No. 1314.

NOVEMBER 4. 1848.

LecturesON

THE CHEMISTRY OF PATHOLOGYAND THERAPEUTICS.

SHOWING THE

Application of the Science of Chemistry to the Dis-covery, Treatment, and Cure of Disease.

DELIVERED BY

ALFRED B. GARROD, M.D. LOND.,ASSISTANT PHYSICIAN TO UNIVERSITY COLLEGE HOSPITAL; LECTURER

ON MATERIA MEDICA AND THERAPEUTICS, ETC.

LECTURE XXIX.

Urine continued. P1’obable cause of discrepancies in some ofSintoWs re.sults. Cause of the Acidity of the Urine, and modein which Uric acid is held in solution. Amount of Urine andspecific gravity liable to vary. Total amount of excreted solidsremains nearly constant. Dr. Prout and Becquerel’s average.Urina sanguinis, urina chyli, urina p0<. Average amountof the diferent cort-stititents of the Urine excreted by the healthyadult in twenty-four hours. Lecanu’s conclusions. Lehma7tW8experiments on the influence of Diet on the urinary excretion.Origin qf the various constituents of the U1"&Igrave;ne. CompositionQf the Urine in the lower animals. Analysis of the Urine ofthe Lion &c., by Hieronymi ; of the Horse, by Bous8&Iacute;ngault, &c.

WHEN wo last met, you will remember that I pointed out toyou the comparative results obtained by different chemists,from their examination of human urine, when estimated inthe 100 parts of dry residue. We then found that those ofBerzelius, Marchand, Lehmann, Becquerel, and Day, agreedvery closely with each other, in the relative amounts of ureaand other organic matters; but those of Simon were found todiffer considerably. I then stated that this discrepancy mightperhaps be produced from the subjects of his experimentssuffering from indigestion; but I think it may also partly beascribed to some error in his experiments, for on looking at hisanalysis of the 1000 parts of urine, it will be seen that, com-pared with the specific gravity of the fluid operated upon, hefound a much larger amount of solid matters than the otherobservers, and much larger than would be given by using Dr.Christison’s formula-viz., multiplying the excess of specificgravity over water by 2.33; for example, in one analysis ofhealthy urine, having the specific gravity 1012, he finds

forty-four parts of solid constituents, whereas, calculated fromChristison’s rule, it should have been only 27.96, so that heobtained nearly one-third more. Perhaps Simon did notthoroughly dry his solid constituents, and if we assume suchto be the case, and make the corresponding increment to theurea, we shall find his results very similar to those of theother observers. Of course this correction would cause adecrease in his extractives, which are seen to be much higherthan those of the before-named chemists.

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Cause of Acidity of the Urine, and Mode in which the UricAcid is held in Solution.-Formerly it was sunposed that theacidity of healthy urine was owing to the presence of freelactic acid; but as uric acid is deposited from strongly acidurine in the form of urate of ammonia, as shown by Dr. Prout,this view cannot be held, for the addition of a single drop offree acid is sufficient to cause the precipitation of the wholeof the uric acid. Liebig ascribes it to the presence of a super-phosphate in the fluid,-that is, of a tribasic phosphate, withonly one atom of fixed base. He also shows, that a solutionof the common phosphate of soda, which is alkaline, will be-come acid when uric acid is dissolved in it, and will hold insolution a considerable amount of this latter body. Dr. BenceJones has also shown, that the solubility of the uric acid andurate of ammonia is greatly increased by the addition of somesalt to the solution, as common salt. Dr. Bird comes to thefollowing conclusion as to the mode in which the uric acid isheld in solution in urine:" Uric acid, at the moment of sepa-ration from the blood, comes in contact with the double phos-phate of soda and ammonia derived from the food, forms urateof ammonia, evolving phosphoric acids, which thus producesthe natural acid re-action of the urine. If the whole bulk ofthe urine be to that of the urate of ammonia formed, not lessthan about 2701 to 1, the secretion will, at the ordinary tem-perature of the air, remain clear; but if the bulk of the fluidbe less, an amorphous deposit of urate will occur. On theother hand, if an excess of uric acid be separated by thekidneys, it will act on the phosphate of soda of the double

