Ammonia mechanism: an experimental study of the part played by ammonia, fixed base and phosphate in the elimination of acid from the body

Abstract

Being convinced that dietary influences have been a prolific source of confusion in the past, decided to use fasting subjects. we had also come to the conclusion that the role played by fixed base in the neutralisation of acid can be more accurately studied, if some acid other than hydrochloric acid is used. v'e chose sulphuric acid. In choosing maximum dose we were guided by the normal daily acid production in fasting cats - our experimental subjects. This also corresponds to the magnitude of the excess acid production in phorhizinized dogs and cats. Vie did not wish to get too far away from the rate at which acid may be formed in the tissues spontaneously, so that our results may be expected to have more bearing on the fate of acid produced under natural conditions than is the case with some previous work.

ACID PER OS.: Sulphuric acid was given from 30 c.c. to 125 c.c. per kilogram weight in single doses to starving cats. About 8O% of the total amount of the acid given was recovered from urine as sulphate. It was found that ammonia neutralised about 60%; of the acid given by the mouth and subsequently recovered from the urine, or 50% of the total amount given. This figure for ammonia is very much higher,. than (20 or 30%) had been observed in experiments performed on animals that had been fed during the experiments.

Varying proportions of the acid were neutralised by fixed base. Taking the extreme case noted by us, the amount of fixed base lost is 55 c.c. of 0.1N base in a cat of 2.55kg. weight. This corresponds to a loss equivalent to 6.7 volume per cent carbon- dioxide, - a small fraction of the normal range of variation in the bicarbonate content of plasma. If acid feeding deprives the body of fixed base at all, it draws only on a supply which is not particularly needed and which is, therefore, not tenaciously retained.

No appreciable change in phosphate excretion was noted in any of the experiments.

PARENTERAL ADMINISTRATION OF ACID. INTRAVENOUS INJECTION.

Approximately the same dose of sulphuric acid was given as per Os. To approximate the rate of absorption when acid is given by mouth, the acid was given at from about 0.015 c.c. per kilogram per minute to about 0.09 c.c.. per kilogram per minute. It was noted that little or no increase in ammonia took place, and that a sufficient rise in residual fixed base excretion occurred to account for all the acid injected. But in every experiment profound secondary changes occurred, chief among which. were haemolysis interfering with the action of the kidney and hyperpnoea. The latter alone would explain the apparent absence of ammonia production; over -ventilation evidently setting free more than enough fixed base to neutralise the acid, so that ammonia production was rendered unnecessary. ' "'e were forced to the conclusion that this method of parent - eral introduction of acid defeated the object we had in view, i.e. to see whether acid entering the systemic circulation directly is neutralised by ammonia at all. Such neutralisation had been denied by Keeton. We therefore tried parenteral administration under less severe conditions, i.e. Subcutaneously, and it served the purpose well.

100 per cent. of the acid when administered by this route was recovered from the urine. Increased ammonia production neutralised about 40% of the acid. This average is based on two experiments only, while the average for alimentary route administration is based on a very much larger number of experiments, and we are not sure the causes of the peculiar results of intravenous injections are wholly absent here.

No increase in phosphate excretion in urine was noticed in response also to the parenteral administration of acid.