in other words, when there is no urine to tell us when we have succeeded in getting an adequate amount of alkali into our patient, the reaction of the saliva serves as a useful guide. Ordinarily this is neutral to litmus paper, but it turns acid in various intoxications. Alkali should be given until it again turns neutral or even slightly alkaline to this indicator.*

ACETONE BODIES

(Acetone, Beta-Oxybutyric and Diacetic Acids)

Introduction.-The acids which appear in the urine are in part the normal or physiological products of the chemistry of the body, in part of abnormal nature.

Under the first heading come, for instance, phosphoric and sulphuric acids, which are formed for the most part through the oxidation of the phosphorus and the sulphur found in the various proteins. With other things unchanged, a high protein diet will, therefore, tend to make the total acidity of the urine (whether measured by titration or by hydrogen-ion determination) run up, because such a diet increases the amount of sulphuric and phosphoric acids formed in the body. Mere increase in consumption of protein need not, however, at once mirror itself by an increased titration or hydrogen-ion acidity, as discussed in the previous section, for it all depends upon the amount of alkali available in the body, or consumed with the protein, as to how much overplus of acid will be present. For this reason the ordinary mixed diet, which contains enough alkali in the vegetables and fruits that go with it, yields a total mixed urine but slightly acid or nearly neutral, for the alkali of the vegetable side of the diet neutralizes almost exactly all the overplus of acid resulting from the oxidation of the proteins. Finally, when for the ordinary mixed diet there is substituted the so-called vegetable or milk diet, the overplus of alkali may so far exceed the production of acid that a urine distinctly alkaline in reaction may be voided throughout the twenty-four hours. Man is then like the herbivora which for this reason secrete normally an almost persistently alkaline urine.

Abnormal Acids of the Urine.-Among the abnormal acids found in urine, two groups deserve special attention. The one of these is represented by lactic acid, the other by beta-oxybutyric and diacetic acids. A qualitative test for lactic acid is readily made, but it is of too little importance to the general practitioner to demand this effort. But a qualitative or quantitative estimate of at least some one of the second group is of tremendous importance; wherefore this should be made regularly.

Acids of the type of lactic acid appear in individual organs of the body or in the body as a whole whenever there is an interference with

The ordinary litmus paper is well-nigh worthless. It should always be tested for its sensitiveness before dependence is placed upon it. Only the neutral litmus paper of the best manufacturers has proved of service in the writer's hands.

the normal oxidation processes in the involved parts. Lactic and other acids may in consequence appear under a large number of widely differing circumstances. They will appear, for example, whenever the intake of oxygen by the whole organism is shut down directly, as in poisoning with inert gases like hydrogen or nitrogen, or when there is a gross interference with the intake of oxygen, as in edema of the glottis, pressure of an aneurysm upon the bronchi, etc. A lack of oxygen to the body may also be induced, even in the presence of an abundance of this gas, if the oxygen absorbing powers of the blood are reduced. We shall therefore have lactic acid in the urine in the severer anemias, after large hemorrhages, or in poisoning with carbon monoxid. Again, the oxygen supply may be plentiful, the oxygen carrying power of the bloc normal, but the functional capacity of the heart so low as not to guarantee an adequate circulation. In all uncompensated heart lesions, therefore, be they due to valvular lesions, to muscular lesions or to pericarditic effusions which embarrass the action of the heart, a lack of oxygen will be manifest, from which all the body tissues will suffer, resulting in an abnormal production of lactic and other acids in them, and these acids will appear in such urine as is excreted. What is true for heart lesions is true also, of course, for respiratory lesions which interfere mechanically with the intake of oxygen, like extensive pleuritic effusions or large pneumonias.

Finally, there is possible a local abnormal production and accumulation of lactic and other suboxidation acids in any tissue if its oxygen supply is shut off directly (as in arteriosclerosis or pressure of a tumor upon the afferent or efferent blood-vessels) or more indirectly through intoxication of the parenchyma of the organ which, even in the presence of a normal circulation, results in an inadequate utilization of the oxygen in that organ. It is not ordinarily remembered how many "diseases" are in essence nothing but such local edemas due to a swelling of the involved tissues following an abnormal production and accumulation of acid in them. Under this heading belong parenchymatous nephritis (edema of the kidney), glaucoma (edema of the eyeball), "uremia" (edema of the brain), passively congested liver (cloudy swelling of the liver), etc.

