nitrogen is somewhat different. As a direct source of energy its value is small. But there is, as we shall see later, a certain value in protein food, even as a source of energy, notwithstanding the fact that its nitrogen is almost immediately excreted unoxidised. It appears as if the amino-acids, produced by the action of enzymes on this protein food, after de-amination by the liver, leave certain residues which are, for some reason or other, more readily oxidised and utilised as sources of energy, perhaps because the two processes are parts of the same reaction, or, in other words, because of the " nascent " state of the ketonic or hydroxy-fatty acids formed.

It is clear that, for the growth or repair of structures containing nitrogen, this element must be supplied. The same may be said of sulphur and phosphorus, which are always found as constituents of cells. Notwithstanding what has been said as to the value of nitrogen food, it is astonishing how little is absolutely necessary for the mere maintenance of life even in the higher animals. M'Collum (1911, 1, p. 212) found that pigs may be fed on a diet free from nitrogen for more than three weeks, without losing weight. Nitrogen is always excreted, none the less. In M'Collum's pigs, the nitrogen excreted per day amounted to O'.Sl g. per pig of 84 Ibs. weight. This then, in the case referred to, is the minimum amount which must be given, theoretically, if the loss of nitrogen is to be prevented. The amount of nitrogen given off from wear and tear is sometimes known as the endogenous protein metabolism. The value of 0'31 g. just given should be contrasted with that of 12 to 15 g. excreted on ordinary diet. In these particular animals, it appears that the minimum quantity required for repair is only about 2 per cent, of the whole protein metabolism on an ordinary diet. The question of the nitrogen minimum will come up for discussion subsequently.

Finally, it is obvious that products of secretion, containing particular elements, require the supply of some food containing these elements. For example, the hydrochloric acid of the gastric juice must have chlorine. To form the haemoglobin of the blood corpuscles, iron is necessary ; since a number of these corpuscles are regularly broken up, new ones must be formed. Probably most of the iron required is obtained from the debris of the old cells, so that comparatively little further supply is needed.

To avoid misapprehension, it must be mentioned here that recent investigations have shown the necessity of minute quantities of certain organic substances, whose nature is as yet not understood. Details will be found below. The green plant is able to obtain its carbon from the carbon dioxide of the air, its hydrogen from water, and its nitrogen from nitrates in the solutions bathing its roots. It is possible, therefore, to grow such plants as the bean, or better, the wallflower, from the seed to flowers and fruit, with its roots immersed in a solution containing merely potassium nitrate and some other inorganic salts, sulphates and phosphates of calcium. A trace of iron must be present. But this growth is only possible in the light and it is by the aid of radiant energy from the sun that the assimilation of carbon is made possible.

The methods by which instructive experiments of this kind can be performed will be found in the works of Darwin and Acton (1894, pp. 51-55) and of Macdougal (1901, pp. 223-232), in addition to many other textbooks of practical physiology of plants. The green colouring matter, chlorophyll, by means of which the carbon assimilation of the green plant is effected, has been said to be the most interesting substance in existence, and, beyond doubt, the mechanism by which alone the higher animals themselves are enabled to maintain their life is of the utmost importance. The question will be discussed in Chapter XIX.

When we investigate the fungi, many of them highly organised plants, but devoid of chlorophyll, we find, as would be expected, that they cannot obtain their supply of carbon from carbon dioxide alone. Sugar appears to be their best source of carbon, but most carbon compounds, unless poisonous, suffice, with the exception of the very simplest ones, such as formic acid and urea. What is perhaps more remarkable is that the higher fungi are unable even to use nitrates as a source of nitrogen, which the green plant is able to do. These higher fungi require ammonium salts, amines, or amino-acids ; although urea cannot afford them carbon, it suffices as a source of nitrogen. Moulds and certain bacteria, lower fungi, are able to obtain nitrogen from nitrates, so that this capability is not entirely limited to the green plant, and it is not necessarily connected, as might be thought, with the use of the sun's energy for the assimilation of carbon. At the same time, we must remember that the obtaining of nitrogen from nitrates is common to all green plants, whereas it is only a few of the simplest fungi that possess it, and we find, moreover, especially amongst the bacteria, very specialised requirements as to the chemical nature of their food-stuffs. I may instance the fact that it was found impossible to cultivate the tubercle bacillus with success until glycerol was added to the medium. On the other hand, there are some bacteria which possess the very remarkable aptitude of using methane as a source of carbon (Sohngen, 1905). In this connection we may note that, although certain bacteria are able to utilise particular substances for food, it does not follow that this food is that on which they thrive best. In want of better, they can put up with it.

The animal organism, even in its lowest forms, the protozoa, is satisfied with nothing less complex than glucose as source of carbon. As regards nitrogen, the requirements appear to be different according to the purpose to which it is to be put, growth, maintenance, or source of energy. The experiments of Grafe (1912) appear to indicate that ammonium salts, in presence of excess of carbohydrate, may replace wear and tear in the dog and pig, although no tissue is laid on. Further facts bearing on this question will be found in the section on " Protein Metabolism " below, together with its probable explanation.