II. On the Association of Urinary Deposits, with remarks upon their probable Causes.-By W. HENRY KESTEVEN, M.R.C.S.

My object in the present communication is to bring forward certain conclusions with reference to the concurrence of, and the pathological and therapeutical significance, of some common forms of urinary deposits, when in excess. These conclusions are based upon the chemical and microscopical examination of deposits from morbid urine, in cases of which I have for several years preserved notes and drawings. The deposits to which I refer are uric acid, calcium oxalate and oxalurate, and ammonio magnesian or triple phosphate. If we refer to works on physiology we find two, at least, of these substances among the normal constituents of urine, viz. uric acid. and ammonio-magnesian phosphate. Of the third, calcium oxalate, although it cannot be said to be constantly found in urine, Dr. Golding Bird has shown that it is often present from various causes during health. In the specimens which I have examined with reference to the present observations, these substances were always in excess.

Uric Acid.-That the appearance of an excess of this acid in the urine is caused by a faulty condition of the blood there is no doubt. The difficulty lies in saying in what that faulty condition consists, and where, or in what organ, that morbid condition is brought about.

Uric acid, when in excess, in common with some forms of albumen and with calcium oxalate, is a product of what is called "retrograde metamorphosis "-in other words, of a degeneration of tissuein contradistinction to regeneration or repair. My conclusion with regard to this question, based on the facts about to be adduced, is that this faulty condition of the blood takes place in the respiratory organs. The blood, from various causes, is not properly oxygenated. In consequence of this vice in its nutrition, the tissues generally are badly nourished, and instead of the urine containing its normal proportion of uric acid, this constituent is in considerable excess. Any circumstance, or combination of circumstances, that prevents the blood from receiving its due supply of oxygen, will produce an excess of uric acid in the urine, e.g., a strumous diathesis, so often associated with tubercular mischief, a weak heart, confinement to the house arising either from disinclination or disability for exercise. Any of these circumstances may be regarded as giving rise to this condition in a greater or less degree. The following facts bear strongly in this direction. In 150 carefully recorded microscopical observations I find twenty-seven in which uric acid was in excess. Of these twenty-seven observations six were taken from the urine of children, three from that of a young pregnant woman, four from

Of

adult men, three from old men, and eleven from aged women. the six observations from children, four were from different specimens of urine of the same child, a girl, aged six years, and two were from a boy, of about the same age. Each of these children was markedly strumous. The three observations taken during pregnancy occurred in the same patient, who was suffering from albuminuria. She was, by my advice, staying at home, maintaining a recumbent position, as she had edema of the feet and ankles. In the fourteen observations from old people the presence of excess of uric acid in the urine was associated either with corpulency and difficulty of breathing, asthma, weakness of the heart's action, emphysema, and in some of the cases from all these conditions combined. In the four observations from adult men three were from a man with asthma and emphysema of the lungs. In the fourth observation in this class I cannot so distinctly attribute the condition to derangement of any one or more

organs.

From these observations it is fair to conclude that the main cause of an excessive excretion of uric acid is due to a vicious nutrition of the blood, consisting in a defective supply of oxygen, in consequence of an impairment of the pulmonary function.

Calcium Oxalate.-Crystals of this salt are most commonly met with in the form of an octahedron. They are also said sometimes to assume the form of a dumb-bell, but it is now generally admitted that this form is another chemical compound which has received the name of Calcium Oxalurate. Among my observations I have thirtynine in which an excess of calcium oxalate has been found. In twenty-two of these it was the only crystalline substance represented. In fourteen instances there was also uric acid in excess, and in the remaining two there was also calcium phosphate. In nearly every case from which these observations have been taken there has been found also, either at the same time or at some other period, an excess of uric acid in the urine. In many of them, there have also appeared a few dumb-bell crystals of calcium oxalurate. Further, among the specimens above referred to, in which uric acid has been in excess, I have sometimes found these same dumb-bell crystals.

From these circumstances I conclude that in many cases one and the same cause may be operative in producing these seeming differences. This cause, however, is not always equally efficient, and hence the difference in the resulting appearances. Taking for granted that the cause of these is a deficient supply of oxygen, we shall see from the chemical composition of uric acid, as compared with that of oxalic acid, that it is in the production of the former of these acids that this common cause is most potent. The chemical symbol for oxalic acid is H2C2O4, a

non-nitrogenous substance. That for uric acid, HC,NO; this therefore contains, besides the nitrogen which oxalic acid has not, more carbon and hydrogen, and less oxygen. It is therefore not difficult to conceive that a substance which, like uric acid, contains more of the products of decomposition, should be called into existence when the decomposing cause is more potent, and that a substance like oxalic acid should be formed when the cause is less potent. The substance before alluded to, calcium oxalurate, would seem, from its name, to be an intermediate step between these two substances. The fact that it is found sometimes in specimens in which uric acid is in excess, sometimes where the oxalate is in excess, and lastly, in specimens where both have been found, also bears out this view.

These facts and the coexistence of these substances in the same urine, the occasional substitution of one for the other in urine taken at different times from the same patient, manifestly lead to the conclusion that they are nearly always the result of one and the same cause. That cause, as already pointed out, is a faulty condition of the blood, consisting in a deficiency of oxygen, brought about by impairment of the respiratory function.

