From these considerations it is apparent that it is possible to influence the excretion of uric acid by artificial measures. The urates that appear in the urine are directly derived from the blood, and may be assumed as the index of their quantity in the circulating fluids of the body. That quantity rises with increasing alkalinity of the blood, and falls with every decrease of such alkalescence. Every addition of an alkaline substance to the blood causes a rise of the alkaline tide; every addition of acid or acid-forming substance causes a fall in the solvent power of the blood so far as urates are concerned. Flesh food, as well as acids, wines, beer, and other acid beverages, all tend to diminish the capacity of the blood for urates, and to cause their detention in the body. Hence the accumulation of uric acid that takes place as a consequence of a highly nitrogenous diet, especially when accompanied by acid beverages that reduce the alkalinity of the blood. So long as the accumulated urates can be kept harmlessly stored in the tissues, the health of the individual does not suffer; but there is a limit to endurance, and the existence of a large deposit of uric acid in the body is a continual menace to the equilibrium of the bodily functions. A copious perspiration, or a more than ordinarily alkaline meal, or a failure of appetite through lack of exercise, may raise the alkalinity of the blood, and immediately the accumulated urates begin to dissolve and to pass into its current. If now present in excessive quantity, the circulation is disturbed by excitation of the vasomotor nerves, the arterioles contract, the pulse becomes slow and tense, the course of the blood in the capillaries is retarded, and all the functions of the body are depressed. For want of a vigorous capillary circula tion the brain becomes sluggish, depressed, and irritable, causing cor responding changes in the feelings and temper of the individual. The respiration may become labored and insufficient; the heart beats slowly and laboriously; the glandular structures connected with the alimentary canal and elsewhere throughout the body receive too little blood, and become, therefore, incapable of supplying their normal secretions. The processes of digestion are correspondingly impaired. The liver, the kidneys, and the other excretory organs are all similarly hampered in function. If the store of a.ccrimulated urates be small, the difficulty is soon relieved by its discharge through the kidneys. But if the accumulation be large, and if therapeutic aid be not afforded, the embarrassment of the organism goes on increasing, until the thermogenic and nutritive functions of the tissues are re leased from the control of the nervous system. Local inflammation and fever may then be set up ; inflammation at the point of least re sistance, usually in seine overtaxed joint—and fever as a consequence of general intoxication and disorder. When thus tumultuous crisis has been reached, the patient is said to be suffering with articular gout. Obviously, the disorders that lead up to this climax cannot he without symptoms ; consequently every attack of gout is preceded by a long array of minor disturbances, such as headache, neuralgia, asthma, dyspncea, palpitation, dyspepsia, lithiasis, hemorrhoids, cold feet and hands, mental depression, bad temper, etc., that are depen dent upon morbid states of the circulation and a faulty nutrition throughout the body. These morbid states appear to be due to the excessive presence of urates in the blood. The final crisis is usually precipitated by some extraordinary incident that is sufficient to drive the urates out of the blood into the tissues from which they had been taken up, or into such structures as had been recently injured or over worked. Sydenham speaks of the occurrence of an unusual appetite for food as a common incident on the day preceding an explosion of gout. If, now, the gouty subject should indulge in a hearty meal of animal food washed down with copious draughts of acid wine or beer, his blood would be at once overcharged with acids and urea. Its alkalinity would be reduced, and the urates would be speedily driven out of the circulation. They would be largely deposited in such tissues as were least alkaline. Hence, after walking or other active exercise, the joints of the lower extremities--the great toe, after a dance, for example—would be the most acid of all the structures of the body, and there the urates would find lodgement. This process is most likely to occur during cold weather, when the acidity of the blood is increased through lack of perspiration. It would naturally be at its height during those hours of the day when the acidity of the blood is the greatest—that is, during the hours after midnight.
In all these particulars clinical experience agrees with theory. But when we consider the history of chronic adynamic gout, it is not so easy to follow out such an analysis. So Many complications exist that the clinical picture is often blurred, and the sharp outlines of conformity with the doctrines of Garrod and Haig cannot be always continuously traced. Thus, it is frequently urged that uric acid and its compounds cannot be competent to excite such morbid disturbances in the body, because they are not poisonous, and probably exercise a merely diuretic effect, like that which is produced by urea. Eb stein and others, however, have experimentally shown that the intro duction of urates into the tissues produces local irritation, especially if such salts be in a state of solution' that enables them freely to penetrate the part. It must also be noted that in those who have
acquired the arthritic predisposition there exists a morbid over-sensi tiveness of the nervous system, and doubtless of all the tissue ele ments, that renders them inordinately liable to disturbance by causes that might be readily tolerated in perfect health. It is, therefore, impossible to draw negative inferences from laboratory experiments with uric acid upon healthy subjects.
