Since the publication of the treatise which forms the text for the preceding remarks, and which emphasises the necessity for a limitation of the carbohydrates in the diet in certain diseases, quite a considerable literature has accumulated with reference to a pathological condition of acidity which is unquestionably the product of an exaggeration of the very procedure advocated by Hare. As this condition of acidosis is most frequently associated with diabetes, it will be necessary to make a brief reference to this malady. Nowadays it is recognised that diabetes is not a single disease, and that glycosuria, which is the manifestation of a co-existing hyperglycemia, is produced by many varied pathological conditions. We make a distinction between a mild and a severe form of disease, the former disappearing on a diet of meat and fat, plainly showing that the glycosuria was alimentary, and that the limit for the assimilation of carbohydrates had been reduced. In some, glycosuria only appears when sugar is eaten on an empty stomach; in some, it is averted by exercise. In others, glycosuria is only present when sugar is being absorbed from the intestine, indicating a weakening of the functions of the liver and an inability to convert the sugar quickly enough into glycogen.

Hyperglyaemia is generally attributed to a failure of the muscles to utilise the sugar presented to them, and this may happen even although the muscle cells are endowed with the usual ferment, probably because of the lack of a second necessary activating ferment. In any case, as much as one kilogram of sugar may be eliminated each day in a serious case of diabetes. The form in which the sugar is present is usually glucose, but it may be fructose, pentose, maltose, or even dextrin-like compounds. In very severe cases the urine possesses a peculiar fruity odour, now known to be due to the presence of aceto-acetic acid or diacetic acid, a substance which becomes converted into acetone by the loss of carbon dioxide. The occurrence of acetone in the urine (acetonuria) is not peculiar to diabetes, but is common enough in narcotic poisoning, e.g., from chloroform, in digestive disturbances, cyclic vomiting, acute yellow atrophy of the liver, phosphorus poisoning, eclampsia, the vomiting of pregnancy, scurvy, typhoid and other fever patients, dysentery, cancer, inanition, and has been noted also even in healthy people who have been fed exclusively on protein and fat. It is, however, especially found in diabetics when the diet has been too suddenly deprived of carbohydrates.

The symptoms vary according to the rapidity of its onset, in slight cases loss of appetite, pain in the abdomen, nausea and constipation being present, and severe cases being characterised by progressive dyspnoea, somnolence, and subnormal temperature. If recovery takes place naturally, it is because the organism has had time to form a sufficient quantity of ammonia to combine with and neutralise the acid, thereby keeping the reaction of the blood and tissues within normal limits. When, as in diabetic coma, death takes place, it is an example of true acid poisoning, both blood and tissues displaying a decided acid reaction. This is occasioned by the formation of β oxybutyric acid, which is only partially oxidised to diacetic acid, and both of these acids unite with the free alkalis of the blood, neutralising them and so causing the acid reaction. Hence during coma the amount of carbon dioxide in the blood is lessened and oxidation is diminished, as is evidenced by a reduced temperature and the excretion of other products of decomposition in the urine.

Naunyn applied the term "acidosis" to the appearance of large quantities of non-combustible organic acids in the urine, and this should be distinguished from "relative acidosis," an expression used to signify an abnormal excess of mineral acids over the fixed alkalis, or, in other words, a deficiency of alkalis. Harrower, whilst recognising that the blood never becomes really acid, proposes the term "acidaemia" for this condition of hypo-alkalinity, and asserts that it can always be discovered by an increase in the acidity of the urine - as evidenced by titration with decinormal soda - a diminution of the quantity of urea and an increase in that of ammonia. He believes that this condition is either actually due to or is very closely associated with intestinal autotoxaemia, and suggests a low-protein diet with intestinal antiseptics, alkalis, laxatives, open-air exercise, tonic hydro-therapy, and sodium succinate as a stimulant to the hepatic metabolism. The most important form of acidosis, as expressed by the quantity of acid products excreted, is that just described as associated with β oxybutyric acid, but the variety characterised by the presence of large quantities of lactic acid in the blood is scarcely less prominent, and as much as from 10 to 20 grams of this acid may be excreted in some liver diseases due to impaired hepatic function. In addition to this cause Ryffel, as we have seen, states that an accumulation of lactic acid in the blood may arise from an excessive supply of carbohydrates. During exercise sufficiently violent to cause dyspnoea, large quantities of lactic acid are formed in the muscles and, being absorbed into the blood along with an increased amount of carbon dioxide, all the signs of acidosis are produced excepting coma. In this way as much as .5 per cent. of lactic acid may be excreted by the kidney. But imperfect oxidation of any kind, such as a diminished supply of oxygen to the tissues or a diminished power of using oxygen, will produce the same effect. Lactic acid is always associated with the metabolism of carbohydrates and proteins, just as we shall presently see acetone bodies belong to the metabolism of fats. In a well-fed person, therefore, in whom such pathological condition exists, one expects to find an excretion of lactic acid and sugar, whereas in a person who is starved acetone bodies are encountered.

