No. 1148.

AUGUST 30, 1845.

LECTURESON

ORGANIC CHEMISTRY:DELIVERED DURING THE WINTER SESSION, 1844-45, IN THE

University of Giessen.

BY JUSTUS LIEBIG, M.D., PH. D., F.R.S., M.R.I.A.Professor of Chemistry in the University of Giessen.

URINARY CALCULI-THE MANNER OF THEIR FORMATION-URIC

ACID CALCULI-URATE OF AMMONIA-OXALATE OF LI1BIE-

PHOSPHATE OF LIME—AMMONIO-PHOSPHATE OF MAGNESIA—

MIXED, OR TRIPLE PHOSPHATE--CYSTIC OXIDE, OR CYSTINE-ZANTHIC OXIDE, OR ZANTHINE.

GENTLEMEN,—I think I may now assume that you are sufficientlyacquainted with the metamorphoses which uric acid undergoeswhen acted on by various chemical agents, since I have enteredso fully into the subject in the course of the last few lectures. Inow propose to present you with the chemical history of urinarycalculi, a subject full of interest to chemists, but more especiallyso to physiologists and pathologists.

Uric acid is always present, to a small amount, in the normalurine of man. It is partlv to its presence that this fluid owes itswell-known acid reaction. In unhealthy conditions of the

organism, the proportion of uric acid in the urine is greatly aug-mented, and accumulating in the bladder, it gives rise to theformation of stones, or calculi. But, in addition to uric acid, thereare other matters which enter into the composition, or altogetherconstitute those concretions which claim our attention, andamongst these there are two organic substances particularlydeserving of a minute consideration, as an appendix to our ex-position of the series of bodies formed from uric acid-namely,CYSTIC OXIDE, and ZANTHIC OXIDE, or CYSTINE and ZANTHINE.I shall, moreover, take the opportunity of this lecture to treat ofthe subject generally, and include those urinary concretionswhich consist of inorganic matters.Under the names urinary concretions, stones, or calculi, (for

these terms are synonymous,) are comprised all substancesdevoid of organization found detached in the urinary bladder.Similar concretions, indeed, are also formed in other animalfluids, as the bile and the saliva. Wherever they are produced,they may arise from very various causes.Most of the fluids of the animal body, but more especially those

destined to be evacuated from the system, hold in solution certaincompounds, which are kept dissolved only by very weak affinities,and therefore, as soon as the fluid has left the body, they becomedeposited in a solid form. When, therefore, these fluids areretained longer than is ordinarily the case, or when, in conse-quence of unhealthy conditions of the organism, these matters,which, in the normal state, exist only in minute quantities, areproduced in larger proportions, they deposit themselves in a solidform, and the process being frequently repeated, concretions areformed, and, as we are now contemplating especially the case of ’ithe urine, are deposited in the bladder. In this manner those ’,calculi are generated which consist of uric acid and the urates. ’,

Calculi may, however, be formed, when neither the propor-tionate amount of solid matter in solution is increased, nor thefluid retained a longer time than natural in the bladder, becausethe urine may, from various causes, undergo such a change inits constitution, that those conditions essential to the solubility ofcertain compounds may be absent, and consequently these com-pounds necessarily become precipitated.

Phosphate of lime is perfectly insoluble in pure water; its

solubility in urine depends upon the existence of free acid in thatfluid. If, from any cause, the urine becomes alkaline, as, for

instance, when organic salts with alkaline bases are taken intothe stomach, which, as is well known, are converted into car-bonates during their passage through the organism, then theconditions essential to the solubility of phosphate of lime areremoved, and this salt is precipitated. All calculi consisting ofphosphate of lime are produced in this manner.The calculi containing ammonio-magnesian phosphate are also

produced in a manner precisely analogous to this. In manyanimal fluids, particularly the urine, phosphate of magnesia isfound in solution. Normal urine contains no ammonia, but when,from any cause, ammonia is generated, the phosphate of magnesiano longer remains in solution, but is precipitated as ammonio-phosphate of magnesia.

