Both the oxygen carrying capacity of hemoglobin as well as the respiratory ferment of cell respiration can be poisoned through anticatalysors like HCN. It occurs through a transformation of iron in a complex compound with CN which thereby becomes inactivated. Exactly like hemoglobin, the respiratory ferment can be poisoned by carbon monoxide. Warburg was able to again detoxify this combination of carbon monoxide and the respiratory ferment by radiation, and indeed with various strengths according to the wave lengths of the light. The corresponding facilitation of dissociation of CO-hemoglobin by ultra-violet rays was previously known. 595
METABOLISM, BLOOD FORMATION, GROWTH
Up to a certain degree the oxidative action can be augmented by increased introduction of iron: at least metabolic investigations with animal diets of iron rich food shows an essentially higher
O2 use than the normal animal. A markedly increased new formation of blood also occurs but an increased destruction maintains the equilibrium so that the normal number of red blood cells is maintained. Distinct actions of iron are apparent only with a previously disturbed equilibrium.
A physiologic role of iron in growth is made probable through the combination of functional iron in the cell nucleus in the nucleo- albumins. Likewise with a continuous iron free diet, animals of the second generation are retarded in growth and the aplasia of the thymus observed may be connected with this.
In the age of sexual maturity the influence on the generative organs stands in the foreground and this is made distinct in the human the disturbance of iron metabolism in chlorosis.
IRON AND CHLOROSIS
The classical field of standard iron therapy, chlorosis, today has more historical and theoretic interest than practial interest because this disease has become very rare. One cannot escape the impression that this malady of the female puberal period has been markedly influenced in the last few decades but suitable foods and clothing (access of the activating sunlight).
If the decrease in the red blood cells and even more in the hemoglobin has once occurred, then the food iron in its organic combination proves inactive, even though it provides the necessary building material. Iron therapy is concerned with an “active” iron or one which can easily be made active. For this, ionized iron seems best adapted from the start. But for the dose, the physical state is obviously important. For the same which is accomplished by a dose of several grams per day is achieved by drink cures in the Stahl springs in which not even 0.1 gram is introduced in a day. Even this amount is essentially more than the physiologic requirement.
In chlorosis one is not concerned simply with a deficiency in iron. This may be concluded from the fact that in the chlorotic much more iron is found in the urine before the administration and improvement. The failure in chlorosis lies in the incapacity to bring the iron into hemoglobin formation and to promote the new formation of blood in the bone marrow, so that active iron is necessary for blood formation. In the anemias after loss of blood the situation is different. Here the organism has the capacity to obtain active iron from inactive. On this account after the exhaustion of deposits in the liver, spleen and bone marrow, iron in any form is correct, and an iron rich diet is sufficient. Ind- eed in the anemias from blood loss feeding of liver, kidney, and blood improves the new formation of blood better than iron. Pure iron preparations often prove inactive, less pure act very well, likewise from the addition of vegetables or their ashes. It is also probable that in the simple anemias from blood loss an intermediate reaction is necessary for the conversion of pure iron into a form capable of combination. One assumes that traces of copper complete this catalytic activation.
In endogenous chlorosis the situation for the utilization of iron in the formation of hemoglobin is still much more complicated. Because here the disturbance of iron metabolism lies distinctly in the opposed inter-relationship with the hormones of the female sexual organs. The incretion of the corpora lutea regulates the periodic process of maturation, the transformation of the uterine mucousa and menstruation. In this periodic process obviously special demands are made upon the iron metabolism. One might well imagine that in the process, the need for active iron is especially great. For this reason disturbances in iron economy or iron utilization are manifested earliest in this event.
Thus on the hand the defective adaptation in sexual maturity is a precondition for chlorosis, on the other chlorosis makes itself distinctly obvious in the disturbances of the corporalutea which regulate menstruation. The periods are very irregular, often missing, conception does not occur in the severe chlorotic and defective sexual sensation is frequent. If pregnancy should occur then in general it is curative.
In chlorosis, then, it is necessary to activate the disturbed iron content, to improve the utilization of iron. Large amounts of iron are not needed for this, in case sufficient regard is taken for the chemical and particularly for the physical form. As stimulative therapy with small doses the iron therapy of chloros- is would still not be homoeopathic. It would be only if the excessive or too long continued introduction of the iron stimulus in the healthy provoked symptoms similar to those of chlorosis. And this is to a vast extent the case as we shall see from the results of drug provings. We should not be surprised particularly in this respect if we have liberated ourselves from the much too narrow consideration of quantity. The disturbances in the drug proving with iron show that the usual cell functions for the utilization of iron are no longer sufficient and they are signs of a relative over-demand in an artificially induced situation.
