JEROME, M.B. (Lond.), Lecturer in Medical Pharmacology and Materia Medica. (From the Pharmacological Department, Oxford.)

Transcription

1 THE RELATION OF THE DEGREE OF ACIDITY OF THE URINE AND THE PERCENTAGE OF URIC ACID THEREIN CONTAINED TO THE PRECIPI- TATION OF THE LATTER IN THE FORM OF URIC ACID GRAVEL. BY WILLIAM J. SMITH JEROME, M.B. (Lond.), Lecturer in Medical Pharmacology and Materia Medica. (From the Pharmacological Department, Oxford.) IN the September number of this Journal for 1897 I gave an account of an experiment on myself extending over several months; and it was mentioned that between August and December, 1896, which I will call period (A), the urine deposited uric acid regularly, while in period (B)-March and April, 1897-it did not. It is generally, if not universally admitted, that the acidity of the urine and the percentage of uric acid in it, are factors which influence the deposit of uric acid. The object of the present paper is to consider how far these factors are sufficient to explain the precipitation of uric acid in period (A) just mentioned. The urine of 24 hours was decanted from the uric acid sediment which had formed; this was dissolved in water and a measured qtuantity of NaOH soluition, with the aid of heat; the solution was added to the urine, which had first been heated on the water-bath to 50 C. to dissolve suspended uric acid, the whole was then diluted and afterwards cooled to 10 C., the volume being made up to 2500 c.c. in period (A). In (B) the urine Mwas heated and cooled in the same manner, to make the conditions of the experiment alike in the two cases, the dilution being to 3000c.c. The acidity was estimated by solutions and phenolphthalein. This, thoiugh not the most

2 316 W. J. S. JEROME. accurate method, and unfit for ascertaining the absolute, is available for the determination of the relative, degree of acidity when the differences are as great as they were in the present instance. It was chosen because it can be done quickly, other work connected with the experiment leaving little time for this part. For the uric acid estimation the Ludwig-Salkowsky method was used. The reader is referred to the paper just mentioned for details respecting quantity of urine, outpuit of uric acid, diet, etc. TABLE 1 relating to period (A) in whtich deposition of uric acid occurred. In this Table determinations of acidity were made on most but not on all days of the week. The daily average given for each week is of course calculated for the number of days on which determinations were made. Daily average. Daily average. Total acidity Percentage of for 24 hrs in acidity in c.c. Date of c.c. of deci- of decidetermination normal solution normal solution Aug. 2 to 7 incl Aug. 9, 11, 12, Aug. 16, 17, 19, 20, Aug. 23 to 27 inc1. 491X0 30*3 Aug. 31, Sept. 1 to 5 inci Sept. 7 to 11 cinc Sept. 14, 15, Oct. 11 to 17 incl Oct. 19, 20, 22, 23, Oct. 26, 27, 29, 30, Nov. 1 to 7 inc Nov. 8, 11, 12, Nov. 15 to '0 Nov. 22, 25 to 28 incl Nov. 29 to Dec. 4 inc Dec. 6, 8, Dec. 14, Dec. 20 to 23 inc1. 525'6 25'3

3 DEPOSITION OF URIC ACID. 317 TABLE 2 relating to period (B) in which there was no deposition of uric acid, except while thymus was being taken. Date Total acidity for 24 hrs, in c.c. of solution 1897 Normal period. March ,, ,, &0,, April ,, Total (6 days) 3138&0 Daily mean Cod's roe period. April ,, Total (2 days) Daily mean Asparagus period. April ,, ,, Total (3 days) Daily mean 496&0 Asparagus after-period. April ,, ,, Total (3 days) Daily mean 5260 Per( entage of Iacidity in c.c. of So] lution 28@ [ [ ,1I2 Date 1897 April 13,, 14,, 15 Total acidity for 24 hrs, in c.c. of solution Thymus period. 554* Total (3 days) Daily mean Thymus after-perio April I, & *0 Total (4 days) Daily mean Percentage of acidity in c.c. of solution Id Diminished- nuclein-period. April ,, ,, ,,, Total (4 days) Daily mean The above figures show plainly that the percentage of acidity was distinctly greater in period (A) than in period (B).

4 318 W. J. S. JEROME. Highest daily amounts 0/0. (A) (B) Aug. ' 21 48&8 March ),3 42A4 April [4 38-3,, lyi ,, Highest averages of the short periods. (A) (B) Aug. 16 to /0 April 3 to /0 9to ,, 16to ,, 23 to 27 30'3 March 28 to April Sept. 14 to April 20 to 23 21U2 Daily mean of the whole Period (A) /0 Daily mean of period (B) exclusive of time when thymus was taken /0 It is perhaps worth while in connection with this subject to compare the degree of acidity with the amount of uric acid deposited in a given time from urine passed at different periods of the 24 hours, even though the observations relate to different days, and those not belonging to either (A) or (B). TABLE 3. Date Time Qua ntity of uriine c.c Jan. 5 8 a.m.-10 a.m. 10 a.m.-1 p.m. 1 p.m.-4 p.m. 4 p.m p.m p.m p.m. Jan p.m.-1 am. 1 a.m a.m a.m.-8 a.m. The averages for three other days 8 a.m.-10 a.m. 10 a.m.-1 p.m. 1 p.m.-4 p.m. 4 p.m p.m p.m p.m p.m.-8 a.m Total acidity in c.c. of solution '1 69' (Jan. 1, 2, 4) were Total Percentage of aciditty acidity f S * IPercentage of acidity in c.c. of solution