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Beside the foregoing, there is another cause of the formationof urinary concretions. In diseased conditions of the system,peculiar compounds are not unfrequently formed which are

never produced in the healthy organism, and being perfectlyin-soluble in urine, are immediately deposited in a solid form fromthat fluid. In this manner oxalate of lime calculi are formed,and those concretions of organic matter termed cystic oxide andzanthic oxide.But beyond these chemical causes of calculi, certain mechanical

conditions have almost always more or less influence upon theirformation in the urinary bladder. When any of these stateswhich I have enumerated exist, and, in consequence, depositsoccur of uric acid, urates, insoluble phosphates, oxalate of lime,&c., in small quantities, it does not necessarily happen thatcalculi are formed, but, in most cases, the urine flowing off,carries with it through the urethra the sediments suspended in it,or already deposited. When, however, the bladder containsmucus, these sediments are apt to adhere to it, and become unitedinto masses. Very often a foreign body, which has accidentallygot into the bladder, forms the nucleus upon which these sedimentsare deposited, and to which they adhere, the irritation theyoccasion on the internal surface of the bladder induces the secre-tion of mucus in which the urinary deposits accumulate, and theythus become the direct cause of the formation of calculi.The calculi formed in the human bladder differ, therefore, in

their composition; and whilst there is a great variety, the fol-lowing may be taken as the characteristic of most of them :-

1° calculi, composed of URIC ACID.20 ditto ditto URATE OF AMMONIA.

3° ditto ditto OXALATE OF LIME.

40 ditto ditto PHOSPHATE OF LIME.

50 ditto ditto AMMOKIO-PHOSPHATE OF MAGNESIA.

60 ditto ditto A MIXTURE OF PHOSPHATE OF LIME

and AMMONIO-PHOSPHATE OF MAG-NESIA.

70 ditto ditto CYSTIC OXIDE or CYSTINE.

80 ditto ditto ZANTHIC OXIDE or ZANTHINE.

URIC ACID CALCULI.

The calculi which are most frequently found in the bladderare those composed chiefly of uric acid. They are generally ofa reddish-brown or yellowish colour, which is derived from thecolouring matter of the urine. Their surface is sometimes smooth,sometimes rough ; their size, of course, very variable. The frac-ture of these calculi sometimes presents a crystalline texture; atothers, it is smooth, and often they are made up of concentriclayers. They are rather hard, so that they may be just scrapedwith a knife. Calculi are never composed of perfectly pure uric

, acid; they always contain hardened mucus, which binds the uricacid together, and small quantities of alkaline urates, urate oflime, phosphate of lime, and ammonio-phosphate of magnesia in

, admixture. In the inverse proportion to the prevalence of these; impurities, these calculi present the characteristic properties of. uric acid. You will, however, be able, under all circumstances,,

to distinguish them from all others, if you remember the behaviour, of uric acid with nitric acid, which I minutely described to youin a former lecture. The best way to apply nitric acid as a test,, is to place a fragment of the calculus to be examined upon aplatina spatula, and drop upon it some common nitric acid. When, uric acid is present, a lively effervescence ensues, with the cause

of which you are well acquainted. Evaporate the resultingsolution by a low heat, and add ammonia, when a purple colouris produced, characteristic of the presence of uric acid.

’ URATE OF AMMONIA CALCULI.

L Calculi composed of URATE OF AMMONIA are of much rareroccurrence than the former, particularly in a pure state. They

are generally found in children. They present various shades of,

colour, between a whitish-grey and a light-brown; they havet usually a smooth surface and earthy fracture, and are made up ofconcentric layers, which are easily separated from each other.r As I have just stated, they very seldom occur pure, commonly) containing uric acid and small quantities of the phosphates. It is.

very easy to distinguish these calculi from those composed ofuric acid. They dissolve in boiling water, except there are ad-

mixtures of other substances; whilst uric acid is, as you mustremember, very slightly soluble. When you have examined a

calculus, and proved it to contain uric acid, and it also yields am-) monia when treated with potass, this must not be supposed to provethat it is urate of ammonia; the generation of ammonia mayS also arise from the decomposition of ammonio-phosphate of mag-, nesia present in the calculus.

- OXALATE OF LIME CALCULI.

