THE DEVELOPMENT OF ACID-BASE CONTROL 



E. M. WiDDOWSON and R. A. McCance 



Medical Research Council, Department of Experimental Medicine, 

 University of Cambridge 



General Principles (as they apply to adults) 



When the body of a healthy person is provided with the 

 diet normally eaten in Europe and the United States, it 

 produces in its metabolism more non-volatile anions than 

 cations. These "surplus anions" are excreted by the kidney 

 partly in combination with titratable hydrogen ions (the 

 titratable acidity) and partly as ammonium salts. The 

 ammonium salts usually account for rather more than 50 per 

 cent of the total. If the excess of non-volatile anions increases, 

 the pH of the urine falls and the titratable acidity increases, 

 but the excretion of ammonia also increases because a fall in 

 the pH of the urine is one of the things which raises the output 

 of ammonia ; and consequently the percentage of the surplus 

 anions excreted as ammonium salts remains about the same. 

 The excretion of ammonium salts is also increased (a) if the 

 pH of the urine is maintained at its lower limits for some 

 time by the continuous administration of acid or acid-forming 

 drugs. This is thought to be due to an increase in the activity 

 of the enzymes in the kidney which catalyse the formation of 

 ammonia and particularly of glutaminase (Davies and 

 Yudkin, 1952). (b) By an increase in the acid "load" (Rector, 

 Seldin and Copenhaver, 1955). Both (a) and (b) increase the 

 percentage of the surplus anions excreted as ammonium 

 salts, and good examples of the effects which may be observed 

 after continuous high dosage are given by Ryberg (1948). 

 As the pH of the urine rises progressively above 6-5 the 

 percentage of the total output of surplus non-volatile anions 

 excreted as ammonium salts may also rise and ultimately 



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