2. _Of the Action of Poisons through Absorption._—If doubts may be

entertained whether poisons ever act by the transmission of local impulses, from the part to which they are applied, along the nerves to the organ upon which they act, no reasonable doubt can be entertained that many poisons act through the medium of absorption into the blood. Poisons are believed to act through the blood for the following reasons. First, they disappear during life from the shut cavities or other situations into which they have been introduced; that is, they are absorbed. Several clear examples to this effect have been related by Dr. Coindet and myself in our paper on oxalic acid. In one experiment four ounces of a solution of oxalic acid were injected into the peritoneal sac of a cat, and killed it in fourteen minutes; yet, on opening the animal, although none of the fluid had escaped by the wound, we found scarcely a drachm remaining.[20] In recent times Professor Orfila has proved that various poisons, such as arsenic, tartar-emetic, and acetate of lead, disappear in part or wholly from wounds into which they had been introduced.[21] Next, many poisons act with unimpaired rapidity, when the nerves supplying the part to which they are applied have been previously divided, or even when the part is attached to the body by arteries and veins only. Dr. Monro, _secundus_, proved this in regard to opium;[22] and the same fact has been since extended by Sir B. Brodie and Professor Emmert to wourali,[23] by Magendie to nux vomica,[24] by Coullon to hydrocyanic acid,[25] by Charret to opium,[26] and by Dr. Coindet and myself to diluted oxalic acid.[27] Magendie’s experiment was the most precise of all: for, besides the communication with the poisoned part being kept up by a vein and an artery only, these vessels were also severed and reconnected by two quills. Farther, many poisons will not act when they are applied to a part of which the circulation has been arrested, even although all its other connections with the body have been left entire. This has been shown distinctly by Emmert in regard to the hydrocyanic acid; which, when introduced into the hind-leg of an animal after the abdominal aorta has been tied, produces no effect till the ligature be removed, but then acts with rapidity.[28] An experiment of a similar nature performed by Mr. Blake with the wourali poison yielded the same result.[29] Again, many poisons act with a force proportional to the absorbing power of the texture with which they are placed in contact. This is the criterion which has been commonly resorted to for discovering whether a poison acts through the medium of the blood. It is applicable, however, only when the poison acts sensibly in small doses; for those which act but in large doses cannot be applied in the same space of time over equal surfaces of different textures. The difference in the absorbing power of the different tissues has been well ascertained in respect to a few of them only. The most rapid channel of absorption is by a wound, or by immediate injection into a vein; the surface of the serous membranes is a less rapid medium, and the mucous membrane of the alimentary canal is still less rapid. Now it is proved of many poisons that, when applied in similar circumstances to these several parts or tissues, their activity is proportional to the order now laid down. Lastly, it has been proved of nux-vomica, that if the extract be thrust into the paw of an animal after a ligature has been tightened round the leg so as to stop the venous, but not the arterial circulation of the limb, blood drawn from an orifice in a vein between the wound and the ligature, and transfused into the vein of another animal, will excite in the latter the usual effects of the poison, so as even to cause death; while, on the contrary, the animal from which the blood has been taken will not be affected at all, if a sufficient quantity be withdrawn before the removal of the ligature. These interesting facts, which are capable of important practical applications, were ascertained by M. Vernière.[30] On weighing attentively the arguments here brought forward, it seems impossible to doubt, that some poisons are absorbed into the blood before they act, and that their entrance into the blood is not a mere fortuitous antecedent, but a condition essential to their action. But it is farther held that poisons which act through absorption, do so by being conveyed in substance along with the blood to the part where their action is developed,—that their action eventually depends on the organ, whose functions are thrown into disorder, becoming impregnated with poisoned blood. Now, the arguments detailed above do not absolutely prove this conveyance and impregnation. They show that poisons enter the blood, and act somehow in consequence of entering it; but they do not prove in what manner the action subsequently takes place. It was at one time indeed supposed that the same facts, which prove their admission into the blood, proved also their transmission in substance to the organs acted on by them. But Dr. Addison and Mr. Morgan have shown that this is not a legitimate conclusion, and that a different theoretical view may be taken of the facts,—namely, that the action may really take place by the poison producing on the sentient extremities of the nerves of the inner membrane of the blood-vessels a peculiar impression which is conveyed through the nerves to the part ultimately affected.