5 DEPOSITION OF URIC ACID. TABLE 4. Time Total Quantity allowed for Quantity quantity of urine deposition of of urine put aside of uric uric acid Date Time c.c. c.c. acid deposited 1897 Jan. 6 8 a.m.-10 a.m nil 10 a.m.-1 P.m. 200 do do p.m.-4 p.m. 185 do p.m p.m. 159 do p.m p.m. 249 do Jan p.m a.m. 186 do a.m a.m. 491 do a.m.-8 a.m. 138 do Temp. varied during experiment from C. to 140 C. 319 The general parallelism betweeni the lines corresponding to rise and fall in the (legree of acidity and in the amount of uric acid deposited is too striking to be wholly accidental. Tables 1 and 2 prove that the deposition of uric aci(i is not inconmpatible, as might be expected, with a high degree of acidity; they suggest somewhat forcibly that it is favoured by the acidity; but they do not show that this is the sole cause of the precipitation; indeed they contain evidence which, supported by other facts, indicates that the contrary is the case. Thus (1) there occur: Period (A) with deposit of Period (B) without deposit of uric acid. uric acid. Percentage of Percentage of acidity acidity Nov. 20, X2 March 28, X0 Dec. 6 21X6 April Aug ,, ,, ,, 16 25'5 (2) The percentage of acidity given in the preceding tables is that of the undiluted urine, but this after having been treated in the manner described and diluted, in period (A), to 2500 c.c., more often than not again deposited uric acid, and this sometimes so quickly that the filtration, measuring, etc., necessary for the several parts of the experiment had to be done as hurriedly as possible. On certain days 250 c.c. of such diluted urine were put aside for 48 hours, and the uric acid PH. XXIII. 22

6 320 W. J. S..JEROME. deposited after being washed, first with dilute H10, and then with water, was dried at 1100 C. and weighed, with the following results: Uric acid deposited Percentage grms. of acidity Temp. Nov. 25, C C.,, C C. Dec C.,, C C. (3) On Nov c.c. of the diluted urine were mixed with 2-75 c.c. NaOH solution and 7 25 c.c. distilled water, bringing the total acidity to 50 c.c., the aci(iity 0/, to 19-2 c.c., and the volume to 260 c.c. On Nov c.c. decinorimal HC1 were added to 250 c.c. diluted urine, and then enough distilled water to make the voluine 260 c.c. while the total acidity was 50 c.c., and the percentage of acidity 19 2, as on the previous day. On Nov c.c. diluted urine were mixed with 10 c.c. distilled water. Each specimen was put aside for 48 hours, and the precipitated uric acid was then collected and weighed. Uric acid Percentage sediment of acidity grms. Temp. Nov. 18, C.-160 C.,, C.-160 C.,, C. 160 C. Though the urine was left 48 hours in order to make the differences in the amount of the deposit on the several days as marked as possible, the precipitation began generally within 24 hours, being e.g. fairly abundant on Nov. 19 and 20 when the urine was examined after 7 and 24 hours respectively. I pass to the consideration of the influence of the percentage of uric acid on the deposition of this in the urine. In period (B) the only days on which uric acid was deposited were those on which thymus formed part of the diet, the sediment on April 13 and 14 being abundant, and consisting on April 15 of a few crystals only. During this time the uric acid output had risen from the daily mean of the normal period, viz. *8010, to that of , while on April

7 DEPOhSITION OF URIC ACID the amount excreted was Weintrandi had previously found the uric acid increased by the taking of thymus, and his patient's urine also deposited uric acid on standing; it seemed probable, therefore, that, even in the healthy, the taking of a sufficient quantity of nuclein in the food would cause the urine to precipitate some of its uric acid. To test this, I induced A. B., who was apparently quite healthy, and whose urine had no tendency to give a uric acid sediment, to take calf's thymus twice daily, with the result that an abundant urinary deposit was caused, consisting of a mixture of uric acid and urates, the former appearing first and preponderating. The sediment, after having been separated by filtration through a small filter, was dissolved in dilute NaOH, and the uric acid precipitated from this solution, while warm, by HCl. The filtrate was diluted to 3000 c.c. TABLE 5 showing the amount of uric acid got from the urinary sediment caused by eating calf's thymus. Total Quantity (3p. 0/U qr. acidity acidity Uricdacid of of urine in c.c. in cc. deposited urine in diluted Total of deci- of deci- Total in Date 24 hrs. to nitrogen. normal normal uric acid. 0/o uric 24 hrs. c.c cc. grms. solution solution grms. acid grms. June nil 24* ' * ,, nil ,, H 29t ' slight, not,r weighed , July 1$ ' / abundant, not weighed ' slight nil _ * These two days must be taken together, as the urine was collected late on the 24th. t Urine passed between 3 p.m. and 7 p.m. on this day was lost. $ Urine passed between 3 p.m. and 5.30 p.m. on this day was lost. The increase in the degree of acidity and the enlarged percentage of uric acid were probably the chief, and possibly the sole, factors in determining the precipitation of uric acid in this case; and on June 29, if not also on July 3, the latter only of these causes could have been operative. I pass, therefore, to enquire what part a high percentage of uric acid played during the periods (A) and (B). I Berl. klin. Woch., xxxii. 1895, p

