[Reprinted from the Boston Medical and Surgical Journal of January 19,1887.1 / OXALURIA. BY F. W ELLIS, M.D., OF SPRINGFIELD, MASS. By oxaluria we mean the presence of oxalate of lime in the urine. It is not a disease - it is, at most, only an expression or symptom of disease. It is doubtful if we are justified in considering the presence of a slight amount of calcic oxalate in the urine as ab- normal. Traces of its presence in urinary sediments from individuals in apparently excellent health are very frequently met with. In some instances, the oxalic acid may be ingested in the vegetable food taken, for oxalic acid and the oxalates are found in very many plants. It is not likely, however, that these cases of slight oxaluria are always due to this cause. Every practitioner who has occasion to make frequent microscopical examination of the urine must be impressed with the number and variety of the cases in which calcic oxalate is encountered in this secretion. This frequency of occurrence tends to make us under- estimate the importance of the subject. When we reflect upon the importance of the chapter in medicine nd surgery devoted to urinary calculi, and when we ecall the fact that one of the most frequent, and cer- tainly the most dreaded, constituent of the calculi is calcic oxalate, nothing further is needed to indicate the interest that every physician should take in the subject of oxaluria. The calcic oxalate, or mulberry calculus, is harder than the other varieties, and, conse- quently, is the most difficult to crush and remove by 2 litholapaxy. It is apt to be rough, and, as a result of this irregularity of surface, excite a great amount of irritation. Even when it does not form the main sub- stance of the concretion, it often serves as the nucleus and starting point of others. For these reasons, every fact that tends to enlarge our knowledge of the mode of origin of calcic oxalate in the economy, and the causes of its deposition in the urinary tract, must be a desirable addition to medical science. Regarding the subject from this standpoint, no practitioner can ques- tion its importance. There is, however, great diversity of opinion as to the diagnostic significance of calcic oxalate deposits in the urine. Since the first recognition of this sub- stance as a urinary constituent, numerous contradic- tory statements have been made regarding the signifi- cance of such an occurrence. After an attentive perusal of the literature of the subject, and a careful consideration of the various theories advocated to ex- plain the origin of the oxalic acid, one cannot escape the impression that something essential to the success- ful elucidation of the question has been overlooked, or has not yet claimed sufficient attention. One of the mistakes generally made is that of re- garding oxaluria as a disease, and not as a symptom. Oxaluria, like albuminuria, is a symptom. The causes of albuminuria are widely different in their character, and the same may be true of oxaluria. Hence, in seeking for an explanation for the appearance of oxa- late of lime in the urine, we have no right to expect a single one applicable to every case. In treatingof oxaluria and oxalmmia, it will be useful, at the outset, to consider some of the undisputed facts bearing upon the subject. First, we know that oxalic acid is a poison. Fatal cases of poisoning with this substance are not uncommon. The careful experi- 3 ments of Koch1 demonstrate that the soluble oxalates paralyze the muscles, heart, and nervous system. A solution of neutral oxalate of ammonium injected be- neath the skin of a frog caused fibrillary muscular contractions, and paralysis of the voluntary muscles and the heart. The lethal dose, for the frog, was found to be 12£ m lligrams of the salt. Experiments upon warm-blooded animals gave quite similar results when the drug was injected subcutaneously. Another well-ascertained point is, that a certain pro- portion of the oxalic acid or oxalates introduced into the body through the stomach or subcutaneously reap- pears in the urine under the form of calcic oxalate. In the experiments of Koch just mentioned, crystals of oxalate of lime were constantly found in the kidney, and in that organ alone. In cases of poisoning by the acid, a large amount of calcic oxalate crystals can be obtained from the urine. These two facts having been determined ; namely, that oxalic acid is a poison, and that it manifests its presence in the system by its elimination in the urine as calcic oxalate, are we justified in assuming from these premises that whoever voids oxalate of lime in the urine is being poisoned? The views of different writers upon this point are very discordant. No un- equivocal answer can be given to the question until investigations have been made to determine the effects following the long-continued administration to animals of small doses of oxalic acid and the oxalates. I am not aware of any such experiments having been made. Another subject for experimental investigation is the action of solutions of calcic oxalate upon the physio- logical processes. I think that we have very little reason to expect, a priori, that solutions of calcic 1 Wirkung der Oxalate. Archiv. f. exp. Path, und Phar., Bd. 14, s. 153. 