Cornell University Library The original of this book is in the Cornell University Library. There are no known copyright restrictions in the United States on the use of the text. http://www.archive.org/details/cu31924031268489 Cornell University Library arV 18911 On the morbid conditions of the urine de 3 1924 031 268 489 olin.anx MOEBID CONDITIONS THE UBINE ON THE MORBID CONDITIONS OF THE URINE DEPENDANT UPON DERANGEMENTS OF DIGESTION CHARLES HENRY RALFE, M.A., M.D. CAITJS COLLEGE, CAMBB.TDGK ; FELLOW OP TIE BOTAL COLLEGE OP PCYSICIANS, LONDON ; ASSISTANT FUTSICTAN TO TUIt LONDON HOSPITAL; LATB SENIOR VI3ITINU PHYSICIAN TO THE SKAHBN's HOSPITAL, GfiEBWWICa ; AND TBACHER OP PHYSIOLOGICAL CHEMISTRY IK THE MEDICAL SCHOOL OF ST SBOKOB'S HOSPITAL LONDON J. & A. CHURCHILL NEW BUBLINGTON STKEET 1882 Y UNIVERSITY \ LIBRARY TO GEORGE EDWARD PAGET D.C.L. Oxoh. & Doeh., LL.D. Edim., M.D. Cam tab., F.E.S. REGIUS PROPESSOR OP PHYSIC IN THE UNIVERSITY OP CAMBRIDGE PRESIDENT OF THE GENERAL MEDICAL COUNCIL THE FOLLOWING PAGES ABE INSCEIBED WITH RESPECT AND ESTEEM PEEFACB In the present work it is intended to confine the attention to those urinary derangements which are the result of chemical changes occurring within the body, as distinct from those morbid conditions of the urine which are directly associated with disease of the renal organs or of the genito-urinary passages, or those which, like diabetes and temporary albuminuria, are the result of disturbance of the circulation in the hepatic and renal vessels. During the last twenty years physicians have paid but little regard to these derangements, which during the earlier part of the century were the subject of ex- haustive research and furnished the materials for keen discussion and controversy. Three causes may be assigned for this neglect. In the first place the atten- tion of pathologists has of late years been almost ex- clusively directed to histological research. Secondly, owing to the dominant position uric acid has assumed in humoral pathology there has been a tendency to refer these derangements to the same category and to speak of them somewhat indiscriminately as connected with " gouty " proclivities, and thus to overlook some of their distinctive characters. Lastly, there is no department of clinical medicine which is generally so perfunctorily performed as the examination of the urine in disease. Vlll PBEFACE As a rule, we are content with determining the pre- sence or absence of albumen or sugar, the nature of deposited matters, and recording the specific gravity and reaction without, however, reference being made to the conditions as regards time, food, &c, at which the urine was passed. Whilst it seldom happens that any attempt is made to determine the actual acidity or the amount of solid matter passed daily, yet it is almost entirely by this means that we can hope to obtain an insight into the nature of the metabolic changes occurring within the body. But whilst this branch of urinary pathology has been comparatively neglected of late years, physiological chemistry has made considerable progress, and this is especially the case with reference to the physiology of digestion. Not only have recent discoveries elucidated much that was obscure, but they have also opened up new points of view. It is, therefore, with the aid that physiological chemistry now affords us that it is pro- posed to pass under review the facts connected with the subject of the morbid conditions of the urine dependant on derangements of digestion. Much of the material of which the present volume is comprised has already appeared in the pages of the ' Lancet ' during the last five years. The encouragement the author received during their publication in a separate and detached form leads him to hope that now they are arranged in a more systematic manner, they may prove serviceable towards the elucidation of these still difficult problems in chemical pathology. Queen Anne Stbeet, Cavendish Sqttabe, W. March 15th, 1882. CONTENTS CHAPTEE I PAGE FORMATION AND REMOVAL OB ACID FROM EBB BODY . 1 CHAPTER II Dyspepsia Associates with an Acid Condition of the Ueine . . . . .20 CHAPTER III Dyspepsia Associated with an Alkaline Condition of the Ueine . . . . .36 CHAPTER IV Debasements Associated with Deposits of Ueic Acid (Relationship to Lith^mia and Gout) . 65 CHAPTER V Derangements Associated with Deposits of Oxalate of Lime . . . . .99 CHAPTER VI Derangements Associated with Excessive Elimination of Phosphoric Acid .... 116 APPENDIX Effect of Bicarbonate of Potash on the Acidity of the Urine .... 