urea secreted in twenty-four hours, 0.5 grammes of uric acid are on an average discharged in the same period. Whether the fluctuations in the quantities of both are parallel or not, has yet to be ascertained. In disease this seems to be the

case, as will presently be shown.

Pathological changes in the quantity of Uric Acid discharged during twenty-four hours.

As a question clearly put is half the answer, we may be permitted here to consider what proximate conditions of the system a rise or fall in the quantity of uric acid beyond the normal limits is likely to indicate. A deficiency may be due to a diminished production in the system, as in anæmia, or to retention, as in certain stages of gout and rheumatism. It is at least questionable whether the retention is always due to diseased action of the kidney. Any disease, however, which interferes with the secreting power of the kidney by changing its structure, such as Bright's disease, is certain to cause retention of uric acid in the blood, in proportion to the retention of the other constituents of urine. (Scarlatina seems to make an exception. I have certainly found that, in some cases of this disease, where uric acid is frequently present in excess from the beginning, so as to be precipitated in a cloud by the addition of an acid, the amount of uric acid does not decrease parallel to the fall of urea, when, with albuminous urine, dropsy appears; but it seems to be the normal amount, nay even more, at a time when the amount of urea is about half the normal average. Hundreds of observations will, however, be necessary to establish whether such a process is the rule or the exception.)

An excess of uric acid may be due to excessive production in the body, particularly when the increased excretion lasts for a certain time. It may, however, be owing to the discharge of accumulated uric acid, after retention in the blood. In both cases, the symptoms accompanying or preceding the excessive excretion must be our guides in distinguishing between these conditions.

As a general rule, i. e., one liable to exceptions, it may be assumed that an excessive production of uric acid accompanies an excess in the production of urea. In inflammatory diseases, fever, and certain other zymotic diseases, an increased amount of uric acid is met with. The observations, however,

'Med.-Chir. Transact.,' vol. xxx, p. 186.

require to be reduced to figures, and repeated with special regard to time.1

The following observations of Becquerel are entitled to attention, as referring to the total quantities of uric acid discharged in twenty-four hours:

occur.

Deposits of Uric Acid and Urates.

The physical properties of deposits of uric acid and urates having been already described, I will now offer a few remarks on the circumstances and the conditions under which they As the deposits of urates are much more common than all other urinary deposits taken together, it is of particular importance to define their value as a pathological indication. This I shall attempt at the conclusion of this paragraph.

Uric acid itself is not soluble in the blood, at least not more than in water; it is only so in combination with a base -ammonia, soda, or lime. Uric acid, when occurring in the blood, is always met with as urate of soda or urate of ammonia. As venous blood is used for the examination (or mixed blood, if taken by cupping), the urate must have been an acid one, since the free carbonic acid, at the temperature of the body or at that of the common air, would not permit any neutral urate to exist, but would withdraw one equivalent of base. In venous blood, therefore, the urate must always be an acid one; and this is important to bear in mind. The question now arises whether the urate must also be an acid one in arterial blood; whether there is a sufficient amount of carbonic acid still present in arterial blood to keep the urate acid; or whether this cause of its acidity no longer exists in arterial blood, or, if present, is in any way neutralized by the presence of oxygen. Though it is not exactly ascertained how much of its carbonic acid the blood loses in its passage through the lungs, yet the data we possess are quite sufficient

From the omission of this attention, many of the analyses of Becquerel and L'Heritier are useless for our purposes.

to put the question at rest. Magendie1 found in 100 grammes of venous blood 0.078 grammes of carbonic acid, in 100 grammes of arterial blood 0.066 grammes of carbonic acid. The blood in becoming arterial had, therefore, lost only 154 per cent. of its carbonic acid. Considering the small amount of uric acid salts which, under normal circumstances, is at any time present in the blood, we are quite justified in the conclusion that the 0066 grammes of carbonic acid present in 100 grammes of arterial blood are sufficient to keep the urate acid. If it should be urged that there is some ammonia in the blood, which might make the urate neutral, I refer the objector to putrefying urine, in which, notwithstanding a large amount of free ammonia, the urates still remain acid. The urates, wherever we meet with them, are acid salts, and from the very property of the neutral urates to be converted into acid salts by the mere influence of carbonic acid, their occurrence in the economy is impossible. If, therefore, Vogel2 assumes that neutral urates may occur in the urine (and, as he believes, by the supervening of an acid in the urinary passages, may be transformed into acid salts, which being less soluble form a deposit), he thereby contracts a theoretical debt, which we are sorry to say he will never be able to pay.

Granting therefore that uric acid is already formed in the arterial blood on reaching the kidney; that it can only remain in solution as a urate, and that an acid one; and that after having passed the kidneys it still continues to be an acid urate; where, I ask, are now the difficulties surrounding the explanation of the secretion of uric acid in the form of urates?