4 oxalate ■should not possess toxic properties. Ringer 2 has endeavored to show that the soluble oxalates arrest function by the withdrawal of lime from the tissues. He asserts that a lime salt must be present in the circulating fluid, to sustain the contractility of the cardiac muscle. He reports the following striking experiment: The detached ventricle of a frog's heart was enclosed in a Roy's " tonometer," and was sup- plied with an artificial blood mixture through a perfu- sion canula. A small amount of a five per cent solu- tion of oxalate of ammonium was then added to the circulating mixture. The ventricular contractions immediately grew weaker, and contractility ceased in a few minutes. The nutrient fluid was then diluted, but the ventricle remained inactive. A small amount of a one per cent solution of calcium chloride caused a speedy return of the spontaneous contractions. Ringer reports another interesting experiment which will chiefly interest us : He prepared two solu- tions, one containing chloride of calcium, and the other oxalate of ammonium. The proportionate amount of these ingredients were such that equal quantities of the two solutions nearly neutralized each other, a slight excess of the lime salt remaining. Of course, the combination of these substances produces oxalate of lime. It was found that when quantities of the two solutions sufficient to just neutralize each other were added to the fluid supplied to a frog's ventricle, the cardiac contractions became weakened. A suffi- cient amount of the oxalate of lime must have been dissolved by the circulating fluid to poison the cardiac muscle. Hence Ringer admits that oxalic acid exerts a direct poisonous action upon the muscle, and what he asserts of oxalic acid, in the light of this experiment, would seem to be true of calcic oxalate. Although s Practitioner, Vol. 34, p. 81. 5 these experiments need confirmation, and require to be supplemented by a variety of others performed upon warm-blooded, as well as cold-blooded animals, it does not appear that we have any theoretical reasons for doubting that considerable amounts of oxalate of lime circulating in the blood must have a deleterious action upon the functions of the body. It is true, the urine of persons in apparently good health may some- times contain a relatively large amount of calcic oxa- late sediment. Roberts 3 states that " subjects of mulberry calcu- lus, especially children, are often in the enjoyment of blooming health." As an offset to this assertion, however, we have the authority of Ultzmann 4 that weakly and anaamic children are the ones that are particularly predisposed to oxalate of lime calculus. Chambers5 asserts that under-fed children living in the country often have oxalate of lime in the urine. According to my own experience, a copious sediment of oxalate of lime is not often found for a considerable period in the urine of persons in vigorous health. Its long-continued presence in this secretion is generally indicative that some of the functions of the individual are not being performed as they ought. The oxalate is very insoluble in water. This prop- erty tends to render obscure the explanation of its mode of elimination from the system. The acid phos- phate of sodium, which is ordinarily present in fresh, normal urine, has been found to have a solvent action upon the calcic oxalate. This would explain why the oxalate is held in solution in fresh urine, and its grad- ual deposition, as the acid phosphate becomes con- verted into the neutral phosphate, in consequence of chemical changes taking place in the urine. This ex- 3 Urinary and Renal Diseases, fourth edition, p. 103. 4 Die Harnconcremente. 3 Manual of Diet, p. 271. 6 planation, however, does not account for the solution of the oxalate in the blood, from which the urine is secreted. It has been found that some other saline solutions have a slight solvent action on the oxalate. The oxalate, moreover, is not perfectly insoluble in water. Storer6 gives the solubility of calcic oxalate in water as 1-500000. It has been estimated that ten ounces of water are capable of dissolving 1,000,000 of the crystals. That the oxalate can be dissolved in the stomach, is proven by the fact that it reappears in the urine after the ingestion of foods containing it. There can be no doubt therefore, that the substance can be dissolved, or held in solution in the alimentary tract, blood and the urine ; but the laws regulating its solution and deposition have yet to be discovered. Why it should be deposited in the