Other products of metabolism capable of producing acidosis in varying degrees are uric acid, oxalic acid, aromatic acids and fatty acids (lipacidsemia). All these acids being eliminated as salts in the urine cause the organism to lose a portion of its alkali, but as a rule this loss is easily covered by the alkali in the food or the reserve store in the cells. The normal alkalinity value of the blood is estimated to be about 300 mg. of NaHO for each 100 c.c, but, as Gamble has shown, this, in diabetics, may be reduced to from 200 to 230 mg.

The drain on alkali may exist for a long time without damaging the store in the system to any serious extent, and even in diabetes as much as 10 or more grams of β oxybutyric acid may be excreted in the urine for years without serious cause for alarm. But this is simply due to the fact that it is not the excreted acid which occasions the trouble, but that which remains in the body to exert its poisonous action, and it is of importance to note that neither the acetone nor the diacetic acid, which are comparatively harmless, are responsible for the poisoning, but the β oxybutyric acid alone.

Acetone is only occasionally produced from the fatty acids formed from the decomposition of proteins, for even when an excessive quantity of proteins is ingested the excretion of acid products is not very noticeable. But an exclusive diet of fats, sodium palmitate, oleic acid, or sodium oleate is rapidly followed by the excretion of large quantities of acetone, although the addition of carbohydrates suffices to diminish or altogether prevent their formation. Acetone and diacetic acid are oxidation products of β oxybutyric acid. Doubtless in normal circumstances oxybutyric acid is first formed, almost immediately oxidised to acetone and diacetic acid, and only in the presence of carbohydrates is the oxidation continued to carbon dioxide and water.

Automatic Protection Of The Tissues Against Acids

The tissues are able to protect themselves from the deleterious effects of acids by using an available alkali, ammonia, not absolutely essential for other purposes, and animals which manufacture a large supply of ammonia from their food can withstand acid intoxication longer than those forming less. Walter injected dilute hydrochloric acid into the stomach of rabbits, which are incapable of forming ammonia for protective purposes, and dyspnoea soon supervened, but this and other symptoms rapidly disappeared after a subcutaneous injection of bicarbonate of soda. As a result of the neutralisation of acids with ammonia, it appears in the urine in abnormally large amounts, and in this way becomes an index of the extent of the acid intoxication.

In most slight cases of diabetes the relation of ammonia nitrogen to the total nitrogen is 1: 10 instead of the normal 1: 16-33, but in more severe cases the ammonia nitrogen may be increased to as much as 25 per cent. of the total nitrogen. In ordinary circumstances the amount of ammonia in the urine depends on the adjustment between the acid products of metabolism and the supply of bases in the food, and whenever more ammonia is excreted than can be accounted for by the food ingested, then an abnormal amount of acid is being excreted. By far the larger proportion of ammonia formed from food is converted into urea, and in proportion as it is required for neutralising acids the excretion of urea must suffer. Every gram of ammonia present in the urine in excess of the amount directly due to the food is equal to an excretion of 612 grams of β oxybutyric acid. The administration of alkalis can neutralise this acid, but cannot prevent its formation in diabetes, although when injected into the blood it can arouse a patient from coma.