In chlorosis the otherwise normal demand for functional iron in the red blood cells is already excessive. In both cases entirely similar manifestations. If in the same period a sufficient supply of oxygen is to be obtained by the tissues in the presence of decreased amounts of hemoglobin then the velocity of the stream must be accelerated in the vessels. Actually in chlorosis the gas exchange is not reduced, but the circulation velocity is increased and therefore many symptoms of excited circulation with irregular blood distribution. Other less important vital events as maturation and menstruation will become irregular or entirely neglected.
If on the other side the previously normal iron containing cell begins to fail under the continuous stimulus of iron, then this signifies that the limits of possible functional increase have been surpassed, and the reduction of function may be avoided by a blockade of active iron. Actually in certain concentrations the ferrous salts are able to transform oxyhemoglobin into the functionally incapacitated methemoglobin.
The solution of the apparent paradox also lies in that the regulation of iron economy by the cells constantly using it, employs the same trends and ways if the physiologic breadth of iron utilization is not exceeded on any side. Thus iron therapy can be used in many cases where there is an excess of iron in the body but its utilization fails. There the symptoms similar to “iron disease” will appear and the therapeutic stimulus of active iron help to overcome the blockade in iron economy. Likewise in chlorosis there is finally no deficiency in material, but only inability to utilize it.
The employment of iron in the school occurs essentially in respect to chlorosis and the secondary anemias. In the other states of weakness one depends upon its so-called roborant and tonic action. The explanation as a stimulant to oxidation in the cells is still necessary. In drug attempts the improvement of the general well being is observed as a primary action.
TOXIC ACTIONS, UNTOWARD ACTIONS, CONTRA-INDICATIONS The local protein precipitating, astringent or corrosive action of soluble iron salts in large amounts can be overlooked since they are not characteristic of iron but common to all heavy metal salts. The use of iron chloride for the arrest of non-arterial bleeding may be merely mentioned. But in regard to the tendency to bleeding in the drug picture of iron it is noteworthy that the ferrous salts in vitro as well as in vivo can reduce the coagulability of the blood while the protein precipitating ferric salts precipitate and dissolve the red blood cells. Of slight interest for us are the manifestations or intoxication from intravenous administrations: soluble, ncn-protein precipitating iron compounds (as ferrous salts) prove extremely toxic in animals when introduced directly into the blood. In frogs there is an initial increase in reflex excitability, then motor paralysis consequent to depression of the central nervous system; in mammals lowering of the blood pressure and inflammatory manifestations in the stomach and intestine with diarrhoea. Nothing similar is observed in man although the amounts of iron introduced in any from the digestive canal probably are not too small. It can only be that the iron is for the most part, made harmless in the intestine and only a little is absorbed. After the oral administration of massive doses, inky taste, dark discoloration of the teeth (by iron sulphide or iron tannate), injury to the teeth, gastric pain and a series of dyspeptic symptoms as offensive eructations, nausea, vomiting moreover persistent constipation and colic are observed as so-called unto- ward actions.
With the undoubted favorable action of iron preparation in many cases of chlorosis many believe that numerous unpleasant untoward actions must be anticipated. Recently very large doses of ferrum reductumhave been recommended in refractory cases of anemia. Lewin 596 places the blame for certain untoward effects on too great dosage and refers to that fact that on older times the special effectiveness of smallest doses of iron was stressed. Also worthy of note is a further remark by him: there are individuals who react to the smallest doses of any iron preparation with congestions. “Other well nourished people after longer use have an anemic people, even children, show an unexplainable intolerance towards certain iron preparations.” Moreover “in the febrile patient the body warmth and febrile symptoms will be increased by iron.” Apart from this, previously present digestive disturbances show an aggravation or some other type of unpleasant untoward action which is apparently associated with an abnormally increased absorption of iron from the intestine. Lewin also refers to the characteristic experience of other observes on the aggravation of disease by iron: with an existing tendency to atheroma of the vessels, plethora, in certain forms of gout; moreover the acceleration of a beginning tuberculosis under the picture of chlorosis in young girls by iron; the contraindication in patients who have previously had tuberculosis, in whom the skin is fine, transparent and the veins are visible as blue viol- et structures. The inhalation of powder, vaporized liq. ferri sesquichlorat after hemoptysis can readily excite renewed bleeding. A deeper significance lies at the basis of most of these aggravations and contra-indications than merely signs of a special sensitivity to iron.
