It is evident, then, that the liver is an important factor in the disposal of ammonia, and that if the liver is functionating properly, it can effectually prevent the passage of ammonia from the alimentary tract to the systemic circulation. It does this by changing the ammonia to urea, the changes being represented by the following formulae:

1.

Nh4hco3.Nh4nh2co2

=

3CO(Nh2)2 +

Co2 +

5H2O

Commercial ammonium carbonate

Urea

2.

Nh4nh2co2

=

CO(Nh2)2 +

H2O

Ammonium carbamate

Urea

3.

(Nh4)2Co3

=

CO(Nh2)2 +

2H2O

Neutral ammonium carbonate

Urea

It becomes a question, then, whether any of the ammonium hydroxide or carbonate administered by mouth gets through the liver without being changed to urea. If all the ammonia is changed, then no ammonia gets into the circulation to exert a systemic action, and the only effects of these ammonia preparations taken by mouth must be the local and reflex ones. It is possible, of course, that some of the ammonia gets through the liver without change, or passes into the circulation by way of the lymphatics without immediately entering the liver, and so exerts its systemic effects before it is changed to urea. If any escapes the liver, it is probably changed to urea by the muscles. Some of it is absorbed as ammonium chloride, which it forms with the hydrochloric acid of the gastric juice.

Ammonium carbonate administered hypodermatically escapes the liver for a time, and exerts a strong systemic poisonous action; but even when it is administered in this way, it is soon changed to urea by the muscles and liver. Nervous System. - Following the inhalation of the gas or the swallowing of the preparations, there is an immediate reflex stimulation of the vasoconstrictor and respiratory centers in the medulla, and perhaps of the vagus or the accelerator centers. This effect is evidently reflex, from the surface irritation; for it is almost instantaneous, and manifests itself before the drug can be absorbed. This prompt, though ephemeral, reflex stimulation is taken advantage of to relieve mild collapse, as in fainting or feelings of faintness. If the drug is absorbed into the systemic blood-stream, as when administered intravenously, and perhaps when given hypodermatically, there is a direct stimulation of the vagus and vasoconstrictor centers. There is also increased irritability of brain and cord, so that after large doses there may be convulsions like those from strychnine, followed by coma and death.

Circulatory Organs

The immediate result of the reflex effect upon the vagus, vasoconstrictor, and accelerator centers is a rise in arterial pressure, though the rate of the heart is variable, according as vagus stimulation predominates, or accelerator. After absorption, as from hypodermic dosage, there is slight direct stimulation of the vasoconstrictor and the vagus centers and of the heart muscle, so that arterial pressure is raised; but, owing to the rapid change of the drug in the system, this is of short duration. Very large doses depress the heart muscle at once, or after a brief period of stimulation.

The whole action is so brief that ammonia, whether inhaled or given by mouth or hypodermatically, is of use as a circulatory stimulant only momentarily, and it has its great value in just those passing depressions of the circulation which show in feelings of faintness or fainting.

Respiratory System

A strong inhalation, or a concentrated dose by mouth, will stop the respiration for a moment; and this is followed by a reflex stimulation of the respiratory center from the local irritation. If the drug is absorbed, there is a direct stimulation of the center. So, in any case, breathing is deepened.

When taken by mouth, the bronchial, nasal, and throat mucus are believed to be rendered more fluid, and for this reason the carbonate is used in cough mixtures. But, as noted above, the carbonate is in all probability changed either to the chloride or to urea, hence it does not act by its alkaline property to fluidify the mucus. In addition, ammonia is not excreted by the lungs (Magnus) or in the bronchial mucus, for after the administration it has been found neither in the bronchial mucus nor in the expired air (Mayr). The probability is that if unchanged in the stomach it has a nauseant action, and acts reflexly to increase and fluidify the bronchial secretions. In those cases in which it is changed to the chloride it may be excreted by the bronchial glands. (See Ammonium Chloride.)

Secretions

As just stated, it tends to loosen and fluidify mucus. This effect is especially to be noted in the nose, throat, bronchi, and stomach. Both urea and ammonium chloride are diuretic.

Elimination

The carbonate and hydroxide are changed to the chloride or to urea. In the latter case the excretion of urea is increased without increase in general metabolism. The blood is not rendered more alkaline, as it is by the hydroxides and carbonates of the fixed alkalies, and the urine reaction is probably unaffected.

Toxicology

1. From Swallowing

Ammonia water, swallowed undiluted, causes great local irritation and inflammation of mouth, throat, esophagus, and stomach. There may be vomiting. The inflammation may go on to ulceration or general sloughing; and, if the patient recovers, may leave cicatricial constrictions which will give trouble in after life. If the burns are very extensive, death may result from shock. The ammonia fumes may get into the larynx and produce edema of the glottis. Treatment: In the mouth or stomach, the poison may be neutralized by mild acids, such as vinegar or lemon-juice; the pain and inflammation may be lessened by bland oils or fats, such as olive or linseed oil, lard or butter, or by the white of egg, milk, or demulcent mucilaginous drinks.

2. From Inhalation

Strong ammonia fumes inhaled, as from the escape of the gas in ice-plants, or when the liquid is swallowed, may cause swelling and inflammation of the larynx and bronchi, and through edema or spasm of the glottis may cause asphyxia and death. The treatment is to give plenty of air or inhalations of oxygen. If the glottis is closed so as to prevent breathing, intubation or tracheotomy should be performed. If there is edema of the glottis, the tissues should be cut at once to relieve the swelling.

Effects After Absorption

If the poison is absorbed, there may be strychnine-like convulsions, collapse, coma, and asphyxia, death being due to paralysis of the respiratory center or to the convulsive interference with breathing. The treatment is artificial respiration, oxygen, absolute repose, external heat, and other treatment for collapse or convulsions.