Principles of General Physiology

A brief account of the phase rule is given in the text, in connection with the possibility of its application to the case of hemoglobin. It is found that an exponential formula expresses the relation of haemoglobin to oxygen in presence of salts or acid. The difficulty of interpreting this formula in terms of mass action is pointed out. The intervention of phenomena of aggregation are suggested by the fact that haemoglobin behaves as if in colloidal solution.

Organs, lungs or gills, are provided by which a large surface of blood is exposed to the medium which contains oxygen, that is, to the air or water. Mechanical means of periodic change of the medium enable efficient oxygenation, together with escape of carbon dioxide. The question as to whether sufficient oxygen can be taken up by mere diffusion is discussed. It is found that the only results which cannot, as yet, be explained thus are those of Douglas, Haldane, and their co-workers on the condition attained after some days' acclimatisation to high altitudes. Even in vigorous muscular work there is no need to assume special oxygen secreting power on the part of the cells of the alveoli of the lungs.

The amount of air pumped in and out of the lungs is regulated by the action on the respiratory centre of the hydrogen ion content of the arterial blood. This concentration in hydrogen ions is determined, under ordinary conditions, by the carbon dioxide tension in the alveolar air of the lungs. Under special conditions, as in acclimatisation to low barometric pressures or by feeding on substances which increase the acidity of the urine and blood, other acids, non-volatile, formed in tissue metabolism, assist in the stimulation of the centre.

There seems to be no evidence that the excitability of the respiratory centre to carbon dioxide is sensibly affected by want of oxygen, until the oxygen tension has become very low. In asphyxia, at a certain stage, products of disintegration of the cells of the nerve centres themselves act as exciting agents on these centres. But these products are not to be regarded as normal stimulants. The function of the reflex nervous mechanism, whose afferent fibres are contained in the vagus nerves, is to regulate the rate of respiration. An expansion of the lungs, resulting from stimulation of the centre by carbon dioxide, is cut short by the inhibiting reflex from the vagus endings in the lungs, and the centre prepared for another stimulation by carbon dioxide. The reflexes are subject to the laws of double reciprocal innervation.

A short account is given of the phenomena of mountain sickness, due to want of oxygen only. " Acapnia," or want of carbon dioxide, plays no part in them. WE have already had occasion to refer to the electrical changes occurring in nerves, muscles, and glands when excited to activity. With the exception of the electric fish, these responses are chiefly of interest on account of the light they throw on the physiological processes themselves, and they frequently serve as a valuable means of investigating these processes. Perhaps the most striking of these cases is the use now made of the string galvanometer in researches on the heart, both in health and in disease.

At the time when physiological phenomena began to be systematically worked at from the point of view of accurate measurements, the electrical phenomena naturally attracted much attention, on account of the methods available for the precise determination of the value of electrical currents, and much valuable work was done at that time. Since so much depends on the instruments used, it is worth while to give some attention to the principles involved in the construction and use of these instruments. Many of these principles will be found to apply to the methods used in other investigations, such as the measurement of sudden changes of pressure, as in the heart beat.

The two factors of electrical energy, capacity and intensity, lead to the division of the instruments used into two main classes ; those for the measurement of current, galvanometers, and those for the measurement of potential, electrometers. But, as we shall see, the galvanometers used in work on the electrical changes of tissues allow, as a rule, so small a current to pass that they behave practically as electrometers, and the indications given by the two kinds of instrument are very much the same. The reason why the galvanometers have so high a resistance is, of course, on account of the very high resistance of the external circuit, the tissues, and the galvanometer gives the largest deflection when its resistance is equal to that of the outer circuit.

Galvanometers. — All of these depend on the relative movement of a magnet and a wire through which a current flows. In one type, such as that known as the Kelvin form, the magnet moves under the influence of a current in a wire surrounding it ; in the other type the magnet is stationary, and may be either a permanent magnet, as in the D'Arsonval pattern and many forms of commercial ammeters and voltmeters ; or it may be an electromagnet, as in the string galvanometer of Einthoven. In this second type, the wire conveying the current moves. In the D'Arsonval instruments the wire is in the form of a light rectangular coil ; in the Einthoven form it consists merely of a very fine wire stretched between the poles of a powerful electro-magnet. When a current passes through the wire of the string galvanometer, the wire is deflected to one side or the other, according to the direction of the current, and the movement is magnified by a microscope and photographed by projection on to a slit, behind which is a moving sensitive surface.

