be supplied from the tissues, and the individual will become emaciated; hence a diabetic on an ordinary diet is badly nourished, and hence the huge appetite characteristic of the disease.
2. Grave Cases.—From the products of the splitting of proteids sugar can be formed, probably in the liver, and in the more serious form of the disease, even when carbohydrates are excluded from the food, a greater or lesser quantity of the sugar thus formed escapes consumption and may be excreted. Theoretically, 100 grms. of proteid can yield 113·6 grms. of glucose, i.e. 1 grm. of nitrogen will be set free for each 7·5 grms. of glucose formed. In the urine of grave cases of diabetes on a proteid diet, the proportion of nitrogen to sugar is about 1 to 2. This may mean that the theoretically possible amount of sugar is not yielded, or that some of the sugar formed is used in the economy. Both hypotheses may be correct, but the latter is supported by the fact that even in grave cases the decomposition of proteid may be diminished by giving sugar, and that in muscular exercise the proportion of sugar may fall.
In the course of the disease the amount of sugar which the tissues can use varies from day to day. It is in the utilization of glucose—the normal sugar of the body—that the tissues chiefly fail. Many diabetics are able to use laevulose, or the inulin from which it is derived, and lactose (milk-sugar) to a certain extent. It has, however, been observed that under the administration of these sugars the excretion of glucose may be increased, the tissues, apparently by using the foreign sugar, allowing part of the glucose which they would have consumed to escape.
The increased decomposition of proteid, rendered necessary to supply the energy not forthcoming in the sugar, leads to the appearance of a large quantity of nitrogen in the urine—azoturia—and it also leads to the formation of various acids. Sulphuric acid and phosphoric acid are formed by oxidation of the sulphur and phosphorus in the proteid molecule. Organic acids of the lower fatty acid series β oxybutyric and aceto-acetic acid with their derivative acetone also appear in the course of diabetes. They are in part formed from the disintegration of proteids and in part from fats, as the result of a modified metabolism induced by the withdrawal of carbohydrates. To neutralize them ammonia is developed and hence the proportion of ammonia in the urine is increased. By the development of these various acids the alkalinity of the blood is diminished. The development of these acids in large quantities is associated with extensive decomposition of proteid, and is sometimes indicative of the onset of a comatose condition, which seems to be due rather to an acid intoxication than to the special toxic action of any particular acid.
Myxoedema.—The thyroid gland forms a material which has the power of increasing the metabolism of proteids and of fats; and when the thyroid is removed, a condition of sluggish metabolism, with low temperature and a return of the connective tissues to an embryonic condition, supervenes, accompanied by the appearance of depression of the mental functions and by other nervous symptoms. The disease myxoedema, which was first described by Sir William Gull in 1873, was shown by Ord in 1878 to be due to degenerative changes in the thyroid gland. It affects both sexes, but chiefly females, and is characterized by a peculiar puffy appearance of the face and hands, shedding of the hair, a low temperature, and mental hebetude. The symptoms are similar to those produced by removal of the thyroid, and are indicative of a condition of diminished activity of metabolism. The nervous symptoms may be in part due to some alteration in the metabolism, leading to the formation of toxic substances. The administration of thyroid gland extract causes all the symptoms to disappear.
Cretinism may now be defined as myxoedema in the infant, and it has been definitely proved to be associated with non-development or degeneration of the thyroid gland. The characters of the disease are all due to diminished metabolism, leading to retarded development, and the treatment which has proved of service, at least in some sporadic cases, is the administration of various thyroid preparations.
Exophthalmic Goître—Graves’s Disease or Basedow’s Disease.—This disease chiefly affects young women, and is characterized by three main symptoms: increased rate and force of the heart's action, protrusion of the eyeballs, and enlargement of the thyroid gland. The patient is nervous, often sleepless, and generally becomes emaciated and suffers from slight febrile attacks. The increased action of the heart is the most constant symptom, and the enlargement of the thyroid gland may not be manifest. Various theories as to the pathology of the condition have been advanced, but in the light of our knowledge of the physiology of the thyroid the most probable explanation is an increased functional activity of that gland or of changes in the parthyroids. Gout has often been divided into the typical and atypical forms. The first is undoubtedly a clinical and pathological entity, but the second, though containing cases of less severe forms of true gout, is largely constituted of imperfectly diagnosed morbid conditions. The accumulation of urate of soda in the tissues in gout formerly led physicians to believe in a causal relationship between an increased formation of that substance and the onset of the disease. Sir A. Garrod's investigations, however, seemed to indicate that diminished excretion rather than increased production is the cause of the condition. He found an accumulation of uric acid in the blood and a diminution in its amount in the urine during the attack. That uric acid is increased in the blood is undoubted, but the changes described by Garrod in the urine, and considered by him as indicative of diminished excretion and retention, are rendered of less value by the imperfections of the analytic method employed. More recent work with better methods has thrown still further doubt upon the existence of such a relationship, and points rather to the accumulation of uric acid being, like the other symptoms of the condition, a result of some unknown modification in the metabolism, and a purely secondary phenomenon. The important fact that in leucaemia (von Jaksch), in lead-poisoning (Garrod), and in other pathological conditions, uric acid may be increased in the blood and in the urine without any gouty symptoms supervening, is one of the strongest arguments against the older views. That the gouty inflammation is not caused by the deposit of urate of soda, seems to be indicated by the occurrence of cases in which there is no such deposition. The source of the uric acid which is so widely deposited in the gouty is largely the phosphorus containing nucleins of the food and tissues. These in their decomposition yield a series of di-ureides, the purin bodies, of which uric acid is one. Their excretion is increased when substances rich in nuclein, e.g. sweetbreads, &c., are administered. While uric acid itself has not been demonstrated to have any injurious action, the closely allied adenin has been found to produce toxic symptoms. After the discovery of this source of uric acid, physiologists for a time inclined to regard it as the only mode of production. But it must be remembered that in birds uric acid is formed from the ammonia compounds coming from the intestine and muscles, just as urea is formed from the same substance in mammals. Uric, acid is a di-ureide—a, body composed of two urea molecules linked by acrylic acid—an unsaturated propionic acid. It is therefore highly probable that in many conditions the conversion of ammonia compounds to urea is not complete, and that a certain amount of uric acid is formed apart from the decomposition of nucleins.
Sir William Roberts has adduced evidence to show that uric acid circulates in the blood in a freely soluble combination or quadurate—that is, a compound in which one molecule of an acid salt BHŪ is linked to a molecule of the acid BHŪ.H2U. These compounds are said to be readily decomposed and the bi-urates formed, which are at first gelatinous but become crystalline. The deposition of urate of soda in joints, &c., has been ascribed to this change. Francis Tunnicliffe, however, has published the results of certain investigations which throw doubt upon this explanation. The most recent investigations on the metabolism of the gouty have shown that there is undoubtedly a slowing in the rate of elimination of uric acid and also of the total nitrogen of the urine with occasional sudden increases sometimes connected with a gouty paroxysm, sometimes independent of it. Whether this is due to the action of some toxin developed in the body or is caused by a constitutional renal inadequacy is difficult to decide. Certain it is these renal diseases often develop in the course of gout.
Rheumatism.—Rheumatic fever was formerly regarded as due to some disturbance in the metabolism, but it is now known to be a specific micro-organismal disease. The whole clinical picture is that of an infective fever, and it is closely related to gonorrhoeal rheumatism and to certain types of pyaemia. A number of independent observers have succeeded in isolating from cases of rheumatic fever a diplococcus which produces similar