salt; and hence, on cooling, the urine will deposit a crystallinesediment of uric acid sand, very probably mixed with amor-phous urate of ammonia, the latter always forming a layerabove the crystals, which always sink to the bottom of thevessel." Very much has been written upon this subject; thediscussions, however, do not possess the interest they formerlydid; but should you wish to become acquainted with them, Imust refer you to the works of Berzelius, Dr. Prout, andothers.We will now direct our attention to the amount of urine,

and of its principal constituents, which is thrown out by thekidneys in health; also, the influence of age, sex, time of day!.diet, and regimen. We shall take twenty-four hours, or acomplete day’s urine for comparison; for unless this is at-tended to, our results are apt to be very erroneous, as thequantity and quality of the excretion is apt to vary greatlywhen only that passed in a short time is examined. Manylaborious observations have been made on this subject; butwe shall confine our attention to a few of the most trustworthy,and shall only give the mean results.Both the quantity of urine and its specific gravity are very

liable to variations in the same individual, although we shallfind that the total amount of solids contained in it remainsvery constant ; very many circumstances influence thisquantity-that is, its watery portion; for example, it is in-creased by the free use of diluents, (as the foreign light wines,)and diminished by abstinence from these; the state of theskin also influences much the quantity; so, also, certain mentalemotions, as fear, and certain diseased conditions, as hysteria;by these latter it is greatly augmented, although only tem-Dorarilv.Becquerel states that the mean amount passed in twenty-four hours by the male is about forty-four fluid ounces, and bythe female forty-eight ounces, the specific of the former being1018.9, of the latter, 1015.1, which gives for the mean of thetwo sexes forty-six fluid ounces, specific gravity 1017. Dr.Prout considers that in this country the mean amount isthirty-five fluid ounces, of specific gravity 1020, or taking seasoninto account, forty ounces, of specific gravity 1015, in winter,and thirty ounces, specific gravity 1025, in summer ; thisstatement is doubtless very near the truth.The time at which the urine is passed alters much its

character-indeed, to such an extent, that three varietieshave been named, which are, urina sanguinis, or that passedin the morning before anything has been taken, and which,therefore, is less influenced by food, either solid or liquid;urina pot2s, that passed soon after drinking copiously, andurina cibi or urina chyli, or that passed soon after the digestionof a good meal. The first variety has usually an averagespecific gravity and medium depth of colour; the second is oflow specific gravity, and pale; the third, the greatest density,and the darkest tint. For clinical examination, if we can onlyprocure small quantities of the patient’s urine, we shouldexamine that passed in the morning, or urina sanguinis, andit is also often useful to compare it with the urina chyli of thesame individual.

In our last lecture, the mean results of the analysis ofhealthy human urine was given, estimated in the 1000 partsof that fluid; if we take into consideration the quantity passedin twenty-four hours, we shall find that, according to theseobservers, the amount of the different constituents of the urineexpressed in grains is as follows :-

Lecanu, from a series of experiments on the urine of manyindividuals, has deduced many very interesting conclusions:-

1. That in the same individual urea is excreted in equalquantities in equal times.

2. That the same remark applies to uric acid.3. That the excretion of urea and uric acid varies much in

diferent individuals in equal times.4. That both sex and age influence the amount of excretion

of both these substances; that it is greater in men than inwomen, at the same age and in the same state of health; andgreater in adult women than in old persons or young children.

5. That the amount of fixed salts bear no relation to eithersex or age, the chloride of sodium being most liable to vary,owing, no doubt, to the very varying quantities contained inthe food.The average amount of urea and uric acid excreted by adult

u

494

men and women, and also by old person-! and children, isseen in the table which is contained in Dr. G. Bird’s work onUrinary Deposits, taken from the Journal de Phannacie. I

You will observe that Lecanu’s average of the amount ofurea is very much greater than that of Becquerel; the differ-ence is greatest in the adult male, and is probably due to thedifferent kind of individuals (as to size, occupation, &c.) uponwhom the experiments were performed.More recently some very interesting experiments have been

made by Lehmann, on the influence of diet on the urine; hisexperiments were performed on himself, and the diet he em-ployed were, first, an ordinary mixed diet, then one purelyanimal; next, a pure vegetable one; lastly, a diet destitute ofnitrogen.

1. Ort ordinary Diet, with amount of 1’l2tid only sufficient to

allay ?7tM’.&mdash;The average amount of urea excreted in twenty-four hours was found to be nearly 500 grains, and of uric acid,about 18.3 grains, and therefore the relation of the uric acidto the urea was one to twenty-seven.