kidney or bladder of one patient, and another, whose urine is loaded with it, should escape, demands further investigation to determine. And, of the many unsolved problems connected with the subject of oxaluria, this is perhaps the most important. When the laws governing its solution and precipitation within the body are made manifest, we may reasonably hope to be able to pre- vent the formation of calculi composed of it in oxa- luric patients. There seems to be no doubt that mucus favors the crystallization of calcic oxalate; acting in this respect, very likely, like a foreign body. The crystals are generally found in the urine intimately mixed with the cloud of mucus that slowly falls to the bottom of the receptacle. The starting-point of many calculi is probably formed by a clump of mucus that has occasioned the crystallization of oxalate of lime about it. There can be no doubt that the larger portion of the oxalic acid excreted, is manufactured within the "Ralfe, Morbid Urine, 7 body. There have been those, however, who have disputed this. Owen Rees first elaborated the theory that oxalic acid is produced from the decomposition of uric acid outside the body. The discovery of oxal- urate of ammonium in the urine by Schunck. lent some support to this theory. Oxaluric acid is a de- composition product of uric acid, and is easily con- verted into oxalic acid ; hence it was inferred that uric acid transformed into oxaluric and then oxalic, was the source of oxaluria. Basham gives an excel- lent exposition of this theory of the causation of oxa- luria, in Reynolds's "System of Medicine."7 He there affirms in a very dogmatic manner, and with very scanty evidence, that " oxalate of lime, as a sediment in the urine, is of no other significance than that of a lithic acid diathesis." An excess of oxalate of lime in the urine meant for him an excess of uric acid in the system. It is an easy matter to demolish this theory. In the first place one of the cardinal doc- trines of Basham and his school, namely, that the ox- alurate of ammonium of the urine is changed to oxalate, was disapproved by Neubauer.8 He found that in progressive decomposition of the urine, the oxalurate of ammonium is changed directly into car- bonate of ammonium, and not into oxalic acid and urea. Oxalic acid has been found in the blood by Cantani and Garrod. This oxalaemia cannot be ac- counted for by Rees's theory. The explanation, ac- cording to this theory, of the origin of renal concre- tions of oxalate of lime, would be very difficult. It is exceedingly improbable that the decomposition of oxalurate of ammonium can take place almost instan- taneously after the secretion of a urine of normal re- action and perfectly free from every trace of ferment- i American edition, Vol. 3, p. 619. • Neubauer and Vogel. Analysis of the Urine. Am. Ed. p. 169. 8 ation. Renal calculi of oxalate of lime, however, are very common. This is abundantly proven by the experience of Can- tani,9 who cites numerous instances. I have recently had under my own care a case of the kind. The gen- tleman had been a recent sufferer from renal colic, and had experienced several severe attacks. He had presumably been treated for lithuria. Upon examina- tion of the urine I found it loaded with oxalate of lime. The patient had luckily saved a calculus of about the size of a pea, that he had passed through the urethra. I found this, upon analysis, to consist almost wholly of calcic oxalate. I never found any excess of uric acid in the urine. If the urine and the calculus had not been carefully analyzed, it would have been natural to have considered the case one of lithiasis, and to have treated it accordingly. Oxalate of lime is probably a much more common cause of renal colic than is generally supposed; and for this reason the urine of patients afflicted with this disease, should always be carefully examined. Oxalate of lime may be found, indicating the cause of the painful paroxysms. Another fact disapproving the theory of Rees, and ne that, may not be generally known by the medical profession, is that oxaluria is common among horses. Williams 10 speaks of its occurrence in horses that are irregularly worked, like hunters, and those too abundantly fed with saccharine substances, as turnips and carrots. I have examined the urine of a number of horses and I have found oxalate of lime very fre- quently. In a stable containing five horses. I found abundant deposits of oxalate of lime in the urine of three of the inmates. In one instance the urine was 9 Die Stotfwechselkrankheiten. 