137 b CORKIGENDA On page 11, and again on p. 16, the formula for Acid Sodium Carbonate and Normal Sodium Carbonate should be NaH 2 C0 3 and NajHCOg respectively, and not NaHC0 3 and Na 2 C0 3 , as given in the text. On page 37, second line of formula, for =C 2 H 4 (Aldehyde) \ H 2 OC 4 H 8 2 + 2C0 2 + H 4 , read =C 2 H 4 {Aldehyde) +H 2 | C 4 H 8 2 + 2C0 2 + H 4 ; and again, on next line, for C 2 H 4 (Acetic Acid), read C 2 H 4 2 . On page 83, foot-note, for free acidity of London porter, read 200 grains instead of 4000. MOEBID CONDITIONS OF THE URINE CHAPTER I ON THE FORMATION AND REMOVAL OP ACID FROM THE BODY Acid and acid salts are continuously entering the blood. (1) They may he introduced into the body from without in the food. The quantity, however, thus derived under ordinary conditions is comparatively small, since nearly the whole of the saline constituents of the food are alkaline, or become so by conversion in the system. Still, a small quantity of acid sodium phosphate is derived from the juice of flesh, and this passes no doubt unchanged into the blood. (2) Acid, too, is generated in the alimentary canal from fermen- tative decomposition of the saccharine matters taken with the food, or of the amylaceous principles that have been converted into sugar. In health this fermentative process is most active at the lower part of the small intestines, and in the first portion of the large intestine. (3) Lastly, acid is generated in the tissues of the body. Thus, in a condition of inactivity the lymph fluid of all tissues is alkaline or neutral ; on activity being evoked the reaction becomes acid. This is well seen in what 1 A ^ 2 FORMATION AND REMOVAL follows the contraction of muscles, in which the con- traction wave gives rise to sarcolactic, carbonic, and other volatile fatty acids, and probably glycerin-phos- phoric acid. Of these acids the carbonic passes directly into the blood in a free state. With regard to the other acids, their distribution and combination with the inorganic bases, likewise set free by the process of tissue oxidation, is so bighly complicated that little is known about them. It is probable, however, that the lactic and other organic acids are converted in carbonates, probably acid (bi-) carbonates, and that some portion of the phosphoric acid enters the blood as acid sodium phosphate; since Maly* has conclusively determined the presence of acid sodium phosphate and acid sodium carbonate (bicarbonate), the latter an acid salt with an alkaline reaction. In spite> however, of this constant entrance of acid into it, the blood of the living body is always alkaline, no doubt because the chief acid salt (sodium bicarbonate) has an alkaline reaction. What the degree of alkalescence of normal blood is has not been determined, but it is probable that, like the temperature and specific gravity, it has certain definite limits which cannot be passed in either direction without causing disturbance of healthy nutrition. . In fact, great difficulty is experienced in reducing the alkaline reaction of the blood, f Hoffmann, who fed pigeons for a considerable time on food yielding only an acid ash (yolk of egg), found that however great the tendency of uric acid and of the acid salts of phosphoric acid to combine with bases, yet these were * " Untersuchungen uber die Mittel zur Sailrebildung im Orga- nismus." R. Maly. ' Z. fur Phys. Chimie,' 1877. t " Ueber der Uebergaug von f reien Saurer durch das alkalische Blut in den Ham." ' Z. fur Biologie,' vii. OF ACID FROM THE BODY. d not withdrawn from the alkaline blood, but were evidently withheld to maintain its alkalinity. Lascar,* by introducing diluted mineral acids into the stomach, succeeded in reducing the alkalescence of the blood but not considerably, and the conclusion he arrived at was that the organism retained free alkali with great energy. In some of his experiments the quantity of acid introduced into the stomach would have made the whole animal acid if it had been absorbed and excreted again. From this Lascar infers that the organism possesses certain " regulative mechanisms " which maintain the equilibrium between the acids and alkaline bases in the system; These experimental facts seem to be borne out by what occurs in scurvy; That disease, as has been well established, is brought about by the prolonged and complete withdrawal of the organic vegetable acids and their salts from the dietary of those affected. These organic salts, as is well known, by oxidation in the blood yield alkaline carbo- nates. Now* the alkaline carbonates are the salts chiefly concerned in maintaining the alkalescence of the blood, and it appears when these are largely with- drawn, as happens when scurvy is induced, the proper degree of alkalescence of the blood is maintained with difficulty, and in order to secure it some other alkaline salt is retained instead of being excreted. Thus, I found, after the withdrawal of fresh vegetable food for eighteen days, the total quantity of phosphoric acid passed in the twenty-four hours was slightly reduced, whilst the phosphoric acid in combination with the alkaline oxides was reduced nearly one half. Again, in a case of scurvy, it was found that the alkaline phos- * "Zur alkalescence des Blutes." 'Archiv fur Physiologie.' PBiiger, 1874. 4 FOBMATION AHD REMOVAL phates increased rapidly on the resumption of an anti- scorbutic diet, although the amount of phosphoric acid ingested was the same in scorbutic and antiscorbutic rations respectively. These two facts pointing to the conclusion that the alkaline phosphates are retained in the system when the alkaline carbonates are with- drawn, and discharged when these are again supplied.