Urinary concretions which consist of OXALATE OF LIME occuri frequently. They are distinguished by their external appearance:, those with a rugged surface, dark colour, and larger size, aree termed MULBERRY CALCULI, whilst smaller ones, with a smooth

226

surface, are known as HEMP-SEED CALCULI. These calculi arealways very hard, and imperfectly laminated. They almostinvariably contain small quantities of uric acid, phosphates, andanimal matter of uncertain composition. They are insolublein water and alkaline fluids, but generally dissolve completely inacids. The mulberry calculi are easily distinguished by theirbehaviour before the blowpipe: the oxalate of lime is convertedinto a carbonate by heat, and this latter salt loses its carbonicacid at a higher temperature, and becomes caustic lime. After

being subjected to the action of the blowpipe, therefore, mulberrycalculi may be slaked by water, and impart to it an alkaline re-action. As, however, many calculi contain some amount ofcarbonate of lime, which, if submitted to the process I havedescribed, would produce the same result-namely, a residuum,which slakes on the application of water,-you should never

omit the employment of the usual tests for the presence of oxalicacid. For this purpose the calculus is to be pulverized andboiled with carbonate of potass; by this means carbonate of limeand oxalate of potass will be formed; filter, and add an excessof acetic acid to the filtrate, to decompose the surplus of carbo-nate of potass, then, if a solution of sulphate of lime be added,oxalate of lime will be precipitated.

PHOSPHATE OF LIME CALCULI.

Calculi composed of PHOSPHATE OF LIME are very rare. Upto the present moment no one has had an opportunity of examin-ing such except Dr. Wollaston. Those which he has describedhad a smooth surface and a chalky fracture, in which distinctlayers could be perceived. They contained an organic matterby which the phosphate of lime was agglutinated, and they con-sequently became black before the blowpipe. By the continuedapplication of heat they again became white, and finally fused.

A’iII310NIO-PIEEOSPHATE OF MAGNESIA CALCULI.

Those calculi which consist of AMMONIO-PHOSPHATE OF

MAGNESIA are met with frequently, but those in which thisdouble salt is combined with phosphate of lime are still morecommon. Both these species of concretion are similar in appear-ance ; their surface is generally rough, and they have internallyan earthy or chalky appearance, very rarely exhibiting a crys-talline structure. Sometimes, however, they are covered withcrystals externally, and occasionally cavities are found in themfilled with crystallized ammonio-pliosphate of magnesia. Thereis little difficulty in recognising these calculi, or in discriminatingbetween the two kinds, notwithstanding the similarity of theirexternal appearance. Ammonia is evolved from both kindswhen acted on by caustic potash. Both dissolve readily in nitricand muriatic acids. To an acid solution ammonia is first to beadded, until a feeble alkaline reaction is exhibited, when a slightprecipitate forms, then acetic acid, until the precipitate disappears.The addition of chloride of iron, and boiling the solution, causesall the phosphoric acid to be deposited in the form of phosphateof iron. The filtered liquid is then to be tested in the ordinarymanner for lime and for magnesia.We now arrive at those urinary concretions which, as I have

told you, contain certain peculiar organic substances; of thesethere are two species; and it is both interesting and useful tobecome acquainted with their composition and properties. Thesecalculi occur but very rarely. One of these species of calculi,however, has been observed more frequently in France. It wasoriginally discovered by Dr. Wollaston, and is called cysticoxide, or cystine. It contains, as a constituent, sulphur.

CYSTINE CALCULI.

Cystic oxide calculi, as I have already told you, are of rareoccurrence; they consist of somewhat compact crystalline masses,of a yellowish or greenish colour, and smooth surface. Theymay be broken into fragments without difficulty; their fractureis crystalline, with the lustre of wax, and their fragments aretranslucent at their angles. Such calculi generally consist of

pure cystine; sometimes, however, their surface is coated withphosphates.

Urinary calculi composed of cystine are readily soluble in thefixed alkalies and in ammonia. They are thus distinguishedfrom those consisting of phosphate of lime, oxalate of lime, orphosphate of magnesia, these being insoluble in ammonia; whilstthey are distinguished from those containing uric acid by theirsolubility in acids.

