In cases of acute poisoning, the principal changes occur in the stomach and intestinal tract; redness and inflammation of these parts may be found within a few hours of administration; ulceration is not uncommon, gangrene and perforation are rare. In exceptional cases no marked redness has appeared, though arsenic has been found in the stomach (Taylor). Under full arsenical influence there is marked tendency to fatty degeneration of all. tissues; in acute cases this is preceded by inflammatory change, and according to Dr. Pinkham (Boston) it may be induced within forty-four hours (Medical Times, ii., 1878). Jaundice occurs, and after death the liver-cells, the renal tubules, and the intestinal glands are found choked with granules and fat-globules, their epithelium being detached or destroyed. Salkowsky found these changes in poisoned animals within three to six days, the glycogenic function of the liver being impaired very early (Virchow's Archiv, Bd. xxxiv.); it is noteworthy that in such cases the fourth ventricle may be punctured without causing glycosuria. Virchow described a swollen state of Peyer's patches and the solitary glands, with fatty degeneration of epithelium and "rice-water" secretion containing a fungus that had been thought peculiar to cholera (Archiv, Bd. i., 1870). C. Gies has recently given additional evidence of fatty degeneration of tissue under continued small doses of arsenic, but notes also that the subcutaneous fat was increased, and the animals gained weight. Increase of fat and of weight have been observed in chronic arsenical poisoning in man (Boston Journal, 1876).

Tolerance

Arsenic Eating

Under certain conditions the system may be brought to "tolerate" full, and even toxic doses of arsenic as of some other drugs, without showing the usual physiological effects. To produce such result, it is necessary to begin with very small doses, and increase them by degrees: thus Flandin, giving at first 1/65 gr. of arsenious acid to animals, gave, after nine months of progressive increase, 15 gr. per diem without poisonous symptoms (quoted by Stille).

Taylor distinguishes between "habit" and "tolerance," meaning, by the latter term, only that power of bearing large doses which is shown in certain exceptional states without any preparation; thus, opium may be tolerated in tetanus, alcohol in fever, and antimony in pneumonia; and with regard to the ordinary form of tolerance as induced by habit, he remarks that it is mainly restricted to products of the vegetable or organic kingdom - as opium, tobacco, ether, strychnia. He doubts whether any human being can obtain by habit any real tolerance of such mineral drugs as corrosive sublimate and arsenic; and certainly experiments on the point can never be pushed far in our own experience.

Yet, on the other hand, evidence in the affirmative does exist. I understand that at Whitbeck (Cumberland) the inhabitants habitually use a natural water which contains nearly a grain of arsenic in the gallon, and are remarkably healthy and long-lived (Chemical News, August, 1860). Professor La Rue reports the case of a man who so far accustomed himself to the drug that he could take 3 or 4 gr. "without more effect than cold water" (Boston Medical and Surgical Journal, 1866); but the main evidence seems curiously localized in parts of Austria and Styria, nor can it be any longer dismissed as "pure fable" (Christison) or a "Styrian theory" (Taylor), since the reports of Vogt and Tschudi in 1854 (Medical Times, ii.; Wiener Med. Woch., No. 28). M. Heisch, a trustworthy witness, has recorded his personal experience to the effect that he took 3 gr. as a daily dose for many years; he began it, when appointed director of arsenic works at Salzburg, with the object of protecting himself from the effects of the fumes; he retained good health, but when he attempted to leave off the drug suffered from restlessness, insomnia, faintness, and finally from lung-symptoms (Lancet, 1860). Professor Schafer records that 1/20 to 1/10 gr. is an initial dose commonly used for the first fortnight, then it is omitted for the same period, and then resumed and gradually increased to 5 gr. or more (Nothnagel, p. 241)- Heisch says that 23 gr. have been taken for a dose. Arsenious acid is the usual form, but sometimes orpiment is substituted. Dr. Maclagan saw doses of several grains swallowed, and he afterward detected arsenic in the urine (Edinburgh Medical Journal, 1864); and I have myself learnt from persons at Salzburg that the habit was very common, and have seen men who had taken from 5 to 10 gr. daily for many years, with occasional intermissions, and who looked robust and healthy. Near Harz-burg they have the curious custom of regulating their doses by the moon -they gradually increase to the full moon, and then diminish and take purgatives of aloes: some avoid drinking with their dose of arsenic, others avoid fat, and others keep to a farinaceous diet, but the majority eat and drink anything. The practice prevails mostly, if not entirely, among the working-classes, but is not confined to men. Its effect is said to be to increase fat and stoutness, and yet to render them more equal to exertion, and especially to mountain-climbing without difficulty of breathing; also to give freshness to the complexion, brightness to the eye, and general vigor to bodily function.1 It is agreed that much depression and emaciation occur on the withdrawal of the drug from those who are accustomed to it, and although a certain number who commence early to take it continue its use to an advanced age, yet it is said, and we can well believe it, that it does much harm and even proves fatal in an insidious manner to many persons, especially among the young. We cannot depend upon securing an indiscriminate tolerance of arsenic; nothing of the kind has been reported in this country, but on the contrary many have suffered from a foolish imitation of the Styrian custom.

1 Gubler explains these effects by diminished oxidation and tissue-change (v. p. 40), suggesting the connection of muscular fatigue with formation of sarco-lactic acid; he presumes this to be lessened by arsenic alike in thoracic, respiratory, and other muscles. They can therefore work longer, there is less carbonic acid to be discharged by the lung, and less labor or hurry in respiration.