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is decreased; the chlorides are decreased ; and as unnatural constituents there are albumen, casts of tubes, epithelial cells, and mucus. These conditions of the renal secretion are those common during the absence of pyrexial disturbance dependent on local inflammatory lesions. In pyrexial states the urine may become highly coloured, and may even give an abundant proportion of urea.*

CAUSE AND CAUSATION OF URÆMIC COMA. We know as a primary fact that uræmic coma is the result of arrested secretion of urine

The proposition is proved by the direct experiment performed on inferior animals, of arresting the urinary secretion, either by removal of the kidneys, by ligature of the renal vessels, or by division of the renal nerves. When any one of these experiments is carefully conducted, the symptoms and pathology of uræmia are produced with as much accuracy of detail as can be desired.

The symptoms caused by suppression of the function of the kidney (I speak from my own experimental observation conducted on dogs) vary somewhat according to the degree of the operation. If both kidneys be removed from action, uræmia is an inevitable fact. If one kidney only be suppressed in function, uræmia in the majority of cases is again the fact; but occasionally there is this exception, that the

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* For the most perfect history extant on the condition of the urine in acute and chronic uræmia, I refer the reader to Dr. Parkes's work On the Urine, chap. v, pp. 376-394.

IOUS

animal recovers without the occurrence of any serious mischief. Granting the accession of uræmic symptoms after either operation, they are not usually presented for ten or twelve hours. The first symptom then observed is a rigor, which subsiding leaves the subject sleepy and motionless. For some time, however, he may be roused without much difficulty ; but on the occasion of all such attempts he is, as a general rule, disposed to vomit. He will refuse food, but will often partake freely of water. Dogs in this state never express anger nor sign of acute pain. At intervals there are paroxysms of convulsion, but very subdued in kind, and apparently occurring during periods of oblivion. After the development of the first rigors, the temperature of the body rises ; I have seen the thermometer in the mouth rise, for example, six degrees beyond that at which it stood before the operation. The respiration, so soon as the somnolency is established, becomes markedly irregular; it will vary ten or even twenty in number per minute; at the same time, it rarely exceeds fifty inspirations and expirations per minute. Corresponding with this irregularity of respiration, the action of the heart is equally unbalanced. There may be a variation of so many as twenty and from that to thirty beats per minute ; and here too, as in the human subject, this peculiarity may be marked, that the irregularity shall extend over a long space, and so observed shall become very obvious, while per beat it shall not stand out at all distinctly. If these symptoms have been induced by the removal of but one kidney, the probabilities are, that once or twice in the first eighteen hours after the operation a small quantity of urine will be passed. On exami. nation the fluid will be found albuminous, and perhaps containing blood or fibrine.

The symptoms thus detailed usually continue for twenty-four or thirty hours without any striking modification. At last the gap in the respirations becomes more distinct, an interval of even ten seconds intervening between two inspirations, followed by a series of rapid expirations. At this stage the pulse will cease to beat altogether during the intermission of the respiration; but as the hurried breathing is remanifested, the action of the heart will follow, and be so quick as scarcely to admit of being counted. The temperature of the body, previously raised, now begins to fall; convulsive actions give way to an entire passivity and prostration of muscle. The coma continues, and at last death takes place as from universal muscular paralysis. The heart seems to me to die first.

After death, post mortem rigidity is fully developed. The blood in both systems is usually dark, and is often either fluid or in a soft jelly-like condition ; it coagulates slowly if found fluid, or may not coagulate at all. There is great vascular congestion of the lungs, the abdominal viscera, and the brain; and sometimes there are effusions of serum into the serous cavities, in which effusions urea may be found. The muscles are dark; and the endocardial surface may be stained deeply. The alimentary tract may also show signs of redness and congestion.

Thus between uræmia as it occurs from disease, and as it is induced by the synthetic process, there is identity both as regards symptoms and pathology The proposition founded on this identity accepted, we have next to ask—What is there in normal urine, (for we may take the urine as normal) capable of producing the toxæmic symptoms of uræmia ? :::::

Setting aside hypotheses which have been invented merely as verbal trophies, there are certain speculations which demand our careful attention. Let us note them.

The earliest accepted view is that which attributes the symptoms of uræmia to retained urea, which in fact accepts urea, or, in more correct words, cyanate of ammonia, as a narcotic poison. This view has been by some eminent authorities set aside, to be recently revived and most ably advocated by a distinguished American physiologist, Dr. Hammond.

Another hypothesis is one put forward by the justly eminent Frerichs. He argues that the retained urea, undergoing decomposition in the body, is converted into carbonate of ammonia. The carbonate of ammonia thus produced is, according to Frerichs, the toxic agent.

There have been at various times certain other hypotheses put forward, which have more or less ignored urea as a producing cause, either in a direct or indirect sense, and in substitution for it have suggested as the poisonous agent other constituents of the urine; as the water in excess in the blood, or the constituents of the urine altogether. Into all these later hypotheses a certain vagueness enters, which throws. us back at once on the first and fundamental proposition, and leaves us with that alone in our possession as a fact.

Men who know nothing of the immense difficulties of conducting physiological researches may, I am aware, be ready with their criticisms; and may twit their more inquisitive and laborious compeers on their failures in satisfactorily settling a question on the surface of it so simple. But, in truth, in actual practice the question is one of immense difficulty, requiring for its solution not only actual experiment, but experiment so devised as to give, on the one hand, direct affirmative or negative replies, and on the other hand to be so far free of side influences, that the facts which are either affirmatively or negatively given shall not admit afterwards of interpretation by any new reading of their cause.

Let us, in considering this question, divest our minds for the moment of all thoughts respecting the immense interests which attach to its solution ; let us throw aside every prejudice or weight of past learning that may so easily beset us ; let us make no ambitious strain towards divining the riddle; let us use no oracular obscurities, chemical or physical ; let us ask the aid of bare common sense, rest on it alone, and, at the risk of being considered puerile, question nature with the simplicity of a child.

We know now with tolerable accuracy the composition of the urine; and we can prove therefore that a certain fluid, the constituents of which we can

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