Urea is decreased in diseases of the liver with destruction of liver substance. It may or may not be decreased in nephritis. In the early stages of chronic nephritis, when diagnosis is difficult, it is usually normal. In the late stages, when diagnosis is comparatively easy, it is decreased. Hence estimation of urea is of little help in the diagnosis of this disease, especially when, as is so frequently the case, a small quantity of urine taken at random is used. When, however, the diagnosis is established, estimations made at frequent intervals under the same conditions of diet and exercise are of much value, _provided a sample of the mixed twenty-four-hour urine be used_. A steady decline {66} is a very bad prognostic sign, and a sudden marked diminution is usually a forerunner of uremia. The presence of urea can be shown by allowing a few drops of the fluid to partially evaporate upon a slide, and adding a small drop of pure colorless nitric acid or saturated solution of oxalic acid. Crystals of urea nitrate or oxalate (Fig. 19) will soon appear and can be recognized with the microscope. _Quantitative Estimation_.--The hypobromite method, which is generally used, depends upon the fact that urea is decomposed by sodium hypobromite with liberation of nitrogen. The amount of urea is calculated from the volume of nitrogen set free. The improved Doremus apparatus (Fig. 20) is the most convenient. [Illustration: FIG. 20.--Doremus Hinds' ureometer.] * * * * * Pour some of the urine into the smaller tube of the apparatus, then open the stopcock and quickly close it so as to fill its lumen with urine. Rinse out the larger tube with water and fill it and the bulb with 25 per cent. caustic soda solution. Add to this 1 c.c. of bromin by means of a medicine-dropper and mix well. This prepares a fresh solution of sodium hypobromite with excess of caustic soda, which serves to absorb the carbon dioxid set free in the decomposition of urea. When handling bromin, keep an open vessel of ammonia near to neutralize the irritant fumes. Pour the urine into the smaller tube, and then turn the stopcock so as to let as much urine as desired (usually 1 c.c.) run slowly into the hypobromite solution. When bubbles have ceased to rise, read off the height of the fluid in the large {67} tube by the graduations upon its side. This gives the amount by weight of urea in the urine added, from which the amount excreted in twenty-four hours can easily be calculated. If the urine contains much more than the normal amount, it should be diluted. To avoid handling pure bromin, which is disagreeable, Rice's solutions may be employed: (_a_) Bromin, 31 Potassium bromid, 31 Distilled water, 250. (_b_) Caustic soda, 100 Distilled water, 250.