Pursuing this line of investigation, Haig ascertained that there can be no excess of uric acid in the blood unless there has been previous retardation of its elimination, so that accumulation has taken place within the body. He does not deny the possibility of excessive formation of the substance, but he cannot discover any satisfactory evidence of such an occurrence. He does, however, find that there is a definite ratio between the formation of urea and of uric acid, viz., uric acid : urea :: 1 :35. When the two substances are voided with the urine in this proportion to each other, no pathologi cal symptoms are manifested, the kidneys are merely washing out the surplus nitrogen after a normal fashion. But, if this ratio be dis turbed, so that uric acid and urea are to each other in the urine as 1 :20, for example, uric acid is present in an abnormal, pathological quantity, due, not to increased acid formation, but to the circulation and discharge of urates that had been previously detained in the tis sues, where they had been formerly precipitated from the blood which has now become sufficiently alkaline to admit of their resolution and transportation to the kidneys. During this process of resolution and transportation, the surcharged blood excites the brain and nervous structures, and the patient experiences headaches, or other active symptoms, until the surplus urates have been discharged from the body, or have been, by therapeutical measures, driven out of the blood back into the tissues whence they came. We are now in a position to understand the way in which the discharge of uric acid may he modified by the daily routine of life and by the different fIC cident6 to which the individual is liable. During the cold winter weather, when perspiration is reduced to a minimum, the retention of acids that should be normally discharged through the skin serves to reduce the alkalinity of the blood and its solvent power over uric acid. Hence it follows that in bright, cold weather the blood and the urine will contain less uric acid, while its quantity will be increased in those fluids during hot weather. Consequently, uric-acid com pounds may accumulate in the tissues during cold weather by reason of the over-acid condition of the blood. But with the return of warm weather the alkalinity of the blood rises, and the circulating fluids dissolve out from the tissues the urates that were deposited during the time of cold. Circulating with the blood, on their way to the kidneys, these substances now excite the vasomotor nerves, and powerfully influence the whole vascular apparatus. In this way is effected the condition of slow, high-tension pulse, scanty urine, headache, and other symptoms that accompany a surcharge of urates in the blood and urine. But, as the spring and summer advance, the surplus urates are more or less completely washed out of the body, and a normal equilibrium is once more established. With the return of changeable autumnal weather, a new disturbance is liable to be set up. After the heat of summer, the cool weather checks perspiratioL, the appetite revives, and uric-acid compounds begin again to accumulate. So long as a certain degree of acidity in the blood is maintained by the absence of perspiration and by an acid forming diet, the urates may be kept out of the blood, away from the nervous apparatus, and the patient feels cheerful, vigorous, and com fortable. But let one of the warm days of autumn excite perspira tion, which perhaps is exaggerated by heavy clothing and overheated rooms—at once the alkalinity of the blood increases ; it dissolves out the retained urates, and the susceptible patient experiences all the discomforts that are due to an excess of uric-acid compounds in the blood. Tn this way it is possible to explain many of the minor mor bid symptoms that are manifested by arthritic subjects long before they ever experience any articular crises.
But it is not through the weather that these people are chiefly affected. Their diet is a matter of vital importance. In the first place, it is evident that the ingestion of acids, may diminish the alkalinity of the blood. If so, the carrying power of that fluid is diminished as to urates. They are precipitated among the tissues, there to remain until the solvent power of the blood is again restored by an increase of its alkalinity. Again, the formation of acids in the alimentary canal, by reason of disturbances of digestion, may overcharge the blood with lactic acid and other substances belonging to the fatty-acid series. And, finally, the albuminous constituents of the food, with every increase of consumption, cause an increase of urea and uric acid that must be voided with the urine or be otherwise rendered harmless, if the normal alkalinity of the blood is to be maintained. In these ways the solvent power of the blood, so far as urates are concerned, is in a state of constant fluctuation. The periodical ingestion of food with every meal thus becomes a disturbing cause, so far as that solvent power is concerned. With every ordinary meal a considerable quantity of alkaline salts is introduced into the circulation, but their effect may be either wholly or in part neutralized by the acids and acid-forming sub stances that are at the same time introduced as a portion of the food. Other substances also, such as iron and the metals gener ally, waters that contain calcic salts, opium, strychnine, the iodides, antipyrin and various coal-tar compounds, the nitrites, and certain h3Tosulphites, have the same power to reduce the alkalinity of the blood and to cause retention of the urates until the normal alka linity is restored.