* All experiments made on animals with a view to reduce the alkalinity of the blood or to neutralise it have ended sooner or later in the death of the animal, and if the process has been a slow one, the definite patho- logical changes will be found to have occurred in the blood and tissues, closely resembling the changes found in the bodies of patients dying from scurvy, viz. dis- solution of the blood globules, ecchymosis in the heart, blood stains in the mediastinum, gums, and mucous surfaces ; whilst the muscular structure of the heart, and the muscles generally, as well as the secreting cells of the liver and kidneys, become granular and even distinctly fatty. Lastly, Dr Gaskell f has shown, experimentally, that a dilute alkaline solution acts upon the muscular tissue of the heart so as to produce a powerful contraction, whilst dilute acid solutions pro- duce an opposite effect, and that the muscle of the smaller arteries are acted upon in the same way. These facts seem to point to the conclusion that one factor at least upon which the constriction of the muscles both of heart and arteries depend, is the alkalinity of the fluid surrounding them. It is not unreasonable, therefore, to surmise that variations of the degree of alkalinity would not be unlikely to lead to disturbances of circu- * ' Inquiry into the Pathology of Scurvy,' by the Author. Lewis, 1877. t ' Journal of Physiology,' vol. iii, No. 1, 1880. OF ACID FKOM THE BODY 5 lation and so effect a secondary chemical influence on nutrition, as well as a direct one Acid is discharged from the blood by four channels. (1) By the lungs, (2) the skin, (3) with the gastric juice, and (4) by the urine. The escape of carbonic acid by the lungs is effected by means partly mechanical and partly chemical, since carbonic acid exists in the blood in two conditions, loose and stable. By loose carbonic acid is meant that carbonic acid which is given off to a vacuum, and is physically absorbed as well as retained in solution by the alkaline carbonates and phosphates ; this loose carbonic acid escapes from the lungs into the atmosphere in obedience to the law of pressures. On the other hand, the stable carbonic acid is in combination with some base and can only be separated from the blood by some chemical means. How this decomposition is effected is not yet deter- mined. The amount of carbonic acid exhaled by the lungs of a healthy adult has been shown by Dr Edward Smith* to average about 950 grammes in the twenty- four hours. The rate of excretion, however, is not uniform, being subject to external influences such as the amount of bodily exercise taken, the nature of the food, and the effect of the meal hours. Thus, Dr Smith has shown that the ingestion of food produces a marked increase on the elimination. Thus, in a mean of eight experiments, he found the rate of excretion before break- fast to be 6'8 grains per minute, after breakfast 9 grains ; before a midday dinner the excretion was 8'6 grains, and was continued at the same rate per minute after- wards ; before tea the rate was 7'9 grains per minute, afterwards it rose to 9'5 grains. Dr Smith considers * 'Transactions of Royal Society,' 1860. "Experiments in Respiration." 6 FOBMATIOK AND BEMOVAL the fact that no increase occurred after the dinner meal in his case was owing to his dining before his usual hour, and that the action upon the respiration of the previous meal had not passed off. .In some experiments he made with Dr Murie and Professor Frankland an increase was observed. This increase in the exhalation of carbonic acid, or to express it plainly, the acidity of the breath after food, is interesting when taken in connection with the fact that the opposite effect is noticed with respect to the urinary secretion, the acidity of which is depressed by the ingestion of a meal. In addition to the carbonic acid passing off by the lungs, about six grammes of this gas are exhaled by the skin during the same period. The sweat or fluid perspiration has also a decided acid reaction, which is due to the presence of formic, acetic, and butyric acids. The quantity of acid, however, discharged by this chan- nel has not been determined, it probably varies greatly even in health, and a very considerable amount is ex- creted when strong exercise is taken ; whilst in certain diseases, as acute rheumatism, the quantity discharged by the skin is often enormous. The gastric juice is always acid, and its acidity has now been incontestably proved to be due to hydrochloric acid — at least, Eichet has shown that in the fresh secre- tion this is the only mineral acid present. Lactic, acetic, and butyric acids are also met with in gastric juice, the result of fermentative changes occurring in the stomach. In certain morbid conditions, which we shall consider further on, they may be considerably in excess of the hydrochloric acid, indeed, that acid may be very scantily secreted,* and thus by causing delay * 'DuSucGastriquechezl'HommeetlesAnimaux.' Paris, 1878. OF ACID FROM THE BODY 7 in gastric digestion lead to the formation of these organic