[33] Loc. cit.
CHAPTER IV.
The Production of Increased Secretion of Fluid into the Intestine by the Saline Purgatives.
One of the most characteristic things to be observed in purgation is the presence of a greater quantity of fluid in the stools. This varies in degree with the different drugs, but even with the mild laxatives the faeces become less solid. With the stronger purgatives they become quite fluid. Since the earliest attempts to explain the nature of purgation there has been the question as to the origin of this fluid. With the discovery of the property of osmosis in salts a new life was given to this inquiry, and Poiseuille[34] advanced the theory that the purgative effect of salts was due entirely to their endosmotic power, the increased fluid of the faeces being caused by the extraction of fluid from the tissues by the osmotic power of the salt. The same view was held by Liebig,[35] whose name is commonly associated with the hypothesis. Rabuteau[36] later on supported this idea and claimed as proof of it the fact that he was unable to produce purgation by the intravenous injection of large quantities of sodium sulphate. He even found that this injection caused constipation, and he concluded that since sodium sulphate purges when given by mouth there must be caused a flow of fluid towards the salt in both cases. This osmosis theory was attacked by Claude Bernard,[37] who pointed out that if the purgative action of salts were due to their osmotic power, sugar must also be a strong purgative. He found further that, contrary to what Rabuteau stated, intravenous injections of sodium sulphate do cause purgation and bring it about more rapidly and powerfully than when the salt is taken by mouth. It was further shown by Aubert[38] that the purgative effect of various salts is not at all proportional to their endosmotic power nor to their concentration. Headland,[39] assuming without experiment that purgative salts act when introduced into the circulation, advanced the hypothesis that when they are given by mouth they are first absorbed into the blood and are later excreted by the intestine. In thus passing through the intestine he supposed that they stimulated the glands to secrete. Brieger,[40] using the method introduced by Colin and Moreau, obtained what he considered an increased secretion into the intestine. Isolating a loop of the intestine, he introduced into it a strong solution of MgSO4. The loop became in a short time filled with a clear yellow alkaline fluid. This he believed was due partly to the water attracting power of the salt, and partly to the production of a real secretion. Vulpian[41] believed that the fluid was due to an inflammatory irritation. Hay[42] made experiments similar to those of Brieger, and found that the introduction into a loop of 10% Na2SO4, caused a considerable increase in the secretion, although no secretion was obtained by a 1-5% solution. Schmiedeberg[43] explained the presence of a greater quantity of fluid in the stools following the administration of the purgative by the supposition that the purgative salts on reaching the large intestine prevent the absorption of water. He states that these salts are themselves absorbed with difficulty and hence reach the lower part of the intestine unchanged. A similar hypothesis is advanced by Wallace and Cushny.[44] They stated that the absorption of fluid was inhibited especially by those salts which form insoluble compounds with calcium. These authors, however, did not take into account the possibility of the secretion of fluid into the intestine being increased by these salts. Hence their method of determining the difference in absorption of the various solutions is open to criticism, since it will be shown in this chapter that some if not all of these purgative salts cause a very definite increase in the intestinal fluid. The absorption of fluid may indeed be diminished by these salts, but it is difficult to say in the experiments of Wallace and Cushny how much of the fluid remaining in the loops is due to inhibited absorption, and how much has been actually secreted by the intestine.
The experiments of Brieger[45] and Hay[46] in the production of increased secretion are quite unsatisfactory on account of the great concentration of the solutions used. Their results may well be ascribed to the local irritating effect of the strong solution, since they did not obtain an increased secretion with weaker solutions.
As stated above in a previous section, I have made a large number of experiments to determine whether or not an increased secretion is actually caused by the saline purgatives, and have found by measurements that with some of the salts this increase is very marked. These results have been already published,[47] and the tables and a part of the description given below are taken from this paper. Rabbits and dogs were used in these experiments. In the case of the rabbits anaesthesia was produced by the subcutaneous injection of 4-5 c.c. 1% morphine hydrochlorate. The rabbits were not full grown, their average weight being not more than 1,200 g. The same amount of morphine was given also to the dogs, and was supplemented by ether. The abdominal cavity was opened and a loop of considerable length tied off with ligatures. In the rabbit the upper part of the small intestine was selected and the upper ligature placed just below the entrance of the common bile duct. The second ligature was tied 25 to 30 cm. lower down. At the lower end of the loop a large mouthed cannula was inserted from which the fluid could be drained by gently lifting the successive parts of the loop, a process made more easy by placing the animal board at a considerable angle with the table. All of this was done as rapidly as possible, so that the loops would be exposed as little as possible to the air. After the loop had been emptied of what it contained in this way, the intestines were covered over with filter paper soaked in warm m/6 NaCl solution, and this again covered with a towel wet with warm water, and over it all a woolen cloth. In this way the loops were protected fairly well from drying and loss of heat. The contact with the wet filter paper did not seem in any way to affect the intestine. Other experiments were made with the filter paper raised from the intestine by a wire tent. I found that if these precautions against loss of heat and drying were neglected the secretion did not take place. The greatest care must be exercised in this respect since the slightest cooling seems to inhibit the secretory activity of the intestine.
The loop which had thus been emptied and returned to moist warm surroundings was left 10 minutes and the normal secretion allowed to collect, and at the end of that period the loop was again emptied with as little exposure as possible and the fluid measured. The cannula was then clamped off and the secretion allowed to gather for a second 10 minutes. This again was drawn off and measured. The quantity secreted was usually fairly constant and quite small, the manipulation undoubtedly increasing it somewhat. When the normal secretion was obtained the purgative salt in an isotonic solution was administered either subcutaneously, intravenously, or locally. The secretion was again allowed to collect, and was drained off and measured after 10 minutes. This was repeated several times and the amounts compared with what was taken as the normal secretion. When the solution was applied locally, a method which is perhaps the most satisfactory, it was allowed to drop on the loops from a pipette, care being taken to have it at body temperature and as nearly as possible isosmotic with the blood. In each case special care was taken to have no interval between the emptying of the loop and the beginning of the succeeding period of 10 minutes. In other words, the loop was always entirely empty at the beginning of each period.
The results of a few of these experiments may be seen in the following reports:—
1. Rabbit. Loop 30 cm. long, upper part of small intestine.
| Loop contained in beginning[48] | 5.0 c.c. |
| Fluid removed after 1st 10 minutes | 0.2 c.c. |
| Fluid removed after 2d 10 minutes | 0.5 c.c. |
2 c.c. m/8 BaCl2, injected subcutaneously.