A large amount of clinical and experimental data combine in support of the view that the element of acid intoxication is a very important one in the etiology of lithemia, rheumatism, gout and the intoxication of diabetes. Most authorities are unanimous in the view that sodium bi-urate is the materia peceans of gout, its precipitation en masse the cause of gouty inflammations, and its irritation of nerve centres the cause of the characteristic nervous disorders. The kidneys undoubtedly play an important part in the causation of gout, for decreased elimination necessarily causes accumulation, and Roose considers that the precipitation of an attack or the acquirement of the gouty habit is quite dependent on the permeability of the kidneys. This is verified in clinical experience, for the alkaline diuretics, by stimulating renal activity, cause increased elimination, often with prompt amelioration of the symptoms.

The following arguments would seem to show improbability of a purely uric acid intoxication:

1. Experimental poisonings with uric acid fail to show the many symptoms so often observed clinically, and usually attributed to the uric acid diathesis.

2. The same causes which operate to produce uric acid in excess also furnish other purins and diamine.

3. Hepatic and renal insufficiency, the acknowledged causes of the retention of uric acid, would necessarily produce a mixed toxemia.

4. The investigation of individual cases of supposed uric acid intoxication shows the presence in the urine of other purins and in the feces of ptomaines and leucomaines.

5. As an immediate result of uric acid intoxication would come disordered metabolism with changed end-products and the formation of auto-toxins.

We may conclude that in this class of diseases there is a mixed toxemia with a preponderance of those auto-toxins which affect the muscles and joints, - the purins in particular, instead of the ptomaines and other leucomaines.

Although acid intoxications are not usually acknowledged as a cause of arteriosclerosis, the writer has observed a number of cases in which syphilis and alcohol could be positively excluded, but in which the acid diathesis, as manifested by its well-known symptoms, was very much in evidence. Galen was the first to observe that an exclusive vegetable diet predisposed to atheroma. Raymond noted it in monastic orders where meat was forbidden, and Treille found a high percentage among the natives of Calcutta and Bombay, but these offer no arguments that the condition was not due to the use of alcohol. Although experimental proof is as yet lacking, it is reasonable to suppose that the same poisons which will cause nerve degenerations, increase of connective tissue and even actual cell destruction in other parts of the body, may cause similar conditions in the intima of the channels through which they must necessarily flow to reach and affect parts of the body so remote from their original source.

Haig offers the interesting theory that uric acid or its salts may be precipitated from solution in the blood whenever the hemic alkalinity is materially lessened, - a thing that is sometimes brought about by nutritive disturbances and excessive muscular exercise; and in Part II we have already stated the particular substances, some of them auto-toxins, which also cause such precipitation. If such precipitations occur in the tissues there may be an irritation due to their mechanical presence and necrosis of the parts immediately adjacent may occur, which will be macroscopic if the deposit is large, minute if it is very small; if the mineral deposit be near a free surface, superficial degeneration may take place and the overlying tissue may slough leaving ulcerations. Illustrative of the former condition is the uric acid infarction of the new-born, in which the collecting tubules of the papillary zone of the medullary portion of the kidney, and even the renal cells, are filled with minute uric acid crystals and concretions, held in place by an albuminous stroma. And of the latter we may cite the ulcerations of endocarditis and endarteritis, in which focal precipitations have occurred in the vascular endothelium causing localized superficial necrosis.

According to Woods-Hutchinson (22) lithemic states, are solely the result and consequence of gastric and intestinal putrefaction, the only therapeutic agents of the slightest helpfulness being those which relieve this condition. Among his conclusions are the following: -

1. The uric acid produced in health comes from two sources, the larger moiety the exogenous, from the nucleins and purins of food; the smaller portion, the endogenous, from the destructive metabolism of the nucleins of the body tissues.

2. Gout and lithemia are mere symptom names for a group of chronic toxemic processes of widely varied origins.

3. The uric acid of gout, like the phosphoric acid which invariably accompanies it, is merely a result and measure of the destructive metabolism of the nucleins of tissue cells and leucocytes, in response to the invasions of poisons which may be organic or inorganic, intrinsic or extrinsic.

Acid intoxication may not only manifest itself as a diathesis, with chronic symptoms of a variable character, but it may also cause profound intoxication of the nervous system with coma, convulsions, and even death. Littin reports a series of five cases in which, after several days of digestive disturbance, the patients showed restlessness, nervous debility, headache and sleeplessness followed by increasing stupor and coma. There was a strong odor of acetone in the breath and perspiration, and the urine showed diacetic acid. Careful examination failed to show any cause other than the digestive disorder, and the symptoms disappeared upon improvement in the cause.

Krause reports a case of retro-bulbar neuritis with progressive coma and death, in which the autopsy failed to show any cause save gastro-intestinal catarrh with 2.5 per cent, oxy-butyric acid in the urine.

Cases like this, verified by post-mortem examination, are of great importance as they show the possibility of fatal acid intoxication in non-diabetic persons.

Edsall (23) reports a case of acid intoxication with cyanosis, unconsciousness, and muscular rigidity in which the urine showed acetone and diacetic acid but no nephritis. In these cases the similarity to uremia, diabetes, internal hydrocephalus, alcoholism and cerebral hemorrhage is very marked.