Inertia of Moving Parts. — When an electrical change lasts a very short time, it is plain that it would be able to move a very light system when it was unable to make any impression on a heavier one. Just as a slight impulse would not cause a visible movement of a cannon ball, but might give considerable motion to a pith ball. This is especially to be taken account of when the electrical change is subject to rapid alterations. The moment of inertia of the moving parts should, therefore, be as small as possible.

Damping. — Suppose that a short-lasting electrical current has set one of these systems into movement. It is clear that, unless there is some influence to bring it to rest, the movement will continue after the current ceases. Now our object is to obtain as true as possible a record of the time course of an electrical effect. When a wire forming part of an electrical circuit moves in a magnetic field, a current is developed in it in such a direction as to oppose further movement. This will occur whether the wire is conveying a current already or not. In the D'Arsonval and the string galvanometers, therefore, as long as the circuit is closed, any movement of the wire produces in it a current tending to stop its movement. The extent of the opposing current depends, by Ohm's law, on the resistance of the circuit, hence also the damping effect. In physiological work this resistance is very large, hence the damping is not any greater than required. In fact, in the D'Arsonval instruments, it is usually necessary to add a short circuit to increase the damping; in the beautiful galvanometer of Moll (1913), made by Giltay of Delft, the damping is regulated by altering the strength of the current producing the magnetic field. In the Kelvin instrument, the damping is usually effected by air resistance to the movement of a vane on the magnet system. When the moving system is heavy, the vane is sometimes made to move in a bath of oil.

Period of Vibration. — Since the moving system must be brought back to its resting position by some force, such as the magnetism of the earth or the torsion of a wire, there will be oscillations similar to those of a pendulum. These would prevent the real value of a deflection from being estimated, so that, except for special purposes, the movement is made as nearly as possible " aperiodic " by appropriate damping. When this is the case, the deflection is reached without vibration 'around it. This is associated, however, with a

slower rate of movement, so that, as a rule, some compromise has to be made. In -any case, the damping should not exceed that necessary for aperiodic movement. To illustrate the point, Figs. 197 and 198 may be consulted. It will be seen that the deflection is aperiodic in both cases, but with a slight tension on the string the deflection is as large with a small current as that with a larger current if the string is tighter. But the rate of movement, or time taken to reach the final position, is more rapid with the tighter string. If rapid changes are to be followed correctly, therefore, the string must be tight enough to move as quickly as the electrical effect to be observed. Fig. 199 (from the book by T. Lewis, 1913) shows the different rate of movement of the string under different tensions. If too slack, it does not follow quick changes, like the first ventricular phase of the heart, with sufficient rapidity to give their full value.

Figure of Merit. — The sensitivity may be considered to be the deflection produced by a given •current. To compare different galvanometers, the period of vibration -and also the resistance should be taken into account, so that D is the deflection in mm. for one microampere at one metre, For the properties to be taken into account in choosing a galvanometer for a particular purpose, the catalogue of the Cambridge Scientific Instrument Company may be consulted. In general, if the deflection required is to be as large as possible, or a very small electrical current is to be detected,

the Paschen form of the Kelvin instrument is the best. If the time relations of a complex change are to be ascertained by photographic record, the " string " galvanometer of Einthoven is to be used. This latter form is that with which most work is now done. Fig. 200 represents the instrument as made by the Cambridge Instrument Company. A camera with moving plate or paper is used with it, and an arc lamp for illumination. The shadow of the string is photographed. A diagram of the mechanism is given in Fig. 201.

In the Oscillograph of Duddell, the movement of the system follows changes of current rapidly by the fact that its own vibration period is enormously high compared with the rate of change of the current to be investigated. This vibration rate may amount to 10,000 per second. The same principle is used for the correct registration of the pressure changes in the heart and the blood vessels. The oscillograph is practically a moving coil galvanometer, with the coil reduced to a thin loop of stretched phosphor-bronze. It is used chiefly for the investigation of the wave form of alternating currents.

