THE NATURE OF THE W ORK OF T H E KID:NEY AS SHOWN BY THE I N F L U E N C E OF ATRO- P I N E A:ND M O R P H I N E UPON THE SECRETION OF URINE.

By W. H. THOMPSON, M.D., F.R.C.S., E~G.; Professor of Physiology, Queen's Collego, Belfast.

(From the Physiological Institute, Leipzic.)

[Read in the Section of Anatomy and Physiology, March 16, 1893.]

IT was shown during the past year by Dr. Grijns, ~ who worked in Professor Ludwig's laboratory, that the tempera- tute of the urine in the pelvis of the kidney, immediately after secretion, is often higher than that of the blood in the aorta.

There is thus a redistribution of the potent]al energy carried by the blood-stream to the kidney, together with the production of heat, such as one is accustomed to associate with the functional activity of " secreting" glands like the pancreas or salivary glands.

Now it is well known that atropine has an inhibitory effect upon the secretory activity of these glands. I t be- came, therefore, of interest to determine how far the kidney would correspond in this respect, if at all, to the glands mentioned. Accordingly, with the advice and permission of Professor C. Ludwig, to whom my best thanks are due, I undertook an investigation into this subject, the results of whieh are given in the following pages.

�9 Grijns.--" Die Temperatur des in die Niere einst,'6menden Blutes und des aus ihr ahfliessenden Harnes." Hte u. Du Bois Reymond's Archiv. f. Phyaio- l,,gie, 1893.

490 The .Vature of the Work of the Kidney.

I. M E T H O D O F CARRYING OUT T H E E X P E R I M E N T S .

For this purpose large healthy young dogs were chosen. The urine was collected by placing suitable cannul~e in the ureters. This was done at a considerable distance from the kidneys, in order to avoid mechanical or other interference with these organs, for, as is well known, this would of itself diminish or arrest the secretion of urine for a time.

The ureters were reached from the front by making a small incision in the abdominal wall, over the outer part of the rectus muscle, at a point somewhat below the crest of the ileum. The sheath of this muscle was then incise([ to a corresponding extent, the rectus hooked inwards, and the posterior layer of the sheath divide& The abdominal cavity was in this manner sumciently opened to allow one finger to be inserted, when the ureter could readily be felt where ir crosses the common iliac artery. I t was then brought to the surface, and the cannu|a securely tied in. This being done, the organ was immediately returned into the abdominal cavŸ and the wound closed around the stalk of the cannula.

When the observation commenced, the urine was led from the cannul~e into ordinary glass measure cylinders of 30cc. capacity. Into these it could be seen dropping periodically, two or three drops at a time, corresponding to the rythmic contractions 5f the ureters.

In the first experiment I attempted to collect the nrine f,'om the bladder by a catheter and syphon arrangement, but at once discarded this method as not being sufficiently accurate.

The urine was collected in the way described for the drug was then administered by intravenous and the urine collected for a second hour. At of this second hour the glasses

an llour,

injection, the end

were once more changed and

By DR. W. H. THOMPSOI~. 491

the urine again collected f o r a third hour. In many of the experiments a fourth, or even a fifth collection was made.

The amount was at once recorded in each case, and the urine preserved for the analysis which in most instances was commenced on the day of the experiment. In order to prevent dccomposition, however, the urine was immediately brought into small tightly-corked flasks, thymol having previously been added, and the whole preserved in ah ice chest. When the experiment was completed, the animals were killed by means of ah anmsthetic, and the kidneys re- moved for examination.

II . METHODS EMPLOYED FOR MAKING THE ANALYSES OF

T H E URINE.

The analyses made were, first, an estimation of the total nitrogen, and second, an estimation of the amount of urea in each specŸ of urine taken.

The total nitrogen was estimated by the method of Kjeldahl.

For estimating the urea, the method chosen was that introduced by MSrner and Sjiikvist2

This is a method which I venture to speak very highly of. Indeed, none of the methods ordinarily employed in this country can, I think, compare with it for accuracy. The only drawback ir has is the cost of carrying out the analysis in this country, owing to the large quantities of alcohol and ether consumed.

The other methods at one's disposal are, I believe, much too inaccurate for scientific purposes. Liebig's gives in reality ouly an approximate estimation of the total nitrogen. This is seen when its results are compared with those of the Kjeldahl method. The hypobromite method is little if at all

~ S~andina~-. Archiv. f. Physiologie, Bd. 2, 1890; also B5dtker. Zeitschr. Physiolog. Chemie., Bd. 17, i892.

