Uric acid

“ The study of this paper should form a part of the work of every advanced student of chemistry. It is a model of all that is desirable in a scientific memoir. The paper on uric acid is remarkable for the number of interesting transformation products described in it, and the skill displayed in devising methods for the isolation and purification of the new compounds. Comparatively little has been added to our knowledge of uric acid since the appearance of the paper of Liebig and Wöhler. ”

“ A second error of the uric acid advocates, flowing from their first error of naming the poison, is to pour their acids and alkalies into the blood with the childlike faith that, like good children, the acids and alkalies will go in there and do just what they were told to do, neutralize the uric acid, and get out. They assume that the chemistry of the acids and alkalies is as simple inside of the body as it is outside of it and that the blood is simply a passive mixture of chemicals. ”

“ When the uric acid amateur chemist comes to study the real poisons of the blood, he will be confronted with a problem even more intricate than uric acid, though that one is intricate enough and still unsolved. ”

“ Also, Flack and Hill, discussing the metabolism of nuclein, hold that some of the uric acid thus formed may be transmuted into urea by an uricolytic ferment present in the liver, muscles, and kidneys. This same agent they consider “probably destroys a considerable amount of the uric acid formed in the body. Indeed, uric acid, even when given in the food, owing to the presence of this enzyme, causes no increase in the uric acid output of the body.” ”

“ Many physicians are convinced that uric acid is absolutely unirritating. Uratic deposits may occur to an enormous extent in gouty persons without the occurrence of any pain or paroxysms. Urates have been injected in large amounts into the bodies of animals as well as administered in their food with no toxic result whatever, or more than purely local irritation. ”

“ This acid is ascribed by some to Urate of Ammonia, which is to a small extent soluble in water. Others consider that it is due both to this and to Phosphoric acid, which is the opinion of Dr. Prout and Dr. G. Bird. Others attribute it to Lactic acid, which is stated by Berzelius, Lehmann, and Simon, to exist in healthy urine. Some consider the acid to consist in a Super-phosphate of Soda. Liebig supposes that it is due to Uric acid, held in solution by the common Phosphate of Soda. He also considers Hippuric acid to be an invariable ingredient in healthy human urine. ”

“ Lastly, the opinion of most authorities is that, while they concede the possibility of synthetic formation, the amount of uric acid produced in this manner is negligible, and that by far the most important mode of formation in mammals is by the splitting and oxidation of nucleins; in other words, that uric acid in the main is derived from the amino-purins by deaminisation and subsequent oxidation, and from the oxy-purins directly by oxidation. ”

“ There are good reasons for believing that uric acid is not in the free state in the body. In the urine it is in combination with alkalies as urates, perhaps also with some organic body. It has been shown that the blood of the gouty is not saturated with uric acid, but can take up more, and that the alkalinity of the blood is not diminished. The excess over the normal is in many cases small; it is said to be absent in some persons, and rarely, if ever reaches the quantity found in leukaemia. ”

“ With a large amount of meat we eliminate two grams of uric acid in every twenty-four hours, and even with an entirely vegetarian diet the urine still contains 0.2 to 0.7 gramme, according to Bunge. Should we be so unreasonable as to refuse a person a cup of weak tea or coffee, after their having been accustomed to such for a lifetime, merely to avoid a few more atoms of uric acid. Especially should we refuse them a weak cup of coffee, remembering that such is a good diuretic and assists in the elimination of baneful products through the kidneys? ”

“ Uric acid exists in the urine in the form of urates, which in concentrated urines are readily thrown out of solution and constitute the familiar sediment of "amorphous urates." This, together with the fact that uric acid is frequently deposited as crystals, constitutes its chief interest to the practitioner. It is a very common error to consider these deposits as evidence of excessive excretion. ”

“ These, together with xanthines, poisonous alkaloids and ptomaines, are formed during the processes of protein and starch digestion and in the breaking down and decay of cells and tissues.
Of these different waste products, uric acid causes probably the most trouble in the organism. The majority of diseases arising within the human body are due to its erratic behavior. Together with oxalic acid, it is responsible for arteriosclerosis, arthritic rheumatism and the formation of calculi. ”

“ The following organs, in their entirety, were analysed, the liver (1,550 gram) , no uric acid; spleen (290 gm.) , 10 mg. uric acid (3·5 mg. per 100 gm.) ; kidney (270 gm.) , no uric acid; lung (930 gm.) , 15 mg. uric acid (1·6 mg. per 100 gm.) ; muscle (440 gram) , no uric acid; and intestine (420 gram) , no uric acid.
It will be seen that uric acid was either absent or present in minimal amounts, and these results Schittenhelm and Wiener interpreted as confirming their long advocated contention as to the destructibility of uric acid in the human organism. ”

“ We know that, following the intake even of non-purin-containing foodstuffs, an increase in uric acid excretion ensues, and that the same is the outcome of the stimulation of general nuclein metabolism. [199] Is it not conceivable that the responsible toxin acts in like fashion, and haply by disturbing the orderly sequence of those exquisitely delicate enzymatic reactions which culminate in the formation of uric acid, and with which potentialities every living cell in the organism is dowered? ”

“ As we are aware, the amount of uric acid excreted in the urine increases markedly on a purin-rich diet. But recent researches [138] appear to raise doubts as to whether the uric acid content of the blood rises correspondingly. Thus, according to Walker Hall, “a state of uricæmia is said to exist if the amount of uric acid in the blood exceeds 0·8 mg. per 100 c.c.” The figure he considers is probably too low for, after an average meat breakfast, the blood uric acid rises to 1 or 2 mg. per 100 c.c. in normal adults, or even higher after an excessive intake of purin-rich foods. ”