In order to obtain cystine in a pure state, cystic oxide calculiare dissolved in caustic potass, and acetic acid added in excess tothe boiling hot solution; upon cooling, the cystine separates incolourless, transparent, lamellar crystals. When a filtered solu-tion of cystine in ammonia is left to evaporate gradually, moreperfect crystals are obtained.

Cystic oxide was first ascertained to be a peculiar animal sub-

stance by Dr. Prout, to whom we are indebted for so many in-vestigations in organic chemistry. It was afterwards analyzedby Pelouze, and his results corresponded with those obtained byDr. Prout. From these analyses the following formula wasdeduced:—

C6 N H6 OsBaudrimont, however, subsequently discovered that cystine

contains sulphur; and Thaulow has shown that the amount of itssulphur is no less than 25.5 per cent. The results of his analysesin other respects accords perfectly with that of Dr. Prout. Thetrue formula for cystine, therefore, is-

C6 N H4 04 S2The error of Dr. Prout and Pelouze, in overlooking the sul-

phur as a constituent of cystine, arose, unquestionably, from theatomic weights of sulphur and oxygen bearing so simple a rela-tion to each other.The properties of cystic oxide are the opposite of those of an

acid, but very similar in character to urea. It combines withsome acids, forming crystalline salts, and therefore, in such cases,acts the part of an organic base. With muriatic acid it combinesdirectly, in the same manner as ammonia, forming an anhydroussalt, which consists of one equivalent of muriatic acid and oneequivalent of cystine-

C6 N U, 0, S, + ci HThe compound it forms with nitric acid consists of one equi-

valent of base, one of acid, and three equivalents of water, ofwhich it loses one equivalent at a temperature of 850-

C6 N Ha 04 82 + N Oj + 2 H 0 + Aq.Cystine forms no combinations with the organic bases. Sub-

jected to destructive distillation, it yields ammonia, with a veryoffensive smell, and other products containing sulphur.

In order to detect the presence of cystine, the suspected cal-culus is to be dissolved in a strong solution of caustic potass, anda few drops of solution of acetate of lead added in excess; theliquid is then heated to boiling. If cystine be present, insolublesulphuret of lead is formed, and precipitates, and oxalate ofammonia remains in solution. This method may be advan-tageously employed to test both calculi and urinary deposits forcystic oxide.

It would be highly interesting to submit cystine to a closerand more rigorous examination; we cannot doubt but it wouldfurnish results of great importance. The knowledge of all theproducts of abnormal secretion in the animal body when per-fected, must necessarily throw light upon the sources whencethey are derived, and the transformations undergone by thehealthy constituents of the body, or its aliments, from which theyare produced.

ZANTHINE CALCULI.

But there is another species of calculi consisting of a peculiarorganic substance, quite different in constitution to cystine. Thiswas discovered by MARCET, and has been termed, zanthic oxide,zanthine, uric oxide, and urinous acid. The designation, ZAN-THINE, appears to be preferable, and by this we shall continue tospeak of it.The calculi containing zanthine are as rare as those with

cystine ; their surface is generally smooth and shining, of awhitish colour, but sometimes without lustre; they are ratherhard, and their fracture exhibits a brownish flesh colour; theyconsist of concentric layers without any appearance of a crystal-line formation. When rubbed or scraped, they acquire the lustreof wax. These calculi show a very characteristic reaction withnitric acid. This acid dissolves them at the boiling point withoutthe evolution of gas. This distinguishes them perfectly fromuric acid calculi. The solution in nitric acid being evaporated,leaves a citron-yellow residue, soluble in caustic potass, and inthis menstruum acquiring a reddish-yellow tint. The charac-teristic purple colour which uric acid gives with nitric acid andammonia, cannot in any way be produced with zanthine.To obtain this organic substance pure, the calculi containing

it must be dissolved in caustic potash, and the solution saturatedwith carbonic acid. The zanthine separates in the form of awhite precipitate, which contains no trace of potash. On beingdried, it forms hard pale-yellow fragments, which acquire lustreon being rubbed. Zanthine is also soluble in solutions of alkalinecarbonates, in small quantities, in boiling water, and in oxalic andmuriatic acids. It also dissolves in concentrated sulphuric acid,forming a yellow-coloured solution, from which nothing is pre-cipitated on adding water.The analysis of some zanthine procured from a urinary con-

cretion which Dr. Langenbeck extracted by operation in 1816,made by myself, in connexion with Professor Wohler, led us toassign to it the formula-

Co NZ H2 O.