492 The Nuture of the ~'ork of tl~e Kidnez/.

better, for not only is the nitrogen of urea liberated, but also, to a great exte¡ that of kreatinin, uric acid, and the ammonia compounds of the urine. Even oxygen is set free under some circumstances.

The Miirner and SjSkvist method has not hitherto, so lar as I aro aware, been employed in this country; a short description of it may not, therefore, be out of place.

The principle upon which it depends lies in the fact, that while urea is readily soluble in a mixture of alcohol and ether, the other nitrogen-holding substances, especially their com- pounds with barium, are very insoluble. The only exceptions to this statement are the ammonia salts, but these are got rid £ during the process, as will be seen.

In carrying out the method, 5 cc. of urine are measured into a small flask of about 200 cc. capacity. To this are adde([ 5 cc. of a mixture which contains 350 grms. of BaCl~, an([ 50 grms. of Ba(OH)~ in a litre of water. The two are mixed, and then 150 cc. of the alcohol and ether mixture ate added. This consists of two parts of ordinary alcohol (96 per cent.) to one part of ether. The flask is now tightly corked, the contents shaken up, and the whole allowed to stand for 24 hours. The solution, which contains urea and ammonia, is then filtered off, the precipitate carefully washed witll about 100 cc. of ~the alcohol and ether mixture, and the filtrate evaporated down to 10 or 15 cc. in a porcelain capsule ozl a water bath. The temperature of the bath must not exceed 60 ~ C.

During the evaporation, the ammonia, previously set free by the baryta mixture, is driven off. Should the urine have been highly acid, it is desirable to add a little magnesia during the evaporation. The contents of the porcelaikl capsule are now carefully washed into a Kjeldahl tlask, and the nitrogen estimated in this manner.

In some of my experiments the arine was slightly tinged

By DR. W. H. THOMPSO~. 493

with hlood, and consequently contained albumin. Ir was, therefore, necessary to get rid of this before estimating for the total nitrogen of the urine itself. In order to do this the urine was boiled in a smatl tightly-stoppered bottle, which was opened after it had cooled, and the pure urine fil tered off. Before boiling, a drop of glacial acetic acid was added. When the quantity of urine was sufficient the amount of albumin was determined, and in all cases was found to be very small. The method of determining it was to estimate the total nitrogen before and after precipitatioa of the albumin: the difference naturally gave the nitrogen of the albumin.

I I I . = A D M I N I S T R A T I O N O F T H E D R U G S .

These were directly injected into the circulation by means of a cannula inserted into the rigl~t jugular vein. In the first four experiments a solution of urea, in normal saline fluid, was also introduced into the venous system. This was judged to be necessary, under the impression that sufficient urine to make the required estimations would not otherwjse be obtainable in the time. The solution was injected in two equal quantities at the beginning of the first and second h,)urs. Later experiments, however, showed that this pro- cedure was unnecessary, and was moreover liable to introduce a source of error; consequently it was abandoned.

Now, Ÿ Ÿ known that atropine may be impure from the presence of hyoscyamine or duboisine. It was, therefore, necessary to ascertain that the drug was pure. This can readily be done by means of the polarimeter; for whereas atropin does not affect the plane of polarised light, the other two drugs bring about a rotation. I accordingly examined" my solution of atropin, with the result that no deviation could be detected in a tube 40 cm. in length filled with the solution I employed--viz., 0"8 per cr This was verifir

494 The Nature of the Wo,'k of the Kid,,ey.

by my friend Dr. Max Siegfried, to whom I am also indebted for other valuable advice and assistance in the course of the investigation.

The amount of atropine administered varied from 1~-2 mgrms, per kilo of body weight of the animal used. The quantity of morphine given varied from 3 to 5 mgrms, per kilo of the body weight.

These doses though ]arge were not by any means fatal. This is shown by the fact that the kidneys had recovered to a very great extent from their influence in the second hour • administration. Indeed, in many cases the amount of urine secreted during this hour exceeded that during the hour prior to giving the drug.

IV. R E S U L T S OF T H E E X P E R I M E N T S .

The number of experiments carried out so far amounts to eleven in all. These are arranged in three classes--those ill which atropine alone was given, those in which atropine with morplline was administered, and, lastly, those in which mor- phine alone was injected. Six exl)eriments, numbers II. to VII. inclusive, fall into the first group, three, numbers I., VIII. , and IX., into the second, and two on]y, X. and XI., into the third.

