As already stated, the deposition of orates in different structures is the most characteristic feature of gout; the origin of these deposits has consequently been investigated by many observers.
Garrod, in his celebrated work on gout, demonstrated that the blood of gouty patients contains more uric acid than in the normal state.
[This was done by mixing a few cubic centimetres of blood-serum or fluid from a blister with 10 or 12 drops of acetic acid. Threads of cotton were placed in this mixture; this was covered by a watch-glass and left alone for from twenty-four to forty-eight hours. After that space of time the thread was thickly covered with characteristic crystals of uric acid, when the blood was taken from a gouty patient, especially imme diately before an attack. The blood of healthy persons or of patients suffering from diseases not accompanied by uri ccemia does not give the same results. F. LEvlsox.] The experiments of Garrod have been repeated by other observers, and it is now generally accepted that in gout, uric acid, in the form of urate of soda, is found in the blood in excess. Different questions now arise: How and where in the body is the uric acid formed and what is its physiological significance? Which is the uric-acid compound circulating in the blood and excreted in the urine, and how are these deposited to form tophi, etc.? What is the origin of the uricmmia in gout, and, if uric acid may also be found in excess in the blood in other dis eases, why are deposits of uric-acid com pounds only formed in gout? The first question was, until the last few years, generally answered by the statement that uric acid, as well as urea, were products of the metabolism of pro teids; the normal result of the complete oxidation of these was urea, only a small amount of proteids being left in a state of lower oxidation and excreted as uric acid. In some persons suffering from a slow and incomplete metabolism—retar dation of metabolism—the oxidation of proteids was less perfect, and a larger quantity of uric acid was formed than in health.
In gout the process of nutrition is pri marily at fault, and conspicuously that part of it which consists in the retro grade changes and elimination of tissue products. Oxidation in its various stages
and degrees is not thoroughly carried out, and the products of the waste and decay of the tissues, not being sufficiently transformed, linger in the blood and sys tem, and appear to take an active part in the disturbances which arise. William Savory (Lancet, Jan. 13, '94).
Much labor has been spent in calcu lating the normal proportion of uric acid as to urea in the urine; this has been es tablished by Haig as 1 to 33. According to this author, every departure from this proportion is pathological.
The old theory of the pathogenesis of gout contended that, when retardation of metabolism took place, much more uric acid than normally was formed; the uric acid accumulated in the blood, and when the blood had thus been loaded with the compounds of uric acid, it de posited them in the articulations, etc.
This theory has been overthrown by recent investigations. Kossel, Horbac zewski, and many other investigators have shown that uric acid is not a prod uct of the metabolism of the proteids, but that it is formed by the oxidation of nuclein—an albuminous compound which differs from the proteids in that it contains a greater proportion of phos phorus. The nuclein is contained in the nuclei of cells, and may be prepared from all cellular structures, such as the spleen, the thymus gland, etc.
It has further been demonstrated by many experiments that the excretion of uric acid in the urine is increased or diminished by all factors (diseases, medi cines, poisons, etc.) which give rise to a more rapid or slower disintegration of the cellular elements of the body and especially of the leucocytes. The inges tion of food causes a temporary leucocy tosis (digestive) followed by an increase of the formation and excretion of uric acid. The amount of uric acid excreted in twenty-four hours is not much influ enced by the nature of the food (animal or vegetable); there is, however, this dis tinction noticeable: that the more easily digestible animal proteids set up digest ive leucocytosis and formation of uric acid much quicker than the vegetable albumins, which are difficult to digest.