222 Discussion 



and finally whether this very large citrate output in the newborn shows 

 the same tremendous lability to acid-base effect as it does in the adult, 

 in whom it can be reduced by quite small doses of acid or increased by 

 alkalinization, say by sodium bicarbonate. 



Widdowson: We have not yet given an acid load to newborn babies, 

 although we should like to do so, but the experiment has been done on 

 puppies. The question about citrate is one for the future. We have so far 

 only studied three babies and this investigation is by no means complete. 



McCance: The puppies have only been studied with respect to acute 

 acidosis (Cort, J. H., and McCance, R. A. (1954). J. Physiol, 124, 358). 

 The difficulty in an animal which is developing very rapidly is to separate 

 the effects of several days' administration of an acid-forming drug and 

 the natural development of the animal at that age. In the acute experi- 

 ments the puppies were very defective in their ability to produce am- 

 monia and they did not make a good response at all. They remained much 

 more acid internally. We have unfortunately not yet tried the effect of 

 altering the pH of the urine upon the excretion of citrates in the newborn 

 baby. 



Scribner : We carried out some experiments in rats which seem to indi- 

 cate that the amount of citrate in the urine depends on the kidney tissue 

 level of citrate rather than on the blood citrate level. After intra- 

 peritoneal injection of either sodium or potassium bicarbonate, urinary 

 citrate increases 10- to 20-fold in one to two hours. Kidney tissue citrate 

 increases two to threefold. Blood citrate rises 10 per cent at most. The 

 response to intraperitoneal injection of citrate is quite different. We 

 used ammonium citrate to get away from changes in acid-base balance, 

 due to, say, injection of citric acid on the one hand or sodium citrate on 

 the other. After the injection of 0-0035 m-mole/kg. ammonium citrate 

 the blood level rises nearly 100 per cent, but there is little or no increase 

 in either kidney tissue citrate or urinary citrate. We concluded from 

 these experiments that the level of citrate in the urine under these 

 conditions is determined by the citrate level in the renal tubular cell and 

 is independent of the amount of citrate filtered through the glomerulus. 



McCance : Dr. Milne, what determines the lower limits of pH which 

 the human and other kidneys can achieve? 



Milne: I think this can only be answered conditionally. First, one 

 must state the stimulus, and secondly one must state the conditions of 

 the kidney at that moment. Ammonium chloride has been used as the 

 usual stimulus and I think no-one has ever produced a pH of human 

 urine below 4 • 4 by that method, but other stimuli seem able to produce 

 a considerably lower pH. The experiments of Schwartz, Jenson and 

 Relman (1955. J. din. Invest., 34, 673) showed this, where they infused 

 sodium sulphate in a sodium-depleted individual. There, quite clearly, 

 they got down to a urinary pH of 4 0, so that is a more effective stimu- 

 lus, and indeed this agrees in the rat. It is very difficult to produce 

 a highly acid urine in rats by most experiments. When it is given 

 ammonium chloride the rat seems to be able to keep up with the am- 

 monium intake and puts out ammonium chloride in its urine almost as 

 quickly as it is either injected or taken in the drinking water. But an 