Do we require such theories as that of Dr. Golding Bird, which begins with an impossibility, and, founded upon an opinion of Liebig, long since abandoned, is merely made for the purpose of explaining the acid reaction of urine by the formation of acid phosphates? But it is best to quote his words, which, at p. 84 of his fourth edition, are thus printed in italics:

"Uric acid, at the moment of separation from the blood, comes in contact with the double phosphate of soda and ammonia, derived from the food, forms urate of ammonia, evolving phosphoric acid, which thus produces the natural acid reaction of urine."

Of course, if uric acid itself is insoluble in the blood, and

Vide Gay-Lussac, Ann. de Chimie et de Physique,' 1844, t. ii. Also, F. C. Donders, Physiologie des Menschen,' Deutsch von F. W. Theile, 1856, vol. i, p. 369.

Loc. cit., p. 198. Lehmann has the same opinion.

is only kept dissolved as a urate, mostly the urate of soda, how can it be separated from the blood, except as a urate? And being secreted as a urate, how can it take ammonia from the supposed phosphate? I will even go further back and ask, how could the uric acid, even if it were free, and as such contained in the blood, remain so, if it were throughout the whole course of the circulation in contact with the very phosphate with whose ammonia it is to combine after separation from the blood? These questions I hand over to the further consideration of the reader. Dr. Bird continues"If the whole bulk of the urine be to the urate of ammonia formed, not less than about 2701 to 1, the secretion will, at the ordinary temperature of the air, remain clear; but if the bulk of fluid be less, an amorphous deposit of the urate will occur."

This is the simple expression of the fact, as we meet it every day, that urates are more soluble in warm than in cold water or urine. But whether they require about 2701 (Dr. Bird), or 2789 (Dr. B. Jones), or 1608 times (vide under urate of ammonia), or even less, namely, only 1100 to 1200 times (vide urate of soda), their amount of water or urine for solution at a temperature of 77° F. (25° C.) is a matter to be decided only by direct experiment.

The theory just quoted is incorrect in one more respect; namely, because it assumes that the common deposits of urates are made up of urate of ammonia only, since the fact is that they mostly are mixtures of the urates of ammonia, soda, and lime; the urate of soda having in almost all cases the decided preponderance.

The conclusion of Dr. G. Bird's "probable explanation of the mode in which uric acid exists in healthy urine," of which I have quoted two passages, is a reiteration of the theory of Liebig on the acid reaction of urine being produced by the solution of uric acid in the solution of the common or tribasic phosphate of soda, whereby urate of soda is formed on the one hand, and an acid phosphate on the other. The passage runs thus:

"On the other hand, if an excess of uric acid be separated by the kidneys, it will act on the phosphate of soda of the doublesalt, and hence, on cooling, the urine will deposit a crystalline sediment of acid sand, very probably mixed with amorphous urate of ammonia, the latter usually forming a layer above the crystals, which always sink to the bottom. of the vessel."

Here again we are met by the difficulty, that uric acid, being secreted in the soluble form of a urate, cannot act on

the phosphate of soda in the manner suggested. If the action were to take place in the blood, the phosphate could not remain acid, and therefore could exert no influence on the urate after secretion. But the most remarkable part of the matter is, that an explanation has been attempted of a fact which does not exist. If any one has ever seen uric acid fall down in any urine on mere cooling, as it does fall down from its artificial solution in the phosphate, he should not omit to publish the fact. I for one never have met with it, nor have any such facts been brought forward by the originator and propagator of that theory, nor by any one else, as far as I am aware. If uric acid is ever formed in that way, it must redissolve on restoring the temperature of the body to the urine. Thus Dr. Golding Bird has defeated his own theory, in unmistakeable words, in § 120, p. 122:

Diagnosis of uric acid deposits.-When heated in the urine, the uric acid deposit does not dissolve; the crystals merely become opaque. They generally become more distinct from the solution of the urate of ammonia, which is frequently mixed with them, and sometimes completely conceals them from view. Hence the best mode of discovering this deposit, is to warm the urine, when turbid from excess of urate of ammonia, in a watch-glass; the acid becomes visible at the bottom of the glass, as soon as the urate dissolves."

Thus an imaginary fact, linked to reality by mere analogy to an artificial chemical process, has been the subject of explanations, which in improbability were only surpassed by what they were intended to explain, and which found their strongest contradiction in the very fact, the misconceived occurrence of which was the problem to be solved.

Deposits of Urates occurring after emission.

The deposits of mixed urates are so very common in the most varied conditions of health and disease, that it would be an endless and useless labour to name those conditions. The attempt to define the characters of urine depositing urates must be futile, because there is almost no description of urine that may not deposit them. Whether acid or alkaline, of high or of low specific gravity, containing much or little urea and colouring matter, urine will, under certain circumstances, deposit urates. Whether occurring in the system (bladder), or out of the body after emission, the conditions of the deposit are identical; there is not a sufficient quantity of water present to hold all the urates in solution at a certain By losing water.- Thudichum.