To assert that the particles of an insoluble substance cannot pass through the homogeneous wall of the capillary or absorbent vessels, is merely to state what follows from an absolute physical law, and is generally admitted by physiologists. But even this fundamental datum has been lately attacked.
Professor Œsterlen of Dorpat has been induced to affirm the possibility of the absorption of insoluble substances, from some experiments which he has made. Finely-powdered charcoal was administered to rabbits for some days. They were then killed, and globules of charcoal, measuring from 1/6000 to 1/3000 of an inch, were found in the blood of the Portal circulation. (Zeitschrift für Rationelle Medizin, 1847.) To obtain these results the microscope was used, a far less certain test in such matters than chemical analysis. Œsterlen reasonably concludes that, if charcoal can so pass, so also can any other insoluble substance. The necessity of solution could then at once be done away with, and the blood continually liable to admixture with all kinds of heterogeneous and crude materials. Œsterlen asserts further that he has found minute globules of mercury under the skin after rubbing in mercurial ointment. (Journal für Praktische Chem., No. IX. 1850.) Now, if these things were true, there could be no need to suppose the solution of insoluble active medicines, for they would be enabled without difficulty to pass through in an undissolved state.
To test for myself the accuracy of such statements, I have made some experiments, the object of which is to discover if some of the most insoluble of our known remedies, which are yet known to obtain entry somehow into the blood, could do so while yet in the insoluble state. They are as follow:—
Exp. 1.—Ten grains of calomel were given to a large dog. It was killed after three hours, allowing this time for digestion. A considerable quantity of blood was collected from the Portal vein, and submitted to analysis to determine whether it contained any compound of Mercury in an insoluble form. The blood was dried and pulverized. The result was boiled for some time in water, and the insoluble part collected. It was dissolved in a small quantity of aqua regia, and the clear acid solution placed in a test tube. A slip of zinc foil was folded round a narrow plate made of gold foil, and introduced into the solution. A galvanic current being thus set up, the minutest quantity of mercury, if present, would have been deposited on the gold, so as to tarnish it. But this did not take place, and when at last the zinc was completely dissolved, the gold remained as bright as before. Thus there was no Calomel, or compound of mercury, present in the insoluble form.
Exp. 2.—Ten grains of strong mercurial ointment (containing half its weight of metallic mercury, with some oxide) were given to another dog. He was killed after the same time, and the Portal blood analyzed carefully in the same way, but here also no mercurial compound was present in the insoluble form.
Exp. 3.—To a third dog five grains of Oxide of Silver were administered. After three hours he was killed. The Portal blood was dried in a water-bath, and reduced to powder. This was boiled for some time in water, which was separated by filtration. Aqua regia was then boiled on the insoluble part. This would convert any silver into chloride. The acid was evaporated off as much as possible, and the solid remainder heated in a small porcelain crucible to dull redness. The result was powdered, and digested in liquor ammoniæ. It was filtered, and excess of nitric acid was added. There was not any precipitate. Had chloride of silver been present, it would have been dissolved by the ammonia, and precipitated by the acid. Thus no insoluble silver compound was contained in the blood analyzed.
Exp. 4.—Ten grains of sulphur were administered in the same way to a fourth dog. On killing it and opening the body, the thoracic duct was found to be full. A considerable quantity of chyle was collected from it. Now, as it is asserted by some, that fat passes undissolved into the chyle, and as I believe that sulphur is digested in the neighbourhood of the bile duct, this chyle was chosen for analysis in preference to blood, as more likely to contain any insoluble sulphur. Besides, the blood would be less satisfactory, on account of the large quantity of albumen and fibrine contained in it, both of them also containing sulphur. The insoluble part of the chyle was obtained in the same manner as with the blood. It was then boiled in a small quantity of a weak solution of caustic potash. By this any free sulphur would be converted into a soluble sulphate of Potassium. The solution was filtered, and a few drops of a solution of the Nitro-prusside of Potassium added. (This is a salt lately discovered by Dr. Playfair. It is a delicate test for soluble sulphurets, with which it strikes a deep purple colour.) No change was produced. Therefore no insoluble sulphur was present in the chyle.
The results of these experiments are thus in direct opposition to those of M. Œsterlen, and support a view of the question which seems even à priori more philosophical and reasonable than that which he has adopted. I believe that no insoluble medicine can in any way gain entry into the blood without first undergoing solution in some way or another.
Prop. IV.—That some few remedial agents act locally on the mucous surface, either before absorption, or without being absorbed at all. That they are chiefly as follow:—
A. Irritant Emetics.
B. Stomach Anæsthetics.
C. Irritant Cathartics.
It has already been shown, during the consideration of the first proposition, that medicines which act on distant parts of the body must be, and are, absorbed before they can so act. This necessity for absorption has been shown to extend even to medicines which act most rapidly on the nervous system. If any medicines could produce a distant effect by a mere contact with the coats of the stomach, such a power would be ascribed to those stimulants and sedatives which, from the suddenness of their action, are called diffusible. Such are Hydrocyanic Acid and Ammonia. Their rapidity of action is to be ascribed to their volatility, whereby they spread over a large surface, and are almost suddenly absorbed and transmitted through the blood. But Hydrocyanic Acid may be absorbed from any surface. It is poisonous when inhaled into the lungs. It rapidly causes death when dropped into the eye of an animal. So also the results of the inhalation of ammoniacal gas are the same as of the ingestion of its solution. I believe that the latter, on account of its diffusibility and rapid absorption, escapes neutralization by the stomach acid, and passes into the blood as free Ammonia.
In the consideration of the first Proposition, I endeavoured to point out that though the proper action of a medicine could in no case be conducted, without absorption, from the mucous surface to a distant part of the system, yet that a remote action of another kind might occur as the result of a change in the nervous system produced by a powerful local impression. I stated that the term Counter-irritation was employed to express this action, the nature of it being but ill understood. A powerful impression on any surface of the body, external or internal, seems to be capable of arresting and diverting, as it were, the attention of the system, and thus, for a time, of checking a morbid process.