Normal metabolism results in the constant formation of acids, especially H2CO3, and disease processes may occasion the presence of still more. A constant loss of alkali results, the neutralization products being eliminated mostly in the urine, and the H2CO3 via the lungs; the body fluids are excellently buffered, the most important buffers being bicarbonate, proteins (especially haemoglobin), and phosphates. In the maintainance of the normal pH, the CO2 (or H2CO3) is the easily variable factor. The onslaught of invading acids is first met by the bicarbonates (acidotic process); hyperpnoea lowers the H2CO3 and a normal pH is maintained until the bicarbonates are reduced to one-fourth (perhaps even to one-eighth) of their normal concentration. If, nevertheless, the pH falls (and only then), the other buffers are used, and, if it reaches 7.0, most of the remaining bicarbonate becomes available. The blood handles the situation, but buffers from the tissues or other body fluids also become available in extreme cases.
As noted above, measurement of one variable will be inadequate exactly to determine the state of acid-base equilibrium. As long, however, as the pH is normal, which is the usual finding in most pathological conditions, including mild acidosis, one determination will suffice. Clinical methods comprise tests for whole blood or plasma CO2 or bicarbonate, alveolar CO2 tension, bicarbonate tolerance, pH of blood or urine, Sellard’s test, NH3 quotient of urine, or presence of abnormal acids (particularly acetone bodies) in blood or urine. The first two methods are the ones of choice, particularly the first, as, by it, one can estimate the reserve of the very important blood buffer, bicarbonate, and its result closely indicates the total buffers.
The tolerance for bicarbonate is a very convenient and practical measure of acidosis, and means the dose of NaHCO3 required to produce a urine alkaline or amphoteric to litmus. A normal finding is 5-10 grams; 20 is required with a mild, 30-40 with a more severe, and more than 40 gm. with extreme degrees of acidosis. In coma, it is usually impossible to produce an alkaline urine.
Certain changes in the urine are recognized and acceptable as indirect evidence of acidosis, but these changes are not synonymous with acidosis, being dependent in part upon renal integrity and other factors. The NH3 quotient of urine (ammonia nitrogen; total nitrogen), as usually determined with patient on a mixed diet, is normally about 5%. Values of 10-40% occur in acidosis. It may be increased by diet, disturbances of protein metabolism, ammoniacal fermentation, etc., and there may be no increase in certain diseases with acidosis. The ammonia probably does protect the blood alkali, but its efficacy is intimately associated with renal function, inasmuch as Nash and Benedict have presented strong evidence to the effect that urinary and blood NH3 is the product of an active synthetic function of the kidneys themselves. Acetone bodies in the urine (ketonuria), in the blood (ketosis), or in the breath, have diagnostic value but are poor indices of severity of acidosis and may be absent in acidosis. Acetone and diacetic acid have the same significance: a progressive increase gives a grave prognosis, and it is generally considered that the presence of β-hydroxybutyric acid indicates greater severity.
Acidotic acidosis is due either to the abnormal formation or ingestion of acid substances, or to decreased elimination of normal metabolic products. Ketosis is the important example of the former, and retention of acid phosphates of the latter. In either case, the body is robbed of its bases. The acidosis of diabetes mellitus is characterized by ketosis and increased NH3 quotient of urine, while that of nephritis is a phosphate retention without ketosis, and, as one would expect, the NH3 quotient is usually not increased. Infantile diarrhoea with ileocolitis shows a marked ketosis, but, lacking the ileocolitis, the ketosis is only moderate and the acidosis is due to phosphate retention.
The appearance of an acidosis in disease constitutes a serious development demanding immediate attention. It is usually present at time of death and may be the immediate cause. We must be prepared for the appearance of acidosis in the course of numerous cosmopolitan diseases, and its presence has been recognized in a few tropical conditions. Before we generally recognized the great importance of the acidosis factor in pathology, there were two standard treatments for yellow fever and blackwater fever, the Sternberg one in the former and the Hearsey one for the latter, both of which had as a basis the administration of alkalis, which is our best means for neutralizing the deleterious action of increased acid production in the body or defective elimination of the same. It was a very important contribution to the therapeutics of cholera when Sellards, recognizing the tendency of the nephritis to produce an acidosis in this disease, made use of intravenous injections of NaHCO3 to combat the condition, thus counteracting the anuria, one of the chief complications leading to death. More recently, the Egyptian workers noted an acidosis in kala-azar, a finding verified and emphasized by Rogers. There is also an acidosis in heat stroke, so that intravenous or rectal injections of NaHCO3 are of value. It will thus be seen that acidosis is a most important condition to keep in mind in tropical conditions, and it will be well to be on the watch for other varieties of disturbance of acid-base equilibrium.
Relative to the administration of bicarbonate in treatment, there is now a decided reaction against the use of amounts that may prove injurious by reason of the danger of alkalosis. There is a tendency to employ it only in decompensated acidosis, and control it by estimations of plasma CO2 capacity, 0.5 gm. NaHCO3 per 19 kg. body weight will raise the plasma CO2 capacity by 1 vol %. It is distinctly contraindicated in cases whose low plasma CO2 is due to acapnial processes. Early administration is desirable in children, and good results are obtained, especially with the older ones. An acidosis, however, once established in infants may cause death despite alkali. In order to avoid over-dosage of bicarbonate, methyl red, which is more sensitive than litmus to early changes in the reaction of the urine, should be employed as an indicator. The appearance of a yellow color upon its addition to the urine is the sign to suspend further administration of alkali.
Glucose is indicated in conditions with ketosis due to carbohydrate deficiency, providing the organism can assimilate it.