[31] They have endeavoured to found this theory upon evidence, that the poison is not carried beyond the venous system; or that, if conveyed farther, it is carried incidentally, and not for the purpose of impregnating the textures of the organ which suffers. The evidence they have brought forward on this head is chiefly the following. 1. Poisons which act on a particular organ at a distance do not act more quickly when introduced into the artery which supplies it, than when introduced into its vein, or even into the principal artery of a distant part of the body.[32] 2. If a poison be introduced into a great vein with a provision for preventing its passage towards the heart, it will act with as great rapidity, as if no obstacle of the kind existed. Thus, if the jugular vein, secured by two temporary ligatures, be divided between them and reconnected by a tube containing wourali, the animal will not be affected more quickly on the removal of both ligatures, than on removing only the ligature farthest from the heart.[33] 3. The arterial blood of a poisoned animal is incapable of affecting another animal. Thus, if the carotid artery and jugular vein of one dog be divided, and both ends of each reciprocally connected by tubes with the divided ends of the corresponding vessels of another dog, and extract of nux-vomica be introduced into a wound in the face of one of them,—the animal directly poisoned alone perishes, and the other remains unharmed to the last.[34] These are at first view strong arguments against the transmission of poisons with the blood to the organs remotely acted on; and the facts on which they are founded are on the other hand easily explained under the new theory advanced by the authors, that the medium of action is the nerves which supply the inner membrane of the blood-vessels. But their inquiries, however ingenious and plausible, have not stood the test of physiological scrutiny. Their first experimental fact has been contradicted by Mr. Blake; who has found that the wourali poison, which does not begin to act for twenty seconds when injected into a vein, will produce obvious effects in seven seconds only if injected into the aorta through the axillary artery.[35] The second experiment, showing that poison confined in a vein will act although prevented by a ligature from reaching the heart, is held by the opponents of Dr. Addison and Mr. Morgan to be fallacious, in as much as the blood behind the ligature may be carried backwards till it meets with an anastomosing vein and is so carried by a collateral vessel to the heart. To the third experiment it may be objected, that there was, in the mode in which they conducted it, no satisfactory evidence that the reciprocal circulation was kept up by the carotid artery and jugular vein. And this will appear an important objection to every one practically acquainted with experiments of transfusion. For on the one hand it is exceedingly difficult, in such complicated experiments, to prevent coagulation of the blood in one vessel or another, before the connection of all the arteries and veins is established; and on the other, it may be urged, as Mr. Blake has done, that the pressure of the blood in the distal end of the carotid artery in the animal not directly poisoned may be equal, or even superior, to the pressure in the proximal end of the same vessel in the other animal,—so that the blood may not pass from the latter into the former, although it should continue fluid. In opposition to the theory of Dr. Addison and Mr. Morgan, and in support of the doctrine, that poisons act by being carried in substance with the blood into the tissues of the remote organs on which they act, a variety of important experimental evidence has been brought forward since the publications of the Essay of these gentlemen. In the first place, the concurrent testimony of a great number of recent chemical inquirers establishes undeniably, that poisons absorbed into the veins of the part to which they are applied are to be detected throughout many of the tissues of distant organs. This fact will be enlarged on and illustrated presently. Secondly, on the authority of Mr. Blake, and in contradiction of the experiments of Dr. Addison and Mr. Morgan, it appears that, as already stated, poisons act more quickly when injected into the aorta than into the venous system; a fact which is easily understood, on considering that when injected into the aorta they reach their destination directly, whereas, if injected into