In this way, it may be possible to reconcile some of the apparent disagreements of observation. When normal urine is rich in urea, it is acid, and the blood is also more highly charged with acid. The proportion of uric acid to urea may then fall to 1 : 35, or even less ; there is apparently less uric acid in the urine and in the blood. But if the amount of urea be reduced, acidity of urine and blood will fall, and the urates will increase in both. Such oscillations are con ditioned by the diet, and by the time of the day. During the time, the blood and urine are rendered less acid by the absorption of food from the alimentary canal, and they can therefore hold in solu tion and can transport a larger quantity of urates. During the fast ing period of night, the conditions are reversed : the blood and urine become more acid Znd are less capable of carrying urates.
Now when by the agency of disease a similar modification of the urine is effected, the quantity of urates that are voided is correspond ingly modified. During an attack the highly concentrated acid urine receives a smaller excretion of urates because the over-acidu lated blood cannot transport them (Garrod). They are retained in the tissues, and remain there until the subsequent reaction occurs, when the now abundant, limpid, and alkaline urine receives from the less acidified blood the excess of urates that have been retained in the body during the febrile paroxysm. But if the patient has been a vigorous and voracious feeder till the time of the attack, his urea and uric acid may be so abundant as to prevent the reduction of nitro genous excreta that would have been otherwise apparent. With re turning health, he resumes his faulty habits, and very little, if any, reduction can be noted at any time (Bouchard).
The quantity of urea that is voided with the urine does not ex hibit any special variation that cannot be explained by the change of diet in an acute attack of gout. Heavy feeders, who indulge in animal food till the outset of the attack, show little reduction of urea until fever and loss of appetite cause abstinence from the nitrogenous ele ments of food. In like manner, the degree of appetite and of indul gence during chronic gout determines the quantity of urea. Hearty eaters void the fall amount, while cachectic patients and vegetarians yield only a comparatively small quantity.
The phosphates exhibit less agreement with the character of the diet, because they are so largely the result of metabolism within the tissues. For this reason, the quantity will vary according to the rate of disassimilation. In young and vigorous patients the dis charge of phosphates may be actually increased during an attack ; but with old, atonic, and cachectic subjects, there will be a reduction below the normal figure. Much also depends upon the state of the kidneys in the determination of this matter.
A highly acid state of the urine forms a common characteristic of arthritic subjects. During the state of comparative health that precedes or follows an attack, the persistent acidity of the urine is a notable fact. This is due to the presence of the acid phosphate of sodium, a salt which, if it should exist in the blood, would interfere with the solution and excretion of urates. On the contrary, the di sodic hydrogen phosphate (Na,HP03 which is the normal sodium phosphate of healthy blood, is an excellent solvent of urates, hence the advantage of a highly alkaline state of the circulating fluids, en abling them to transport and to discharge in a soluble state the uric acid salts with which they come in contact. Sir W. Roberts has
shown (Lanrct, June 18th, 1892) that these salts normally exist in the fluids of the healthy body in the form of quadri-urates, which are easily soluble and are readily passed through the kidneys. But, in the uratic deposits which infiltrate the joints and other structures of the gouty, the urates are present as bi-urates, the most stable and insoluble salts that are formed with uric acid. In the ready transformation of quadri-urates into bi-urates, and rice versa, lies, according to Roberts, the. explanation of many of the phenomena of gout. The uratic sediments that are so frequently precipitated from the urine as it cools, consist of quadri-urates which are soluble at the temperature of the body. The crystals of uric acid, like grains of red pepper, that are deposited from highly acid urines, are liber ated by the decomposition of quadri-urates that have been held in solution at the normal temperature. These quadri-urates are very unstable, and, after their precipitation from the urine as it cools, they break up into uric acid and bi-urates. Contaminated with urinary pigment, the bi-urates constitute the brick-dust sediment that is re dissolved when the urine is again heated. The liberated uric acid rapidly crystallizes in various modifications of the rhombohedral form, and sometimes exhibits a considerable deposit that is readily distinguished with the microscope from the amorphous bi-urates that form the bulk of the precipitate. According to Roberts (Lancet, June 25th, 1892), this process does not essentially differ from the grad ual liberation of uric acid that takes place slowly in all healthy urine which has been guarded against fermentation. Acted upon by the water of the urine the quadri-urates slowly break up into bi-urates and free uric acid. The bi-urate is immediately retransformed by double decomposition with acid sodium phosphate into a quadri urate, which is again broken up by the action of water; and thus the process goes on until all the uric acid has been set free. The pres ence of pigment, for which urates manifest a strong affinity, seems to exert a retarding influence upon these chemical reactions ; otherwise, there is no apparent reason why uric acid should not be always pre cipitated within the urinary passages. The failure of such inhibition is probably one of the most powerful causes of the deposit of uric acid and gravel that actually takes place in the renal pelves and in the bladder, in certain forms of arthritism. " The conditions of the urine which tend to accelerate the precipitation of uric acid are high acidity, poverty in salines, low pigmentation, and high percentage of uric acid. And, conversely, the conditions that tend to postpone precipitation are depressed acidity, richness in salines, richness in pigments, and low percentage of uric acid—probably the most impo'r taut of these factors is the grade of acidity" (Roberts, Lancet, June 25, 1892, p. 1,401). It is highly probable that whenever simi lar conditions obtain in the blood and lymph, a similar reaction on the part of uric acid may occur in those fluids or in the tissues that they irrigate. In the pathological establishment of such conditions consists the initial process of gout.