The alkali metals act as the univalent cations of salts in the lithosphere as well as in the organism. The elements as such have very slight existence as individuals. In air as well as in water they immediately undergo alterations; their electro- positive tendency, the giving off the outer electrons, goes so far that they decompose water with the production of much heat. In their compounds they dissociate very extensively and they are easily convertible and have a wide range of reaction. This is associated with their great atom volume; because the attraction of the outermost electron is so much the less, the greater the relative diameter of the atom. Lithium with the smallest atom volume falls far behind the other alkali metals in respect to free movability and breath of reaction.
Our consideration can be restricted to the first three members of the group, lithium, Li, sodium, Na, and potassium, K, because rubidium, Rb, caesium, Cs, have neither physiologic nor pharmacologic significance as yet. Of the first three, lithium is not vital to life and is a very much less reactive element than sodium or potassium.
In order to obtain the most comparative picture, we can proceed best from the carbonates of these elements: Li2CO3, lithium carbonate, Na2CO3 sodium carbonate or soda, and K2CO3, potassium carbonate or potash. Here we have the prospect of finding most purely the characteristic trends of the alkali constituent. The carbonate compounds react alkaline, that is, in the dissociation in water, free OH ions predominate. Taking K2CO3 as an example, the dissociation in water occurs according to the formula: K2CO3 Plus H2O <-> KOH Plus KHCO3. So the alkaline reaction remains as the common factor or the working tendency of the alkaline carbonates.
Sodium and potassium are by far the most important members of this group, in the circulation in the earth as in the organism. The sodium and potassium salts are developed through hydrolytic decomposition from the stones of he lithosphere. Sodium bound in sodium chloride, is found for the most part in the sea. On the other hand, potassium becomes adsorbed for the most part to colloidal aluminum particles in humus and from there enters into plants. In about equal total amounts (about 2.4 per cent of the earth surface) sodium and potassium separate even in the earth surface through their affinity to the fluid or colloidal fractions. Similarly in the organism of higher animals sodium and potassium appear in about equal amounts and the same manner of partition between the fluid and colloidal phases is followed. In this case no apparent differentiation through selection has occurred from earth to man. Such examples of the universal task of elements in all natural structures, on the basis of their properties, make likely analogy considerations on the microcosm and macrocosm which were so often used deductively in pronounced ways in the prescientific age, even if with fantastic elaboration. The significance of alkali cations for water regulation, for the acid-base equilibrium and the colloid state of the organism has been discussed in general in the preliminary survey.
Besides sodium and potassium, lithium plays a small role in the earth as a companion, particularly, of sodium. As such it will also be found in the organism without one being able to ascribe any individual action to it at present.
We shall add also to the alkalies ammonium, which, as the ammonium cation, NH Plus 4, behaves as a single atomic alkali cation. And to the ammonium alkali we shall count the preparation causticum which is peculiar to homoeopathy.
Potassium is one of the most important elements in the cell economy, but our detailed knowledge does not extend sufficiently far for us completely to understand its significance. Quantitative estimation is very difficult because it belongs primarily to the colloidal interior of the cells. We do not know how much potassium is fixed in the cells nor in what state it exists.
The two to three grams of potassium which are brought to the human organism daily from plants does not state anything about how much active potassium is brought to the various places and what is excreted as inactive potassium, the reason being that there exists an internal potassium circulation so that what is used at one place can again be used at another.
Potassium has a property which is not known of any other constituent of the organism. As Campbell discovered in 1907, potassium is radioactive, it sends out beta-particles, rapidly moving electrons. Possibly the radioactivity of potassium plays a role in the catalytic excitation of cell life as H. Zwaardemaker has suggested. Through beta-radiation, energy should be furnished which maintains the automatism of the heart and smooth muscles, in which apparently no caloric energy is given off. A heart which has ceased to beat in a potassium-free Ringer’s solution can be brought again to beating regularly through the radiant equivalent of uranium, thorium, or rubidium, and also through alpha-radiation from radium and polonium.
That it is exactly with potassium and its neighbors, rubidium and caesium, that beta -radiation is observed, may well be associated with the great volumes of these atoms. The slight attraction of the negative charge unit the electron, to the nuclear center can make freedom and radiation of independent electrons possible, and these are beta-particles.
COLLOID AND CELL ACTION
The univalent cations agree in that in general they favor the swelling of colloids and reversely their power of precipitation is the least. The above mentioned lyotropic series gives particulars on this. Through the promotion of swelling the univalent cations may ease the entrance and exit of salts and foreign substances from water through the plasma membrane; therefore they stand in contrast to the chief representative of the earthy alkalies, calcium, which is characterized by its caulking action.