Electrometers. — Although there are several forms of instruments used in physical work for measurement of potential, the capillary electrometer of Lippmann is practically the only one used in physiology. It consists of a slightly conical capillary tube, containing mercury, whose point is immersed in 20 per cent, sulphuric acid. The mercury is forced into the capillary tube by pressure until the meniscus of its contact with the acid is at a convenient place. One electrode is connected with the mercury in the tube, the other with a mass of mercury also in contact with the acid. Fig. 202 shows one pattern of the instrument.

When connected to two points at different potentials, so that that which is positive is in connection with the mercury in the capillary, the surface tension at the contact with the sulphuric acid is diminished, and the mercury is forced by the pressure Fir;. 199. Electro-cardiograms of the human heart, taken with different tensions of the fibre of the string galvanometer. The tensions diminish in the series from above downwards. Led off from right arm and left leg. The curve to the right of each figure shows the time taken to attain full deflection when one millivolt is applied. This time increases as the tension of the string diminishes, although the movement is aperiodic in all the cases given. It will be noticed that the rapid changes in R and S are not correctly followed with low tension, but that the slower rate of change in T is equally •well given in all.

on it, which kept it in its place in the tube, further towards the point. If negative, the surface tension is increased and meniscus retreats, since its surface tension, which was previously balanced by a given external pressure, will now only be balanced by this same pressure at a wider part of the tube. Until the mercury has come to rest, a certain charge of electricity flows into the instrument, which behaves as a condenser. After this no current flows. The movement may be very rapid and is completely aperiodic. The contact surfaces of the acid and mercury are polarised, but the theory is somewhat complex, and may be found in Freundlich's book (1909, pp. 184-212). Roughly speaking, it may be said that when the mercury meniscus is positive it becomes oxidised and dirty, when

FIG. 200. General appearance of the string galvanometer, as made by the Cambridge Scientific Instrument Co., in accordance with the pattern designed by Einthoven. A, 'Poles of electro-magnet, itself excited by current through coils BB. G, D, Microscope and condenser, passing through holes in the pole pieces. ft, Screw for centring the string case, which rocks on the two screws K. negative it is reduced to bright metal. Hence the surface tension is low in the former case, high in the latter. The movements are photographed by projection on a slit, behind which a photographic plate is moved. The curves obtained require correction, but the law governing the position of the meniscus at any time after connection with a source of electromotive force is a definite one and readily determined for each instrument (see the papers by Burch, 1890, 1892, and by Keith Lucas, 1909, 2). The curve is a logarithmic or exponential one, with the equation : —

where y is the ordinate of any point P measured downwards from the asymptote, that is, the level at which the meniscus finally comes to rest, t is the horizontal distance of P from a point on the asymptote taken as origin of co-ordinates (that is, time from commencement of charge), a and c are constants, e is the base of natural logarithms (see Fig. 203). It will be seen, on reference to the curve, that the potential difference between the terminals can be determined by taking any point on the curve, without the necessity of its having arrived at the limit of its movement ; in fact, it may be brought back at any point in its course by the application of an opposite potential difference, without interfering with the measurement of that which produced the original movement. The potential difference causing any deflection may be considered as made up of two parts, one represented by the ordinate of the curve at any time, and the other represented by

the vertical distance the meniscus has still to move. The latter is a function of the rate of movement at the time taken, that is, of the steepness of the curve. It is, therefore, measured by the angle made by the geometrical tangent of the curve with the axis of abscissae. The simplest way of analysing a complex curve, obtained experimentally, is that of Keith Lucas (1909, 2, p. 218). Each tube has, of course, to be calibrated, the rate of movement depending partly on the electrical resistance, partly on mechanical resistance to movement, probably friction. The movement is quite aperiodic. The method of drawing tubes will be found in the paper quoted.

