BENCE JOXES ON CRYSTALLTEED PHOSPlIATE OF 11.-On the occurrence of deposits of Crystallised Phosphate of Lime in Human Urine. BY H. BENCE JONES,M.D. F.R.S. F.C.S. IN March 1861 Dr. William Roberts Physician to the Man- Chester Royal Infirmary published a paper in the British Medical Journal on the occurrence of deposits of crystallised phosphate of lime in human urine. Hesays :-“By adding a little chloride of calcium to healthy urine and reducing its acidity to near the neutral point with caustic soda I have often succeeded in obtaining an abundance of crystals,‘ closely resembling those occurring spontaneously in urine.” At this date .I had satisfied myself that healthy urine out of the body could be made to give crystals of phosphate of lime first by simply adding chloride of calcium to the urine; secondly by taking away some of the acidity of the urine; thirdly by totli means sininltaneously.When the fluid waa very acid much chloride of calcium was required to be added ; but if a portion of the acid was removed in LIME IN HUYAN URINE. any way then less cliloride of ca; cium was required to procliice crystals of phosphate of lime. These experiments made me believe that by ,oiling a lime-salt internally phosphate of lime crystals ought to be found in the urine even without adding anything to the water after it mas made. A long delay occurred before I could begin the observations in St. George’s Hospital and ultimately I was obliged to ask my friend Dr. Dickenson to undertake the microscopical examina-tion of the urine of those to whom the lime-salt was given.Although therefore these experiments mere ended long after Dr. Roberts’ publication set as the obserdions recorded in the first part of this paper were made without any Itnowledge that he was experimenting on the same subject our agreement must be considered as accidental and may therefore be taken as the better evidcnce of the truth of our facts PART 1. On the yroductio)h of crystcils. of Phsyhate of Lime ill the b?ine by the additioii of substames ufter it 7~asbeeu passed. IT appeared desirable to determine the circumstances and form in which crystallised phosphate of lime occurred when pure solutions of chloride of calcium arid common phosphate of soda or acid phosphate of soda were mixed together.When a solution of chloride of calcium in excess is precipi-tated by a solution of conimon phosphate of soda the precipitate when examined by the microscope is seen to be partly arnorplious and partly crystalline. The amorphous precipitate according to H eint z is 3Ca0. PO, and the crystalline 2Ca0.H0.P05. When a solution of common phosphate of soda in excess is precipitated by solution of chloride of calcium the precipitate examined by the microscope is amoyphous. If a little acetic acid is first added to the solution of common phosphate of soda and then the solution of chloride of calcium an amorphous precipitate is first seen and this more or less rapidly (in the course of half an hour) becomes entirely crystalline.When lactic acid butyric acid valeranic acid or yery meak hydrochloric acid was used instead of acetic acid the same crystals were observed after a ahoi*t time. if an excess of these acids was lxsed no crystals were formed. When a solution of chloride of calcitini in excess was added to a solution of acid phosphate of soda crystals of phosphate of lime were found by the microscope in from tell to fifteen minutes. 10 BENCE JONEB ON CRYBTALLISED PHOSPHATE OF Wheu there was much acid phosphate in proportion to the chloride of calcium the crystalline deposit was always found. It was clear then that crystalline phosphate of lime was formed if sufficient lime-salt was present and if the acid was not in such excess as to keep the salt dissolved.As the urine always contains common phosphate of soda or acid phosphate of soda with or without free acid and with variable quantities of lime-salt experiments were made to obtain crystalline phosphate of lime lst by increasing the lime-salt by adding chlo- ride of calcium; or 2ndly by diminishing the acidity of the urine by cautious additions of alkali so as to allow the lime-salt naturally present to crystallise out ; or 3rdly by increasing the lime-salt and diminishing the acidity of the urine at tbe same time. In each of these waya crystalv of phosphate of lime were obtained. 1st. By simply adding chloride of calcium to healthy urine. To 50 c. c. of urine a few drops of a strong solution of chloride of calcium were added until a slight precipitate waa obtained.The precipitate that formed was first amorphous but half an hour afterwards beautiful crystalv of phosphate of lime were seen by the microscope. If a great excess of chloride of calcium was added the preci pitatz was almost entirely amorphous. Thirteen different experiments were made with different healthy urines from two men chloride of calcium in solution was added and in each cke crystals of phosphate of lime were found in from half an hour to an hour. Bndlp. Crystalline phosphate of lime was obtained from healthy urine by diminishing the aciditj of the urine by the cautious addition of alkali. To 30c. c of healthy urine a quantity of ammonia was added not sufficient to produce QL precipitate. Aftcr standing 12 hours no crystala of phosphate of lime could