Now the action of alkali ions on the cells does not proceed entirely parallel with that on colloids but, according to the cell substrate investigated, it shows characteristic deviations of the so-called cytotropic or cytotoxic series of cations from the lyotropic series.
With equal molecular concentration, also with equal osmotic pressure-presuming weak hypotonia-hemolysis of the red blood cells through the various neutral alkaline salts occurs at different speeds. The hemolyzing capacity of the cations takes (according to Hober) the following series: Li, Na
A first glance into the significance of cell-binding salts for the orientation of cell colloids to a definite state of swelling, which is different in single species of animals, can be gained from the following results: the blood corpuscles of a species of animals are so much more resistant to hemolysis with saponins, the less phosphoric acid and potassium they contain; on the other hand they are so much more resistant to hemolysis from hypotonia, the more phosphoric acid and potassium they contain. The saponin hemolysis will be favored so much more strongly through combination with potassium, the more phosphoric acid and potassium they contain as binding ions, and so much less the less the blood corpuscle of a species contains of these ions.
Still more important for a decision on potassium action are the connections of potassium to muscle cells. The great content of muscle cells in potassium shows from the start the great significance of potassium in muscle function. The potassium ions seem to possess a special significance for the production of the bioelectric current. The membrane theory of muscle function suggests that in the resting state, the plasma surface membrane is impermeable for potassium ions, but permeable for other ions. From this an electrical double layer results on the cell surface. By stimulation of the muscle a state of alteration of certain cell membrane colloids occurs and thereby an increase of permeability, particularly for potassium ions. on the other hand the interior of the muscle cell seems free from sodium ions. An important influence of sodium ions proceeds from the fluid bathing the intermediary substance.
The potassium salts are not able to give back irritability to a muscle which has lost it in an isotonic solution of cane sugar, while all sodium and lithium salts are able to do so. If one places fresh muscle in isotonic alkali chloride solution, it maintains its irritability longest in NaCl; then follow LiCl, CsCl, NH4Cl, RbCl; and it is lost most rapidly in potassium chloride. For the impairment of muscle irritability one has also the following series of cations: Na
- In this series the contrast of sodium and potassium in respect to muscle is expressed more distinctly. The reduction of muscle irritability is apparently a special property of potassium (the equally acting Rb is not of physiologic nor pharmacologic significance and is left out of consideration). According to Hober, this influence occurs through alteration of the colloid consistency of the plasma membrane and, indeed, through relaxation of the plasma membrane. The removal of muscle irritability by potassium is reversible. Parallel with it goes the influence of potassium salts on the muscle current. Biedermann found that if one brings a place of uninjured, currentless frog muscle into contact with a potassium salt solution for a short time, a rest current of the same direction and electromotive power appears as in a partial destruction. The part of the muscle coming into contact with the potassium salt will be negative in respect to the reminder of the muscle and it will thereby produce a regular rest (cross-section current). If one washes off the salt producing the alteration, then the original state of the currentless muscle is restored. The potassium salts bring the muscle into a state in which, if it is stimulated already, it cannot be stimulated further. Because the excitation, just as the potassium salt, produces a local and transient negativity of the muscle and at the same time brings the muscle into a state of nonexcitability. It is presumed that the excitation process running through a muscle is associated with a change in the state of colloids which is released through an electrolytic process within the muscle. The binding salts, particularly the K and HPO 4 ions, in any case here have the chief role.The potassium ion is the chief carrier of positive charge on the inner limiting membrane. If through potassium ions from without, a migration of potassium ions is made possible, then the potential difference ceases and with it the irritability as long as this potassium influence from without is active. The same ion whose presence within the interior of the muscle fibril is a pre- condition of irritability disturbs or removes this irritability by influence from without. Apart form the influence of the quantity, the concentration, there is also a shifting of action indeed according to the site of influence. A defective potassium function can be conditioned just as well form too few ions within the sarcoplasm as by too many potassium ions without the sarcoplastic limiting layer. By what way, in such a disturbance of potassium balance in the muscle, a regulation follows from medicinal doses of potassium, we will obtain an explanation only when the significance of potassium ions for nerve irritability is better known. The same relations as in the muscle fibrils, in any case, seem to be present. According to Mac Donald, the destruction of a nerve is associated microchemically with the liberation of large amounts of previously un-recognizable KCl at the place of injury. Furthermore, the cations reduce the irritability of nerves in the same series as they do muscle,, here again sodium the least and potassium most strongly.
The influence of potassium ions on the cardiac musculature seems according to experiments available up to the present to correspond to that on skeletal muscles. If a frog heart, brought to a standstill through a Stannius ligature, is treated locally with KCl, then exactly as in a frog sartorius there appears a rest stream which again diminishes by washing off the KCl with Ringer’s solution.