acids. In many cases of acid dyspepsia it is a matter of importance to determine whether the acid in the vomited matters contains a due proportion of hydro- chloric acid or whether the organic acids are in excess. In the former case the acidity will arise from hyper- secretion, in the latter from fermentative changes, or both acids may be in excess. In this case the mischief will probably have arisen in the first place from hyper- secretion of hydrochloric acid arresting digestion ;* the formation of lactic, acetic, and butyric acids being a consequence of this arrest. Till recently we had no ready means of determining the nature of the acid present in the vomited matters, and therefore uncertainty frequently existed as to the conditions under which the acids expelled were formed in the stomach. Eichet, however, has suggested a method by which the nature of the acid can be accurately determined, and has thus supplied us with an additional means of diagnosis in those cases of stomach disease attended with the vom- iting of acid matters. His method is based on the fact that if an aqueous acid solution be shaken with ether the latter removes a constant quantity of the acid. This, in the case of mineral acids, is extremely small, but with organic acids the removal is considerable. The specific ratio which exists, after an aqueous solution of acid has been agitated with ether, between the quantity of acid taken up by a certain volume of ether and that which remains in an equal volume of the solution after it has been treated with ether, is called the " co-efficient of partage," a term originally applied by Berthelot. The co-efficient of partage, in the case of mineral acid, is * Experiments with artificial gastric juice show that the addition of too much acid arrests the digestive action. 8 FORMATION AND BEMOVAL high — ahove 500 — because the quantity of acid yielded to the ether is small; the co-efficient for the organic acids is low for the opposite reason. The following exam- ple will render the matter clearer : 100 grammes of water containing 11 grammes of lactic acid, and 100 grammes of ether agitated with this solution removes 1 gramme of acid ; so when we determine the acidity of the two fluids we find that of the water to be 10 and that of the ether 1. But supposing the degree of dilution to be ten times greater than in the first case, then 100 grammes of water which contains 1 - 1 grammes of lactic acid, agitated with an equal weight of ether, will yield to the ether 0'1 gramme, and retain 1 gramme, the co-efficient of lactic acid is therefore said to be 10. The co-effi- cients of many other organic acids have been deter- mined. Some of the most important as having a bear- ing on animal chemistry are succinic acid c'=6, benzoic acid c'=l'8, oxalic acid c'=9'5, acetic acid c'=l - 4. So far as concerns one acid in solution the operation is simple enough, but when we have to deal with a mixture of two or more we must have recourse to a series of agitations with ether so that we may separate the acid which is the most readily soluble in ether from the one that is less so. By such repeated treatment of the original acid solution with ether, and recording the co- efficient of partage after each operation, we are able to obtain the true co-efficient of partage for each acid present. The acidity of human gastric juice varies considerably according to the statements of different observers. Thus Eichet,* from numerous observations on a patient after gastrotomy, gives the average acidity as 17 with a maximum of 3 - 4 and a minimum of 0'5 per thousand. * Op. cit , p. 68. OF ACID PROM THE BODY 9 Schroeder,* from observations made in a female with gastric fistula, records it as low as 0'2. Schmidt, t from experiments on dogs, gives an average of 2 - 5 and Szabo J with the same animals 3 per thousand. These variations need not be considered contradictory, the acidity of the gastric juice no doubt depending much on the nature of the physiological stimulus that excites it. This suppo- sition receives support from the observations of Schmidt, who found the juice of herbivorous animals had a lower degree of acidity than that from carnivorous animals. One point, however, is certain that the acid is present in a very dilute state, thus confirming the results obtained by experiments with artificial gastric juice, in which a degree of acidity of 0.2 per cent, is found to be most effective. With regard to the amount of acid withdrawn from the blood by the gastric secretion during the twenty-four hours it is impossible to speak with any certainty, since the quantity of gastric juice secreted during that period has never been definitely ascertained. Grriinewald§ in a case examined by him states it as twenty-three imperial pints, but this was undoubtedly under pathological con- ditions. Parkes || considers if we put it at twelve pints we shall be within the mark. Lehmann, drawing con- clusions from experiments on animals, concludes that the secretion of gastric juice in the twenty-four hours amounts to one tenth of the whole weight of their body, * ' Succi humani gastrici vis digestiva.' Dorpat, 1853. t Bidder et Schmidt, ' Die Verdauungssaft.' Leipsig, 1852. J " Beitrage zur Kenntniss der freien Sauren des menschl.Magen- saftes.'' 'Zeitschrift f. Physiologie Chimie,' i, 1877. § Beale's 'Archives of Medicine/ vol. i, p. 270. || " Gulstonian Lecture on Pyrexia." ' Med. Times and Gazette,' 1855, vol. i, p. 333. 10 FORMATION AND BEMOVAL this per man would represent something like 14 lbs. avoirdupois. Unfortunately, as Eichet well observes, the data on which these calculations are founded are very uncertain, since it is extremely difficult to determine the relative proportion of the true gastric secretion and the mucus mixed with it, and also to make allowance for what passes off accidentally during the experiment by the pylorus, and what is absorbed by the veins of the stomach. Moreover, even if these obstacles should be overcome, the intermittent nature of the secretion would make it difficult to arrive at very definite con- clusions. We must now proceed to consider the manner in which the hydrochloric acid of the gastric juice is separated in a free state from the alkaline blood. It is only recently that an explanation has been offered to account for this seeming paradox. In 1874,* in order to elucidate this point, I made in the laboratory of the Charing Cross Hospital a series of experiments, in which I found, by introducing an alkaline solution consisting of sodium bicarbonate (5 per cent.) and neutral sodium phosphate (5 per cent.) into a small U-tube, fitted with a diaphragm at the bend, and passed a weak electric current through the solution, that in a short time the fluid in the limb connected with the negative pole increased in alkalinity, whilst the fluid in the limb connected with the positive pole became acid from the formation of acid sodium phosphate. Now, one of the chief salts in the blood is undoubtedly sodium or potassium bicarbonate — an acid salt with an alkaline reaction, and neutral sodium phosphate has also an alkaline reaction. The decomposition which occurs between them may be represented as follows : * ' Lancet,' p. 29, July 4th, 1874. OF ACID PROM THE BODY 11 Acid Sodium Neutral Sodium Normal Sodium Acid Sodium Carbonate. Phosphate. Carbonate. Phosphate. Na,H,C0 3 + :Na,,H,P0 4 = Na,,CO s + Na, &,, PO.,. The above reaction explains the presence of acid sodium phosphate in urine. To account for the forma- tion of free hydrochloric acid in the gastric juice, sodium chloride is substituted for the neutral sodium phosphate, the decomposition in this case being Acid Sodium Sodium Normal Sodium Hydrochloric Carbonate. Chloride. Carbonate. Acid. Na,H,C0 3 + Ha, CI = Na. 2 ,C0 3 + H, CI. Maly,* however, who subsequently investigated the subject with great care, has come to the conclusion that the hydrochloric acid is derived from the decom- position of neutral sodium phosphate with calcium chloride, thus Neutral Sodium Calcium Tricalcic Sodium Hydrochloric Phosphate. Chloride. Phosphate. Chloride. Acid. 2 Na 2 ,H, P0 4 +3 Ca^C^Cag, P0 4 -r-4Na,Cl-|-2 H, CI. Practically, it matters little which view we adopt, since all the salts named are present in the blood ; the important fact being, that out of the body a -weak electrical current will separate the acid from its base. Whether the decomposition occurring in the body is due to the same agency must for the present remain a matter of conjecture. Still, the experiment of Professor Dubois Eeymond, made with an extremely sensitive galvanometer, which shows that there are no two parts of the body whose electrical condition is precisely the same, and that the differences between them are greater * ' Zeitschrift f. Physiolog. Chimie,' p. 174, 1ST". 12 FOEMATION AND EEMOVAL in proportion to the difference in activity of the vital processes which are being carried on in them, makes such an hypothesis plausible,* whilst the interesting discoveries made by Dr Burdon Sanderson, that electrical disturbance takes place during contraction of the leaf of the Bioncea muscipula, or Venus' s fly trap, points to the same conclusion. Whatever be the nature of agency that effects the decomposition, it must be a powerful one to effect the separation of hydrochloric acid from bases for which it has such a strong affinity as soda or lime. The decom- position, however, once effected in the blood, there is no difficulty in explaining the presence of free hydrochloric acid in the stomach, since Graham showed many years ago that this acid possesses high diffusive power, and passes from a mixture through a dialyser with great rapidity. Acid also leaves the body by the urine, since the re- action of healthy human urine collected during a period of twenty-four hours is always acid. This acidity is reckoned as oxalic acid, that is to say, in determining the amount present we use a solution of sodium hydrate standardised so that each cubic centimetre represents •01 gramme of oxalic acid. The degree of acidity of the twenty-four hours' urine in well-fed adults is generally equivalent to two grammes of oxalic acid. Now, although the reaction of healthy human urine collected throughout the