a vein they must first arrive at the right side of the heart, and then be transmitted through the circle of the pulmonary circulation before reaching even the aorta. Thirdly, the relative rapidity with which poisons act on different animals follows the ratio of the velocity of the circulation in each. Thus, Mr. Blake found, that in the horse nitrate of baryta is conveyed by the circulation from the jugular vein to the carotid artery in sixteen seconds, and that strychnia injected into the jugular vein begins to act on the nervous system after exactly the same interval: That in the dog chloride of barium passes from the vein to the artery in seven seconds, and extract of nux-vomica begins to act as a poison in twelve seconds: That in the fowl the passage of the blood seems to take place in six seconds, and the nitrate of strychnia to act in six seconds and a half: And that in the rabbit the passage of the blood is effected in four seconds only, and the first signs of the action of strychnia occur in four seconds and a half.[36] On the whole, then, it may be considered as well established, that probably all, but certainly some, poisons,—of the kind whose topical action does not consist in causing destruction or inflammation of the textures to which they are applied,—produce their remote effects solely by entering the blood, and through its means impregnating the organs which are acted on at a distance. And farther, if this doctrine be admitted as established, it may also be allowed, that many poisons which do cause topically destruction or inflammation, and remotely the usual sympathetic effects of these changes of structure, also possess the power of affecting distant organs through the medium of the blood. _Of the discovery of Poisons in the Blood._—Such being the case, it becomes an object of paramount interest, with reference both to the practice of medical jurisprudence, to inquire whether poisons can be detected in the circulating fluids, or generally in parts of the body remote from the place where they are introduced. A variety of circumstances long rendered it impossible to determine satisfactorily the question, whether poisons could be detected in the blood, the secretions, and the soft textures of the body. In the first place, we now know that the quantity of the more active poisons, which is required to occasion death, is so small, that, considering the crude methods of analysis formerly trusted to, and the obstacles opposed to the successful application of them by the presence of organic matter, there can be no wonder that chemists, even but a few years ago, could not satisfy themselves whether the objects they were in search of had been detected or not. Then, it was partly known before, and is now fully established, that various poisons are removed beyond the reach of analysis before death, in consequence of passing off with the secretions, particularly the urine. Farther, it seems probable that, of the poisons which act through absorption, several do not remain or at least do not accumulate, in the blood; and that they are not distributed with it throughout the textures indifferently, but are deposited, as absorption goes on, in particular organs, such as the liver,—which it was not much the practice to examine in former investigations. And lastly, some poisons are speedily decomposed on entering the blood: They either cause obvious changes in the constitution of the blood, and themselves undergo alteration likewise; or without the blood becoming appreciably different in its properties from the healthy state, the poison undergoes a rapid change in the molecular affinities of its elements, and so disappears. Of the former course of things distinct illustrations are furnished by nitric oxide gas and sulphuretted-hydrogen gas when injected into a vein in a living animal: of the latter an equally unequivocal example occurs in oxalic acid, which Dr. Coindet and I found to be undiscoverable in the blood of the vena cava of a dog killed in thirty seconds by the injection of eight grains and a half of it into the femoral vein. But the improvements that have been lately made in the methods of analysis for the detection of poisons in a state of complex mixture with organic substances have done away with a great part of the obstacles which prevented a thorough inquiry as to the existence of poisons in the blood and textures of the body. Some important researches of this kind were referred to in the last edition of the present work; and since then many additional facts, of equal variety and precision, have been communicated by different observers, but especially by Professor Orfila. Under the head of each poison an account will be given hereafter of the evidence in support of the discovery of it by chemical analysis in the blood, textures, and excretions. In the present place it is sufficient to state in general terms that the evidence is quite satisfactory in the instances of iodine, sal-ammoniac, oxalic acid, nitre, sulphuret