In all these conditions we may get all the effects of a suboxidation acid poisoning in the organs, though for obvious reasons the total production of acid may be too small to mirror itself in the urine voided by such a patient.

The fate of this lactic acid and of the other suboxidation acids thus formed in the body is the same as that of the more normal phosphoric and sulphuric acids. If enough alkali is present in the body these acids are neutralized as formed, and the effects of the intoxication with the lactic acid may in consequence be much reduced or inhibited entirely. It is for this reason that a proper and frequent examination of the urine, to determine whether its total acidity is being maintained at a safe distance below the highest normal level, is of such great importance; the adequacy of an alkali therapy is determined exclusively by

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such investigation of the urine. Alkali must be fed in sufficient amounts to keep the urinary acidity well below that of the turning point of methyl red, no matter how much is required. The normal human being needs but 5 to 10 grams (1% to 1/3 ounces) of sodium bicarbonate in each twenty-four-hour period to accomplish this purpose, but persons with heart disease, diabetes, carbon-monoxid poisoning, mercury poisoning, etc., may require 100, 150 grams (34, 5 ounces) or even more to accomplish the same result.

Mechanism of the Production of Acetone Bodies. The origin of acetone and of beta-oxybutyric and diacetic acids needs to be borne in mind in order to recognize how much may be accomplished by even a qualitative test for any one of these three substances in the urine. The three materials are closely allied from a chemical point of view, usually appear simultaneously and are derived from a common source. A qualitative test for any one of them, if properly made, may, therefore, be taken to indicate that all three are present in the specimen examined. The importance of finding one of the acetone compounds in the urine lies in the fact that such discovery indicates the existence of carbohydratestarvation on the part of the organism.

When we test by titration or with graded indicators the acidity of the urine, we do not, of course, know whether this acidity is due to the normal phosphoric or sulphuric acids, to lactic acid, or to diacetic, or beta-oxybutyric acid. So far as the effects of the acids are concerned, they all tend to kill the organism. From this point of view we are, therefore, not concerned with their quality. We simply give enough alkali to neutralize all these acids as formed and let it go at that. But as conscientious practitioners, we cannot stop here. We are interested also in the mechanism by which the acids are being produced, for we need to know this in order to better control such acid production. A knowledge of what the factors are which bring about the acid production is, therefore, highly important.

We have already observed how a high acidity due to phosphoric and sulphuric acids may be reduced by cutting down the intake of protein. A reduction in acidity, when due to lactic and this group of suboxidation acids, can be brought about only by giving the patient a better oxygen supply or by aiding him to a better utilization of oxygen in the body. Obviously such a result is brought about only by a removal of the condition or conditions which are making for the interferences with the oxygen supply. It is for these reasons that we order fresh air for the anemic, bed-rest for the cardiac patient, and antidotes in poison cases.

When a patient is being poisoned by beta-oxybutyric and diacetic acids, we can inhibit the process only by improving the conditions which make for better utilization of carbohydrate in his body or by cutting down or out the substances out of which these acids are chiefly formed (fat). Sometimes it is not possible to do as much in this direction as we might wish (as in the severer diabetics), but there is a widespread ard definite interference with a proper utilization of carbohydrate

in a large number of individuals who are in no sense diabetics, but are ill in other directions. Sugar-starvation, moreover, is induced in a large number of patients through bad feeding alone, and since a patient is just as dead if starved to death through bad feeding as he is if he dies from diabetes, the recognition of the existence of a carbohydrate starvation is of paramount importance.

It is now generally held that acetone, diacetic and beta-oxybutyric acids are derived from the fats. Under normal circumstances the fats which we eat or have stored in the fat depots of our body are burned to carbonic acid and water; carbonic acid (in the form of carbon dioxid) is lost through the lungs without cost to the body so far as alkali is concerned; water is similarly lost through some excretory channel like the skin, lung, kidney or bowel. In order, however, to have the fat burn to these ultimate products, a simultaneous burning of carbohydrate is required. The older physiologists used to express this fact by saying that "fat burns only in the fire of carbohydrate." When, for any reason whatsoever, the carbohydrate fire is not kept burning in the body, some or all of the fat ceases to be burned to carbonic acid and water; it is only partially burned, resulting in the so-called acetone bodies (acetone, diacetic and beta-oxybutyric acids). The discovery of acetone compounds in the urine means, therefore, that an inadequate amount of carbohydrate is being burned in the body, or that a disproportionately high amount of fat is being fed the individual. These facts are of importance not only in diabetes, where they have long been used for diagnostic and for therapeutic purposes, but they are of even greater importance in innumerable other medical and surgical conditions where the difference between the status quo and that of the institution of proper carbohydrate feeding is, at the worst, the difference between discomfort and comfort, and, at the best, the difference between death and life itself.

