562 ABNORMALITIES IN METABOLISM 



man. According to Rhamy^* acetone is more toxic (for guinea-pigs) 

 than methyl alcohol, while for rabbits Desgrez and Saggio^^ found 

 acetone the least toxic of the acetone bodies, diacetic acid next, and 

 j8-oxybutyric acid most. Ehrmann'^ also claims that he has pro- 

 duced typical coma with the sodium salts of butyric and of /3-oxybuty- 

 ric acid, but as high as 40 grams of /3-oxybutyric acid have been found 

 in the day's urine of a non-diabetic without any evidence of intoxica- 

 tion. Ewing suggests that the acetone bodies may cause renal 

 injury, which is usually evident in acidosis, and M. H. Fischer's 

 views on the relation of acids to nephritis accord with this fact. The 

 withdrawal of the inorganic bases, especially Ca and Mg, may also 

 be responsible for symptoms, as it is well established that a proper 

 balancing of these ions is necessary for normal cell activity, especially 

 in the nervous system.''^ 



Hurtley^^ sums up the evidence on the toxicity of the acetone 

 bodies by saying that aceto-acetic acid seems to be highly toxic only 

 in depancreatized animals, while oxybutyric acid is practically non- 

 toxic. He favors the view that aceto-acetic acid poisoning is respon- 

 sible for diabetic coma, for it increases in the urine on the approach 

 of coma, and the ratio of aceto-acetic to butyric acid in the urine in- 

 creases with the severity of the intoxication. The increased propor- 

 tion of aceto-acetic acid presumably means that it is being produced 

 in such quantities throughout the body that the liver cannot reduce 

 as large a proportion to oxybutyric acid as it normally does. In con- 

 sidering the possibility that the acetone bodies may be responsible for 

 at least part of the intoxication of diabetic coma we must bear in 

 mind that the evidence of their low toxicity is based on short time 

 experimental intoxications, and that they may be found to be much 

 more toxic than is generally assumed when they are allowed to act 

 for many days and weeks on the nervous tissues, as thej' do in dia- 

 betes. That is, the experimental evidence concerning the toxicitj' of 

 the acetone bodies has not been obtained under conditions comparable 

 to those of diabetic acidosis. 



Origin of the Acetone Bodies. — The chemical nature of the ace- 

 tone bodies is such that they might readily be produced from any or 

 all of the three classes of foodstuffs. 



They might be derived from carbohydrates, as is the closely related lactic acid, 

 but we know that this it not the usual source. On the contrary, administration of 

 a proper amount of carbohydrates under certain conditions may cause tlie acids 

 to disappear from the urine, and acetone bodies may be cHminated in large quan- 

 tities while the patient is on a diet ahnost free from carbohydrates. Carbohy- 

 drates are, indeed, the most active agents in preventing the formation of these 

 ketone bodies, i. e., they are antiketogenic.''* 



" Jour. Amer. Med. Assoc, 1912 (58), 628. 

 '8 Compt. Rend. Soc. Biol., 1907 (63), 288. 

 " Berl. klin. Woch., 1913 (50), 11. 

 "See Cammidge, Amer. Med., 1916 (11), 363. 



" Concerning antiketogencsis see Woodyatt, Jour. Amer. Med. Assoc, 1910 

 55), 2109. 



