556 PHYSIOLOGICAL CHEMISTRY 



Interpretation. Normal adults on a mixed diet excrete on the 

 average 3-15 mg. of combined acetone and acetoacetic acid per day 

 and anything over 20 mg. is usually pathological. Usually about one- 

 fourth of this total is acetone although the proportion varies consid- 

 erably. The amount is considerably increased in pasting and on a 

 carbohydrate-free diet due to the development of acidosis. In severe 

 diabetic acidosis values up to 6 grams per day or even higher may be 

 noted. It is sometimes found in large amounts in intoxications asso- 

 ciated with pregnancy. It may be found in increased amounts in the 

 urine in a great variety of pathological conditions. Quantative estima- 

 tion enables us to follow the course of the acidosis. Ammonia excre- 

 tion is also largely increased in these conditions, being used in the 

 neutralization of the excess acids formed in the body. Usually about 

 three-quarters of the combined acetone and acetoacetic acid excretion 

 is in the form of acetoacetic acid, but the proportion is not constant. 



j8-hydroxybutyric acid may occur in normal human urine to the 

 extent of 20-30 mg. per day. In fasting or on a carbohydrate-free 

 diet very large amounts may be excreted (up to 20 grams per day). 

 In severe diabetes mellitus the largest amounts are found, and excre- 

 tions of 50 or even 100 grams or over per day have been noted. In 

 this condition it is usually the most abundant of the acetone bodies 

 making up from 60-80 per cent of the total. The ratio is, however, 

 by no means constant and it should be borne in mind that in rare cases 

 large amounts of 0-hydroxybutyric acid may be eliminated although 

 the acetone excretion is very low. It is always present in the urine 

 when large amounts of acetone are present. 



Acidosis is due mainly to a disturbance in the metabolism of fats. 

 The fatty acids are ordinarily oxidized to acetoacetic acid, which is 

 either oxidized through formic and acetic acids to carbon dioxide 

 and water, or by reduction forms j8-hydroxy butyric acid. When fat 

 catabolism is increased to such an extent that the body cannot bring 

 about complete oxidation of the products formed, a considerable por 

 tion of the acetoacetic acid instead of being oxidized in this way is 

 transformed into acetone and in more severe cases into /3-hydroxybuty- 

 ric acid which will then be eliminated to varying degrees in the urine. 



The relation of the acetone bodies is indicated in the following 

 scheme. 



... loss of CO2 



CH 3 -CO.CH 2 -COOH > CH 3 .CO.CH 3 



(Acetoacetic acid.) (Acetone.) 



* by reduction 



CH 3 - CHOH - CH 2 - COOH 



(/3-hydr xybutyric acid) 