2. On a ]Jurel!! anirtal diet, sometimes on eggs o2ily.-Tlie iurine was then found to become much paler in colour, larger Iin amount, of a higher specific gravity, 102T, and the additionof nitric acid caused the formation of crystals of the nitrateof urea, re-action very acid.The mean amount of urea excreted in twenty-four hours

was then 819 grains, and of uric acid, 22.6 grains, so that al-though there was a slight absolute increase of the latter body,yet the ratio between it and the urea was actually dimi-nished, being only about as one to thirty-six. This result is

interesting, and contrary to a very common opinion, as show,ing that in the healthy organism the assimilation of a largeamount of animal food does not increase the uric acid. Duringan animal diet, also, the amount of phosphates, especiallythose with an alkaline base, become greatly increased,although the amount taken in with the food were diminished;this is owing to the oxidation of the phosphorus contained inthe protein compounds. The same remark applies to the sul-phates, the acid of which is chiefly derived from the albumi-nous matters.

3. On a vegetable did.-The urine then becomes of a yellow-ish-brown colour, faint odour, acid in its re-action, and some-times deposited crystals of uric acid. The amount is de-creased, the specific gravity remaining much the same aswhen on an animal diet-viz., 1027.5, the amount of solids isdecreased, so also the urea, but not the uric acid. The ureaamounted to 346.5, the uric acid to 15.7, so that the ratio of theuric acid to the urea becomes absolutely increased-viz., asone to twenty-two.

4. On a zoiz-22iti-oqeizLed diet.-The food then consisted ofamylaceous principles, as sugar, starch, and gum, togetherwith oleaginous bodies, as almond oil. The urine becamebrownish red, slightly acid, but having considerable tendencyto become alkaline. The experiments were only performedfor two days after the commencement, as the health becameaffected; the quantity of urine was not affected, but the totalsolids suffered considerable diminution, the urea on the secondday being reduced to 2S5 grains, and on the third to 190 grains,whilst the uric acid on the second day was thirteen grains, onthe third, nine grains ; the phosphates and sulphates werealso diminished. These last results would have been moresatisfactory could the non-azotized diet have been continued,because it probably requires two or three days for the effectsof the previous diet to pass off, and, therefore, we only getapproximations to the results which would follow the want ofnitrogenized nutriment. In the following table is seen, at oneview, the total mean quantities of urea and uric acid, andtotal solids passed during twenty-four hours, when under theinfluence of the different diets, expressed in grains:-

Lehmann also includes the lactic acid, lactates, and ex-tractives in his examination, but as we have found it probable-and we may say, proved-that the former do not exist inhealthy urine, I have not given his results. Probably, a mix-ture of kreatine and kreatinine forms the bulk of what he has

denominated lactic acid and lactates, and did not appearmuch influenced by diet. The extractive matters, however,suffered considerable variation, being greatly reduced on theanimal, and increased on the vegetable, when compared withthe amount on an ordinary mixed diet.

Estimating them in the 100 parts of solid residue, and aspassed in the twenty-four hours, they were as follows :-

,

11I.fluelce of Strong Exercise on the Urine.-Lehmann found,that by strong muscular exertion the urea, sulphates, andphosphates, and what lie termed his lactic acid, (kreatine andkreatinine?) were increased; at the same time, the extractivematters and uric acid suffered a diminution. Lehmann’s ob-servation has been confirmed by Simon and by Dr. Percy.

Sources of the Various Constituents of the Urine.-It becomesa very interesting inquiry, to discover from whence thesevarious components are derived; are they formed by thekidneys, or do these organs merely excrete themWe must consider separately the origin of the different classes

of principles, for the purpose of being enabled to attempt thesolution of this question. We have found the urine composedof water and a solid portion, that the solid constituent may bedivided into an organic and inorganic part, and these againsubdivided into many individual ingredients. The organicportion is seen to consist of mucus and epithelium scales,urea,uric and hippuric acids, kreatine and kreatinine, and ex-