In the following tables I have grouped the experiments in accordance with this arrangement.

1. E~ect on the amount of urine secreted.

TABLE I.--8howing the quantity of Urine secreted per hour.

Except in a few cases, where the quantity of urine was insut~cŸ %wo estimates were always rnade for each sample of urine. The results yielded closely corresponded in every instauce. The numbers in the following tables are in eacll case the averages of these two estimates :---

By Da. W. H. THOMP8ON. 495

ExpeEment l i .

f i l .

A t r o ~ alone given. l~t hour 2nd hour 8rd hour 34 ce. 16 cc. 1 cc. 23~ ,, 18 ,, 201 ,,

IV. 46~ ,, 64 ,, v .a 34�88 ,, 30~ ,,

v ~ . 48~ ,, ~5~ ,, VII . 43} ,, 35~ ,,

A tropine with Mo,Thine given. I . 56 cc. 39 cc.

V I I I . b 17 ,, 9 ,,

60 . 37�89 ,, 54~ ,,

40~ ,,

44 cc.

20~ ,, IX. 16 ,, 9~ ,, 22~ ,,

MorpMne alone given. X . 16~ cc. 11 ~ cc. 15�88 cc.

XI. 18 ,, 15 ,, 26 ,,

When we examine this table we see that a diminution l,as occurred in the quanti ty of urine secreted during the second ]lour, in every case except experiment IV. In the third hour the quantity has, a s a rule, agaŸ Ÿ approximating, and in some of the experiments exceeding, the normal of the first hour. In one experiment, however, the quantity Ÿ almost nil during the third hour--vŸ in experiment II . In this instance the dog died a few moments before the end of this hour, the secretion of urine having beeu almost com- pletely suppressed for more than ah hour.

The dose of atrol)in administered was tolerably large, but I do not at t r ibute the dog's death to this cause. The animal's temperature rose to a great height, and I have no doubt hyperpyrexia was the cause of death. This was one of the experiments in which a saline solution of urea was injected into the circulatŸ I t is to this I attribute the rise in temperature ; at all events, it occurred only in those cases in which the saline solution of urea was injected.

The urine was oollectod in this experiment for periods of 1~ hours in each c a s e .

Uriae colleotod for periods of 2 hours in thia expedment.

496 The Nature of the Work of tl, e Kidn~y.

The Ÿ of the solution of urea also accounts for the exeeption in experiment I V. In this case a large quantity of fluid (500 cc.) was twice injected viz., at tiro beginning of the first and seeond hours much more than was got rid of by the kidneys in the hour. The experiment fonns ah exception all through, no doubt owing to this fact. Ir is not without interest, however, since ir shows that bv introducing a large quantity of fluid into the circulation the effects of atropine may be overcome.

In the morphine experiments the diminution during the seeond hour, and subsequent return during the third, were even more marked than in those where atropine alone was use& Moreover, in most of the tases morphine produced a temporary arrest of the secretion immediately after its administration, lasting from fifteen minutes to two hours.

(a.) TABLE

~Expe¡ li.

/II. 2"86 IV. 4"88

V. 3.71 VI. 1.50

VlI. 3.86

2. Effect on the amount of Urea excreted. II.--Showing the ftuantity of Urea excreted per hour.

A tvopine alone given. 1st hour 2nd hour 3rd hour 3" 16 grms. 1"51 grms. ---

,, 1"64 ,, 2"08 g rms .

,, 5"96 ,, 5"87 ,,

,, 3 18 ,, 5"80 ,,

,, 1"05 ,, 1"44 ,,

,, 3 '34 ,, 3"47 ,,

A tvopine with Morphine given. I. 1"43 grms. 0"69 grms. 1"52 grms.

VIII. b 1"82 ,, 0"51 ,, 1"57 ,, IX. 1"23 ,, - - 1"63 ,,

Morphine alone given.

r

o The qu&utities here ara tho~ excretad in 2 hours in each r

X. 1"59 grms. 0"86 grms. 1"27 grms. XI. 1"73 ,, 0"72 ,, 1"55 ,,

" The quantities in this experiment are those excreted in 1~ hourm in e~ch

By DR. W. H. T~oMvsox. 497

In this table we see that the quantity of urea also is dimiuished dt~-ring the second hour, ,with. a _subsequent returu in the third hour. Thedimiuution is eveu more marked than in the case of the urine. This is~acct)unted for by the ~'act that not only is'the quantity o f uriue diminiShe4' during th~ ser hour, 'but the pcr'ce¡

{ , ~ , , . f

quantity of urea which, ir cpntains is also lowerod. This will be seen on examining the next table. The exceptiou seeu in experiment IV:. has beeu already" e~Ÿ

(b.) T:~BLE IIL---Shoming,~he per-centag~ ~uautity'of Urea ~ntained

Experiment

I I .