10 Principlesand Practice of Veterinary Medicine, 3d ed., p. 419. literally loaded with it. The form of the crystals in this case was not the typical octahedral, but was a four-sided prism with pointed ends. This form is very rarely found in man, and might be easily mis- taken for other crystalline constituents of the sedi- ment, were not careful micro-chemical tests applied to reveal the true nature of the crystals. The horse ex- cretes a large amount of hippuric acid, but very little uric. We have no reason to suspect that the decom- position of hippuric acid is a source of oxalic acid. For these and other reasons the theory that the excreted oxalic acid is formed in the urine outside of the body cannot be sustained. We cannot affirm that oxalic acid is never formed during the decomposition of the urine, but we have abundant proof that this is not the ordinary cause of oxaluria. Some of the other theories to account for the pres- ence of oxalate of lime in tho urine are more prob- able. A conservative resume of these theories is given by Salkowski and Leube.11 They all have the common defect, that while they may seem to be suffi- cient to explain the occurrence of oxaluria in some instances, they are entirely inadequate to do so in others. The theory most commonly accepted is that the oxalic acid originates in defective metamorphosis within the body. Cantani is one of the ablest advo- cates of this theory. In his elaborate work upon the diseases of metamorphosis, he takes the ground that oxaluria is due to a condition akin to that of diabetes. He believes that the oxalic acid originates from the abnormal disintegration of the carbo-hydrates. There are many facts that lend probability to this view. The acid is very readily prepared in the chemical laboratory by the action of reagents upon sugar, 9 11 Lehre vom Harn, s. 419. 10 starch, and cellulose. This fact would seem to render probable the possibility of its formation from the im- perfect oxidation of these substances in the body. Can- tani's mode of treatment for oxaiuria is based upon this theory. He states that the condition is especi- ally common in individuals indulging to excess in sweets and starchy foods. His treatment consists in very largely withdrawing these articles from the food and substituting an anti-diabetic diet. He claims to have permanently cured many patients in this way. But we find other recognized authorities maintain- ing that oxaiuria is the result of imperfect metamor- phosis of nitrogenous substances. This was Beneke's theory. It has been found that oxalic acid cannot be made to wholly disappear from the urine of fasting animals. 1 have found calcic oxalate quite abund- antly present in the urine of a patient subsisting en- tirely upon a moderate amount of milk-punch. Tyson 12 advises that in the treatment of oxaiuria the patient be allowed only a moderate amount of nitrogenous food, and in bad cases no meat at all be permitted. It would be hard to explain the good ef- fects of both Cantani's and Tyson's widely different modes of treatment upon the assumption that the theory of one alone is correct. Before endeavoring to reconcile the apparent incompatibilities existing in the views of these two authorities, it may be well to consider some of the other possible sources of oxalic acid in the body. Various authors have endeavored to trace a connec- tion between the formation of mucus and that of oxalic acid. Hoppe-Seyler 18 states that the crystals of ox- alate of lime are especially abundant in catarrh of the urinary passages, and of other mucous membranes. 12 Boston Med. and Surg. Journal, Vol. 115. p. 365. 13 Physiologisclie Chemie, s. 825. 11 He also affirms that the connection between impaired respiration and the excretion of calcic oxalate has not been proven. Ralfe14 also accepts the possibility of the formation of oxalic acid from the decomposition of mucus, and gives considerable prominence to the theory. He states that crystals of oxalate of lime have been found in the mucus of the gall-bladder, and in the gravid uterus. Fiirbringer also found them in the sputum of a diabetic. Ralfe is inclined to the view that the numerous oxalate of lime crystals found in the urine of patients suffering from spermatorrhoea are derived from the mucus of the genito-urinary pas- sages. Ultzmann 16 has remarked the frequent asso- ciation of oxaluria and spermatorrhoea and urethral disease. He says that he has often caused the oxal- uria to disappear by local treatment of the urethra. I myself, have had several cases of true spermatorrhoea associated with oxaluria. I also recall another inter- esting patient who was troubled with an obstinate prostatorrhoea whose urine was loaded with calcic oxa- late. I have never, however, felt the necessity of at- tributing the oxalate of lime found in such cases to the presence of seminal fluid or mucus in the urine. The case that I have already mentioned of the gentle- man that had suffered from a severe renal colic is sufficient to demonstrate that there is not necessarily any reason for attributing oxaluria to the presence of semen in the urine. In the many specimens of the urine of this patient that I examined I never failed to find a large number of spermatozoa. These speci- mens were passed at different times of the day, some of them during my visits. The formation of the oxalate of lime calculus in the kidney in this case showed that there could be no direct connec- 34 Loc cit. 1S Die Harnconeremente. 