of potassium, arsenic, mercury, copper, antimony, tin, silver, zinc, bismuth, lead, hydrocyanic acid, cyanide of potassium, carbazotic acid, sulphuretted-hydrogen, camphor, and alcohol. _Of the Organs affected by the remote action of Poisons._—Having now taken a general view of the mode in which poisons act on distant parts, I shall next consider what organs are thus brought under their operation. Poisons have been often, but erroneously, said to affect remotely the general system. A few of them, such as arsenic and mercury, do indeed appear to affect very many organs of the body. But by much the larger proportion seem on the contrary to act on one or more organs only, not on the general system. Of the poisons which act remotely through a sympathy of distant parts with an organic injury of the textures directly acted on, many appear to act sympathetically on the heart alone. Taking the mineral acids as the purest examples of poisons that act independently of absorption into the blood-vessels, it will be seen on inquiry that all the symptoms they produce, in addition to the direct effects of the local injury, are those of depressed action of the heart,—great feebleness, fainting, imperceptible pulse, cold extremities. Even the less prominent of the secondary symptoms are almost all referrible to a depressed state of the circulation. In particular, they are not necessarily, and indeed are seldom actually, blended with any material symptom of disorder in the brain; which certainly could not be the case if the general or whole system suffered. With respect to that more numerous class, which act remotely either through the medium of the blood or by the transmission along the nerves of an undiscernible impression made on their sentient extremities, some certainly possess a very extended influence over the great organs of the body; but the greater number are much more limited in their sphere of action. Some act chiefly by enfeebling or paralyzing the heart, others principally by obstructing the pulmonary capillaries, others by obstructing the capillaries of the general system, others by stimulating or depressing the functions of the brain or of the spinal cord, others by irritating the alimentary canal, others by stimulating one or another of the glandular organs, such as the salivary glands, the liver, the kidneys, or the lymphatic glands. Some poisons of this kind act chiefly, if not solely, on the _heart_. The best examples are infusion of tobacco, and upas antiar. Sir B. Brodie observed, that when the infusion of tobacco was injected into any part of the body, it speedily caused great faintness and sinking of the pulse; and on examining the body instantly after death, he found the heart distended and paralyzed, not excitable even by galvanism, and its aortal cavities filled not with black, but with florid blood, while the voluntary muscles were as irritable as after other kinds of death.[37] The upas antiar he found to be similarly circumstanced.[38] Arsenic and oxalic acid are also of this kind. In an animal killed by arsenic, and in which the gullet and voluntary muscles continued long contractile, Dr. Campbell found the heart immediately after death containing arterial blood in its aortal cavities, and insensible to galvanism.[39] Dr. Coindet and I frequently witnessed the same facts in animals killed with oxalic acid: When the heart at the moment of death was completely palsied and deprived of irritability, we saw the intestines moving, and the voluntary muscles contracting long and vigorously from the mere contact of the air.[40] An interesting series of investigations has been lately made by Mr. Blake, relative to the influence of poisons on the heart, when they are directly introduced into the great veins. It does not absolutely follow that an action on the heart manifested in this way proves the occurrence of a similar action when the substance is admitted into the body through more ordinary channels, such as the stomach, intestines or cellular tissue. For on the one hand, some of the substances used by this physiologist cannot be admitted into the blood through ordinary channels in the quantity necessary for developing that action on the heart, which is excited when they are injected at once into the blood-vessels. And on the other hand, the results at which he thus arrives are not always in conformity with what have been obtained by prior observers, who resorted to the ordinary channels for introducing poisons into the body. It is possible, therefore, that Mr. Blake’s researches may not have the extensive bearings, which might at first sight appear, on the physiology of poisons and remedies. Nevertheless they are in themselves full of interest. They show that the salts of magnesia, zinc, copper, lime, strontia, baryta, lead, silver, ammonia, and potash, also oxalic acid, and digitalis, if injected into the jugular vein, produce a powerful and permanent depression of the heart’s action; which is evinced by the hæmadynamometer,[41] indicating diminution of pressure in the great arteries, by the heart becoming motionless or nearly so before the breathing ceases, by its muscular structure presenting little or no irritability when stimulated immediately after death, and by the left cavities being found full of florid arterial blood.