Acidosis 



DONALD D. VAN SLYKE 



NEW YORK 



Historical 



The experimental foundation of our knowledge of acid intoxication 

 was laid by Walter (1877) who fed rabbits varying amounts of hydro- 

 chloric and other acids by stomach tube and observed the effects. He 

 found that "the CO 2 content of the blood is essentially proportional to 

 its alkali content" and that it was reduced to an extent proportional 

 to the amount of HC1 administered. Ingestion of 1 gram of HC1 

 per kilo reduced the CO 2 content of the blood from 27 volumes per cent 

 to 2.5 and resulted in death. The most obvious physiological effects were 

 rapid pulse and hyperpnea. About 15 minutes before death, breathing 

 and pulse slackened, and the animals collapsed. Even at this stage they 

 could be restored by intravenous injection of 0.5 gram of sodium bicar- 

 bonate. Dogs could not be killed by similar doses of acid, and Walter 

 showed that their immunity was due to their power to form ammonia in 

 amounts sufficient to neutralize the acid. 



Stadelmann(a.) (1883) made the clinical application of these observa- 

 tions. He noted that "the symptom complex of diabetic coma greatly re- 

 sembles that of acid intoxication, as revealed by the work of Walter." Of 

 these symptoms the "fearful terminal dyspnea" of diabetic coma vividly de- 

 scribed by Kussmaul (1874) was most striking. It was also known, from 

 work of Hallevoorden, that ammonia excretion is increased in diabetes. 

 Stadelmann was led by these facts to look for proof of acid intoxication 

 in diabetics, and discovered that large amounts of organic acid are ex- 

 creted by patients in or near coma. He accordingly proposed bicarbonate 

 administration as the logically indicated treatment. 



The chief organic acid was identified, by work begun by Stadelmann 

 and completed by Minkowski(a) (1884), as beta-hydroxybutyric acid. 1 



1 Formation of beta-hydroxybutyric acid is always accompanied by formation of 

 smaller amounts of acetoacetic acid, which represents one further step in oxidation. 

 CH a .CH(OH) .CH 2 .COOH + O = CH 8 . CO . CH a . COOH 



beta-hydroxybutyric acetoacetic 



Acetoacetic acid in solution spontaneously undergoes decomposition, gradual at 

 body temperature, into acetone and carbon dioxid, so that acetone is always found 



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