458 CALCIFICATION, CONCRETIONS, AND INCRUSTATIONS 



of the liver that will alter bile compositon in such a way that its capac- 

 ity to sustain cholesterol in solution or suspension will be lowered, ^"^ 

 and this factor also cannot be dismissed as without importance; tran- 

 sient thickening of the bile, such as may occur in any febrile disease, 

 may also very possibly initiate precipitation and stone formation. 

 More and more this last factor is receiving consideration, together with 

 hypercholesterolemia, as of importance in producing cholelithiasis. 

 Rovsing,^^ quoting Boysen's analysis of 200 autopsy cases of choleli- 

 thiasis, which showed that all recent deposits and the centers of older 

 concretions consisted of calcium-pigment, especially emphasizes this 

 transitory concentration of bile. 



It was formerly supposed that the calcium-pigment concretions 

 were produced by the presence of excessive calcium in the bile, derived 

 particularly from lime-laden drinking-water, but it has been demon- 

 strated that increase of calcium in the food does not cause an increase 

 in the amount in the bile. Furthermore, on concentrating bile, 

 which contains both bilirubin and calcium, the free bilirubin separates 

 out and not the calcium compound of bihrubin; and also, Naunyn 

 found that the bile salts prevent precipitation of calcium-bilirubin, 

 even when calcium salts are added in considerable amounts. Appar- 

 ently it is the presence of positively charged protein substances that 

 leads to the precipitation of this electro-negative substance from bile, 

 and hence the formation of pigment calculi is also favored or initiated 

 by inflammation of the bile tracts, particularly as most of the calcium 

 salts seem to come from the mucous membrane ;^'^ later, as we have seen, 

 these pigment concretions often become covered with cholesterol 

 derived from the injured epithelium, and the common mixed calculi 

 are then formed. In view of the fact that much of the pigment in these 

 calculi is composed of the oxidation products of bilirubin, especially 

 bilihumin, it is possible that oxidation processes in the stagnating 

 bile are important causes of the precipitation; Naunyn suggests that 

 bacteria may be the cause of the oxidation. Pigment calculi are par- 

 ticularly important as the starting-point of the larger mixed calculi. 

 Aufrecht,^^ indeed, holds that gall-stone formation usually begins with 

 particles of pigment that are expelled from the liver cells as such, 

 and ordinarily are discharged into the intestine; if they make their 

 way back into the gall-bladder they form the nuclei of concretions. 

 It is possible, Naunyn believes, for the pigment to be later gradually 

 replaced by cholesterol. 



"^ See D'Amato, Biochcm. Zoit., 191.'5 (G9), 353. 



'•^ Hospitalstidende, 1915 (5S), 249. 



"" This commonly-held view is denied by Liehtwitz and Book (Dent. med. 

 Woch., 1915 (41), 1215), who fonnd the calcium content of bile from fistnlns to 

 be from 65-84 mg. per liter, and in bladder l)ile to vary from 85 to 325 mg., but 

 not according to the presence or absence of inflammation. 



»' Deut. Arch. klin. Med., 1919 (128), 242. 