[41] Other poisons act on the _lungs_; but probably few, perhaps none, act on them alone. Magendie found that in poisoning with tartar-emetic the lungs are commonly inflamed and sometimes even hepatized.[42] Mr. Smith and M. Orfila both remarked similar signs of pulmonary inflammation in animals poisoned with corrosive sublimate.[43] But these poisons produce important effects on other organs likewise. A set of novel and important facts setting forth the frequent operation of poisons on the lungs when they are admitted directly into the blood, has been recently brought to light by the researches of Mr. Blake. Many of the poisons mentioned above as acting powerfully on the heart were found by him not to exert any influence upon the lungs, such as oxalic acid and the salts of magnesia, lime, zinc, copper, ammonia, potash, and strychnia. Others, however, such as the salts of strontia, baryta, lead, and silver, as well as digitalis, all of which powerfully affect the heart, and, in addition to these, the salts of soda, which have no action at all on the heart, and hydrocyanic acid, tobacco, and euphorbium, which influence it feebly, or even dubiously,—produce, when injected into the jugular vein, obstruction of the capillaries of the pulmonary circulation, and consequently asphyxia. This is proved by the hæmadynamometer introduced into a vein indicating great increase of pressure in the venous circulation a few seconds after the introduction of the poison; by this instrument introduced into the femoral artery indicating great diminution of arterial pressure, although the heart continues to beat vigorously; by the breathing becoming at the same time laborious, without the heart suffering; by these symptoms preceding any signs of action on the nervous system; by the heart pulsating for some time after death; and in many instances by frothy mucus having accumulated in the air-passages, and congestion and extravasation having taken place in the lungs themselves.[44] A great number of the poisons whose action is remote, operate on the _brain_. The most decided proof of such an action is the nature of the symptoms; which are, giddiness, delirium, insensibility, convulsions, palsy, coma. Some physiologists have also sought for evidence in the body after death, and have imagined they found it in congestion of the vessels in the brain, and even extravasation of blood there; but it will be seen under the head of Narcotic Poisons that such appearances are far from being essential, and indeed are seldom witnessed. All narcotic poisons act on the brain, and most narcotico-acrids too; but very frequently other organs are affected at the same time, and in particular the spine and heart. The influence of poisons on the brain seems to be sometimes induced, not immediately, but indirectly through the intervention of a more direct influence on the pulmonary circulation. Thus Mr. Blake appears to have succeeded in proving that the insensibility and tetanic convulsions which immediately precede death, when certain substances, such as the salts of soda, are injected into the veins, depend simply on the obstruction directly produced in the pulmonary circulation causing increased pressure in the systemic veins, and consequently upon the brain and nervous centre generally. For when the jugular vein was opened after the development of tetanic convulsions, and blood was allowed to flow out, the nervous symptoms ceased, and the animal continued for two hours sensible and without any return of convulsions, dying eventually of hemorrhage.[45] But more generally the effect produced on the brain is direct and specific. Thus opium and its active principle morphia suspend the functions of external relation, which are peculiarly dependent on the brain; while for a long time the respiration and circulation are little affected. Even when the poison is admitted directly into the veins, the pulmonary capillaries are not obstructed, and the heart is only somewhat enfeebled in its contractions;[46] and in ordinary cases of poisoning with these substances the heart continues to pulsate, and the lungs also discharge their office, long after sensibility is extinguished and voluntary motion arrested,—until at length the circulation and respiration become affected consecutively by the depressed state of the nervous system. Some poisons act specifically on the _spinal cord_. Those which are best known to possess such an action are nux-vomica, the other species of plants which, like it, contain strychnia, and also conia and the wourali poison. The tribe of poisons of which nux-vomica may be taken as the type excite violent fits of tetanus, during the intervals of which the mind and external senses are quite entire; and death takes place during a paroxysm, apparently from suffocation caused by spasmodic fixing of the chest. Their action on the spine is quite independent of any action on the brain; if indeed such action exist at all. For when the spinal cord is separated from the brain by dividing the medulla oblongata, the effects on the muscles supplied by the spinal cord are produced as usual.