tractives little known except as including colouring mattersand an unoxidized sulphur and phosphorus compound. Now,of these various organic constituents, we can easily maketwo divisions, the first of these, including the mucus andepithelium are obviously derived from the urinary passages,and are therefore additions made to the urine after itsexcretion by the kidneys, so that we can easily dismiss theconsideration of them. The origin of those in the seconddivision is not, however, so well understood. Urea and uricacid were formerly supposed to be formed by the kidneysfrom matters presented to them by the blood. This view,however, is no longer tenable, as urea is formed when theseorgans are extirpated, and then found in the blood in consi-derable quantities. The same takes place when the functionof the kidneys is injured or destroyed by disease; and uricacid also, as I have before stated to you, forms a small portionof healthy blood, and in certain affections is found in thatfluid to a large extent, frequently becoming deposited in otherparts of the body; so that we may, I think, safely assert thatthey are only excreted matters. They are found, then, readyformed in the blood; but it becomes a question whether theyare formed during the metamorphoses of the tissues them-selves, or from the food taken into that fluid by the chyle.Probably they, or at least one of them-the urea-has a doublesource; for we find that it continues to be excreted in indivi-duals and animals kept for a very long time without food; butwe shall have occasion to speak again on this subject whenconsidering the pathological relations of urea, uric acid, &c.The kreatine and kreatinine are most probably derived from

the muscular system, being formed in them during muscularexertion. They enter into the blood, and either wholly or inpart escape further decomposition; or part of the kreatine issimply changed into luoatinine. Such being the case, weshould expect to find these bodies in increased quantitiesafter strong and prolonged muscular exertion; and you willobserve that Lehmann found what he estimated as lacticacid, and which consisted of, or at least contained them,was so augmented, although the extractives suffered a dimi-nution under the same circumstances. It would be extremelyinteresting to examine this point. As to the source of thecolouring matters, and other extractives, our knowledge isvery limited. Probably the former is derived from somealteration Droduced in the colourins’ matters of the blood:and we have seen that a close relation exists between thepigments of the blood, bile, and urine, that from the urinecontaining most oxygen in its composition. I have had strongreasons for considering that the colouring matter of the urineis formed in the blood itself, having observed that then.the urine is suppressed, as in cholera &c., the uric acid throwndown from the blood is strongly coloured, as we find to be thecase when it is precipitated from urine; but that in othercases, as in gout, when uric acid is alone retained in theblood, it is precipitated of a light colour. Of the origin of thesulphur compound we have no facts to justify our venturing 0

495

un asseruon, cm tt intly possimy ue iormea nom me unassi-milated albuminous matters of the food, or perhaps it may becystine.We have next to consider the inorganic portion, or fixed

salts; and we find but little difficulty in explaining their pre-sence ; the alkaline phosphates being derived partly from the100d, partly from the phosphoric acid formed by the oxidationof the albuminous principles; the earthy phosphates from thefood, and also from disintegration of certain textures; thesame remarks apply to the sulphates; the chlorides are derivedmostly from the excess of these salts in the diet, and becomevery greatly diminished in certain cases when little or none istaken into the system.

Composition of the Urine in the Lower Azzioaals.-Before wefinish our remarks on healthy urine, it may be as well that Ishould say a few words concerning the nature of the urinary.excretion of some of the lower animals, as it may tend tothrow considerable light on the physiology of this fluid, and onthe origin of some of its most important constituents, for weshall, by this means, have the power of ascertaining the effectsof certain influences upon the secretion, which the study ofthis fluid as presented to us by the human subject is incapable.of giving; for example, if we wish to know the influence ofrespiration upon the composition, we have only to comparethe urinary secretion of birds, where we find this function Ideveloped to its fullest extent; and that voided by reptiles inwhom the process is very imperfectly performed.

I

Urine in the Invertebrata.-In the mollusca uric acid hasbeen found by Jacobson and Treviranus in the so-called saccus- <:alcarcus; the latter observer found it also in snails andmuscles; in the gastropoda and cephalopoda it has also been=seen in the coloured secretions of these animals. In insectsit has also been discovered; for instance, in the excrements ofthe house-fly by Dr. Aldrich, in those of the silk-worm by.Brugnatelli, in the form of urate of ammonia, mixed with- C2.r}xmate and phosphate of lime, and phosphate of magnesia;in these it is seen in the tubuli, formerly, but erroneously,thought to be hepatic in their nature. Ileller has also foundurate of ammonia in butterflies, and Dr. Davy in all true in-jects in Barbadoes; he also states that spiders, in place of uricacid, excrete xanthine, or uric oxide. I may remark that I.have found urate of ammonia in abundance in beetles.