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It would hence appear that this substance differs from urieacid only in having a less amount of oxygen in its composition.

We -were, however, unable to make more than one analysis ofzanthine at that time, from the extreme rarity of calculi con-taining it. For the same reason we have not been able to ascer-tain the composition of the yellow substance formed by the actionof nitric acid upon zanthine, which would, in all probability,throw more light upon the constitution of the latter.

Unger has recently discovered a substance in guano, to whichhe applied the term zanthine, believing, from the similarity ofmany of its properties, that it might be identical with the substanceexamined by Wohler and myself; but his analysis gives differentresults as regards the amount of hydrogen, and a still more vari-able amount for the nitrogen.The method I have described for obtaining zanthine from

calculi is not applicable for procuring this substance from guano.Solutions of caustic, potass, and soda, dissolve with it a brownunctuous substance out of the guano, which can only be sepa-rated with extreme difficulty. The substance in question may,however, be easily separated from guano, by employing milk oflime, by digesting these together until the fluid no longer remainsbrown, but becomes of a pale greenish-yellow colour. The liquidis then filtered, and hydrochloric acid added in excess; it is thento be allowed to stand a few hours, when a flesh-coloured preci-pitate is deposited, consisting of about equal parts of uric acid andUnger’s zanthine. In this process the lime forms an insolublecompound with the brown colouring matter of the guano; andthe other matter, which is quite insoluble in lime-water, becomesdissolved, in consequence of the presence of soda and potass salts,which the lime deprives of their acids.The mixture of uric acid and Unger’s zanthine thus obtained

must be boiled with hydrochloric acid, which dissolves the latter,and leaves the uric acid untouched. When this solution cools, a’compound of this zanthine and hydrochloric acid is precipitated ;by repeatedly crystallizing this compound, and afterwards decom-posing it by means of ammonia, the zanthine is obtained per-fectly pure. Recollect, I speak now, and in the rest of this lecture,of Unger’s Zanthine, for it must be left to future investigations todetermine what relation this substance bears to the zanthine ofhuman calculi.Unger procured by this method a sufficient quantity to be able

to submit it to repeated analysis, and thus to ascertain its chemicalcharacter and composition. -

These analyses invariably gave a higher number for its amoun1of nitrogen (46.61) than Wohler and myself obtained in omanalysis of the zanthine from a calculus (36.95) ; they give th(formula-

C10 N$H5 50"With respect to its chemical character, it has the properties of

an extremely feeble base; nevertheless, it has basic relations toacids, although its affinities are very weak. It is decidedly actedon by the mineral acids; when brought into contact with sulphuricacid, heat is evolved, and a sulphate is formed. But its salts are

decomposed even by water. The crystallized sulphate of zanthinecrumbles into a white powder, which is a hydrate of zanthine, oncoming into contact with water. The hydrochlorate of zanthineloses part of its acid when heated above 1000.

But zanthine performs the functions of a weak acid with

powerful bases. Solutions of caustic potass or soda dissolve it,and with the latter it forms a crystalline compound. These

combinations, however, are just as weak as those it forms withacids ; they are decomposed by carbonic acid, or even by water.

Zanthine combines with hydrochloric acid in several propor-tions. The acid salt is constituted as follows :—

C10 Ns Hs O. + 2 Cl H.It is obtained by passing hydrochloric acid gas over zanthine.When this is heated above 100°, as I have already mentioned,and further even by exposure to air, it becomes changed, half theacid escapes, and the compound left is

C10 Ns Hs 0, + Cl Ha neutral hydrochlorate.

Treated with sulphuric acid, in the same manner as above, acompound is obtained, which also crystallizes in yellow needles,of an inch in length, constituted as follows :-

C10 N H, 0, S 03 + H 0 + 2 aq.When treated with a large quantity of water, this yields what Mr.Unger calls a hydrate of zanthine,

.

3 C,. N, H, 0, + 4 H 0

This formula, as well as those given by Mr. Unger, for thenitrate, phosphate, tartrate, and oxalate, are quite anomalies.

I have already observed that the substance in question canalso perform the functions of a weak acid. When treated with aconcentrated solution of caustic soda until no more is taken up,and the solution diluted with alcohol, confused crystalline scalesare deposited. Analysis has shown that these crystals are a com-pound of zanthine, soda, and water, in the following proportions :-

C10 N5 H5 O5+2 Na O+12 H OFurther investigations are necessary to determine the nature of

these compounds, and especially to make out the relation whichthis substance derived from guano bears to human zanthine. Thetwo substances are, indeed, strikingly similar. If we subtractfrom the formula of human zanthine two equivalents of water andadd one equivalent of ammonia, we obtain the composition of thesubstance derived from guano.

It is not by any means unlikely that, in pursuing the investiga-tions on the metamorphoses of uric acid, we may succeed in the pro-duction of zanthine artificially. In the course of our experimentson uric acid, we met with a substance which, in its appearanceand reactions, very much resembled zanthine. When uramilicacid is dissolved in concentrated nitric acid, nitrous acid gas isevolved, the fluid becomes yellow on evaporation, and white crys-talline scales are deposited, which dissolve in boiling water, andrecrystallize as the solution cools. They are also soluble incaustic potass, to which they impart a yellow colour, and are pre-cipitated from this solution by acetic acid. The scarcity ofmaterial prevented us from pursuing further this particularmetamorphosis of uramilic acid.I Upon boiling uric acid with black oxide of manganese, we onceobtained a substance which had all the appearance and manifestedthe behaviour of zanthine ; bit after many attempts, we were notable again to produce any of the same matter.

CONTRIBUTIONS TO CLINICAL MEDICINE.BY JOHN TAYLOR, M.D.,

PROFESSOR OF CLINICAL MEDICINE IN UNIVERSITY COLLEGE, ANDPHYSICIAN TO UNIVERSITY COLLEGE HOSPITAL, LONDON.

PERICARDITIS.

CASE 10.*—4 shoemaher, aged 20, rather delicate, seized withoutobvious cause with acute rheumatism, followed on the fourth dayby symptoms of pericarditis, which speedily subsided, but againreturned.-Morbid condition of the urine; (temporary albumin-uria ; excess of urea, and rapid decomposition;) disappearanceof pericarditis, followed by signs of endocarditis and bronchitis ;CMre.—eM:af7ts : Friction-sound, its characters, variations, andextent; orthopncea without serous effusion ; signs of pericarditisdiminished, but those of endocarditis supervened, after ptyalismwas produced.

JAMES L-, aged 20, admitted into University College Hos-pital on Monday evening, May 6th, 1844. A short, and ratherslender youth, of sanguineo-nervous temperament, and rathersallow complexion. He has been a shoemaker’s apprentice forthe last seven years. During the latter’partof this time his workhas-been laborious ; he has been much confined in-doors ; hisposture, when at work, is necessarily bent; the epigastrium isconstantly in contact with the last, as a result of which, theensiform cartilage appears to be unusually pliable. His fatherdied in his fifty-fourth year ; for many years before his death he

, suffered from asthma; his mother is still living and well, and isnot subject to rheumatism; his brothers and sisters are healthy.

; During the period of childhood, he had the measles, the small-pox,(after vaccination,) and also an attack of typhus fever. He has atvarious times, since he began to work at his present employment,suffered from a throbbing pain, and sense of weight and oppres-sion about the forehead. These symptoms were frequently

*- relieved by the occurrence of epistaxis, to which he has been, very subject for the last twelve years; but a few months ago they

became so distressing, that he was at length compelled to give uphis work, which he accordingly did in March, and since that time

’. he has been altogether free from them.

The report of this case is condensed, from reports presented for theFellowes Clinical Prize, by Mr. Robert D. Harluig, M.B.