[47] Conia, the active principle of hemlock, according to my own researches, produces in the lower animals, howsoever introduced, gradually increasing paralysis, without insensibility or delirium, and without the circulation or respiration being for some time affected, till at length death takes place from stoppage of the breathing by palsy of the respiratory muscles; and after death the heart continues beating vigorously, the muscles contract when irritated, and arterialization of the blood in the lungs may be kept up long by maintaining artificial respiration. In this instance it would appear, that the first effect is arrestment of the functions of the spinal cord; that the paralysis does not depend upon a direct action on the muscles; and that neither the brain, heart, nor lungs can be influenced, except secondarily through the consequences of general muscular paralysis.[48] Many poisons which act on the brain also act on the spinal cord. Other poisons apparently possess the singular property of impeding or arresting the _general capillary circulation_, and produce their tangible effects more or less through the medium of this operation. Such at least are the inferences which seem to flow from the researches of Mr. Blake; who found that many substances, soon after they are injected backwards by the axillary artery into the aorta, produce increased pressure in the arterial system indicated by the hæmadynamometer during life, and frequently congestion of the membranous textures as observed after death. Some substances have no effect of this kind. Others act on the general capillaries in concurrence with a similar action on the capillaries of the pulmonary circulation, such as the salts of strontia, baryta, lead, silver, and soda, euphorbium, tobacco and digitalis. But a few, such as potash and ammonia, with their salts, seem to influence the capillaries of the general circulation only.[49] These are important conclusions, if legitimate; but it cannot be denied, that the facts on which they are based must be very difficult to isolate and observe with accuracy and without bias. The organs not immediately necessary to life may be likewise all acted on by poisons indirectly. On this subject details are not called for at present. It may be sufficient to remark that there is hardly a considerable organ in the body, except perhaps the spleen and pancreas, which is not acted on by one poison or another. Arsenic inflames the alimentary mucous membrane, mercury the salivary organs and mouth, cantharides the urinary organs, chromate of potass the conjunctiva of the eyes, manganese the liver; iodine acts on the lymphatic glands; lead on the muscles; and spurred rye causes gangrene of the limbs. Some poisons, as was already mentioned, may act on one important organ only, every other being left undisturbed: thus nux-vomica in general acts only on the spine. But much more commonly they act on several organs at once; and the action of some of them is complicated in an extreme degree. I may instance oxalic acid and arsenic. Oxalic acid when swallowed irritates and inflames the stomach directly, and acts indirectly on the brain, the spine, and the heart. A large dose causes sudden death by paralyzing the heart; if the dose is somewhat less, the leading symptom is violent tetanic spasm, indicating an action on the spine, and death takes place during a paroxysm, the heart continuing to contract for some time after; if the dose is still less, the spasms, at first distinct, become by degrees fainter and fainter, while the sensibility in the intervals, at first unimpaired, becomes gradually clouded, till at length pure coma is formed without convulsions,—thus indicating an action on the brain. As for arsenic, coupling together the symptoms during life and the appearances in the dead body, it will be seen afterwards to have the power of acting on the brain, heart, and lungs,—the throat, gullet, stomach, and intestines,—the lining membrane of the nostrils and eyelids,—the kidneys, bladder, and vagina; and, what is remarkable, proofs of an action on all these parts may be witnessed in the course of a single case. The effects of mercury are hardly less multifarious. SECTION II.—_On the Causes which modify the Actions of Poisons._ By a variety of causes the action of poisons may be modified both in degree and in kind. The most important of them are—quantity; state of aggregation; state of chemical combination; mixture; difference in tissue; difference in organ; habit; idiosyncrasy; and lastly, certain states of disease.