12 tion between the oxaluria and the spermatorrhoea. The crystals of the oxalate could be found very soon after the urine was passed, long before we could have any reason to suspect that any decomposition had taken place. The form of the crystals in this case was very suggestive. They were apt to be small and of irregular form, resembling those obtained by imme- diate precipitation upon the addition of a solution of oxalic acid to one of calcium chloride. They seemed to denote that the urine was surcharged with the oxalate and that many of the crystals were formed al- most instantly after the secretion or excretion of the urine. Although such cases as the above do not support the theory of the formation of oxalic acid from mucus, there are certain facts that render probable the possi- bility of such an event. It has been found by Land- wehr and by Hammarsten16 that a decomposition product can be obtained from mucin having the prop- erties of a carbo-hydrate. The further decomposi- tion of this carbo-hydrate, which Landwehr calls ani- mal gum (thierische Gummi) might yield oxalic acid. Behrens 17 calls attention to the frequency with which calcic oxalate is found in the vicinity of, or even in, slime-bearing cells of plants. Although it may not be fair to compare the slime of plants with the mucus of animals, there are points of similarity in some of the physical properties of the two substances. Plant slime, moreover, readily yields oxalic acid when treated with nitric acid. I think that, perhaps, I have already dwelt too long upon the conflicting theories that have been advanced to account for the formation of oxalic acid in the bodv. I can only briefly allude to others. The io Studien uber Mucin, etc., Pfliiger's Archiv, Bd. 36, s. 373. n Hilfsbuch zur AusfiilirungMikroskopischen Untersuchungen im botanischen Laboratorium, s. 210. 13 theory of increased oxidation has been advocated to explain certain cases. The objections to the general application of the theory of impaired oxidation would apply to this one. Theoretically, perhaps, in- creased oxidation and metabolism with the formation of incomplete products, would explain some cases of oxaluria, but in default of experimental and clinical proof of the correctness of the hypothesis, we cannot profitably discuss it here. Among all the multitude of diseases and conditions in which oxaluria has been found there is one symp- tom or condition, and perhaps only one, that has been very constantly met with, namely indigestion. The frequent occurrence of dyspepsia and all the symptoms usually accompanying it with oxaluria has been often noticed by various writers. Some have been inclined to make the dyspepsia secondary to the oxaluria, others to make the oxaluria in some way dependent upon the dyspepsia. The acid theory was an out- growth of this last endeavor. It is well known that organic acids are oxidized in the body and converted into carbonic acid and water. It is fair to presume that impeded oxidation of the organic acids that are produced by fermentation in dyspepsia may end m the formation of oxalic acid. This theory would seem to account for the majority of cases of oxaluria better than any of those that we have hitherto considered. But there is another probable source of oxalic acid in the body which has been strangely overlooked. It has been assumed, nearly without exception, that the oxalic acid that originates here is formed either in the blood or in the substance of the organs and tissues. It does not seem to have occurred to the writers upon this subject that oxalic acid can be formed, like vari- ous other organic acids, in the alimentary tract. R riding. clinical observation and experiments have 14 rendered it very probable to the writer that oxaluria may be due to this cause. Although I have consulted the literature of oxaluria quite extensively, I have only found one author who has alluded to this possi- bility. Chambers 18 hints of such an origin in the fol- lowing passage: " Chemists tell us that citric, malic, and other organic acids distributed through the vege- table world are liable to conversion into oxalic, so that it is not necessary that it should naturally be a con- stituent of the food eaten, but may arise during its fermentation or digestion." We are left in doubt as to whether the author means by this that the oxalic acid may be directly produced in the alimentary canal in consequence of abnormal fermentation, or whether from the imperfect oxidation, after absorption, of other products of fermentation. He contents himself with this bare allusion to the possibility of the manufactur- ing of oxalic acid from the food