“ Thus, if fed on a purin-free diet, he passes large quantities of uric acid, and if the latter be injected subcutaneously, elimination in quantity as such ensues; this, in striking contrast to what obtains in all other animals in whom, as before noted, uric acid is mostly oxidised to allantoin before excretion. Now, as MacLeod observes, investigation into the metabolism of nucleic acid has, in man, been hampered greatly, in that the absence of uricase from his tissues, prior to Benedict’s discovery, rendered experimental researches on the lower animals valueless. ”

“ It is a remarkable fact that the waste nitrogen should be excreted in the form of uric acid or urates from such widely differing classes of animals as birds and serpents. Birds have a higher body temperature than man, they are very rapid in their movements and consume a large amount of food proportionate to their weight. They live, as it were, at high pressure. Serpents, on the other hand, have a low body temperature, they are lethargic and can live a long while without food. There is no obvious reason why some animals excrete urea and others uric acid. ”

“ Apart from this general distinction, before gout could with justice be relegated to the same category of disorders, it would be necessary to prove that uric acid was an intermediary and not a terminal product of metabolism. All modern research, however, tends to indicate that uric acid is an end-product, and, moreover, that there are no uricolytic ferments within the body whereby its destruction can be accomplished. ”

“ That the uric acid theory should more than any other have found [34] ready acceptance, is not so much to be wondered at. The one solitary pathological fact that emerged out of the mist of hypotheses was that established by Garrod, viz., the excess of uric acid in the blood. It survived and still survives the corroding test of time. Surely such must be the fons et origo mali, and how obtrusive the uratic deposits, so ready to hand, objective affirmations of the truth of their contention. ”

“ No difficulty is experienced if small quantities of albumen are present, as that body is not coagulated until the temperature rises much higher. A sandy precipitate of free uric acid will not dissolve on warming the urine, and its identity can further be determined by means of the microscope, or by applying a well-known color-reaction. A grain or so is oxidized into reddish alloxan and alloxantin by carefuly evaporating with a few drops of strong nitric acid on a piece of porcelain. ”

“ Because coffee, tea, or cocoa give rise to uric acid, Haig would like to banish them entirely from the diet. We do not feel inclined to follow Haig in such a fanatical view, for after all it is nearly impossible to so live that we should not introduce some small amount of uric acid into the system; we are always producing a certain amount of it in the system, as 365already mentioned, and whether a trifle more or less be taken can make no difference, as minute quantities of uric acid cannot play an important rôle if our kidneys are in good condition to eliminate them. ”

“ On the other hand, Wells, discussing the destruction of uric acid, observes that repeated investigations show “that the tissues of man have no power whatever to destroy uric acid in vitro; the earlier reports of positive uricolysis undoubtedly being erroneous.” His final conclusion, after weighing all available evidence, is that it is highly probable that in man “most of the purin absorbed from the food, and practically all the purin from cell metabolism, is converted into uric acid and excreted as such.” ”

“ Furthermore, Levy’s hypothesis involves the assumption that the excreting functions of the kidney for uric acid and urea are separate and independent of each other, and to discussion of this we now pass on.
The Relationship, if any, between the Amounts of Uric Acid and of Urea, and Total Non-Protein Nitrogen in Human Blood
Taking samples of human blood from (1) unselected insane subjects and (2) chronic nephritics, Folin and Denis determined the amounts therein of urea, total non-protein nitrogen, and uric acid. ”

“ The first, a man aged 36, weight, nearly three hundred pounds, suffered much renal pain, with occasional symptoms of small calculi passing along ureter. The urine had very acid reaction. The microscope revealed numerous crystals. The murexide test likewise proved that uric acid was present in abundance. This patient, wishing to become thin, was put on a beef diet, no potatoes, few vegetables, etc., just the diet to increase the uric acid. He was put on the solvent treatment, giving twelve grains, divided into three doses daily. Each dose was given in a tumblerful of vichy water. ”

“ As uric acid is a satisfactory and unirritating form in which waste nitrogen is expelled from the body of the active alert bird, as well as from the slow moving reptile, it is surprising if a very much smaller quantity acts as a poison in man. ”

“ When the uric-acid formation is established, the substance is either gradually deposited in the body—in the articular cartilages by preference—or is cast out by the kidneys, with irritation of those organs. With this effect are often associated "insufficient" liver and migrainous neurotic affections which are growing more common among town populations. "With an insufficient liver, a meat dietary, and insufficient oxidation, the town dweller is the subject, more than all others, of the uric-acid formation, with all its varied consequences. ”

“ Associated with urea as products of metabolism are uric acid, xanthine, and sarcine. Urea was first artificially transformed into uric acid by Horbaczewski, and its synthesis was effected by Behrend and Roosen. Closely related in chemical composition to these substances are theobromine and caffeine, the characteristic principles respectively of cocoa (the fruit of theobroma cacao) ”

“ In contrast to urea it is very insoluble, but much less so in blood serum than in distilled water, viz., 1⁄40000 of water as opposed to 1⁄1000 parts of plasma. It yields with alkalies two series of salts, viz., the biurate or mono-basic, and the so-called neutral or bi-basic urate, the latter of which is much more soluble. In water the mono-basic urate forms a colloidal solution from which the crystalline salt gradually precipitates.
The greater solubility of uric acid in blood plasma was, by Garrod and Haig, attributed to the alkalinity of the plasma. ”

“ It is a trick of the nostrum exploiter, old but ever popular, to mention numerous drugs which his preparation does not contain; it helps to distract attention from the fact that he does not tell what the preparation does contain!
In the old-time medical journal advertisements, one reads, “Sal Hepatica is the most powerful solvent of Uric Acid known.” (The same advertisement as it appeared in those days in The Journal shows that claim toned down to, “Sal Hepatica is a powerful solvent of Uric Acid.”) ”