DIABETIC COMA 551 



The study of tlif utilization of X\ni acidosis suljstaiici's wlicu injected 

 intravenously at accurately measured rates for considerable periods 

 by AVilder,-"'' furnishes conclusive evidence of the origin of /3-oxy- 

 butyric acid from acetoacetic acid. He found that normal dogs ex- 

 crete ^-oxybutyric acid when it is injected at the rate of 0.4 gm. 

 C 0.0032 gm. molecule) of the sodium salt per kilo of body weight per 

 hour, but not with lower rates. Sodium acetoacetate was excreted 

 when injected in rates of 0.2 gm. (0.0016 gm. molecule) per kilo per 

 hour, and when injected at the 0.4 gm. rate it was excreted accom- 

 panied by )8-oxybutyric acid. Evidently, then, the acetoacetic acid 

 must be converted almost quantitatively into /8-oxybutyric acid. On 

 the other hand, acetoacetic acid did not appear in the urine when 

 larger quantities of /S-oxybutyric acid were injected, and hence it is 

 apparent that not much if any urinary acetoacetic acid is derived from 

 this source. 



As long as a diabetic is burning at least one molecule of carbohydrate 

 to three of higher fatty acids the urine is free from both acids, although 

 small amounts of actone (traces of which— under 0.02 gm. per day 

 — occur in normal urine) -^ may be present; but when for any reason 

 the daily oxidation of carbohydrates falls below this minimum the 

 two acids appear, combined largely with ammonia, but partly with 

 mineral bases. Fats burn in the fire of the carbohydrates and as Wood- 

 yatt ^^* puts it, when the proportion of fat is too great for the fire 

 it "smokes" with unburnt fats and acetone bodies. Normally but 2 

 to 5 per cent, of the nitrogen of the urine is in the form of ammonia, 

 but in diabetic acidosis the proportion may reach from 10 to 25 per 

 cent., the proportion of urea being correspondingly reduced.-^ 



The presence of large quantities of these acids in the urine presages 

 coma, during which the amount of oxybutyric acid often reached 15-20 

 grams per day, and has been known to reach 150 grams (Kiilz claimed 

 to have found 226 grams). Diacetic acid appears in relatively small 

 amounts, rarely exceeding 10 per cent, of the total organic acids of 

 the urine. When oxybutyric acid is present the other two substances 

 are always present,^" but aceto-acetic acid and acetone are said by 

 some to occur in the absence of /^-oxybutyric acid. According to 

 certain observers, in the development of acetonuria, acetone is the 

 first of the three bodies to appear ; ^^ when 0.4 te 0.5 gm. of acetone is 



27b Jour. Biol. Chem., 1917 (.30). 



28 Concernino: normal occurrence of acetone in lilood and tissues, see Halporn 

 and Landau, Zeit. exp. Path, u Ther., 1906 (3), 4t)0. 



2SaJour. Amer. Med. Assoc., 1916 (66). 1910. 



29 According to Y.die and Whitley (biochemical -Tour.. 1906 (1), 11). ad- 

 ministration of excessive amounts of alkali causes, conversely, elimination of 

 increased amounts of organic acids. 



30 See Pavy, Lancet, 1902 (ii). 64 et se</. (general review). 



31 Folin says tiiat perfectly fresh diabetic urine does not contain anv acetone, 

 that which is commonly found being derived from diacetic acid which rapidly 

 decomposes into acetone. 