Urine in the TTertebrata.-In fishes, the urinary excretion isstated to contain a large quantity of uric acid, and the sameremark applies to reptiles and birds. In the chelonia there is’discovered a considerable amount of urea, as I have frequentlyobserved when examining the secretion of the common landtortoise. This fact had been before made known by Marchand,who found the fluid to have the following composition in 1000arts:&mdash;

It was slightly acid, and like pus in appearance. The urineof the turtle has been found by some to contain uric acid;.others, however, have not discovered this principle in it; italso contains urea. In the frog and toad urea has been found.

In the ophidian reptiles, the urinary excretion appears tobe chiefly composed of urate of ammonia; but urea is also a.constituent, although denied to exist in it by some. I maystate that I have crystallized the nitrate of urea from thecommon snake. In birds the existence of urea has been some-times asserted, at other times denied.The experiments on the whole subject requires repetition.When we examine the urine of mammalia, we observe two

distinct kinds, one voided by the carnivora, the other byherbivorous animals. In the former class, the fluid nearly re-sembles that voided by man, especially when he is living onan animal diet. Hieronymi examined it in several of theseanimals, as the lion, tiger, leopard, &c. The composition ofHon’s lI1’in iR seen in the table:

The urine of these animals is of a bright yellow colour,strong in odour, acid in reaction, and the specific gravity variesbetween 1045 to 1076.We observe here that the amount of urea is large, that of

uric acid very small, and that the ratio between urea and uricacid is much greater than in human urine.

In herbivorous animals the urine is alkaline in reaction, ofspecific gravity varying from 1030 to ] 050, and when allowedto rest throws down a deposit of carbonate of lime andmagnesia; the following analysis of that fluid from the horse,by Boussingault, may be taken as a representation of its com-position in 1000 parts :-

The peculiarities observed in the urine of these animalsconsist in the absence of uric acid, (traces of which have, how-ever, been found by Mr. Fownes and others,) the presence of alarge amount of hippuric acid, and the total absence of eitherearthy or alkaline phosphates.We shall have occasion to refer to these analyses when dis-

cussing the pathology of the urinary secretion, to which sub-ject I shall have to direct your attention in our next lecture.

Lectures

ON PARTURITION,AND THE

PRINCIPLES & PRACTICE OF OBSTETRICS.BY W. TYLER SMITH, M.B. LOND.

LECTURER ON MIDWIFERY IN THE HUNTERIAN SCHOOL OF MEDICINE.

LECTURE XIX.

Rupture of the -tlenls; Caitsesofais accident. Excessiventotoraction of the xaterzzs itself. Prevention qf uterine rupture-

I Importance of moderating excessive uterine action. Lacera-

I tion of the perinaeurn causes of tlais accident. Ob8ervati(Jll8on the prevalent plan of szcZyarting the perinaeum bynianual1--)ressu2-e.

RUPTURE of the Uterus is perhaps the most appalling ofall obstetric accidents. When rupture has occurred, therutmost that art can do affords but a faint chance of the

preservation of life. Any suggestions, therefore, whichtend to throw light upon its causes, and to point out measuresfor its prevention, are of great importance. To effect theseobjects, the study of reflex obstetrics will, I believe, provemore adequate than anything which has hitherto been pro-posed.Rupture of the uterus has been attributed to softening

of the uterus during gestation, to deformity of the pelvis, toa cutting action of the sharp linea-ilio-pectinea, to excessivecontractions of the uterus, to mechanical violence throughawkward or ill-timed attempts to turn the child, and to themechanical effects of unskilful instrumentation. Other causesof less note have been enumerated, but the foregoing are themost important. I do not think sufficient prominence hasbeen given to uterine motor action, which, in many cases, isthe sole cause of the mischief, and which plays an importantpart in all. To this point, therefore, I shall principallyaddress myself myself in the present lecture.

It is an interesting and remarkable fact that rupture of theuterus seldom happens to primiparous women. It thus is op-posed to laceration of the perinaeum, which occurs with thegreatest frequency in primipaise. Some practical applicationsmust lie under circumstances apparently so enigmatical. Whatare the peculiar differences between first and subsequentlabours to which we can refer the antithesis which exists be-tween rupture and laceration ? It appears to me, as the actionof the dilatation of the perineum is almost purely mechanical,it is quite natural that its distention in first labours should bethe most dangerous, while in subsequent deliveries its disten-tion or dilatation should be comparatively easy. On the con-

! trary, the actions of the uterus, both of dilatation and &ccedil;ontra&ccedil;-