be found with the microscope.To 80c. c. of urine ammonia was added SO that the urine had a feebly acid reaction. Tbe precipitate whioh formed appeared when examined by the microscope to consist chiefly of crgstallised phoephate of lime. TO30 c. c. of nrine 80 much ammonia was added as gave a neutral reaction. Besides crystals of phosphate of ammonia and magnesia crystals of phosphate of lime were formed. In another experiment the urine was made alkaline; the pre- cipitate then consisted of phosphate of ammonia and magnema and amorphous phoephate of lime. LIME IN HaMAN UBINE. Solution of common phosphate of soda and solution of potmsa also when added to healthy urine occasionally gave on standing for some time crystals of phosphate of lime.3rdly. By increasing the lime-salt and diminishing the acidity of the urine at the same time crystalline phosphate of lime was produced. Four specimens of healthy urine gave with chlosde of calcium no precipitate. Solution of potassa was then added in smallquantity till a slight precipitate was observed ;the urine still had a slightly acid reaction; on examination with the microscope from half an hour to an hour afterwards crystals of phosphate of lime were found. In two other cases some of the aciditywas removed by potassa and eolution of chloride of calcium was then added; the pre- cipitate when examined with the microscope contained crystals of phosphate of lime. In another case in which chioride of calcium gave no precipitate at all the urine wm mixed with a little ammonia to take away the greater part of the acid present and then a solution of chloride of calcium was added.The precipitate conthed crystals of phosphate of lime. That it is not necemary to lessen the acidity of the urine pro-vided the phosphate of lime ie in great excess is proved by the following experiments :-To 60 c. c. of healthy urine a few drops of lst dilute acetic or 2ndly lactic acid were added and then LW) much of a solution of chloride of dciuni as caused only a slight precipitate. After rtanding some hours the precipitate which was at first amorphous waa changed in both caw into beautiful crystals of phosphate of lime. Hence-The two chid conditio~~s, w3kh need not ceexist an which the formation of crystalline phosphate of lime in the urine depends we-1st.An excess of phoephate of lime; and 2ndly. A alight &&ty of the urine in which the phosphab of lime is dissolved. BKNCE JONES ON CRYSTALLISED PHOSPHATE 05’ PART 2.=Oit the production of Crystuls of Phosphate of Lime in the uriiie bg giving preparations of lime as medicine. THEease with which crystals of phosphate of lime were obtained after any urine was passed by adding substances to the urine led me to expect that by giving lime-salts as medicine phosphsttc of limc crystals would with equal rcadiness he detected in the urine. I soon found that it was not so easy to affcct the composition of thc urine bcfore it passed from the body and that careful collect- ing and watching for many hours afterwards was required to arrive at clear results.My friend Dr. Dickenson uridertook the microscopical es- amination of thc urinc in the wards of St. Gcoi*ge’sHospital where T ordcred the yrcparations and quantities of tlic mccliciiie which I wished to try. At first acetate of lime with lime-nratei; and. sometimes with carl)onate of potassa to reduce the acidity of the urine were tried. Then limc-water done or carbonate of lime was used; but ultimately a solution of acetate of lime containing about 15 grains to a draclini of solution gave the bcst results. As examples of our first experiments we give the following,- E.P. aet. 22 admitted Nay If 1861 for dyspepsia.He mas nearly leaving the hospital well mid the urine mas healthy and in all respects natural when lie was ordered June lst 2drachnis of solution of acetate of lime in water cvery six hours (each drachm contained 14.7 grains of acetate of lime). The urine which was passed at night and morning mas repeatedly examined after standing for various periods but nothing but a few crystals of oxalate of limc was observed. On the 4tb eight ounces of lime-water mere given in the day instead of the acetate. On the Gth still only oxalate was found. The lime-water was increased to a pi,nt. On the 8th n drachm of carbonate of potassa in addition mas given. On the Ilth no change haviug bemi observed tlie morning iirine mas faintly acid; and the surfacc mas covered with an iridcscent plate of phosphate of liiiic.The evening urine was faintly acid when passed and 110 crystals of phosphate of lime were found at first. It was again examined forty hours afterwards ; LIME IN HUMAN URINE. it was then alkaline and a white precipitate had fallen which consisted of a considerable quantity of amorphous phosphate with a great number of very characteristic crystals of phosphate of lime. The surface was covered with a phosphatic pellicle. 12th and 13th morning and evening. No crystals of phosphate. 