OBSERVATIONS ON SOME CAUSES OF GALL STONE FORMATION : III. THE RELATION OF THE REACTION OF THE BILE TO EXPERIMENTAL CHOLELITHIASIS.
As previous papers from our laboratory have shown, there exists a well defined tendency for calcium carbonate to come out of solution in the normal liver bile of the dog, and for it to be deposited on certain nuclei not infrequent in the secretion under pathological circumstances. Gall stones that had arisen in this fashion were a frequent occurrence in the intubated animals we studied. The present paper is concerned with the reasons for the absence of such stones from dogs with an intact biliary tract. The solubility of calcium carbonate is known to be markedly affected by the reaction of the fluid in which it is contained. The normal liver bile, out of which it tends to precipitate, is alkaline, with an average pH of 8.20 but in the gall bladder where conditions might otherwise seem especially favorable to precipitation, the secretion undergoes a change toward the acid side, becoming on long sojourn there, strongly acid to litmus (pH 5.18 to 6.00). From bile as thus altered, no carbonate precipitation takes place, even when it becomes greatly concentrated as in fasting animals or after obstruction of the common duct. Furthermore, carbonate which has precipitated out of liver bile on standing dissolves again in it when the fluid is rendered slightly acid in vitro, or, in some cases merely neutral to litmus. There are several obvious reasons for the absence of carbonate stones from the normal ducts under ordinary conditions,-notably the motility of these latter, the flushing that they undergo from an intermittently quickened bile stream, and the cleansing and possibly antagonistic action of the secretion elaborated by the duct mucosa. In the fasting animal, one at least of these influences is almost done away with, the rate of bile flow is so greatly cut down; while furthermore the calcium concentration of the secretion undergoes a considerable increase. But pari passu with these changes there occurs one in the bile reaction, a diminution in alkalinity so great that the pH often approximates that of the neutral point for litmus. That this change is not a direct consequence of the increase in calcium, may be inferred from the findings with stasis bile, the calcium content and reaction of which were observed to vary independently, if in general in the same direction. These adjustments within the organism, some of which may be thought to exhibit an element of the purposeful, when considered with the test-tube experiments, strongly suggest that the reaction of the bile plays a critical part in determining the occurrence of carbonate stones, as furthermore that their absence from the normal gall bladder is a consequence of the changes in the bile reaction there occurring. The changes come about through a functional activity of the bladder. This being the case, one might suppose that the failure to act would be followed by a formation of carbonate stones. There is sufficient evidence available in the literature to indicate that this happens, in rabbits at least. It is important to know whether changes in the bile reaction play any part in determining the cholelithiasis of man. To determine the matter will require a large material. But this much we have shown, that carbonate spheroliths not infrequently serve in human beings as centers in a formation of secondary stones of carbonate and cholesterol, as further that cholesterol precipitation out of human bladder bile can be induced or prevented by slightly altering the reaction of the fluid toward the alkaline and acid sides, respectively. The possibility that cholelithiasis may be a consequence of sins of omission on the part of the biliary channels and reservoir deserves to be considered.
Drury
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Laboratories of The Rockefeller Institute for Medical Research.
McMaster
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Rous
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