8 322 W. J. S. JEROME. From data in the paper already mentioned, are obtained: Mean percentage of uric acid in (A) 0 034,,,,,, in normal part of (B) Mean percentage of uric acid for the whole of (B) exclusive of time when thymus was being taken 0030 Highest percentage in (A) (August 23) 0-056,,,, in (B) exclusive of thymus period (April 1) There occur further: (A) with deposit. (B) without deposit. Aug /0 uric acid April 12 0X036 0/0 uric acid,, ,,,, ,, ,, March ,, Dec ,, April ,, It must be said, therefore, of the percentage of uric acid, as of that of the acidity, that although higher in (A) than in (B), it could not singly, and at all timnes, have caused the deposition of uric acid which occurred, however much it may have helped this process. It remains to consider the influence of the coexistence of a high degree of acidity with a high percentage of uric acid. There are of course for urine in general conceivable combinations of degrees of acidity with percentages of uric acid, which would inevitably, and per se, cause some of the uric acid to fall in the free state, within 24 hours, but there is no evidence that such a combinatioin was always present in period (A); on the contrary the reverse is the case. (A) Diluted urine. Percentage of acidity Quantity in c.c. of Percentage of uric acid Date of deposited in 1896 solution uric acid 48 hours Nov ,, Dec ,, Nov I This Journal, xxii. p

9 DEPOSITION OF URIC ACID. (A) (with deposit) (B) (without deposit) undiluted urine undiluted urine Percentage Percentage Percentage Percentage of of of of 1896 acidity uric acid 1897 acidity uric acid Aug April ,, ,, 16 22' March Dec. 6 21X April The fact that the deposition of uric acid is sometimnes, in part at least, attributable to some other factor or factors than the degree of acidity and the percentage of uric acid in the urine was shown still more strikingly on Jan. 23, when 244 c.c. having been passed at 10 A.M., 100 c.c. were put aside, and nearly i of the total uric acid was deposited within 24 hours, though there was not only an exceptionally low degree of acidity, but also a percentage of uric acid rather more than i less than that which was several times met with without precipitation in period (B). 0/0 of Quantity of acidity uric acid Quantity Sp. gr. in c.c. of 0/) of deposited in of urine. of urine 0/( of uric acid. 24 hrs c.c. (undiluted) nitrogen solution grms. grms. Jan * I have no complete list of the percentage of uric acid in urine passed at different periods of the 24 hours, but the following isolated facts are not without interest when taken in connection with tables 3 and 4. Urine Percentage Quantity of 1897 couected of uric acid urine. c.c. Jan a.m ,, 10 a.m.-1 p.m Feb a.m.-i p.m. 0' Jan p.m.-4 p.m. 0' ,, 13 4 p.m Feb. 2 1 p.m.-4 p.m ,, 3 1 p.m.-4 p.m Jan p.m p.m ,16 4 p.m p.m ,, 21 4 p.m p.m ,, 24 3 p.m.-10 p.m It is to be noted that, though the percentage of acidity was higher in (A) than in (B), and doubtless contributed to the deposition of uric

10 324 acid which occurred W. J. S. JEROME. during the former period, this high percentage was not due to an increased excretion of acid, but to the smaller amount of water present in the urine during (A); the mean quantity of acid passed daily at this time being c.c. against 520 c.c. (or inclusive of thymus-period c.c.) in (B). During the time, however, that a pint of champagne was taken daily instead of whiskey and soda at dinner (August 9 to 23 inclusive) the mean daily acidity rose to c.c., and the percentage to 32-5 c.c., these for the rest of (A) being c.c. and 26-7 c.c. respectively. SUMMARY. 1. The urine may be made to deposit uric acid, in healthy persons, through the ingestion of a sufficient quantity of food rich in nuclein. 2. Some urines, after an ordinary diet, have an abnormal tendency to the precipitation of uric acid. 3. This tendency is not always due either to the presence of a high degree of acidity, or to a high percentage of the uric acid of the urine, or to the coexistence of these two conditions, however much such conditions may favour the precipitation.