This electrometer, although sensitive enough for most work, is less so than the string galvanometer, but, for exact analysis, the photographed records of the former present certain advantages in that the analysis is simpler, following a better known law than those of the string galvanometer (see the paper by Keith Lucas, 1909, 2, p. 210). Other forms of electrometer have been little used in physiological work, although it seems possible that the striny electrometer, in which the string moves between plates with opposite charges, will be found ; useful (for a description of the instrument, see the Cambridge Instrument CO.'B Catalogue of Electrometers).

The Circuit. — The arrangement of the connections is practically identical with that used in the measurement of the electromotive force of a concentration battery (page 192). The diagram of Fig. 204 may be found useful. Rheotomes.—The repeating rheotome, by which corresponding bits are cut out, as it were, from a series of electrical responses by means of contacts arranged to be made and broken by a rotating wheel, is rarely used at the present time. The introduction of more accurate and sensitive instruments and means of analysis of photographic curves has practically displaced it. The use of a device for opening a series of keys at known short intervals of time after one

The fine wire (" string "), CC, is stretched in the narrow gap between the poles X and S of a powerful electro-magnet. When a current passes through the "string" in the direction of the vertical arrows, the wire is deflected in the direction of the arrow a, that is, at right angles to the magnetic field AIS. This small movement is observed, or projected on to a photographic plate, by means of a microscope, ED, the light of an arc lamp being condensed by the lens F on to the string.

another by a pendulum is frequently indispensable, and the most convenient way of doing this is by the instrument described by Keith Lucas (1908, 2). FIG. 202. CAPILLARY ELECTROMETER. — Keith Lucas' pattern. End elevation. The projecting microscope is supposed to be perpendicular to the plane of the paper. Y, Screw for moving capillary at right angles to plane of paper. / K, Notch cut out to contain acid, closed at the sides by cover-glasses K, cemented by hot

gutta-percha. V and VI, Two holes, meeting at the bottom, containing mercury, into which dips the That the electrical phenomena observed in the activity of cells are due to changes of potential, and not merely to changes of resistance, is evident, not only from the fact that they are shown by instruments, electrometers, which do not respond to changes of current only, but also in the ordinary way of demonstrating these electrical responses by means of a sensitive galvanometer. In doing this, any current already existing in the circuit is balanced by an opposing potential difference from the slide wire, in order to bring the deflection to zero before stimulating the tissue. No mere change of resistance can, in such circumstances, cause a deflection ; there is no potential difference to create a current.

Let us next examine the possible sources of potential difference in living We may take it that these potential differences must be due to elect charges on ions. It does not seem probable that phenomena of frictional electricity play any part. In any case, these phenomena themselves can generally be traced Produced by applying a potential difference of 0-01 volt between its terminals at the point P of the tracing. Considerable resistance was introduced into the circuit, so that the rate of

Ordinates — position of meniscus. The divisions along the axis Oy are in O'OOl volt. Abscissa; — time. Ot is the axis and also the asymptote of the curve. The portion of the curve above the line through 5 is the entire normal curve for 0"005 volt, and the portion above P, is that for 0-00165 volt. PN and P, N— Ordinates at P and Pf PT and P, T— Tangents to the curve at P and P.. JtT and N, T, — Subtangents. These are equal to one another. The equation to the curve is

where y is the vertical distance of any point from the asymptote of the curve, and t is the horizontal distance from the origin of abscissae, a and c are constants of a particular capillary tube. to the production of some kind of ions. The question was discussed to some extent in connection with the charge on colloidal particles (page 89). The part played by electric charges on surfaces is treated of in the paper by Mines (1912, 1). That the source is ionic is indicated by the temperature coefficient of the electromotive force of tissues. This was determined by Lesser (1907), for the skin of the frog, and found to be proportional to the absolute temperature. If the source were some kind of chemical reaction, a much higher temperature coefficient would be found.

If the ions arising from electrolytic dissociation of a substance are free to move and intermix, it is clear that no potential difference could be detected. Moreover, the increase of their numbers, whether by increased dissociation or by production of new ones by the splitting up of larger molecules, or by the setting free from a state of adsorption, in itself cannot give rise to any change in potential difference, except a very temporary one. Unequal rate of diffusion from their place of origin is the cause of this temporary electrical state.