Rademacher made extensive use of iron usually in the form of ferrum aceticum. For him iron was one of the three universal remedies, that is, agents which acted on the entire organism. In his method arranged for testing which involved the experiences from case to case with special consideration for the epidemic factor, some few indefinite diagnostic or symptomatic signs for the selection of iron can be unraveled. One indication should be the alkaline reaction of the urine. Many times Rademacher employed iron in febrile diseases, in scarlet fever, in acute rheumatism, pleuropneumonia, recurrent sore throats, but also in skin and mucous membrane hemorrhages, menstrual disturbances and sciatica. A leading motive outside of the scant indication of Rademacher on the state of the urine cannot be found.
His follower Loffler has published (in the Ztschr. Fuir Erfahrungeseilkunst, Bd. 1, 1847, H. 2, p. 62, and H. 3, p. 39), an investigation on himself and 5 (unfortunately exclusively male provers) with liquor ferri acetici containing 8 Percent iron. Increasing doses of this, on an average of 2-3 grams daily (about 0.15-0.25 grams of iron), were taken for 2-4 weeks. The studies were directed primarily toward the blood, and for this reason before and after a bleeding of 120g was done. The findings of the characteristic elements correspond to the state of the existing technique of blood investigation and naturally are not conclusive. A more marked color of the blood cells and a darker color of the blood was constant in 5 provers after the use of iron (in the sixth the behavior was different but he was not healthy; a spongy state of the gums and a tendency to bleeding was removed after the use of iron and his previously dark red blood became much lighter afterwards).
The slowing of the pulse which stands in opposition to other reports from earlier or later times was most striking. (For example Lewin states: Even after very small amounts the increase in cardiac activity can be significant. Perhaps in the investigation of Loeffler, the preceding bleeding played a role) Moreover the pulse tension increased under the use of iron.
In agreement with all other reports stands the observation of congestion to the head, relieved by quiet, lying down and sleep, not relived by cooling; a sensation of heaviness, pressure and excessive fullness in the head.
In the first period of use of iron in small doses there was an increase in strength, later, on the contrary, a general fatigue, a feeling of weakness, of heaviness and lassitude in the extremities of aversion to bodily or mental activity, lassitude, and overpowering tendency to sleep. Moreover an increase of appetite up to ravenous hunger was observed; however soon there was an unpleasant sensation in the gastric region and considerable digestive disturbances were noted; at first a feeling of increased warmth in the gastric region and with large doses a sense of constriction in the mouth and esophagus, annoying pressure in the abdomen, distension and colic in the epigastric region; with doses over 20 drops colic-like pains, nausea, eructations and tendency to vomiting. The gastric region was sensitive to external pressure and the tongue became coated white. The disturbances which in themselves were not long maintained were relieved or minimized by bodily movement after the onset. Apart from the green-black discoloration appearing in the stools (formation of iron sulphide) which was observed from the doses of iron, which were not small, it was noted that the stools became drier, more solid and heavier, at times with urgency for stool, with large doses the consistency of thin paste.
In five of the six provers there was observed a tickling sensation in the urethra and increased urgency to urinate. In one prover it amounted to a tenesmus vesicae to which a tenesmus recti was added. The nervous (neuralgiac as Loffler expresses it) nature of these events becomes obvious in that they appeared only during the day, were increased when the urge was yielded to and disappeared as soon as the urge was conquered by walking. An increased secretion of mucus in the urine was observed only twice.
Also the provings of Hahnemann (Reine Arzneimittlehre, 3 Aufl., Bd. II, S. 119, 1833) was arranged for the most part with ferrum aceticum, only a few symptoms arising from ferrum metallicum.
Ferrum aceticum was also proven in the 15, 9, and 3C potencies by Alb (Ztschr.d.Vereins d. hom. Aerzte Oesterreichs, Bd. II, S. 213, 1857).
Ferrum phosphoricum was proven by Morgan (Amer. Journ. of Hom. Mat. Medorrhinum, Bd. IX, p. 308, 1876), and Moffat (New Amer. Journ. of Hom., vol. 37, p. 218).
Ferrum iodatum by F. Muller (Allg. hom. Ztg., Bd. 50, S. 97, 107, 115, 1855) and Boissiere (Gaz. Medorrhinum deparis, 1842, p. 830).
From these provings as well as other actions known from the untoward effects, the drug picture of iron is derived as it is presented in the following. An exact proving of metallic iron is very desirable for the improvement of our knowledge on the pure effects of iron.
FERRUM METALLICUM AND FERRUM ACETICUM CONSTITUTIONAL TYPE.