14th. Morning urine alkaline with phosphatic pellicle and much deposit consisting chiefly of amorphous phosphate with a few stellate crystals of phosphate of lime. 14th evening nrine.Eighteen hours after it was passed no deposit was found; on the third day many stellate crystals of phosphate of lime were found. The experiment was continued until the 20th; phosphate of lime crystals occasionally but by no means constantly appearing ; ovzlatc of lime was always detected when the urine was acid. K. E,,aet. 30 admitted May 15th for dyspepsia. June 1st. The urine was in all respects natural; he drank a pint of lime-water during the day. June 2nd. A few crystals of phosphate of lime were found. , 3rd. No phosphate of lime; Rome oxalate. , 4th. No phosphate of lime crystals mere fonnd. Iu more than one case carbonate of lime was given in coil-siderable quantity but no crystals of phosphate of lime were detected in the urine; but the results with acetate of lime iu large doses were very decided and very uniform for example,- S.K. aet. 24. admitted with chronic rheumatism July 10. July 20. The urine mas perfectly natural except a small quantity of pus cells the result of a gonorrhoea. He was ordered two drachms of solution of acetate of lime equal to 29-4 grains in water three times daily. The urine was examined night and morning and no crystals except a few oxalate of lime octahedra were seen until- 23rd evening. The urine mas faintly acid with an iridescent pellicle on the surface aad a heavy white precipitate formed which consisted of amorphous phosphate oxalate of lime and very numerous characteristic crystals of phosphate of lime. Three drachma of the solution of acetate of lime were ordered thrice daily.24th morning. Urine faintly alkaline ; amorphous and laminar phosphate of lime were seen but no crystals of phosphate of lime. 18 BEROE JONEB ON OBYSTALLllllD PUOBPHATE OF Mth evening. Urine acid ; very large crrystals of oxalate were men; no phosphate. Four drachms of tbe.oolution of aoetate of limewere ordered. 26th morning. The urine waa acid and showed a few phorphate crJr8tslr. 25th evening. The urine was acid and showed a large depoeit of octahedra but no phoephate. 26th morning. The urine was acid but showed no crystale. 26th evening. The urine waa very faintly acid; numeroue fine crystals of phosphate of lime were found. July 27 morning. The urine was faintly acid; crystalline phoe- phata of lime wm seen and much oxalate.The acetate of lime was ordered to be stopped and only three doses were taken be-tween the 27th of July and the 3rd of Auguet; during which time crystds of phosphate of lime were only twice found by the microscope. August 2. Morning urine slightly acid; no phaepbate crystals. , Evening urine acid; much oxalate bat no phoaphate. Three drachms of the solution of acetate of lime were ordered in water. 3rd. Night water alkaline; few small phosphate of lime crystals were found. 4th. Morning urine alkaline and few phoephate of lime crystals were found. 9th. Evening urine alkaline ; abundant and splendid crystals ofphosphate of lime. 5th. Morning urine faintly acid. Phosphate of lime crystals were found; the experiment was stopped.L. B. aet. 26 admitted with slight rheumatism July 10. July 23. The urine was acid and perfectly natural except thbt it contained a quantity of pus cells the result of gonorrhoea. Two drachms of solution of acetate of lime equal to 29.4 grains were given thrice daily. The urine was examined night and morning no crystals were aeen until 24th evening. Urine faintly acid; a few needles of phosphate of lime wire found and much amorphous phosphate. 25th. Three drachms of the solution were ordered But no more crystals of phosphate of lime were seen until 27th morning. The urine after standing 48 hours gave many fine bundles of phosphate of lime crystals. 27th evening. Urine gave much oxalate but no phosphate.LIME IN HUMAN URINE. 28th morning. Urine faintly alkaline; gave many fine crystals of phosphate of lime. 28th evening and 29th morning. The urine was not kept. 29th evening to 31st. When the acetate of lime was omitted no crystalline phosphate was found. August 3. Three drachms of the solution were again given thrice daily. No crystals were found until the evening of the 7th when the urine was acid and many phosphate of lime crystals were seen. Four drachms of the solution were ordered but the patient dis- likicg the medicine the experiment was stopped. C. W. Eet. 30 was admitted with chronic rheumatism July 10. July 30. The urine was acid and perfectly natural excepting that occasionally a little bladder epithelium was seen.Three drachms of the solution of acetate of lime were ordered thrice daily in water. Nothing was observed until August 3. Morning urine faintly acid ; some decided aggrega- tions of phosphate of lime crystals were seen with microscope. August 3rd evening. Urine acid but no deposit. , 4kh morning. The urine was acid and showed huch oxalate of lime but no phosphate. The medicine had to be omitted in consequence of an increase of rheumatism Conclusion. From the experiments detailed in this paper it follows that the formation of phosphate of lime crystals in the urine does not depend upon the amount of phosphoric acid present but that it does depend firstly on the amount of lime in the urine ; and secondly on the acidity of the urine allowing the crystallization to occur. The increase of lime in the urine or the diminution of the acidity of the urine or the simultaneous' occurrence of both of these conditions does not indicate any diseased condition of the body but may be caused by medicines or by diet.