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was examined every hour for ammonia, but at no time was it detected. It was, however, found in the blood last drawn. There was neither purging nor vomiting. Immediately after death the following post mortem results were yielded :
« The substance of the brain appeared to be perfectly healthy; but there was considerable injection of the vessels of the meninges. The ventricles contained about 15 cubic centimetres of serous fluid. Urea was detected in this by chemical analysis, and by microscopical examination. It was likewise found in the blood from the sinuses.
"The vertebral canal was laid open, and the spinal cord examined. Its substance presented a normal appearance, but there was some congestion of the vessels of its membranes.
“The chest contained a small quantity of serous fluid. The lungs were congested, but were otherwise healthy. The heart was of normal size, and did not appear to be in the least diseased. It contained a considerable quantity of fluid blood; 100 grammes were collected from it and the large vessels. The urea in this quantity amounted to 0.873 of a gramme.
“Upon microscopical examination of this blood, the red corpuscles were found to present a crenated margin, and to be in decidedly less than the normal quantity. The white corpuscles were very much increased in quantity; as much as in well-marked leucocythemia.
"The cavity of the peritoneum contained a small quantity of serous liquid. The membrane was in places slightly congested.
“ The liver was healthy in appearance; but the spleen was considerably enlarged, and contained much more than the normal quantity of blood. The tissue of this latter organ, when examined microscopically, was found to present several important deviations from the normal structure. The Malpighian corpuscles were almost entirely absent, and there was a very great increase in the number of parenchyma cells. These latter were much larger than I (Hammond) have ever found them in the spleen of the dog. The red blood-corpuscles in the splenic blood were generally aggregated in groups, and were of irregular forms.
“ The stomach was opened, and presented nothing abnormal. The contents, consisting of mucus with a few pieces of bone, were of alkaline reaction, and contained both urea and ammonia, the latter in considerable amount.
“ The kidneys were enlarged and very much congested. Upon cutting into them, the blood poured out from innumerable orifices. There was no obstruction to either the renal arteries or veins that was discovered after death. The tissue of the kidneys, when submitted to microscopical examination, showed excessive congestion of the capillaries, and enlargement of the Malpighian bodies. Into many of these latter extravasation of blood had taken place, and the tubes were gorged with this fluid...
“The bladder contained a small quantity of bloody urine.”
There are not in every case such decided results, on the injection of urea directly into the circulation,
as are above given from the experiment by Dr. Hammond. Indeed, the effects which resulted from his experiment may be considered due to the congestion of kidney produced, as much as to the direct influence of the urea injected; for the fact is that urea, after being injected into the veins, is carried out of the body by the kidneys with such rapidity that its toxæmic properties are not elicited, unless some obstruction be induced in the secerning organ. Impressed with a knowledge of these facts, I have recently instituted a different series of experiments, by injecting the urea in watery solution, not into the blood, but simply under the skin or into the peritoneal cavities of animals. The following is an epitome of the results obtained. • Injected in solution into the dorsal cuticular sac of frogs weighing from 600 to 650 grains, urea is a poison, fatal or not according to the dose. Thirty grains of urea dissolved in a drachm of water produce profound coma and prostration in twenty minutes, with death within the hour. There is great collapse of the tissues, but there are no convulsions, death being too rapid for this effect. Previously to death there is no indication of ammoniacal evolution from the animal, but afterwards the putrefactive changes are very rapid.
When doses of fifteen grains are injected in like manner into similar animals, the symptoms do not appear within a period of half an hour after the injection, and life is prolonged nearly to the second hour. In other respects the symptoms are the same. From doses of five to ten grains, injected into frogs of the weight already mentioned, severe symptoms are elicited, but with recovery in the end. Symptoms of prostration and coma appear in from two to three hours, and remain little abated for four hours or four hours and a half; there is usually convulsive movement in these cases towards the end of the third hour, such movement seeming to augur recovery. The bodies of the animals thus treated assume externally a dark aspect; and, while recovery is taking place, the whole skin is covered with a frothy excretion.
In young warm blooded animals, as young rabbits, the injection of sixty grains of urea dissolved in a hundred and twenty grains of water is followed within an hour by tremors and coma; the tremors soon lapse into active convulsions, with rolling on the side, and constant twitching of the ears. In three hours the coma is most profound, and the convulsions more feeble. Death occurs about the fourth hour after the injection; while recovery, if that take place, commences about the same period. The pupils are fixed and dilated, and the breathing is very irregular.
I would suggest to any practitioner who, conversant with acute uræmia as it is seen in the human subject--say in the child suddenly struck down by suppression of the renal secretion during an attack of scarlet fever-has not seen uræmia as synthetically presented, to perform the experiment I have named on a young rabbit; he will be astounded at the analogy of the symptoms induced with those which he has seen in the human sufferer from uræmic toxæmia.
After death from injection of urea into the body of an animal, the muscles are found slightly darker than natural; the blood very dark and loosely coagulated; the surface of the serous cavities suffused, and not unfrequently lined with serous exudation. The kidneys are intensely congested and dark; the alimentary canal is sometimes suffused over its mucous surface.
With these synthetical facts so unmistakably presented to us, we need not, I think, go further for a cause of uræmia than to the urea. For although creatinine, one of the substances which we have noticed as a possible cause of the uræmic symptoms, is in truth an ammonia, and may therefore ultimately be found to have a physiological effect analogous to that of urea itself, we have a sufficient cause of the phenomena, independently of a consideration of that organic compound. The same remark applies to creatine.
Accepting, therefore, the urea as the primary toxic agent in uræmia, we are led to ask further, whether the effects demonstrated are due to urea itself, i.e. to urea acting unchanged as the poison; or, whether it undergoes decomposition, and the veritably acting poison is a product of that decomposition? Whether, in fact, Frerichs is right or wrong in suggesting that the poison is such a product, in the form of carbonate of ammonia ?
The inquiry opens two questions. 1. In the blood, during uræmia, is an excess of ammonia an universal