Undoubtedly, diminished oxidation does indirectly tend to excite various disorders of nutrition. Lack of exercise, for example, re duces the quantity of oxygen that reaches the tissues, and thus leads to their encumberment with imperfectly oxidized products of meta bolism. But this alone does not excite any particular disease. We are yet ignorant of the determining causes that operate under such circumstances to produce gout in one case, obesity in another.
diabetes in a third, and so on through the list of nutritional dis orders.
Such, then, is in brief the uric-acid theory of gout propounded by Sir A. Garrod, and extended by his pupil, Haig. So far as the pathological relations of uric acid with the disease are concerned, they have been very thoroughly worked out, and they serve to explain a large portion of the symptoms of the malady. But this hypothesis still leaves unexplained many of the facts connected with the initial causation of gout. Why does uric acid behave as we see it in arthri tic subjects, while in other cases it is not retained, but passes harm lessly through the blood and out of the kidneys with the urine? Is uric-acid retention the real cause of the disease? The observations of Ebstein possess considerable interest in this connection. He noted the fact that uric-acid compounds are not deposited at random iu healthy tissues. He observed an incipient necrosis of tissue ante cedent to the deposit of urates, and expressed the opinion that with out such tissue-change there could be no uratic infiltration. This, however, is merely a statement of fact, which amounts to saying that certain morbid manifestations of gout must precede the precipitation of urates—in other words, that the gouty diathegis exists before the occurrence of tangible local manifestations in the joints or elsewhere. His observations, therefore, form a contribution to the pathology of the arthritic diathesis, but do not reflect much light upon the original cause of the disease.
Of a more practical character are the opinions of Murchison and his pupils. Remarking the great disorder of digestion that frequently accompanies an attack of gout, and noting the resemblance between many of the symptoms of gouty dyspepsia and the disturbances that follow upon derangement of the liver, they referred the initial morbid process in gout to that organ. They supposed that the formation of urea is chiefly accomplished in the liver, and they inferred that the presence of an excess of uric acid in the blood and elsewhere must be due to imperfect oxidation of nitrogenous alimentary substances in the hepatic cells. In this way a surplus of uric acid is turned loose upon the circulation, and the phenomena of uricacidtemia soon ap pear. It is very true that in certain congestive conditions and chronic inflammations of the liver there is an increase of urates in the urine ; but uratic deposits in the joints or elsewhere never occur in such cases ; and besides there are many gouty subjects who rarely, if ever, exhibit any evidence of serious hepatic disturbance. The corner-stone of this theory is, moreover, not well founded. The liver eaunot be regarded as the principal agent in the formation of urea. 1 t is probable that urea, with other nitrogenous refuse, is formed throughout the body, wherever protoplasm is undergoing oxidation. It is gathered up from all the tissues, and is carried to the kidneys final ejection from the system. Consequently it is improper to speak of the disturbance of relation between the formation of urea and uric acid as a result of hepatic disease alone. If such defective oxidation does actually occur, it is the consequence of a general disorder of metabolism—in other words, it is dependent upon the existence of the arthritic diathesis. In the general deterioration of
function that is characteristic of the diathetic condition, the liver shares; but its disorders are not the prime cause nor the only source of gout. They are a part of the evidence of universal degradation and reversion toward inferior types of organization.
In like manner, the existence of a plethoric condition of the or ganism has been regarded as the cause of gout. Because many arthritic patients are florid and robust, it has been thought that gout was due to an excessive function of the blood-making organs. But there are many gouty patients who are thin and comparatively ill nourished, and many other people, though full of red blood, never experience any gouty symptoms. Still it is true that great energy of the nutritive functions does often favor the genesis of the malady. The absorption of large quantities of acidulated alcoholic beverages causes an excessive irrigation of the tissues in short, a dilution of their protoplasmic basis. In this way, certain metabolic processes may be either hindered or accelerated. The alcohols, and especially the ethers, that are thus introduced, undoubtedly exercise a certain inhibitory influence over the metamorphosis of molecular structure, by their presence alone causing an arrest of oxidation, or at least a re tardation of that process, analogous to what has been recently observed_ by Professor Dewar in connection with the phenomena of fluores cence and phosphorescence. The excessive distention of the stomach, the overtasked condition of the intestinal glands, and the final failure of digestive power, all combine to modify the entire process of as similation and nutrition. In the quantity and quality of the food, in the character of the digestive process viewed in the broadest sense of the term, may be founded the first beginnings of, morbid function which, aided by all the seconda'ry causes that act upon the constitu tion, finally result in a permanent alteration of structure, constituting what is known as the gouty diathesis. this pathological foundation, under the influence of had hygienic conditions, excessive labor, fatigue of mind and body, lack of exercise, traumatism, debauch ery, and everything that tends to depress the sum of vital energy, may be developed the maladies that are allied with gout, or the various disorders that culminate in the articular manifestations which are the most conspicuous evidence of arthritism. It is not improbable that the aromatic sulphates, which are formed in the small intestine, and are increased in quantity by various disorders of digestion, may con tribute to the disturbance of uric-acid equilibrium during their passage through the blood on the way to the kidneys. Haig has shown that the presence of inorganic sulphuric acid salts diminishes the alkalin ity of the blood, and thus causes temporary retention of uric acid. It is not unreasonable to suppose that the organic sulphates may act in a similar manner; but this subject needs additional investigation. There can be, however, no reason to doubt that from the decompos ing contents of an unhealthy intestine many poisonous compounds find their way into the blood and are carried to the tissues, where they profoundly influence the process of metabolism. Unfortunately, however, we are not yet able to trace all the steps in the chemistry of the cell by which molecular exchanges may be effected, retarded, or accelerated.