I I L

V I .

v, V I .

V I I .

I. V I I I .

I X . :

in,;thd U'rine secreted, r . �9

Atropine alone gwen. 1st hotw �9 2nd hotW

9"28 per r ' 9"46 per ~en t :

, 1 2 " 1 6 7, ' ~ 9 " 1 1 , , , .

10"0' , , 9"32 .7,

10"84 ,, !0"42 7," 3"09 ,, 2"95 , ,

l 8"83 ,, 9"34' 7,

. t �9 :

3rd hour

,10 '21 per ceat .

.9"70 10"13

2"62

8"52 i r

A tropine u, itl~ Morphina given. 1"77 per cent .

5"63 ,, !

i

L

) 1

'2"56 per cent:' 3"44 per ' 7 : 7 3 10"70 ,, ,,'

8~58 ,, 6"~0 : , , ' J, i ' �9 . c �9 ~ - * & - r

Mor~hir~s .:alone given,. ,.

c e l l t ,

2 x

w~ see:th~at tl/e per- *1" " " ~~~ J~ ' ' centage of urea conmmea ~n the urine is diminished during

. t?. r r �9 * . " �9 r c : , L / , : u ' , , " r ~ .~ ' " ' " ' ~ " r :" �9 the seco¡ hour. "rhe're'is also in 'this particular a' returu

�9 t ? �9 . . . f (- . ~ . , , . . . �9 �9 durmg the t~hird hora- {owards the normal cortar, on of the first. As will be seen,, there is a greater diminution in-the experiments"where morphine was employed. The only

, . . . : � 9 1 . ~ .

exception in the Cable ia expenment VII. '

X 6

On exammmg the abov ble

e

. , 9"4~ per qent.~ ,: , q-4~6 per ,cen~. ,: :~,, 8"38 !per cent . ~t'82 ,, , " 9 4 ,,. ...... 9"64 ,, ,~ ~ . . . .

498 The Nature of the lu of the Kidney.

3. Effect on the total nŸ excreted in the UrŸ (a ' ) TABLE ] V . Showing the total nitrogen exereted per hour.

A tropine alone given. Experiment 1st hour 2nd hour 3rd hour

I I . 1"58 grms . 0"80 g rms . ] I I . 1"46 ,, 0"92 ,, 1"13 gTms. 1V. 2"57 , 3"08 ,, 2"89 ,,

V. ~ 1"93 ,, 1"65 ,, 2"01 ,, V I . 0"78 ,, 0"55 ,, 0"83 ,,

V i I . 1"93 ,, 1"71 ,, 1"81 ,,

Atropine with MorpMne gimen. I . 0"77 grms. 0"39 grms . 0"84 grms.

V I I I . 1"01 ,, 0"32 , 0"84 , ] X . b 0"71 ,, 0"37 ,, 0"85 ,,

Morphine alone given. X . 0"84 grms . 0"53 grms. 0"70 grms.

X I . 0 97 , 0"49 ,, 0"92 ,,

(b.) TABLE V.--~howing the percentage of total the Urine.

A tropine alone given. Experiment 1st hour 2nd hour

II . 4"33 per cent. 4"42 per cent. ] II . 6"20 ,, .5"10 ,, I V . 5"52 ,, 4"81 ,,

V. 5"69 , 5'41 ,, V I . 1"64 ,, 1"55 ,,

Atropine with Mo~Thine given. I . 1 '38 per cent . 1"01 per cent .

V I I I . 5"95 ,, 3"61 ,, I X . 4"44 ,, 3"91 ,,

Morphine alone given.

nitrogen excreted in

8rd hour

5"50 per cent. 4"78 ,, 5"36 ,, 1"48 ,,

1"90 per cent . 4"16 ,, 3 7 3 ,,

X . 4"43 per cent. 3"48 per cent. 3"89 per cent. X I . 4"49 ,, 2"25 ,, 2"77 ,,

I n t h e a b o v e r a b i e s w e s e e t h a t t h e i n f l u e n c e o f the d l ~ g s u p o n t h e t o t a l n i t r o g e n is s i m i l a r t o t h a t u p o n t h e

" The oblervatiom were made for periods of 1�89 hours in this experiment. b The obeervations were made for peri de of 2 honra in this experiment.

