Hemoglobinuria occurs when there is such extensive destruction of red blood-cells within the body that the liver cannot transform all the hemoglobin set free into bile-pigment. The most important examples are seen in poisoning, as by mushrooms and potassium chlorate, in malignant malaria (blackwater fever), and in the obscure condition known as "paroxysmal hemoglobinuria." This last is characterized by the appearance of large quantities of hemoglobin at intervals, usually following exposure to cold, the urine remaining free from hemoglobin between the attacks.

Detection.—Teichmann's test ([p. 202]) may be applied to the precipitate after boiling and filtering, but the guaiac test is more convenient in routine work.

Guaiac Test.—Mix equal parts of "ozonized" turpentine and fresh tincture of guaiac which has been diluted with alcohol to a light sherry-wine color. In a test-tube or conical glass overlay the urine with this mixture. A bright blue ring will appear at the zone of contact within a few minutes if hemoglobin be present. The guaiac should be kept in an amber-colored bottle. Fresh turpentine can be "ozonized" by allowing it to stand a few days in an open vessel in the sunlight.

This test is very sensitive, and a negative result proves the absence of hemoglobin. Positive results are not conclusive, because numerous other substances—few of them likely to be found in the urine—may produce the blue color. That most likely to cause confusion is pus, but the blue color produced by it disappears upon heating. The thin film of copper often left in a test-tube after testing for sugar may give the reaction, as may also the fumes from an open bottle of bromin.

6. Diazo Substances.—Certain unknown substances sometimes present in the urine give a characteristic color reaction—the "diazo reaction" of Ehrlich—when treated with diazo-benzol-sulphonic acid and ammonia. This reaction has much clinical value provided its limitations be recognized. It is at best an empirical test and must be interpreted in the light of clinical symptoms. Although it has been met with in a considerable number of diseases, its usefulness is practically limited to typhoid fever, tuberculosis, and measles.

(1) Typhoid Fever.—Practically all cases give a positive reaction, which varies in intensity with the severity of the disease. It is so constantly present that it may be said to be "negatively pathognomonic": if negative at a stage of the disease when it should be positive, typhoid is almost certainly absent. Upon the other hand, a reaction when the urine is highly diluted (1:50 or more) has much positive diagnostic value, since this dilution prevents the reaction in most conditions which might be mistaken for typhoid; but it should be noted that mild cases of typhoid may not give it at this dilution. Ordinarily the diazo appears a little earlier than the Widal reaction—about the fourth or fifth day—but it may be delayed. In contrast to the Widal, it begins to fade about the end of the second week, and soon thereafter entirely disappears. An early disappearance is a favorable sign. It reappears during a relapse, and thus helps to distinguish between a relapse and a complication, in which it does not reappear.

(2) Tuberculosis.—The diazo reaction has been obtained in many forms of the disease. It has little or no diagnostic value. Its continued presence in pulmonary tuberculosis is, however, a grave prognostic sign, even when the physical signs are slight. After it once appears it generally persists more or less intermittently until death, the average length of life after its appearance being about six months. The reaction is often temporarily present in mild cases during febrile complications, and has then no significance.

(3) Measles.—A positive reaction is frequently obtained in measles, and may help to distinguish this disease from German measles, in which it does not occur.

Technic.—Although the test is really a very simple one, careful attention to technic is imperative. Many of the early workers were very lax in this regard. Faulty technic and failure to record the stage of the disease in which the tests were made have probably been responsible for the bulk of the conflicting results reported.

Certain drugs often given in tuberculosis and typhoid interfere with or prevent the reaction. The chief are creosote, tannic acid and its compounds, opium and its alkaloids, salol, phenol, and the iodids. The reagents are: