492 PATHOLOGICAL PIGMENTATION 



when this proportion is exceeded the pigment begins to be deposited 

 in the skin and excreted by the kidneys (v. d. Bergh), However, 

 Blankenhorn believes that at times the bihrubin in the plasma is so 

 bound that the kidneys do not excrete it, and yet it may be able to 

 diffuse into the skin.'*^ AVith reduced renal function the amount of 

 pigment in the blood may be increased without hepatic chsease. 



King and Stewart'*^ state that the amount of pigment in a lethal 

 dose of whole bile will cause death, but the bile salts present in the 

 same quantity of bile will not cause recognizable effects; uncombined 

 pigment is more toxic than its calcium or magnesium salts. Bile from 

 which the pigment is removed has very little toxicity. They suggest 

 that calcium is increased in the blood in icterus as a protection against 

 the toxic effects of the pigments. The combining of the calcium with 

 bile pigment, however, renders it unavailable for fibrin formation, and 

 this seems to be an important factor in the hemophilic tendency of 

 icterus,'** and Pettibone records a marked decrease in blood calcium 

 in protracted jaundice.*^ The decrease in available calcium may also 

 be responsible for the bradycardia and some of the mental and nervous 

 symptoms. 



Bile salts are said to be toxic, generally producing depression 

 of the central nervous system, with resulting coma and paralysis; 

 they are also decidedly toxic to cells of all sorts, causing hemolysis and 

 marked destruction of tissue-cells. Small quantities of bile salts 

 stimulate the central end of the vagus, and large amounts influence 

 the heart itself; hence in icterus we observe a slowing, and often an 

 irregularity, of the pulse, and the blood pressure is lowered. Al- 

 though there has been much dispute as to whether the chief effects of 

 icterus upon the heart depend upon action of the bile salts upon the 

 vagus, or upon the intracardiac ganglia, or upon the muscle itself,"'*' 

 yet Weintraud demonstrated that in some cases of icterus administra- 

 tion of atropin, which paralyzes the vagus, stops the bradycardia, 

 indicating the importance of the effects of the bile salts upon the 

 vagus in causing this feature of cholemia. According to Meltzer and 

 Salant,*''' bile also contains a tetanic element which disajipears from 

 stagnating bile; the bile salts contain this tetanizing agent in less 

 amount than does the whole bile. But King'** and others ascribe most 

 of the effects of bile on the heart to the bile pigments, perhaps through 

 abstraction of the calcium. Taurin given in 10 gm. and even larger 



" Corroborated by Meulengracht (Ugesk. f. Laeger., 1919 (SI), 1785) who states 

 that when bilirubin reaches a certain concentration it passes into the tissues, but 

 not into the urine until a higher concentration is readied. 



" Jour. Exi)er. Med., 1909 (11), 07:i 



*" See Lee and Vincent, Arch. Int. Med., 1915 (16), 59. 



^i" Jour. Lab. Clin. Med., 191S (3), 275. 



" See Minkowski, Ergel). der Pathol., 1895 (2), 709. 



" Jour. Exp. Med., 1906 (8), 128; review and literature concerning toxicity of 

 bile. 



" Sec King, Bigelow and Pcarce, Jour. V]\\\n\ Med., 1912 (14), 159. 