B y D R . W . H . TKO~XPSO~. 499

urea I t differs in che particular, however. The diminu- tion of total nitrogen is not so marked as is the diminution of urea. This will be more clearly shown in later tables, and its probable bearing will then be commented upon.

Iu Table V. there are two exceptions viz. , experiments II. and VII. In both of these we find ah increase in per- centage of urea, and also of total nitrogen. I t is possible, howevcr, that a slight exaggerat ion of the increase has appeared in experiment II., since there was very little urine at my disposal to make the analysis for total nitrogen. Seeing, however, that both the ro'ea and total nitrogen ~.~)rrespond in the two exper iments- - tha t is to say, bo th ate increased-- I think we must regard them as genuine exceptions. Exper iment VII. certainly is: the figures are in each case the mean of two very closely corres- ponding estimations.

4. In the following tables I propose

nnknown nitrogen. (a . ) TABLE VI.---Showing the quantity of

excreted per hour.

A tropine alone given.

Effect on the nitrogen other than that in Urea.

to call this nitrogen

Experiment 1 st hour II. 0"ii grm.

]II. 0"12 ,, IV. 0"29 ,,

V. ~ 0"20 ,,

V I . 0"08 ,, VIL 0"12 ,,

" unknown" nitro#en

2nd hour 3rd hour 0"10 grm. ---- 0"15 ,, 0"15 grm. 0"30 ,, 0"16 ,, 017 ,, 0"27 ,, 0"06 ,, 0"16 ,, 0"15 ,, 0"19 ,,

Atropine with Morphine gh'en. 0"09 grm. 0"07 grm.

0"17 ,, 0"09 ,,

0"06 ,, - -

IB V I I I . b

l X .

�9 Qaantities here given are for 1 ~ hours. b Quantities here given aro for 2 hour8

0"13 grm. 0"11 ,,

0"09 ,,

500 The Nature of the Work of the KŸ

M ~ i n e alone given. Experiment 1st hour 2nd hour 3rd hour

X. 0"10 grm. 0"13 grm. 0"11 grm. X I . 0"16 , 0"15 ,, 0"20 ,,

(b.) TAm.v. VII.---Ehowing the percentage of " un]cnown " nitrogen in the Urine excreted.

]Experiment II.

III. 0"52 IV. 0"62 V . 0"65

V I . 0 .15 ) ' I I . 0 .29

A tropine l~t hour

0"32 per cent.

alone girven. 2ad hour

0"60 per cent. ,, 0"85 ,, ,, 0"47 ,, ,, 0"55 ,, ,, O" 17 ,, ,, 0"42 ,,

i . 0"19 per cent.

V I I I . 0"96 ,, I X . 0"38

X . 0 5 9 per cent. X I . 0"90 ,,

A tropine with Morphine given. 0"18 per cent. 0"98 ,,

Morphine alone 9iven. 1"09 per cent. 1"01 ,,

3rd hour 0"74 per cent. 0"74 ,, 0"75 ,, 0 6 3 ,, 0"25 ,,

0"47 ,,

0"29 per cent. 0"55 ,, 0"40 ,,

0"68 per eent. 0'70 ,,

I n this instance I purpose first to examine Tab le VI[. which shows the influence of the drugs upon the per- c en t age of " u n k n o w n " n i t rogen conta ined in the urin(~ secreted. The reason of doing this is because the per- cen tage table i l lustrates more cl'ear[y the maŸ result ob ta ined -viz., that during the second hour the unknown

increase again sufering a nitrogen is relatively increased, this diminution in the third hour.

There are three except ions ; except ion, exper iment IV., the others and V. In exper iment I. we find ah

one of these Ÿ our o|(1 are exper iments I. increase, however ,

occurr ing in the th i rd hour, ins tead of the usual retur~~ towards the normal. I t would appear , therefore, tha t the increase was deIayed ¡ this ins tance tilI the th i rd hora'.

By Da. W. H, Ttto][PSO.'~, 50[

There is no adequate explanation for the exception in experiment V.

When we now examine table VI. we find ir corresponds with table VII., in so far that many of the experiments, while showing a diminution in the quantities of urine, of urea, and of total nitrogen, during the seeond hour, still show that the absolute amount of unknown nitrogen is actually increased.

In those cases where an increase has not occurred in the sccond hour, we find ir taking place in the third.

The tables also show, what [ take to be of very consider- able interest, that in those experiments where morphine was used either alone of in conjunction with atropine, this rclative increase in the unknown nitrogen is much more marked.

(~.) TABLE V I I I . nitrogen bears to the total nitrogeu.

A tropine alone given.

Showing the proportion which the " unknowu"

Experiment 1st hour 2nd hour 3rd hour I I . 7.0 1 1"9 - -

11[. 8.5 16"7 13"3 IV. 11"2 9"7 5-3

V. 11"4 10"0 11 '8 VI . 9"6 11"2 17"4

VI1. 6"5 6"8 10"5

A tropine with Morphirte givea. 18"0 27 3

I. ]3"6 V I I I . 16"6

I X . 8"6

Morphine alorte given. 11"9 23"8 16"6 30"9

Xo XI.

This table illustrates, in a more

15"6 13"2 10"7

15"3 22"2

strikŸ manner, the facts already shown by the two preceding tables , viz., the re]ative increase in mlknown nitrogen during the second

50~ T],e _h'at~tre of the Work of tl, e KŸ T.

hour, with (in the great majority of the expe¡ return towards the primitive condition in the third hora-.

5. lnfluence of the drugs upon blood-pressure.

Ir now became a question to determine whether tl~(~ drugs produced their inhibitory effects upon the secretiol~ of urine by lowering blood-pressure of not.

I, therefore, made some experiments to examine their effects upon blood pressure. In the first (experiment IX.b) atropine was administered to a dog in proportionate dose t~) that employed when the urine was collected. Aft(,r half ah hour had elapsed, when, as I had seen in the previous experiments, the effects of the drug were at its height, I guve a corresponding dose of morphine.

The results were, that atropine produced a slight, but very transitory, fall of pressure, followed on the other hand by a continued moderate rise. The fall endured fbr tess than one minute.

Morphine, on the contrary, immediately brought about a marked fall. This fall to a certain extent accounts for the preliminary arrest and subsequent diminution in the secrc- tion of urine under the influence of the drug in questiol~. ] t does not, however, wholly account for it. This will be seen when we examine experiments X. and XI., where a blood-pressure tracing was taken side by side with the colleetion of urine.

In experiment X. the mean pressure during the hom- before morphine was given, stood at 128 mm., Hg., thc quantity of urine being 16~ ce. lmmediately after the administration of the drug the pressure sank to 47"5 mm., but steadily recovered till in a quarter of ah hour it had reaehed 94"5 mm., at whieh point the secretion of urine recommeneed. During the hour, beginning with the re- establishment of the secretion, the mean pressure was 97"8 mm., and the quantity of urine secreted 11~ cc. la

By Da. W. H. THo~IPSO~r. 503

the following hour the quantity secreted reached 151 cc., but the mean pressure only registered 105 mm. Thus in this third hour the quantity of urine was almost as great as that in the first hour, whereas the mean blood-pressure was considerably lower, than that of the same hour.

The results of experiment XI. are, in this respect, still more remarkable, because here the blood-pressure had returned to a point which under ordinary circumstances ought to have caused a secretion a considerable length of time before this was re-established. Moreover, during the third hour, when the quantity of urine much excceded that of the first hour, the mean blood-pressure was lower by some millimetres than that even of the second hour, and consequently lower than that of the first.

The actual figures are as follows : Mean blood-pressure of first hour - Q u a n t i t y of ur ine ,, -

1 1 7 " 9 m m . , H g . ;

18 ce. ; 117"5 mm., H g . ;

15 ce . ; 115-5 mm., Hg . ;

26 cc.

Mean blood-pressure of second hour - Q u a n t i t y of ur ine ,, - Mean blood-pressure of third hour - Q u a n t i t y of urine ,, -

I t is to be regretted that, up to the present, the number of experiments in which blood-pressure was recorded is so small. But even as the case stands there can, I think, be no hesitation in aecepting the statement that diminutiou of blood-pressure does not by any means wholly account for the lessened secretion of ua-ine, brought about by the adminisfration of morphin.

The numbers in experiment IX.b, previously alluded to, are as follo ws : - -

Blood-pressure before g i v i n g atropine - 127 mm., Hg . ,, 1 3 s e c a . a f t e r , , - 1 0 7 ,, , , 4 4 , , , , - 1 2 4 " 5 ,

, , 1 0 m i n s . l a t e r - - 1 3 6 " 5 , ,

, , 1 0 , , - - 1 4 3 ,

, , 1 0 , , - - 1 4 4 ,

5O4 The Natm.e of the Work of the Ki&~ey.

Morphin was now administered, which brought the pressure dow~a to 45"5 mm., Hg., followed by a steady and fairly rapid recovery fill within the hour ir stood again at 96" 5 ~ ~ , , H g.

6. lnfluence of the drugs upon temperature. In the earlier expe¡ no systematic record of

temperature was taken ; it was, however, observed in those Ÿ which the saline solution of urea was introduced that the animals exhibited signs of increased temperature, such as "panting," &c., with which one is familiar in dogs. In experiment II., on noticing these signs to a very marked degree during" the second hour, the temperature was taken aud was found to be 42"3 ~ C. It probably tose still higher, and indeed there is little doubt on my mind that this dog died from hyperpyrexia.

In the later atropine experiments tho usual effeet was a slight fatl during the course of the experiment, with one of two exceptions, in which a moderate rise occurred after administration of the drug, which gave place to a slight fall still later.

In the experiments where morphine, either alone of in eonjunction with atropine, was given, the temperature fell to a small extent during the course of the experiment. Part of this faI1 is probably due to the length of time the dogs were kept on the tab]e with the abdomen upwards, thus allowing a greater escape of heat. The tigre'es are gŸ in the separate record of experiments at the end.

7. Summa~ T of results with dedue~tions.

The main paints established by the research so lar as it has gone ate

(a.) With ~'egard to atroTin , that i t - - (1) Diminishes the quantity of urine.

By DR. W. H. T~oMPso~. 505

(2) Diminishes the total quantity and percentage quantity of urea.

(3) lncreases relatively, and in many cases a3solutely, the amount of nitrogen other than that contaª in urea.

(4) Its effects cannot be attributed to the influence which it exerts upon blood-pressure.

(b.) With regard to morphin, the results are that it Mso �9 (1) Diminishes the quantity of urine, causing even

a temporary arrest of the secretion. (2) Diminishes the total and percentage quantitŸ

of urea, even more markedly than does atropin. (3) [ncreases the excretion of the "unknown" nitrogen. (4) While diminishing the blood-pressure, its effect

upon the sccretion of urine cannot be wholly attributed to this cause.

In conclusion, I may say that in so far as these experi- ments bear upon the nature of the work of the kidney, they tend to show that the production of urine is to a certain extent by a process analogous to the mauufacture of the secrction by other glands which are influenced by atropine. Moreover, the increase of the unknown nitro- gcnous compounds, side by side with the decrease in the excretion of urea, may, I think, fairly be taken the one as the counterpart of the other, and ir so this fact, coupled with the production of heat during the activity of the gland, would lead us to infer that part of tl~e urea is possibly ~,~aaufactured in the kidney out of o~~e of other of wlmt 1 have c(dled the unk~wwn nitrogenous compounds.

~YNOPSIS OF THE INDIVIDUAL EXPERIMENTS.

The numbers in the following r›191 represent the per- centage quantities of the different constituents of the urine. l~rea is represented by the nitrogen which ir contains, th~ substancc itself being given in Tables II. and III.

5C,6 The Natttre of the Wor~ of the Kidney.

EXl~EItrM~.NT I. Dog, 24 kilos. 200 cc. of a solution containing 0"1 per cent. urea, aud 9 per cent. grape sugar injected at beginning of first and second hours. 0"048 grm. atropin with morphin given.

Urine Total N. Nitrogen Unknown Nitrogen Temp. Remarks cubic of reine of urea nt~rogen of albumen

centtmetl~s per cent. per cent. per cent. 1st hour 56 1"38 1"19 0"19 ~ Urine col- 2nd ,, 89 1"01 0"83 0"18 - - ( lected by 3rd ,, 44 1"90 1"61 0"29 j catheter

XPERIMENT

injected. 1st hour" 2nd ,, 3rd ,,

I I . -Dog, 42 kilos. 0"064 grm. a~ropin given. 34 4"65 4"33 56 5"02 4"42 1

200 cc. urea solution (0"125 per cent.) twice

0"32 0"60 42"3 ~

•XPERIM-ENT I I I . - -Dog , 29 kilos. injected. 0"04 grm. atropin given.

1st hour 23"5 6"20 5"68 2nd ,, 18"0 5"10 4"25 8rd ,, 20"0 5"50 4"76

E XPERIM~.NT twice injected.