Undoubtedly the processes of metabolism within the tissues result in identical conditions through the formation of acids and acid salts, chlorides, sulphates, phosphates, etc., which are discharged into the blood, and there influence its degree of alkalinity. Under normal conditions, the urates in the blood are held in solution by the neutral disodic phosphate which precipitates the urates into the tissues. Under such conditions the blood and the urine become poor in uric acid, but rich in acid sodium phosphate. Consequently, it is a matter of daily observation that the quantity of uric acid in the urine varies inversely as the acidity of that liquid—urinary acidity being chiefly due to the presence of acid sodium phosphate. The fluctuation of urinary acidity, therefore, serves in some degree to indicate the relative quantity of uric-acid compounds that are at any time present in the blood. This, however, is true only when the test is applied to freshly secreted urine.
As a consequence of these facts it is possible to explain the fluc tuations of urinary acidity and discharge of urates that occur during each day of twenty-four hours. As night advances the urine becomes more acid. This signifies an increase in the acidity of the blood from which the urine is derived, and a corresponding reduction in the soluble urates in those liquids. But as the day progresses, and the blood is charged with the products of digestion, its alkalinity rises with various remissions dependent upon the intervals between meals, until the effects of the evening meal are dissipated during the night. Consequently, the urine is less acid by daytime than during the night; and more uric acid can be taken up into the blood and voided with the urine during the " alkaline tide" of the day than during the " acid tide" of thr.: night. Hence the severity of hemicrania—a uric acid headache—as the day advances, and its subsidence by night. Hence in acute gout, the incidence of articular pains and other mani festations during the " acid tide" after midnight, when the alkalinity of tlio blood is at its minimum. and the soluble urates that had been taken up into the blood during the preceding day are now being again disclia•ged upon the tissues in a violent and tumultuous Passing once more in review the results of these interesting ex periments and observations, it appears that the uric-acid compounds which are voided with the urine are derived : (a) from the nitroge nous constituents of the food; (b) from uric acid, urates, caffeine, or other vegetable alkaloids that have been taken, ready formed, with the food; and (c) from the urates that have been previously detained in the tissues by reason of their insolubility. Under normal con ditions the total amount of urates formed in the body should be exactly balanced by the quantity that is discharged with the urine; and in the long run this is the fact. Urea and uric acid will then appear in the urine in the proportion of one part of uric acid to about thirty-five parts of urea, and there will be no retention of urates in the tissues, nor any morbid symptoms that can be ascribed to their accumulation in the body. If alkalies or compounds of salicyl ic acid be taken into the blood there will be for a day or two an ex cessive quantity of urates iu the urine, but this excess soon subsides to the normal figure, and alkaline medication can no longer cause an increase beyond the ordinary ratio of 1: 35. This fact seems to in dicate that the daily formation of uric acid bears a constant relation to the formation of urea, and that, when the normal ratio in the urine is disturbed, it is owing to a fluctuation in the quantity of solu ble urates in the blood. Temporary retention of urates may occur in the liver, the spleen, the joints, or other organs and tissues of the body; but, in a state of health, the quantity that is thus kept back by reason of the varying capacity of the blood is restored to the cir culation so soon as the alkalescence of the blood becomes sufficient to hold in solution all the urates that it reaches. As the alkalinity of the blood is continually varying during the course of each day and night, the quantity of urates that are in circulation and that are passed into the urine is correspondingly varied; but, if reckoned clay by day under normal conditions, it will be the same from day to day. As a fact, however, the daily quantity that is excreted is not uni formly the same, because of changes in the quantity and quality of the food. Uric acid may be taken ready formed in soups and gravies, or its elements may be taken in such combinations as caffeine (tri methyl xanthin) or other vegetable alkaloids. It will be then either detained for a time in the tissues until the blood can transport. it to the kidneys, or it will appear in the urine in a quantity relative to urea that is above the normal ratio. In like manner, the same result will be manifested when an increase of solvent power enables the blood to take up urates that have been temporarily detained in the liver, spleen, joints, awl other part', of the body.