With a substance necessary to life as iron which appears bound to the nucleus in all cells, which participates essentially in growth, regeneration, metabolism and securing of energy and blood formation, we may expect it to be a constitutional remedy in a narrow sense. The constitutional type of iron may be described as follows: a thin, graceful, irritable person, usually feminine, with irritable circulation, delicate transparent skin and widened veins. In ferrum aceticum there is excessively rapid growth, pallor, easy exhaustion in children. Ferrum metallicum is used more often as a remedy for the female puberal period. There exists a tendency to rushes of blood in which the face changes from pallor to a fiery red on the slightest occasions, thereby the mucous membranes are pale, the extremities, especially the legs are cold and the feet swell easily; tendency to bleeding, particularly from the nose and lung, in conjunction with congestion to the headache or chest, palpitation or superficial breathing; danger of transition into chronic tuberculous processes; great lassitude and weakness even up to fainting repeatedly necessitate lying down, the irritability of the circulation and the symptoms dependent upon it are better from prolonged moving around. Heat and cold in general have little influence, in spite of chilliness in the ordinarily cold extremities, rushes with sudden sensation of warmth to the head and the febrile state. Many complaints are worse at night and on sitting, the nocturnal restlessness occasions the moving around, but the weakness ever compels lying down. From the irritability in the evening which may lead to an increase of temperature, sleeping is impaired, and restlessness and sweating may appear. The congestive, pressing, hammering, beating and pulsating headache, especially in the front and temples is relieved at times by lying down, but also by counter-pressure); cough, bending, in general sudden movement, moreover alarm aggravates the headache. Application of cold does not relieve it (in contrast to the hyperemic congestion of Belladonna which is also aggravated by lying down). The headaches of ferrum tend to recur periodically.
Perhaps the constitution in its change between the irritability in the circulation in its change into weakness, is to be designated best according to the division of v. Grauvogl as the oxygenoid. The attendant hyperesthesia is indeed not particularly stressed (it exists chiefly toward noises) and the further signs of v. Grauvogl, the aggravation before rain and storm and the improvement after the appearance of them have not been noted particularly in the picture of iron. But that the type described is particularly susceptible to the influence of oxygen, permits the best characterization of its nature. Iron as an activator of oxygen and the oxidation process in metabolism physiologically is standard for this constitution. (Also in the syndrome of anemia more oxygen is used than corresponds to the functional capacity of the organism, namely the blood.)
Thus the drug picture of iron in many trends goes to the anemic chlorotic picture of disease. Moreover it is also striking that the too long continued use of iron again striking that the too long continued use of iron again aggravates the condition. Outside of the signs already mentioned there are: a vertigo with suffusion of the face, swishing in the head, ear noises, sensations of faintness, worse on looking downward, on looking at flowing water.
FEMALE SEXUAL FUNCTIONS ———————– In conjunction with the chlorotic syndrome stands the functional disturbances of the female sexual organs in the picture of iron. Most characteristic are the intermittent menses or the amenorrhoea and the delayed menstruation with anemia, moreover irregular menorrhagia with marked excitability of the circulation, fiery red face, ear noises, copious discharge of now fluid, now clotted blood with labor-like pains in the pelvis and the abdomen, an increased nocturnal bleeding. Also to be mentioned is the marked appearance of varices and of acne during the period. The menses are exhausting and accompanied by considerable headache. A catarrh of the mucous membrane with watery or milky leucorrhoea occurs. Anesthesia during coitus and the decided sensation of pain in the so uteriexternum is the indication for iron as a remedy for sterility.
CIRCULATION ———– The excitability of the circulation is quite irregular. Cardiac palpitation and palpitation in the pit of the abdomen readily in the from nervous causes. The pulse varies markedly in the frequency as well as the tension. The congestion to the head and the chest, the irregularity of blood distribution have been mentioned. The rushes to the chest lead to oppression “With desire to breathe deeply, or to respiratory action with almost invisible movement of the chest and great expansion of the nasal orifices on expiration,” that is, a superficial respiration. The respiratory limitation corresponds to a pseudo-plethora which is relived by moving about. All these symptoms are worse while resting quietly. Thus the following report is also to be understood: “nocturnal oppression at the pit of the stomach, worse on rest and lessened by mental or bodily occupation.” Stitches in the chest occur occasionally.
A sudden congestion of the respiratory mucous membrane lies at the basis of the dry cough with bloody expectoration. The tendency to pulmonary bleeding, considered in school medicine as a contra-indication, is exactly an indication of homoeopathic suitability and dosage under certain conditions. A prover in Loffler’s experiment reports: “in the morning on awaking a painful sensation in the larynx with cough and rasping, which increased up to pressure in it but which diminished towards noon and a similar sensation under the upper third of the sternum. On hawking and coughing pale, tenacious but blood stained sputum was expectorated which often repeated up to 4 in the afternoon. In Hahnemann’s protocols bloody expectoration is reported many times.