twenty-four hours is acid, yet if separate samples of the urine passed during this period be taken, considerable variations in the character of the reaction will be observed. The constancy with which these variations occur under different diurnal physio- * Dr Poore, 'Text-book of Electricity in Medicine and Surgery.' Smith, Elder, and Co., 1876. OP ACID FROM THE BODY 13 logical conditions was first studied by Dr Bence Jones. That physician pointed out that the acid reaction of the urine increases and diminishes inversely with the secre- tion of the gastric juice. He found, by examining the urine at short intervals during the day, that an increase of acidity was observed in the urines passed before meals, and that a decline in the acidity occurred shortly after food had been taken, and acid was consequently with- drawn from the system ; its maximum decline being attained in about three hours, when the acidity begins to rise. In some instances not merely was there depres- sion of the acidity, but the urine became neutral and even alkaline. These observations of Dr Bence Jones have been repeatedly confirmed by subsequent investi- gators ; and the ebb and flow in the intensity of acid re- action of the urine, to which the term alkaline tide has been aptly applied, is a recognised physiological fact, though explanations different from that offered by Dr Bence Jones have been advanced to account for the phe- nomenon. Dr Eoberts,* for instance, is disposed to attri- bute the occurrence of the alkaline tide after meals to a different cause — namely, to the entrance of the newly- digested food into the blood. For if, as he says, the normal alkalescence of the blood is due to the prepon- derance of alkaline bases in all our ordinary articles of food, a meal is pro tanto a dose of alkali, which must, for a time, add to the alkalescence of the system, and con- sequently of the urine. Dr Bence Jones's view receives considerable support from clinical and physiological experience. Since in those cases attended with frequent vomiting of intensely acid fluid it has often been noticed that the urine passed immediately after the ejection of * " A Contribution to Urology.'' ' Memoirs of the Manchester Lit. and Phil. Soc.," 1859. 14 FORMATION AND REMOVAL the fluid becomes alkaline ; the same effect is produced in dogs experimentally when pounded glass or other indigestible substance is introduced into the stomach to provoke the secretion of the gastric juice, which is with- drawn as soon as secreted by washing out the stomach with water by means of a stomach-pump, showing in both instances that the alkalinity of the urine was caused by the withdrawal of acid from the stomach, and not by the addition of alkali to the blood. That the in- gestion of food, especially vegetable food, contributes, in a slight degree, in the production of the alkaline tide, is very probable, but that it is mainly concerned in the phenomenon is out of the question, otherwise the alka- linity of the urine would be in direct proportion to the quantity of food ingested, which is certainly not the case. Indeed, the acidity of the urine can be depressed, and even rendered alkaline, otherwise than by the with- drawal of acid from the stomach, or by the ingestion of food. And it is this circumstance, hitherto unexplained, that has rendered many physiologists unwilling to accept Dr Bence Jones's as a complete solution of the pheno- menon. Dr Hermann Weber* some years ago observed that whilst breakfast decidedly had an influence in lowering the acidity, yet when he went without that meal the acidity was still lessened, though not to so great a degree. This observation of Dr "Weber I have repeatedly been able to confirm, the mere act of rising always producing a decided depression in the acidity of the urine. The use of the cold douche, or sweating in the vapour bath, both have the same effect, quite inde- pendently of food or the activity of the stomach. There is another channel, however, by which acid is * Professor Parkes, ' On the Composition of the Urine in Health and Disease,' p. 55. Churchill, 1860. OF ACID FKOM THE BODY 15 withdrawn from the blood besides the gastric secretion, and that is by the lungs. In the explanations hitherto advanced to account for the phenomenon of the alkaline tide in the mine this fact has not received attention. Dr Edward Smith, in his researches ' On the Elimina- tion of Carbonic Acid,' has, as we have seen (p. 6), showed conclusively that the exhalation of carbonic acid by the lungs is increased by food and diminished by fasting, and that the amount exhaled during sleep is considerably less than is set free in the waking state. It therefore happens that the time when most carbonic acid is being exhaled corresponds with the time when observers have noticed a decided diminution in the acidity of the urine, whilst the circumstances that dimi- nished the exhalation of carbonic acid — namely, sleep and fasting, are attended by a rise in the acidity of the urinary secretion. The following table gives the average result of several observations made by myself to deter- mine the ebb and flow of the tidal variations in the acidity of the urine. Time. Total acid as oxalic acid. Acidity per hour :is oxalic acid. 11 p.m. to 8 a.m.