The result in any case is diuresis, unless the molecular concentration of the plasma is decreased. For example, a hypotonic sodium chloride solution intravenously, because of its low salt content, will make a hydremia without diuresis (Davis).

Of dialyzable substances, those with a pronounced diuretic action are:

(A) Inorganic Salts

Sodium sulphate, sodium chloride, and sodium or potassium bicarbonate, but the only ones employed as diuretics are the bicarbonates.

(B) Organic Salts

The acetates, citrates, and tartrates, which break down into carbonates in the blood. They are potassium acetate, potassium citrate, potassium bitartrate, potassium and sodium tartrate, liquor ammonii acetatis, and liquor ferri et ammonii acetatis (Basham's mixture). The best of these is potassium acetate. (See Imperial Drink, page 88, and A. B. C. mixture, page 102.)

(c) Urea. (d) Dextrose. - (See Glucose.)

All these substances tend to have an effect upon the urination in direct proportion to the osmotic pressure which they exert. In hydremic plethora, if the kidneys are not functionating well, as in chronic nephritis, and there is water retention, the excess of water tends to transude through the systemic capillaries and to favor the production of edema and dropsy.

Water

Ordinary drinking-water is hypotonic, and is practically unabsorbed by the stomach. But it imbibes salts from the food or mucus, or from the superficial cells of the alimentary tract, or takes up the sodium chloride which is formed in the duodenum by the neutralization of the hydrochloric acid of the gastric juice. Hence it becomes a salt solution, and, instead of passing on through the intestine to the rectum, is absorbed. Therefore when excess of water is ingested the excess does not normally pass out with the feces; and under ordinary conditions of absorption, no matter how much is drunk, does not produce a movement of the bowels (Starling). So the ingestion of large quantities of water leads to a condition of hydremic plethora, which results in increased urination. Water in large amounts is, therefore, diuretic, and in its elimination tends to carry out certain dissolved substances, especially urea, sulphates, and phosphates. Leonard Hill says it only washes out the urea stored in the tissues and does not provoke increased destruction of tissue protein; but Hawk has gathered some evidence that copious water drinking results not only in a removal of stored-up urea, but also in increased protein destruction.

The body has a great capacity for the storing of water, so that even when the excretory apparatus is impaired, excessive amounts of water can be taken for many days before dropsy sets in. In these cases it is evident that a diuretic is indicated before dropsy is apparent. But water should not be given, for in dropsical conditions large quantities of water serve only to increase the already "water-logged" condition of the patient.

II. Measures Which Increase the Tubular Secretion, and III. Measures Which Decrease the Tubular Absorption. - Between these two, we cannot at present discriminate. The diuretics which act upon the tubules, however, may be divided for practical purposes into -

1. Those which are non-irritant to the kidney, and consequently in the larger doses do not produce inflammation - caffeine, theobromine, theophylline, diuretin, agurin. (See Caffeine.)

Caffeine itself, because of its dominant other effects, is little employed as a diuretic, but the action of the series is obtained by theobromine and theophylline (theocine) and their soluble combinations. Usually in conditions with undiseased kidneys, as in the edema of cardiac insufficiency, and less often in kidney cases, they are effective diuretics, and the author has in several instances seen the urine flow for twenty-four hours reach 200 to 300 ounces (6 to 9 liters) after two or three doses of 20 grains of theophylline or theobromine sodio-salicylate. In one dropsy case at the City Hospital the drug was continued for seven days with a high daily urine output and a total loss of 60 pounds in the patient's weight. However, because of their tendency to cause renal fatigue, Christian recommends that they be given in full dosage for a period of two or three days only, followed by a similar period without any diuretic. Both drugs are irritating to the stomach, theophylline being more so than theobromine; and in such case their soluble compounds in 5 per cent. solution may be given intravenously.

In acute and chronic nephritis the indication for the use of these drugs is not so clear as in the cardiac cases; indeed, with theophylline in renal cases Christian found that kidney efficiency as judged by the index of urea excretion was more often decreased by their use than increased, and with caffeine even in normal persons Benedict noted a degree of nitrogen retention. In a case of kidney disease at St. Luke's the urine rose to 300 ounces (9 liters) the first day, and remained high for the seven days during which the drug was administered (see Caffeine).

2. Those which are irritant, and in overdose may produce inflammation. They are:

(a) Volatile oils, and resinous or aromatic drugs, especially the oils of sandalwood, juniper, turpentine, the balsam of copaiba, and the drugs buchu, cubeb, kava-kava, matico, uva ursi, and cantharis. These are less prescribed as diuretics than as urinary antiseptics. The oil of juniper is present in "gin."

(b) Certain drugs which contain irritant glucosides and are mostly used in the form of infusion; for example, scoparius or broom, which contains scoparin, asparagus, which contains asparagin, and triticum, which contains triticin.

(C) Calomel

A dose of calomel at the beginning of diuretic treatment will often hasten, or at least appear to hasten, the on-set of diuresis. This is particularly true in venous stagnation. It may act by irritating the kidney cells; but its action is more probably due, not to direct diuresis, but to the relief of the kidneys through the removal of fluid by the bowels.