Study by animal experiment of the nature and distribution of the pathological changes produced in the tissues by corrosive sublimate: with special reference to the early phases of cell-degeneration and to changes in the blood-fat (illustrated)

Abstract

Several years ago two cases of mercurial poisoning came to autopsy in the Royal Infirmary, Edinburgh. Microscopic examination of the liver in each of those cases revealed the presence of a fairly marked degree of mitosis. Such mitosis could manifestly be explained in either of two ways. On the one hand, it might be regarded as a direct effect of the mercury whereby the nuclei of the liver -cells are stimulated to divide. On the other hand, it might be looked upon as merely the sequel to a destruction of liver -cells produced by the toxic action of the mercury: in this case mitosis would be a purely regenerative phenomenon secondary to degeneration of liver-tissue. The immediate aim of this research was to discover which of these views is the correct one. If it could be shown that mercury does really exert a specific influence on the cells of the liver whereby their nuclei are stimulated to undergo mitosis, we would, indeed, be in possession of a fact of prime importance. For then we would be in a position to say that in mercury we had a drug capable of controlling the growth of liver-cells in so far as by administering it we could at will produce their division and proliferation. While working out the answer to this question 1 simultaneously made an investigation into the nature and distribution of the pathological changes produced by mercury in most of the other organs, kidney, heart, spleen, intestine, etc. Particular attention has been paid to the earliest phases of degeneration. For example, a special endeavour was made to define the relation between the various kinds of granules which appear in the cells of the kidney when that org- :an is subjected to intoxication - the granules of ordinary cloudy swelling, the mitochondrial granules and those of fatty degeneration. Such an investigation is timely, for as Lorrain Smith states - "It is clear that the interrelations of the granules which appear in degenerative conditions of the protoplasm, to each other, and to the normal structure, must be Lt he subject of much more investigation before we can reach a conception of their relation to those changes in metabolism from which degeneration results." Further, wherever phenomena have been encountered involving fundamental pathological principles an attempt has been made to interpret the phenomena observed with a view to increasing our knowledge of these principles. This is .exemplified in the case of certain changes in the spleen. As a result, moreover, of observations made in the earlier stages of the research my attention was ultimately directed to certain alterations produced by mercury in the amount of fat in the circulating blood. The findings hereafter recorded in this connection constitute, perhaps, the most interesting of my contributions to the pathology of mercurial intoxication. I have discussed the etiology of these changes in blood-fat so far as is possible and have indicated lines along which further research may with advantage be directed. Corrosive sublimate, being one of the best known mercurial compounds and one of the easiest to administer, was chosen as the drug whose effects were to be investigated