The reduction of irritability or paralysis of the heart muscle through potassium has been confirmed by experiments on living frogs and rabbits. In order to obtain this necessarily slight increase of potassium-ion content of tissue fluid, in consequence to the rapid equalization capacity of the kidneys and transference to nonsensitive tissue cells, the potassium salt must be injected subcutaneously or intravenously. If the K2O content in the blood increased from the normal 0.025- 0.03 per cent to 0.07- 0.08 per cent, then diastolic cardiac standstill occurs. On subcutaneous injection in frogs the pulse frequency sinks and again increases after some time. The blood becomes strongly carbonic-acid containing; the heart is darkly colored. That the cardiac action is conditioned primarily and not through a defect in oxygen can be proven through a study conducted in an oxygen atmosphere. The action occurs on the heart muscle alone, because it also occurs in the ganglion-free heart muscle. In rabbits one also observes sinking of the pulse frequency and single momentary sudden standstill of the pulse curve.
Potassium added alone to sodium chloride as nutrient fluid of the heart prolongs the heart beat, reduces the tonus and leads finally to diastolic cardiac standstill. Potassium is here the outspoken antagonist to calcium.
Kolm and Pick have shown that the potassium content of the blood and heart wall is one of the most important pre-conditions for the self-regulation of the heart. It proves that the influence of potassium on the various sections of the heart is different. One can recognize to some extent the physiologic function of potassium on the heart of cold-blooded animals.
(1) KCl stimulates stimulus production in the upper heart, which expresses itself in an increase of inotropy, at times also in chronotropy.
(2) CaCl2 causes diastolic standstill in the heart washed free from potassium; the appearance of calcium contracture is bound to the presence of potassium in the heart.
(3) KCl depresses the tertiary centers of the automatically beating heart even in doses which are non-toxic for the heart as an entirety and which even stimulate the sinus and auricular activity; it is able to remove the excitation of the automatic ventricular centers set into stimulation by calcium and barium chloride.
(4) The capacity of potassium to release contracture of a heart which has been induced by calcium depends upon an increase of impulse which goes from the upper heart (sinus and auricle) to the ventricle found in preparation for contracture from calcium.
(5) On the automatically beating ventricle, potassium chloride is not able to conduct into contracture a heart which has been prepared for contracture by calcium chloride; much more a contracture induced by calcium or barium chloride in the automatic beating ventricle will be released through the addition of KCl.
(6) Potassium salts are able to prevent fibrillation through increase in the nomotopic stimulus and depression of the tertiary ventricular centers.
The toxic actions of potassium are not observed in a resorption from the gastro-intestinal canal because a definite increase of the amount of potassium ions in the blood plasma is not able to take place in consequence to the equalization processes of the organism. But if symptoms have been observed from small doses of potassium salts which point toward an affinity to skeletal and cardiac muscle which was discovered experimentally much later, then it must be considered that the type and form of the preparation administered and furthermore a special potassium sensitivity must have been responsible for the symptoms. In order to disturb the potassium economy it does not necessarily follow that the point of departure must be taken from an increase of concentration in the fluid perfusing the tissues, but it is possible that from especially fine subdivision the route may be entirely over the vegetative nervous system, that a catalytic -like disturbance of the potassium-ion potential occurs, particularly when there is already a labile equilibrium in this direction. The excitation of an accelerated potassium- ion wandering can act disturbing in the one case, regulating in another. In any case, observations free from objections made in homoeopathic provings with potassium salts cannot be denied because the possibility of explanation available for the effects known from animal experimentation cannot be utilized at present. For the explanation of the mechanism of ion effects directly up- on the receptive cells, pharmacologic animal experiment can, however, offer a certain basis.
The influence of alkali salts on smooth muscle is of another type than upon striated muscle. Here the plasma-membrane resistance does not seem to exist with an elective permeability. Consequently, the potassium ion acts more strongly de-swelling, shortening and tonus increasing than does the sodium ion.
The influence of an increase of potassium from with out on the skeletal muscle and cardiac musculature is equally tonus reducing, on the contrary in smooth muscle tonus increasing. If, now, one accepts the finding of Dufurdi that the irritability of the vagus is increased through potassium salts, so it seems that this action can be connected with the action of potassium on the receptive organs as a vagus effect.
