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analytically read off, is capable of producing the specific symptoms of uræmia. We turn naturally from this knowledge to an examination of the constituent parts of the urine, and ask, respecting each of them, one after the other, can this be the poison ? We discard several at once, from a comprehension of the fact that the symptoms they produce when present in excess in the body are not of a character analogous to the symptoms of uræmia : by this principle we exclude, with safety, uric, hippuric, and phosphoric acids; the chloride of sodium; the sulphates of potassa and soda; the lime and magnesian phosphates ; and the iron. We have, again, the cells of epithelium and mucus derived from the bladder and mucous tract, which to a certain amount are present in every specimen of urine. We may exclude these organic products as the cause of uræmia ; for, although it has been stated that urine containing them is poisonous on injection into the veins of healthy animals, while urine from which they have been freed by filtration is not poisonous on such injection, it has never been shown that the symptoms produced by the injection of unfiltered urine are those of uræmia. Further, it is obvious that in uræmia arising from obstruction in the renal vessels, or from any other cause by which the secretion of urine is prevented at the source of the secretion, the epithelial cells and mucus derived from the conveying mucous channels beneath the source, cannot for a moment be considered as the cause of the symptoms.
Thus by the exclusion process we are driven at last to these constituent parts of the urine, the water,
the urea, the creatine and the creatinine. Are they by retention the cause of uræmic coma?
There can be no doubt that water in excess in the blood produces symptoms similar to those presented in some forms of uræmia. Some years ago I demonstrated this fact by producing in animals artificial dropsy. The facts elicited by these inquiries will be found in my essay on the Coagulation of the Blood; but the summary of them may be briefly stated as strictly in place here.
When an amount of fluid, equal to a fifth part of the weight of an animal (dogs were used exclusively in my experiments) is injected into the peritoneal cavity, death is the result. Very shortly after such injection the animal becomes drowsy, and eventually quite comatose; the coma advancing in proportion as the fluid is absorbed into the blood. The animal may now and then, at long intervals, get up and attempt to walk with a drowsy tottering gait, but quickly reclines again and sleeps on. The ordinary period of death is from ten to twelve hours after the operation; the death is so quiet that it seems like a continuation of sleep.
If the amount of water injected be less in weight than a fifth of the body of the animal, the symptoms induced are identical in character with those already described, but the animal gradually recovers from his somnolency; he remains feeble for a few days, refuses food and drink, passes large quantities of urine, presents loud anæmic bruit in the neck, staggers in his walk, and is very cold over the whole of the surface of the body. The first indication of convalescence is a desire for food. At least three days elapse before the animal begins to run about healthily; but when recovery is set up it proceeds rapidly, and no ill effects seem to follow.
Such are the general symptoms of an excess of water in the blood; but there are other special modifications in the blood itself possessing great interest. If blood be drawn while the animal is suffering from the effects of the injection, that fluid is found thin, of red colour, and very feebly coagulable. In extreme cases the property of coagulation is lost altogether; and if it be attempted to extract fibrine by agitation of the blood, the experiment fails. Even the coagulation of the albumen by heat is feebly presented. The blood consequently flows with great ease from a wound; and the anæmic hæmorrhagic diathesis is set up. The red corpuscles are much changed; they are greatly enlarged, and assume an oval form. As recovery occurs, these abnormal conditions gradually pass away; but for many weeks the corpuscles retain their diseased outline and character. In a case of extreme anæmia in the human subject, my friend and colleague, Dr. Leared, observed the same modifications in the blood-corpuscles that I have described as occurring in the dog after the production of artificial anæmia and dropsy.
If the symptoms thus induced by the introduction of water into a healthy organism, be compared with those observed in acute uræmia, a certain analogy at once strikes the mind; e. e., there are the same de
cided prostration and coma. But here the analogy ceases. There is no period during which the heat of the body is increased; there are no convulsions; there is no dilatation of the pupil; there is no vomiting; there is no stertor in the breathing; and lastly, there is none of that irregularity of the respiration and circulation which so peculiarly distinguishes uræmic intoxication. · On the other hand, there is one symptom which is exhibited after the injection of water into the organism which is not present in uræmia, or at all events is not necessarily presented; I mean anæmic bruit.
Taking the symptoms, then, as derived from both sources from true uræmia on the one side, and from surcharge of water on the other—we are bound to altogether exclude from the argument the hypothesis of excess of water as the cause of acute uræmia. When we admit that the coma of uræmia is possibly in some cases increased by suppression of mere aqueous secretion, we admit honestly and necessarily an intensifying source of one particular symptom; but we fail to trace anything more than a coincidental fact, even in this concession.
From the consideration of water as a cause of uræmic coma, we pass to urea. Is this a poison, and is it the poison ? : The answer to these questions is to be found only by experiment on inferior animals. To solve the question by this means many hands have been employed, and different opinions have been arrived at. An absence of uniformity in the mode of conducting
the inquiries has, I think, led to the differences observed.
Administered by the mouth to an animal, urea can scarcely be called a poison, unless the dose be enormously large. A dog weighing ten pounds takes a drachm of urea with little result; but in rabbits the dose named excites vomiting and convulsion, and sometimes leads to death. Taking it all in all, the method of experimenting by administering the substance by the mouth is most imperfect. In some cases the compound is decomposed in the stomach ; in other cases it is in part absorbed into the blood, and passes off by the kidneys; in many instances it is vomited in great portion soon after it is swallowed, or it may pass off by the bowels in a brisk purge; however it is disposed of, it does not definitely and clearly bring out the true uræmic symptoms as they are elicited on suppressing the renal function by extirpation of the kidney. .'
Administered by direct injection into the veins, urea can be made to induce symptoms essentially uræmic. Dr. Hammond records an experiment in which the injection of five grammes of urea, or 77.17 grains in solution in water, into the jugular vein of a dog weighing 38pounds, at 10 a.m. produced after the lapse of 45 minutes slight spasms of the muscles of the eyelids, and in 50 minutes severe general convulsion; the convulsions continued for fifteen minutes with great violence, when coma followed and lasted until 6 p.m., when the animal died. There was no excretion of urine after the injection of urea. The breath