during imperfect di- gestion. Medical literature, however, has recorded many facts that lend great probability to this theory. Food that does not digest ferments, or decomposes, much in the same way as it would under similar con- ditions of warmth and moisture outside of the body. Decomposition and putrefaction play a part in the disintegration of the food in the intestines, even in normal digestion, and this part is a much more exten- sive one than is commonly supposed. Every phy- sician will be profited by reading the section in Her- mann's Handbuch der Physiologic, in which Maly 19 describes the activity of bacteria in reducing the con- tents of the intestines to the condition that they have in the faeces. The intestines, particularly the lower portion of them, are swarming with bacteria. The faeces are filled with a great variety of micro-organ- '» Manual of Diet, p. 271. 19 Pankreasfaulniss, Bd. V, Abth. 2, s. 218, 15 isms. Any one can easily convince himself of the truth of this statement by microscopical examination. Given warmth, moisture, innumerable bacteria and a quantity of easily decomposable organic matter, putre- faction is inevitable, unless some substance be present to arrest the action of the bacteria. Bile is the nat- ural disinfectant of the intestines, but this is incapa- ble of preventing all putrefactive changes in the ali- mentary tract. Indican, one of the most constant constituents of the urine, is ever a witness of the in- sufficiency of this anti-fermentative action of bile. In- dican is derived from indol, and Maly states that there can be no indol or inflammable gas produced in the intestines without bacteria. He further affirms that the products of pancreatic decomposition do not have any physiological uses. Digestion is essentially a process by which insoluble substances are converted into others capable of being absorbed into the blood. True digestion is accom- plished in a relatively short time. Very likely, too, the digestive ferments may have some restraining in- fluence on the action of the bacteria. But when diges- tion is delayed, or is not accomplished, the micro- organisms present in the stomach and intestines assert their power; and we could scarcely devise more favorable conditions for the cultivation of bacteria than exist in the lower part of the intestines. That these bacteria manufacture, in many instances, very virulent poisons, has been abundantly proven by recent researches upon the subject of ptomaines. It is a con- stant source of wonder to one investigating the sub- ject that cases of poisoning of this origin are not more common than they appear to be. But, in all proba- bility, ptomaines are not the only poisonous sub- stances manufactured in the alimentary canal. Many organic acids are produced during the fermentation of 16 food. Brieger 20 has isolated various species of bac- teria existing in the faeces, and has cultivated them outside the body. He also studied the action of these micro-organisms on fermentable solutions, and ob- tained, in this way, various organic acids. He does not record the finding of oxalic acid ; but it is not evident that small amounts of the acid would have been recognized by the methods of analysis that he employed. Investigations of this character are very important, and promise to shed a good deal of light upon questions of great physiological and pathological interest; and it is very desirable that this line of ex- perimentation be followed out. Fliigge places oxalic acid in his list of substances resulting from the activity of bacteria. If oxalic acid can be manufactured by bacteria outside of the body, it seems altogether probable that the same process can take place in the intestines. Salkowski21 states that crystals of oxalate of lime are not infrequently found in microscopical examination of the contents of the large intestine. He does not say what the probable origin of these crystals is. Either they must have been taken into the body in the food, or they must have been due to the combination of oxalic acid manu- factured in the alimentary canal with lime, unless we are disposed to admit that oxalic acid may be elimi- nated through the intestines, which seems in no way probable. We should also bear in mind that octahedral crystals of oxalate of lime, like those ordinarily found in the urine, are not common in plants containing the acid and its salts. The crystals in plants are apt to exist in irregular aggregations of these octahedral forms, or as needle-shaped crystals. We, therefore, have good reason to suppose that the oxalate crystals 20 Zeitscliriftfiir physiologischen Chemie, Bd. VIII, s. 306, 21 Salkowski und Leube, Lebre vom Harn., s. 114. 