* 8 a.m. to 11 p.m. 11 p.m. to 1 p.m. 1 p.m. to 4 p.m. 4 p.m. to 7 p.m.* 7 p.m. to 11 p.m. 1'14 grm. 0-21t „ 0-40 „ Oil „ 029 „ 0-07t „ 0-12 grm. 007 „ 0-20 „ 003 ,. 0-09 ., 0-02 „ The acid reaction of the urine is chiefly, if not altogether due to the presence of acid sodium phosphate. * Breakfast at 8.30 a.m.; hrnfih at 1 p.m.; dinner at 7 p.m. t These samples were sometimes neutral, rarely alkaline. 16 FORMATION AND EEMOTAL and occasionally to an excess of acid salts of hippuric and uric acids. I have already (page 10), when speaking of the presence of free hydrochloric acid in the gastric juice, showed how the seeming paradox of the separation of an acid secretion from an alkaline fluid like the blood can he explained. And I pointed out, in the case of urine, that it was the result of the decomposition of a salt with an alkaline reaction but having an acid constitution, like sodium or potassium bicarbonate with another alkaline salt, the neutral sodium phosphate, thus Acid Neutral Normal Acid Carbonate. Phosphate. Carbonate. Phosphate. Na, H, C0 3 + Na 2 , H, P0 4 = Na 2 , C0 3 + Na, H 2 , P0 4 . Maly* believes that acid sodium phosphate as well as hippuric and uric acid exists in a free state in the blood, and that the reaction of that fluid remains alkaline on account of the preponderance of alkaline salts. He has shown that if an alkaline mixture con- taining neutral sodium phosphate and acid sodium phosphate be placed on a dialyser, the acid salt passes into the surrounding distilled water ; hence he considers the excretion of acid urine through the renal parenchyma to be simply a process of dialysis. Maly's explanation has the merit of simplicity, but it does not wholly account for many of the phenomena connected with the variations in the reaction of the urine. If, on the other hand, the view that the acidity of the urine is caused by the reaction between acid sodium carbonate and neutral sodium phosphate be accepted, it will explain another paradox which has * Op.cit. OF ACID FBOM THE BODY 17 been observed by Bence Jones,* Beneke,f Parkes,$ and myself, § to occur after the administration of the bicarbonates (acid carbonates) of ammonia, potash, and soda, under certain conditions, viz. causing of an in- creased acidity of the urine. This point will, however, be more fully referred to when we consider the action of alkaline remedies in the treatment of dyspepsia. So long as the discharge of acid from the system passes off regularly, and is distributed in normal pro- portion among the secretions concerned in its removal, its presence on the mucous surfaces with which it comes in contact is unfelt. When, however, the production of acid is excessive, or the distribution of the acid among the various secretions is irregular, so that one becomes more highly charged with acid than the others, then the secondary effects due to " acidity " make themselves manifest. These, when the formation of acid is only slightly in excess, or is only temporarily induced by casual disturbances, may be limited to slight heartburn in the case of the stomach, some itching or nettle-rash of the skin, a little bronchial catarrh, or some degree of irritability of the urinary passages. When, however, the formation of acid is excessive or long continued, the secondary diseases it gives rise to become formidable in their nature. Attacks of acute dyspepsia, accom- panied with paroxysms of pain, cramp, vomiting, and diarrhoea, so severe and often so long continued as to reduce the patient to the utmost stage of prostration. Intractable skin diseases, like lepra, psoriasis, and * ' Philosophical Transactions,' 1850, part 2, p. 673. + 'Archiv des Wissenschaftlichen Heilkunde,' 1854. "Studien zur Urologie," p. 444. J ' Composition of the Urine in Health and Disease,' p. 297, 1S60. § ' Lancet,' Nov. 9th, 1878. 2 18 FORMATION AND REMOVAL eczema, severe asthmatic paroxysms and chronic bron- chitis, frequent attacks of gravel and other renal and urinary affections. Excessive formation of acid, deter- mined probably by certain textural and neurotic condi- tions, is very likely the cause of the severe inflammation of the structures in and around joints, such as we witness in gout and in attacks of acute rheumatism. Indeed, an over-acid state may be considered a predisposing as well as an exciting cause of both these diseases, since the nutri- tion of the tissues undoubtedly becomes impaired* by the supply of faulty nutritive material, and so the conditions which favour an attack of acute gouty or rheumatic inflammation are developed. These are the most palpable and direct manifesta- tions of an outburst of an over-acid state, but there are many other ailments, such as palpitations and flutterings of the heart ; exaggerated pulsations of large arteries ; irregularities and intermissions of the pulse ; aching pains in the limbs ; burning patches ; neuralgia ; me- grim ; vertigo ; noises in the ears ; depression of spirits, sleeplessness &c. ; which many writers describe as arising from irregular manifestations of the gouty state, and which Dr Murchison,t with an equal show of reason, refers to disorder of the liver, but which, without com- mitting ourselves to any definite theory, may be con- veniently considered as arising from an accumulation of acid in the system when they occur in persons who have no claim to be considered gouty, nor in whom any * This is well shown in changes which take place in scurvy, a disease closely allied in many respects to gout and rheumatism, and which develops after the withdrawal for some length of time from the blood of the alkaline salts supplied by vegetable food. t ' Croonian Lectures.' " On Functional Derangements of the Liver." 