564 ABNORMALITIES IN METABOLISM 



acidosis as determined by examination of the blood, and severe acidosis 

 may occur with Uttle or no acetonuria. 



Furthermore, we may have high urinary ammonia not only be- 

 cause of excretion of diacetic and oxybutyric acids as in diabetic 

 acidosis, but also from excretion of excessive quantities of lactic acid, 

 as in puerperal eclampsia, pernicious vomiting of pregnancy, acute 

 yellow atrophy, and other conditions associated with severe injury to 

 the liver. As high ammonia excretion is characteristic of diabetic 

 acidosis, the presence either of acetone bodies or high urinary 

 ammonia was formerly considered to indicate the existence of acidosis, 

 but it is now recognized that as a general rule there is not a severe 

 acidosis in these hepatic diseases, the intoxication being dependent 

 on neither lactic acid nor acidosis, but upon poisons of unknown 

 character. This group of diseases has been considered in previous 

 pages. Because of its significance as one of the chief organic acids 

 formed in metabolism, rather than as a cause of serious acidosis, we 

 may in this chapter briefly consider lactic acid and its relation to 

 disease. 



Sarcolactic Acid often is found in the urine, but in origin and significance it is 

 entirely different from the acetone bodies, and it probably is never present in 

 sufficient amounts to cause an acid intoxication by abstraction of alkalies from the 

 blood. In vitro, we obtain sarcolactic acid whenever sugar is placed in an alkaline 

 solution, provided the siipply of oxygen to the solution is deficient; but if the oxygen 

 supply is adequate, sugar will not yield lactic acid with alkalies (Nef). Similarlj', 

 an isolated surviving muscle, when asphyxiated by any means, shows a rapid ac- 

 cumulation of lactic acid, which fails to occur when sufficient oxygen is supplied. 

 This lactic acid comes chiefly from sugar, but about 25 to 30 per cent, of it can have 

 its origin in protein (or fat?) (Woodyatt). If an organism as a whole is insuffi- 

 ciently supplied with oxygen, lactic acid accumulates in the tissues and appears 

 in the urine, disappearing when the oxygen supply is restored. Lactic acid often 

 appears after poisoning with a large number of drugs, which Loewy has classified 

 as drugs whose action in the body resembles that of lack of oxygen (arsenic, phos- 

 phorus, hydrazine, chloroform, etc.). These poisons are all characterized by 

 causing impoverishment of glycogen, fatty liver, and acute degenerative changes 

 especially in the liver cells and the endothelium. Therefore the assumption seems 

 justified that the poisons and conditions which lead to lactic acid excretion depend 

 ultimately upon impairment of the interchange of oxygen in the cells. Wood- 

 yatt states that, as far as known, lactic acid has never been demonstrated in any 

 tissue in which deficient oxygenation can be excluded, and regaids lactic acid as 

 the metabolite of asphyxia or its equivalent. Over against this view is that of 

 Embden and his associates, which is shared by others, that lactic acid is a normal 

 intermediary in the breakdown of the sugars in the bodj^ its direct anteceilent 

 being a triose, but perusal of their work only emphasizes that in all the conditions 

 in which their data were obtained asphyxial conditions were present; furtliennore, 

 this conception of lactic acid as a chief intermediate in normal sugar cataluilism 

 is not in liarmony with the best ideas of carbohydrate cliemistry (\\'oodyatt). 

 This avitlior lias furthermore found, by direct observation of tlie utilization of 

 lactic acid when injected intravenously, that it cannot well bo an important inter- 

 mediate in carbohydrate catabolism.*" (See also discussion of lactic acid under 

 Diabetes, Chapter xxiv). 



It is possible that the presence of lactic acid in the \irine may also result from 

 d(!fective transformation of ammonia into urea by a diseased liver, tlie acid neu- 

 tralizing, and being excreted with, the ammonia; in this case no defective oxida- 

 tion need be assumed. However, administration of phlorhizin to phosphorus 



'" Harvey Society Lectures, 1916. 