It has also been claimed that in other diseases besides gout, such as affections of the liver, lead-poisoning, enlargement of the spleen, and leukemia, there is an excess of uric acid in the blood and in the urine without any symptoms of gouty disorder. In such cases the uric acid in the urine may rise in relation to urea to at least three times the normal ratio (1:12 instead of 1: 35). But it is probable that these facts may be explained by a reference to the circumstance that in such cases the •diseases are local—inflammation of the liver or of the spleen. Under such conditions the alkalinity of those organs is largely reduced, and for a long time uric-acid compounds would accumulate in them. Then, under the influence of the faulty digestion and malnutrition that is thus set up, the formation of urea and uric acid would be diminished, and the blood would become capa ble of transporting accumulated urates to the kidneys where they would appear in the urine greatly in excess of the urea. Any one who has had experience of chronic malarial poisoning has been able to verify in his own sensations the effect of such a surplus of urates in the circulation, producing depression of spirits, debility of mind and body, and an endless train of cachectic symptoms that speedily vanish under the influence of stated doses of a mineral acid by which orates are driven out of the blood. So long as the kidneys remain intact it is probably impossible to excite anything more than the minor symp toms of uricacidremia, and it has not yet been shown that these are absent from the symptomatology of the diseases in question.
As for the uricacidEemia of lead-poisoning, it cannot be considered an objection to the uric-acid theory of gout, since saturnism is a well known cause of arthritic disease ; and lead operates for its production precisely like other substances that cause storage of urates In the body.
Again, it has been objected that genuine gout may occur without any trace of uric acid in the blood. But it is a well-known fact that urates are entirely absent from the blood in the vicinity of an affected joint during an arthritic crisis. Inflammation drives uric acid out of the blood, or converts it into more perfectly oxidized compounds, so that presently the entire circulation of the patient is freed from urates. Obviously, the ptesence or absence of uric acid in gouty blood will be determined by the proximity of an inflamed joint, by the stage of the disease, and by the degree of vigor with which ex cretion is performed.
The researches of Beneke, Ebstein, Bouchard, and others, refer ring various diseases of nutrition, such as gout, diabetes, obesity, lithiasis, etc., to a retardation of the process of oxidation in the tissues, were supposed to throw great light upon the pathology of gout. But, while it may be true that retarded oxidation does occur in all nutritional diseases, the discovery of the fact fails to advance oar knowledge. How can a mere delay of oxidation produce gout in One patient, and diabetes in another? Evidently, the cause of delay must still be sought, and we have only taken an additional step with out reaching any final result. Could it be shown that uric acid is formed in excess in gouty and that urea is at the same time diminished, the hypothesis of diminished oxidation might receive a plausible support, since urea represents the more highly oxidized product. But there is no satisfactory evidence of any such disturb ance of equilibrium in the formation of the two substances. The observations of Lecorche and Bouchard indicate that the amount of uric acid that is excreted by the gouty is not reduced below the nor mal standard. Garrod thought that the elimination of urates was less in gouty subjects than in the healthy, but he recognized the fact of fluctuation iu the process. Haig has shown that the process of elimination is liable to sudden interruptions, followed soon after by compensatory increase iu the opposite direction. In non-arthritic subjects these alterations serve to balance each other, but when the gouty diathesis exists there is a slight inclination in favor of accu mulation of urates, so that finally the tissues are saturated, and a cri sis occurs by which the system is evacuated and normal conditions are temporarily restored. In this way it is possible to reconcile the observations of Garrod and Bouchard. According to this hypothesis, it is unnecessary to postulate an increased production of uric acid, and certain experiments seem to contra-indicate such formation; hence the doctrine of retarded oxidation receives no support from the ob servations of Haig. He calls attention to the greater importance of a disturbance in the. normal ratio between uric acid and urea in the blood, since large quantities of those substances may pass harmlessly into the urine so long as the iroportion of 1: 33 remains unchanged. It is when a considerable amount of uric acid in excess of the normal ratio appears in the circulating fluids that disorder of the bodily functions is initiated.