370 THE METABOLISM OF THE CARBOHYDRATES 



are deep and strong, in striking contrast to the muscular weakness 

 of the rest of the body. 



This coma is associated with the presence in the urine of 

 certain organic acids, especially of /3-oxy-butyric acid, CH 3 -CHOH- 

 CH 2 COOH, and its oxidation products, aceto-acetic acid, CH 3 -CO- 

 CH 2 COOH, and acetone, CH 3 -CO-CH 3 . These substances can 

 usually be detected in the urine in diabetes previous to the onset 

 of the coma, and during the coma they considerably increase in 

 amount. It has, not unfrequently, been noted that during the 

 comatous state the breath smells of acetone, and further, that when 

 this state supervenes, the amount of acetone in the urine becomes 

 less, while that of its precursors, /3-oxy-butryic acid and aceto- 

 acetic acid, becomes greater. 



These facts would seem to indicate that the coma is due to an 

 excess, either of acetone or of the acids in the organism. 



The smell of acetone on the breath has been taken to point to 

 an intoxication by this substance as the cause of the condition. 

 Such a view would seem to be substantiated by the fact that when 

 acetone is given to dogs in the dosage of 4 grm. per kg. body weight 

 intoxication symptoms follow, like those produced by ethyl alcohol, 

 and if this dose be doubled, death may result. A closer examina- 

 tion of this result, however, instead of proving the contention, at 

 once disproves it, for if 8 grm. per kg. be the minimal lethal dose, 

 then at least 500 grm. would require to be produced in a man of 70 

 kg. to cause death, and it is inconceivable how such could be the 

 case, especially since, in most cases, it would all have to be derived 

 from proteid and fat. 



Let us then consider whether the acids may not be the cause 

 of the intoxication. They increase in amount in the urine at the 

 expense of acetone, just before, and during the coma, and if 

 bicarbonate of soda be given by mouth to the patient, or if faintly 

 alkaline intravenous saline injections be made, still more of the 

 acids appears in the urine. Moreover, the condition of coma 

 seems to be frequently alleviated by the administration of alkali, 

 and there can be little doubt that, in many cases of diabetes, 

 attacks of coma can be warded off by the regular exhibition of 

 alkali. The alkali neutralises the excess of acid in the organism. 

 All these facts indicate an excess of acid in the tissues as the possible 

 cause of the coma. 



What, then, is the effect of excess of acid in the organism ? 