500 cc. urea solution (0"083 per cent.) twice

0"52 0"85 0"74

IV.- -Dog, 42 kilos. 500 cc. solution 0-048 grm. atropin given.

1st hour 46"5 5"52 4"90 0"62 2nd ,, 64"0 4-82 4-35 0"47 8rd ,, 60"5 4"78 4"53 0"25 4th ,, 58"0 4"44 3"92 0"52 5th ,, 55"75 4"46 4-01 0"35

of urea (0-05 per cent.)

]~,XPERTMENT V. solution introduced. N.B. f o r an hour and a ha l f in each

Dog, 29~

l sŸ period 34~ 5"69 2nd ,, 80�89 5-41 8rd ,, 87"5 5-36

:EXPER1MENT VI. Dog, 23 solution administered.

1st hr. R. K. 29~ 1"67 L . K . 19 1"52

2nd ,, 35~ 1"55 8rd ,, 54~ 1"48

kilos. 0"036 grm. atropin given. No urea The observations in this ex periment were mude case.

5"04 0"65 4"86 O'55 4"73 0"63

kilos. 0"044 grm. atropin given. No urea

1"54 0-13 0"00 ~ 39.5 ~ C. 1"34 0"18 0-03 I 1"37 0-17 0"06 40"0 ~ C. 1"22 0"25 0'03 40"5 ~ C.

EXP]~ItI~I~T Vl I . - -Dog , 2 ~ kilos. tion administered.

1st hr. R. K. 22~ T,. K. 21�89

2nd ,, 85~ 8rd , , 40~ 4th ,, 86~

4"25 4"57 4"78 4"44 4"50

4.01 4"23 4.36 3"98 4"10

0"56 grm. atropin given. No urea solu-

0"24 0"09 t 38.8 o C. 0"34 0"42 Trace 38-8 ~ C. 0.46 ,, 88"2 ~ C. 0"40 ,, 38'4 ~ C.

B y D R . W . I I . T H O ~ I P S O N . 507

E XPERI,',IENT V I I I . - - D o g , morph in given. N.B. periods of two hours.

Urine cubic

centimetres 1st per iod 17 2nd ,, 9 3rd ,, 20~

18,j kilos. 0"042 grm. a t ropin , w i t h 0"14 g rm. The observat ions in each case ex tended over

No u rea solut ion injected. Nitrogen Temp. Remarks

of albumen. Total N. Nitro~en Unknown of urine of urea nitrogen per cent. per cent. per cent.

5"95 4-99 0"96 3"61 2"63 0"98 4-16 3"61 0"55

Dog, 17�89 kilos. EXPERIMENT I X . phin adminis te red . No u rea solut ion injected.

l s t h r . R . K . 8 4"51 4'11 0"41 None ~ 39.0oC. L . K . 8 4"37 4"06 0"31 ,, f

2nd ,, R . K . 4i~ 4"15 blof enough ur ine to t 39"0 ~ C. L . K . 4~ 3'66 e s t ima te u rea ~ "

3rd ,, R . K . 12~; 3'95 3"48 0"47 } 39"4 ~ C. L . K . 10�89 3"51 3"17 0"34 ~ "

4th ,, 19 4"22 3"78 0"44 ,, 38"4 ~ C.

38"6 ~ C. T h e u r ine 38"3 ~ G. w a s s u p -

38"0 Q C. pressed for ~ hr .

0"027 grms. a t rop in wi th 0"09 grm. mor-

Ur ine sup- pressed f o r �89 hr .

EXPERIMENT X.--Dog, urea solut ion.

23�89 kilos. 0"12 grm. morph in Blood-pressure taken.

adminis te red . No

1st hour 16~ 5"02 4"43 0"59 - - 39"8 ~ C. U r i n e s u p - 2nd ,, 11~ 4'57 3"48 1"09 - - 40 2 ~ C. pressed 3rd ,, 15~ 4"59 3"88 0"69 39"5 ~ C. f o r l a 4th ,, 14~ 4"84 4'15 0"69 - - 3 8 8 ~ C. mins .

E XPERIMENT X I . - - D o g , 30 kilos. 0"12 grm. mor ph i n injected. Blood-pres-

- - 40"2 ~ C. Secre t ion 39"8 ~ C. a r r e s t ed 39"6 ~ C. for 2 hrs . 39"0 ~ C. 2 mins .

sure taken. No urea solut ion in t roduced. 1st hour 18 5"39 4'49 0"90 2nd ,, 15 3"26 2"25 1"01

3rd ,, 26 3'67 2"77 070