Zondek found that enrichment of potassium in the nutrient fluid which is nourishing a frog heart acts as a vagus stimulus (calcium enrichment acts like a sympathetic stimulus). On the other side, vagus stimulation leads to intracellular potassium shifting (sympathetic stimulation leads to alterations of the calcium content of a cell). Between parasympathetics and potassium apparently exists a reciprocal relation such as we know exists between nerves and hormones. This relationship is represented best in the study of Loewi. Accordingly materials form in the isolated heart after stimulation of the parasympathetic nerves which again influence another heart in the same way. IF a cold-blooded heart filled with Ringer’s solution is faradically stimulated through the vagus, then the fluid which is obtained from the heart is able to bring about a vagus effect in a normally beating heart. According to Loewi the product formed through vagus stimulation naturally cannot be potassium because in his studies the action was removed by atropine which is not the case in increased potassium effect. At present we can only interpret the finding in that by a stimulation through a nerve to a muscle cell, the ion shifting thereby provoked is again able to evoke the same action as the nerve stimulation. This activation of a mixture of ions through the vital process of nerve muscle excitation in this same direction best enlightens us on the fineness of such reciprocal actions upon one another and makes the action of drugs in high dilution understandable when sensitivity exists, whether in a proving on the healthy, or in a potassium patient. Would not the suitable potassium preparation succeed in stimulating through the medium of the vagal connections, and intervene in a vicious circle?
If one recalls that voluntary muscle also has a vegetative innervation on which its tonus is dependent, then one can consider how it is possible to regulate the potassium balance between the inside and outside of the muscle fibrils by the vegetative nerves, and thereby the tonus through potassium as a remedial agent.
Placing potassium and the vagus parallel need not be overstretched as has occurred in the counterbalancing of the relations of K:Ca as the vagus: sympathetic by S. G. Zondek. Indeed, in general, a potassium preponderance corresponds to increased vagus influence and it is also very probable that the tonic action of potassium intermediates and regulates via the vagus. But, for example, the influence of potassium and calcium ions in the regulation of the heart does not agree throughout with the functions of the vagus and sympathetic. While the vagus depresses all parts of the heart from the sinus node to the ventricle, potassium stimulates the upper part of the heart.
The diuretic action of large amounts of salt in the healthy, which is opposite to the effect in patients with damaged capillaries, need not be considered in detail here. There it is merely concerned with an osmotic equalization which has nothing to do with special affinities of the single ions. Of most significance is that potassium acetate is especially useful as a diuretic because potassium carbonate which arises out of it in the organism diffuses less than, for example, sodium chloride.
Like all alkali ions potassium draws water to the place where it is riches itself. With increased administration in the blood by an addition in substance, that is, hypertonic solution, hydremia is the result. But how long this persists depends upon the excretory capacity of the salt concerned. In general, the potassium ion is just as permeable as sodium ions for healthy kidneys, so that equalization rapidly ensues. But isotonia can also be restored through the excretion of other salts and it may result in enrichment of potassium ions in special places, indeed according to the permeability conditions of single types of cells for this or other ions. So a relative preponderance of potassium ions, for example in the subcutaneous tissues, will provoke a local edema. One likewise knows of such alkali edemas from sodium salts.
The drug picture of kali carb. is based chiefly upon the results of provings in Hahnemann’s Chronic Diseases, 2nd ed., vol.4, p 1, 1838.
The kali carbonicum constitution is characterized through chilliness, weak circulation, weakness and relaxation of muscles and tendency to edema. The vegetative symptoms correspond in general to an increased excitation of the parasympathetic nervous system, the so-called vagotonia. The rapid physical and mental exhaustion is combined with irritability.
Kali carbonicum belongs to the cold remedies which seems to be characteristic for all compounds with cation preponderance. The kali carb. patient is especially sensitive to cold, perceives the slightest, draft, seeks the warm room. He feels the cold to a certain extent in the nerves, they pain in the cold. He also complains about cold in single parts, especially neuralgias which shoot here and there with pain in the cold parts; by the application of heat they move to other parts. In general, the pains rapidly change location. Cold sweats appear on the involved parts and there is profuse general sweating on slight provocation. Here we can well recall the sweating of the vagotonics. The sweat glands are indeed innervated by the parasympathetic. This is worthy of consideration in the type of sweating in the kali carb. picture. Especially frequently observed is the partial sweat, for example on the back with the lumbar and sacral weakness so characteristic for kali carb. and with the associated sticking pains, or on the forehead with headaches. The head is sensitive to cold; headache on walking in cold wind, dries to cover the head outside of warm rooms, headache on forced inspiration through the nose with burning pain in the region of the frontal sinus. In cold winds the nose opens, desire and burns and headache develops. On re-entering a warm room the nasal secretion from nasal and postnasal catarrh recurs and the headache ceases and the patient feels better. Just as the pains, so also should the head neuralgias be conditioned by the cessation of nasal secretion in the cold. Feeling of cold also is felt in the auditory passages, as though cold air blows in.