So far as I can determine I am unable to satisfy myself that any constant relation, other than that mentioned, exists between the excretion of uric acid and urea. By testing samples of twenty-four hours' urine from day to day. it is quite possible to corroborate two of Dr. Haig's statements, however: (1) that exposure to cold causes a temporary diminution in the excretion of uric acid - which I attributed to an increased metabolism; (2) that salicylates cause a distinct and decided increase in the excretion of uric acid, even on a purin-free diet. This has been explained in various ways, notably by Walker Hall and Kellogg, the latter of whom asserts that, like all antiseptics, salicylates act as irritants, primarily on the intestinal mucous membrane, hence producing indigestion and absorption of imperfectly digested peptones, and secondarily on the tissue cells, reducing metabolic activity. Haig declares that they form a soluble compound with uric acid (salicyluric acid) and excrete stored-up or retained uric acid. This, however, has not been corroborated. A much more likely hypothesis is that, like alcohol, they inhibit the action of the uricolytic enzyme and so prevent the destruction or metabolism of uric acid. Minkowski admits the beneficial influence of the salicylates on gout and allied ailments, but attributes it to their analgesic properties and their power to promote perspiration.

2. According to Folin, "The volume of urine eliminated depends directly upon the amount of water consumed, and in no way has any constant relation to the loss of nitrogen. It is, indeed, largely a personal peculiarity, and to a great extent varies inversely in proportion to the amount given off by the skin." I have made frequent observation in my own case in the morning hours, when proportionately large quantities of uric acid are being expelled by the kidneys, and when, according to Haig, there should be a difficulty in passing urinary water. I have invariably found that a pint or a pint and a half of hot water swallowed at 6 a.m. is all excreted before 8 a.m., and this would not be the case if colloid uric acid blocked the capillaries of the kidneys.

3. There is room for considerable difference of opinion regarding the nature and causation of the acidity of the urine. The acid reaction is dependent on the acid products of metabolism formed by the combustion of such neutral substances as albumin and lecithin, the contained sulphur giving rise to sulphates and the phosphorus to phosphoric acid. Many other organic acids, such as oxalic acid, uric and hippuric acids, with aromatic oxy-acids are found in normal conditions, while in pathological conditions oxy-butyric and diacetic acids are also found. In any case the acidity is never due to free acid, but always to acid salts, the most common of which is acid sodium phosphate, and it unquestionably varies even in normal circumstances, because the organism is possessed of a regulating mechanism for keeping the acidity within certain limits.

The most important modifying factors are diet and digestion. The former is exemplified in herbivorous animals and vegetarians, where the reaction is alkaline because of the excess of alkaline salts of such organic acids as tartaric, citric, and malic, contained in the food. These are oxidised into carbonates, which determine the alkaline reaction. That this is due to the diet is manifest, because during starvation, where herbivorous animals are living on their own tissues, the reaction of the urine becomes acid. In carnivorous animals likewise, where the urine is normally acid, feeding on vegetables causes the urine to become neutral or alkaline.

During active digestion, on account of the formation of free acid in the stomach, the bases with which it has been combined are liberated in the blood, and passing into the urine, diminish its acidity, or mayhap render it alkaline, thus producing the alkaline tide, while an acid tide is to be noted during fasting conditions, e.g., several hours before breakfast. This is rather inconsistent with the dictum that the acidity of the urine varies inversely with the excretion of uric acid, because it is just in the early hours that Haig asserts the greatest quantity of uric acid is excreted.

It is, however, a moot point whether uric acid is ever excreted as such. We must remember the great insolubility of uric acid, and its tendency to form supersaturated solutions, as well as the much greater solubility of the acid urate of sodium. Camerer's observations in connection with this salt are of great interest. He mixed a saturated solution of acid urate of sodium, which showed an alkaline reaction, with a solution of acid phosphate of sodium. This solution of mixed salts was perfectly clear at 37° C. and displayed an acid reaction with litmus. By cooling the mixture the reaction became alkaline and uric acid was deposited, the acid phosphate of sodium (NaH2PO4) having attracted the soda from the urate salt, forming disodium phosphate (Na2HPO4), and thus setting free the uric acid in a crystalline form. Heating the solution again restores the original acid mixture of salts. Now in the urine a considerable quantity of the uric acid is present as the mono-sodium salt, but not all of it, because all the uric acid cannot be precipitated by an addition of acid. Even after acidification a part of the uric acid remains in solution, and it is worth remembering that urea is a good solvent for uric acid.

It is obvious that the term "acidity" both as regards the urine and the blood, must be regarded as purely relative, depending largely on the indicator used. Acid sodium carbonate, e.g., is chemically an acid salt, yet it turns red litmus blue, is neutral to phenolphthalein and alkaline to methyl-orange. Carbon dioxide again exists under tension in simple solution n the blood, and this it could not do unless the plasma acted as an acid. We can hardly be surprised, therefore, that regarding the acidity of the urine Folin makes a decided departure from the views usually held. He considers that the current belief that the acidity of the urine is regulated by variations in the relative proportions of the two forms of "acid phosphates" is erroneous. In common with most observers, he admits that there is no really good method for determining the degree of acidity of the urine, and in his interesting article on the subject makes many suggestions of decided value. Haig is so far correct regarding the acidity being proportional to the amount of urea, in that the greater the amount of protein food that is taken the greater will be the urea and the acidity, but the same remark obviously applies to the uric acid. It is a fact, however, that where a sufficient amount of alkali is present in the blood an alkali-protein appears to inhibit the uricolytic enzyme.