Counteraction of Acetone Production.-In diabetes we have the picture of an organism which, in the midst of plenty of available carbohydrate, is unable to use a sufficient amount of it, in the severer cases, to make possible a proper burning of the fat to carbonic acid and water. In the case of the diabetic, therefore, after we have once allowed him an amount of carbohydrate which will just satisfy all his capabilities for using such, we can cut down or stop the production of acetone compounds only as we eliminate fat from his diet. It is for this reason that in recent years the elimination of fat from the diet (as particularly well emphasized by Allen) has become one of the first and most important rules in the treatment of diabetes.

The author, in his practice, makes it a rule, after this first elimination of fat from the diet, to cut down the carbohydrate, but only to the point where the patient will just spill a trace of sugar. (See the succeeding paragraphs on sugar in the urine.) Such a combination of low fat intake, with full utilization of such powers of carbohydrate metabolism as the patient may have left, will obviously yield the lowest possible amounts of the acetone bodies.

But the presence of acetone, beta-oxybutyric, or diacetic acids is discoverable in an enormous number of conditions in which proper administration of carbohydrate will suffice to do away with the condition entirely. Or, to turn the matter about, a large number of patients, through inadequate carbohydrate feeding alone, are made ill, or bad medical or surgical risks, or, to put it flatly, are actually killed by being given an insufficient amount of carbohydrate daily.

It is just as disastrous for the human body to be deprived of an adequate intake of carbohydrate by any of a large number of circumstances, as not to be able to use this carbohydrate properly after being taken in, as is the case in diabetes. The insane, for example, who starve themselves, the individuals with esophageal obstructions who can swallow nothing, the patients who with gastric or duodenal ulcers are not allowed anything, the eclamptics, comatose or nauseated individuals who cannot or will not take proper amounts of food, indi— viduals who, like the surgical patients, are being "prepared" for operation by being kept upon a wholly inadequate "light" diet in our ordinary hospitals-all these show the presence of acetone compounds in their urines. Such acetone compounds also appear when, in consequence of acute or chronic infections, the carbohydrates are not fed in adequate amounts or, if so fed, are not properly used in the bodyUndoubtedly, in the past, our typhoids, our chronic pus cases and our patients with the severer types of tuberculosis as often succumbed from carbohydrate starvation as from the diseases themselves.

These points are emphasized because the presence of acetone compounds in the urine calls for an active administration of carbohydrate. In the case of the diabetic, of course, the point to which such carbohydrate administration may be pushed has definite limits set upon it; but in the case of the other conditions enumerated above we need have no such fears. It is too often forgotten how much carbohydrate must be consumed daily by the average individual in order to keep the balance. Generally speaking, 500 grams (a pound) are needed. This figure should be kept in mind because it brings home how perfectly inadequate are our ordinary schemes when active mouth feeding cannot be used daily. The body, moreover, runs short of carbohydrate very rapidly. Two or three days are already bad. The patient who is being starved, either because insane, because the victim of some gastrointestinal lesion, or because he is persistently nauseated or vomiting, or for any other reason whatsoever, begins at the end of this time to become the victim of an acid intoxication, and unless something is done he becomes, in proportion to the intensity of this intoxication, a bad medical or surgical risk. The common notion that a few teaspoonfuls of glucose by rectum, a glass or two of milk, or a little gruel two or three times daily is all that the sick man needs, is something to be condemned thoroughly. Too often a persistent nausea and vomiting is the result of an acid intoxication, and maybe of the carbohydrate starvation type. One or two adequate carbohydrate administrations may "cure" such, but it is idle to think that a pint or two of a 2 per cent. glucose solution