This section is from the book "Materia Medica And Therapeutics Inorganic Substances", by Charles D. F. Phillips. Also available from Amazon: Materia medica and therapeutics.
Most of the glandular organs are liable to become congested, and stimulated under the influence of mercury. This has been noted not only of the salivary glands as already described, but also of the pancreas and intestinal glands, the kidneys and the liver, the testis and lymphatic glands of axilla and groin (C. H. Jones: Medico-Chirurgical Transactions, vol. xxxv., etc.). As illustrating the effect on the pancreas, Dr. Copland recorded a case, where, in addition to salivation, deep-seated epigastric pain set in, with nausea and diarrhoea of thin fluid resembling saliva; after death the gland was found large and congested. Radziejewski found, on analyses of the stools after giving calomel, a large proportion of leucin, tyrosin, and indol (pancreatic secretion), which he did not find after other purgatives (Reichert's Archiv, 1870). That calomel also stimulates the intestinal glands has been demonstrated by Rutherford.
The mode of its action on the liver is still a subject of discussion, and the conclusions of some physiologists on this subject are opposed to those of many practical physicians. Up to a recent period, mercury was universally regarded as a typical "cholagogue," in the sense of its stimulating both the secretion and the excretion of bile, and hence was commonly employed, both in cases of deficient secretion to stimulate, and in cases of excessive secretion to "carry off" the excess.
The early experiments of Murray were taken to corroborate the theory of "cholagogue" action, for, after giving purgative doses of calomel to dogs, he found increased discharge of bile, mucus, and serum from the bowels (quoted by Morehead, 1841). Buchheim also reported an increase in the amount of bile discharged by dogs with biliary fistulae. Still more important evidence was furnished by the analyses of Michea, which were made first upon the normal stools of six healthy subjects without detecting bile; then, with nearly like result, upon the green stools of persons suffering from diarrhoea; then upon the greenish motions which occurred in eight healthy persons after taking calomel, and in all of which bile was clearly detected; and lastly, upon discharges produced by different saline and resinous purgatives, and in which no bile was found (Lancet, i., 1849). Although these observations show an increased discharge of bile under calomel it is clear that they do not necessarily prove an increased secretion by the liver-cells, and therefore experiments on animals as to this point were undertaken. Kolliker and Muller, after giving calomel to dogs with biliary fistulae and collecting the bile discharged, reported contradictory results - the secretion being in one instance increased, while in two others it was diminished (1855). Scott, experimenting with large doses of calomel on four dogs (also with fistulae), recorded diminution of both fluid and solid biliary constituents in all the animals (Beale's Archives, i., 1858). Mosler, with two dogs, obtained a similar result (Virchow's Archiv, xxxii.); and Hughes Bennett, reasoning from the experiments of the Edinburgh committee, announced, as a positive fact, that mercury really lessened the biliary secretion in man as well as in animals (1868). The experiments on which this physician founded his important conclusions require a brief consideration: they were made upon forty-one animals, and on account of difficulties in the operations, etc., results considered satisfactory were only obtained in nine instances - in four of these calomel was used: a permanent fistulous opening into the gall-bladder was very carefully effected, and about fourteen days afterward the bile was collected on a sponge. The first dog, before taking any drug, secreted a daily average of 82 gr. bile-fluids, and 5 gr. of bile-solids; after taking 4 to 12 gr. calomel daily, it secreted only a daily total average of 60 gr.; but it must be noted that the animal's condition was much impaired, it took little food, and soon afterward died. The second dog got smaller doses (1/12 gr.) every hour; the general health became affected, and it soon died: the average bile-secretion was about the same, before and after giving the drug. The third dog received some blue pill in addition to the small doses of calomel, and the bile-average was diminished one-half; the animal suffered much. The fourth dog got purgative doses, with an average bile-diminution while under their influence; on one day, however, when blue pill was given, the average was increased (British Medical Journal, i., 1869). Such results scarcely warranted Dr. Bennett's conclusions, which were, indeed, publicly controverted by Christison, Fraser, and other members of the same committee. Rohrig (of Kreuznach) reported that large doses of calomel slightly increased the bile-secretion (Strieker's Jahrb., ii., 1873), but we may take the more recent experiments of Rutherford and Vignal as showing, so far as experimental research can show, that the drug does not really do so. They proved (1) "that doses of 10 gr., 5 gr., or 2 gr., several times repeated, placed (without bile) in the duodenum of a fasting dog, produced a purgative effect varying with the dose, but so far from increasing bile-secretion, usually diminished it; (2) that there is no difference in the result if the calomel be given in 1-gr. dose, several times repeated, mixed with bile and introduced into the duodenum "(British Medical Journal, ii., 1875-76; Practitioner, December, 1879). On the other hand, the same observers found that corrosive sublimate in doses of 1/8 and 1/16 gr. powerfully stimulated the secretion of bile, while it did not stimulate the intestinal glands (British Medical Journal, ii., 1877). They further instituted experiments which showed that calomel does not become changed into corrosive sublimate to any appreciable amount under the influence of the organic secretions. Rutherford himself notes that the experiments referred to do not prove anything as to the action of mercury on the bile-expelling apparatus, and we may grant that they are correct without any denial of the clinical fact that a purgative dose of calomel will increase the amount of bile discharged by the bowel; it may do this, not necessarily by a previous stimulation of the liver, but either by irritating to unusual contraction the gall-bladder and gall-ducts, or by lessening a congested condition of these parts, through the discharge induced from intestinal glands.
Dr. Lauder Brunton has further pointed out that the clinical fact of calomel relieving "bilious conditions," receives from the experiments of Schiff and Lusana an explanation not at all inconsistent with Rutherford's conclusions (Practitioner, vol. xii.); these experiments go to prove that the liver not only secretes bile, but also excretes it, separating from the blood a part of that which (normally) circulates in it: for after effecting biliary fistulae in animals, bile flowed at first freely - afterward, in much diminished amount, independently of any drugs. This diminution was accounted for by the passing away of bile so soon as formed, and the consequent impossibility of its being reabsorbed from the duodenum into the circulation, to be again excreted, for if fresh bile were passed into the blood by intravenous or cutaneous injection, then the amount of excreted bile was again increased. Schiff further showed not only that bile can thus circulate without giving rise to jaundice, but that it probably always does so, passing from the liver to the duodenum, thence into the blood, and so to the liver again, a portion only, more or less changed, passing out by the faeces.
This tallies with the observation of Murchison, that "by increasing the elimination of bile, and lessening the amount circulating in the portal blood, mercury is a true cholagogue, relieving the liver thus, more than by merely stimulating it to increased secretion" (Lancet, i., 1874). The green, liquid, spinach-like stools produced by calomel have been variously attributed to intestinal irritation, to altered haematin (Golding Bird, 1845), and to subsulphate of mercury (Thudichum); it is possible that they may contain sometimes mercurial compounds, but they certainly often contain bile. According to Simon's analysis of the fifth stool passed after a large dose of calomel, it was fluid, green, without faecal odor, of acid reaction, and contained mucus and epithelial cells, fat, choles-terin, bilin, and bile-pigments - no mercury whatever ("Animal Chemistry," vol. ii.).