17 found in the intestines are due to oxalic acid formed in the digestive organs. Of course, if oxalic acid is formed here, there is no reason why it should not be absorbed into the blood and give rise to oxaluria. I have made microscopical examinations of the faeces of several oxaluric patients. Although I have found octahedral crystals here, I have never been convinced by chemical tests that they were composed of oxalate of lime. For several obvious reasons, it is not a very easy matter to detect minute crystals scattered through such a mass of detritus as exists here. Such exam- inations, however, are promising, and should be re- peated. It seems to me, in the light of what has been said, that we have a right to assert that the theory of the formation of oxalic acid in the digestive organs is a very probable one. Several experimenters have un- consciously corroborated this theory. Fiirbringer22 made an elaborate series of experiments to determine the influence upon the excretion of oxalate of lime of the ingestion of alkaline bicarbonates, lime-water, and uric acid and the urates. The results of these experi- ments were mostly negative. In one of his observa- tions, however, he casually records a great increase in the oxalic acid excretion coincident with diarrhoea. This occurrence is to me very suggestive. An ordi- nary diarrhoea means increased fermentation and pu- trefaction in the intestines. If oxalic acid has a source in this putrefaction, then the association of oxaluria and diarrhoea ought not to surprise us. Hammerbacher28 afterwards repeated some of these experiments of Fiirbringer, and investigated the effect of alkalies upon the excretion of calcic oxalate in dogs. He mingled enormous doses of bicarbonate of 23 Deutsches Archiv. fur Klin. Med., Bd. 18, p. 143. 22 Pfliiger's Arch., Bd. 33, p. 89. 18 soda with the food of these animals, and found' that the amount of calcic oxalate in the urine was consider- ably increased. In one instance, at least, the large doses given caused vomiting and loss of appetite. The doses given ranged from five to twenty grammes. When we compare these weights with those of the dogs experimented upon, we see that the doses were excessively great. The digestion must have been pro- foundly disturbed by them. If the food did not digest it putrefied, and oxaluria was the result. This may not be the correct explanation, but it appears as prob- able as any that we can give. It does not, however, seem to have occurred to the author. Mills 24 performed some experiments upon a dog in " nitrogenous equilibrium," to determine the effects of various forms of diet upon the excretion of oxalic acid. He notes that a very large amount of the acid was ex- creted upon a dog following diarrhoea. The fact speaks for itself. I may add that oxalic acid is frequently found in the urine of hogs. Calculi consisting of almost pure calcic oxalate are sometimes found in the bladder of these animals. I have examined hogs urine only once; but in this instance I found a great number of calcic oxalate crystals, after allowing the urine to stand for a long time. When we consider the char- acter of the diet, and the habits and environment of these animals, we have every reason to suppose that bacteria have an especially attractive field of operation in their intestines. Williams 28 says that oxaluria in horses is apt to be accompanied by symptoms of acid-dyspepsia. The horses in which I have most often found oxaluria are those that are highly fed and little exercised : such M Journal of Physiology, Vol. V, p. 231. " Loo. cit. 19 animals are, of course, specially liable to digestive troubles. Brunton 26 remarks that the deposition of oxalate of lime is usually connected with disturbances of the digestive system; and he further states that he has observed, in a hospital ward, that a deposit of this substance is commonly found in the urine after the patients have had cabbage for dinner. This occur- rence serves to strengthen the theory of the formation of oxalic acid from the decomposition of food. Prob- ably nothing would be more likely to afford an intes- tinal bacterium a greater opportunity for the exercise of its functions than an abundant supply of cabbage. The association of icterus and oxaluria has been noted by certain writers. Murchison27 thought that oxaluria might be connected in some way with liver trouble. As bile is the natural disinfectant of the it - testines, when its flow is obstructed decomposition can more readily take place. This would be a natural ex- planation of the occurrence of oxaluria with icterus. Indigestion means an increased opportunity for bac- teria- an opportunity that they are always ready to seize. The writer does not claim that the theory advanced here to account for the formation of, at least, some of the oxalic acid excreted from the body has been de- monstrated beyond controversy, but it certainly de- mands consideration. If it be true, then the treat- ment of oxaluria resolves itself into that of dyspepsia. 26 Pharmacology and Therapeutics, p. 377. 27 Functional Derangements of the Liver, p. 75.