With regard to the treatment of the morbid conditions, indicated by the appearances of these deposits in the urine, it is commonly laid down in the text-books that when we have to deal with uric acid in excess we should give alkalies; and such mineral acids as nitric and hydrochloric acids, when we meet with calcium oxalate; and we are further told that what "favours in the first would be detrimental in the second;" that what would be of service against the oxalic deposit is likely to encourage the lithic. The view here taken of the nature of these pathological conditions militates against these rules. The more rational treatment of patients suffering from these morbid conditions seems to consist in the adoption of such means as will obviate or do away with the cause of the morbid condition, that is to say, by ensuring a more liberal supply of oxygen to the blood. As the causes of the deficiency of this important ingredient are many, so the means adopted to obviate them must be numerous. But there is no doubt that one of the most successful methods of treating these complaints is the removal of patients suffering from them to places where they may breath a purer air.

Ammonio-magnesian Phosphate.-This salt was formerly called triple phosphate; it appears in the urine in various forms, the most common of which is that of triangular formed prisms, with obliquely truncated extremities. Dr. Beale says-" It is most generally found in urine which also contains phosphate of lime in granules or amorphous masses.' Ammonio-magnesian phosphate can be produced in any urine by the addition of a strong solution of ammonia. When thus produced it has a peculiar penniform appearance; this,

ور

however, is only an early stage in the formation of the complete prism. Amongst my recorded observations I find eighteen in which this salt is figured as being in excess. On closer study of these observations I have noticed the fact that the urine from which they were taken was always alkaline, with the exception of one or two specimens, which are recorded as slightly acid. Besides these eighteen observations there are five in which there was found calcium phosphate, either alone or with some calcium oxalate; these are all noted as slightly acid.

There are not many observations in which ammonio-magnesian phosphate and calcium phosphate are recorded as coexistent.

It has been mentioned that it is possible to produce penniform crystals of ammonio-magnesian phosphate in any urine by the addition of strong solution of ammonia; also that these penniform crystals are merely modifications of the perfect prism. These facts, taken with the constant alkalinity of those specimens in which there has been found an excess of the salt, point at once to, at least, one cause of the appearance of these crystals.

Among the normal constituents of urine, is the substance called urea. This, like many other highly complex chemical compounds, is very unstable in its nature. It is readily decomposed, and one of the results of its decomposition is the production of ammonia. The presence of this ammonia causes the formation and deposition of the crystal of ammonio-magnesian phosphate. The formation, however, of the crystals in this way takes place much more slowly, comparatively speaking, than when strong solution of ammonia is added to the urine; and this is the reason probably why the perfect form of the crystal, and not the penniform modification, is found in urine which has been left to itself. The appearance, then, of these crystals in the urine may be brought about by any cause which will detain the urine in its passage from the kidneys a sufficiently long time to disturb the weak connections which bind together the constituents of the urea.

These causes may, of course, exist in any part of the urinary passages the urethra, the bladder, the ureters, or the pelves of the kidneys themselves. One case which came under my notice deserves attention from its peculiarity. At a post-mortem examination I found the ureter plugged at the upper extremity with a whitish mass, portions of which were also found on the folds and interstices of the lining membrane of the pelvis of the kidney. On examination this was found to be composed of epithelial débris and innumerable crystals of ammonio-magnesian phosphate.1

Besides the alkalinity mentioned above there is also recorded in many observations the existence in them of scales of vesical epi

'Pathol. Trans.,' vol. xxiv, p. 18:

thelium, and in some also of pus-cells. Although these epithelial scales and pus-cells have been found in other specimens, they are more often found associated with this salt than with any other, and the fact must be borne in mind that their existence would not have been recorded at all had they not been in excess. Their presence proves that there has been in these cases some considerable amount of vesical irritation. Ammonio-magnesian phosphate, as is known to clinical observation, is at times present in the urine of patients suffering from eruptive fevers. This is partly, I apprehend, to be accounted for by the fact that in most illnesses the urine is retained for a longer time in the bladder than in health, and further, by the fact that a larger quantity of urea is excreted during attacks of acute illness. A discharge of phosphatic urine is said to be consequent on several kinds of nervous disorders-hysteria, epilepsy, mania, &c. Having regard to the comparatively large quantity of phosphorus which enters into the composition of nervous matter, there is, perhaps, some ground for the assertion that the nervous discharge which takes place in these disorders is associated with the appearance of phosphorus in the urine.

We should, however, bear in mind the more simple cause of its production, namely, the decomposition of the urea; and although it is possible that a discharge of nerve force over and above the normal amount may give rise to an excess of phosphatic salts in the urine, it must be admitted that the ammoniacal cause is the more likely of the two.

Ammonio-magnesian phosphate is, therefore, different from the other substances considered in this paper. It is not so directly a morbid product as they are. The main significance of it is that it points to the fact of a certain amount of urinary retention; beyond that it does not go, and to find out the site and cause of the retention we must appeal to other symptoms.

Shortly, to sum up our conclusions:-With regard to uric acid, calcium oxalate, and calcium oxalurate, these observations prove that they are often coexistent in the same urine, and that they may be found separately, in different specimens of urine from the same patient. This shows that something more than a chemical examination of urine is required for clinical purposes. That requirement is met by the use of the microscope, and thus its value as an instrument of clinical research is enhanced.

The cases in which the appearances recorded in my observations have occurred, and the relation which these appearances bear to one another, seem to prove that the cause of them is to be found in the vititation of the blood, by impairment of respiratory function. This being the case, the necessity of some modification of the usual method of treatment of these disorders is indicated. Finally, I conclude from the specimens of urine which I have examined that