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, some of the sugar thus formed escapes consumption and may be excreted. Theoretically, 1 grm. of nitrogen will be set free for each 7.5g. of glucose formed. In the urine of grave cases of diabetes on a proteid diet, the proportion of nitrogen to sugar is about I to 2. This may mean that the theoretically pos sible 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. Under the administration of these sugars, however, 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 leads to the appear ance of a large quantity of nitrogen in the urine—azoturia—and 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 (3 oxybutyric and aceto-acetic acid with their derivative acetone also appear. They are in part formed from proteids and in part from fats. 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 (acidosis). The development of these acids in large quantities precedes the onset of diabetic coma.
I. 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 con dition 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 func tions 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 char acterized 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. 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 the symptoms to disappear. (See GOITRE.) 2. Cretinism (q.v.) may be defined as myxoedema in the infant, and is associated with non-development or degeneration of the thyroid gland. The characters of the disease are due to diminished metabolism, leading to retarded development, and the treatment which has proved of service, at least in some cases, is the ad ministration of various thyroid preparations.
3. Exophthalmic Goitre (Graves's Disease or Basedow's Dis ease) 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 enlarge ment of the thyroid gland may not be manifest. The condition is caused by increased functional activity of that gland or by changes in the parthyroids.
(q.v.).—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. That uric acid is increased in the blood is un doubted, but recent work points to the accumulation being, like the other symptoms of the condition, a result of some unknown modification in the metabolism and a purely secondary phenom enon. 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 gouty symptoms supervening, is one of the strongest arguments against the older views. The source of the uric acid 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 excre tion is increased when substances rich in nuclein, e.g., sweet breads, etc., are administered. While uric acid itself has no injurious action, the closely allied adenin produces 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 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.
Rheumatic fever was at one time regarded as due to some disturbance in the metabolism, but it is now be lieved to be of streptococcal origin. Excluding peculiar changes in the joints which occur in rheumatoid arthritis and in Charcot's disease and are almost certainly dependent on affections of the nervous system, a large number of individuals suffer from pain in the joints, in the muscles and in the fibrous tissues, chiefly on exposure to cold and damp or after indiscretions of diet. This so called chronic rheumatism appears to be a totally distinct con dition from rheumatic fever; and although its pathology is not determined, it may be due either to a diminished elimination or an increased production of some toxic substance or substances, but so far we have no evidence as to their nature.
(see RICKETS ; MEDICAL RESEARCH) is undoubtedly a manifestation of a profound alteration of the metabolism in childhood and is now regarded as being in large measure a food deficiency disease (avitaminosis).
See Carl von Noorden, Metabolism and Practical Medicine (19o7).