1874.. OF ACID FROM THE BODY 19 marked disturbance of hepatic function is noticed. One point that should be considered with reference to these affections is their extreme motility — the paroxysmal nature of their onset, the suddenness with which they disappear or transfer themselves from one region or organ to another. These sudden changes afford ad- ditional support to the view that these derangements are caused by chemical alterations in the quality of the blood, since we notice similar variations within physio- logical limits in the secretions of various organs, a certain ebb and flow, as it were, dependent on conditions affec- ting their functional activity. And when we proceed to reflect on the vastness and complicity of the chemical circulation going on in the body, a circulation the im- portance of which was little considered till Professor Parkes drew attention to it in the ' Gulstonian Lectures ' of 1855,* we can hardly wonder if a pathological check occurring to the elimination of matters ready for their discharge by their natural passage causes an outbreak in another, directed by the same influence that regulates the delicate chemical variations which take place within physiological limits. * ' Med. Times and Gaz./ 1855, vol. i, p. 333. CHAPTEE II DYSPEPSIA USUALLY ASSOCIATED "WITH AN ACID CON- DITION OE URINE (ACID DYSPEPSIA) The mucous membrane of the stomach furnishes two secretions : one, which is continuously secreted during fasting, alkaline in reaction, thick and tenacious in con- sistence ; the other, the gastric juice, thin, limpid, and acid, which is only secreted when a stimulus is applied to the walls of the organ. In health the quantity of gastric juice secreted from the walls of the stomach apparently depends more on the general requirements of the system than upon the quantity of the food intro- duced into the digestive cavity. In disease both the quality and the quantity may be considerably altered. The observations of Dr Beaumont on the stomach of Alexis St Martin showed that in febrile conditions of the system, occasioned by whatever cause, the villous coat becomes red and dry, and the secretions become dimi- nished, and when this condition is considerable no gastric juice will be evoked by the alimentary stimulus. These observations of Dr Beaumont have been confirmed by Blondlot and CI. Bernard. On the other hand, it has been shown experimentally that Under certain nervous influences the secretion is considerably increased. The conditions under which this takes place are not, however, well understood, because the channel by which they are ACID DYSPEPSIA 21 conveyed has not been definitely determined. Bernard* found that section of the vagi during digestion caused the reddened mucous surface to become pale, whilst irri- tation of the nerves, or section of the fourth ventricle, above their origin produced dilatation of the gastric vessels, and induced an abundant secretion of gastric juice. Kutherfordf also found that the gastric mem- brane flushed during digestion, became pale when the vagi were cut, and that stimulation of the central end of either nerve caused reddening of the gastric mem- brane, whilst irritation of the peripheral end produced no constant effect. Lastly, it has been found that when all the nerves that supply the stomach have been divided, gastric juice of normal acidity and digestive power will still be secreted when a stimulus is supplied to the mucous surface of the stomach, alkalies and dilute alcohol being among the most potent, which shows that the nerve centres on which the secretion depends exist in the walls of that organ. From a consideration of the foregoing facts, it is probable, therefore, that when hyper secretion occurs pathologically it is connected with either direct or reflex irritation of these nerve centres. This may be produced either by a morbid condition of the blood, such as may result from an excess of acid developed or retained in the system, in a gouty state, or the taint of malarial poison, or by actual disease of the stomach itself, especially those forms in which the deeper structures are involved, or by disturbance in the other organs conveyed to the nerve centres of the stomach by reflex agency. ChomelJ has described an acute affection, which he * ' Lect. Syst. Nerv.,' vol. ii, pp. 438 and 461. t Rutherford, • Phil. Trans. Edin.,' xxvi, 1870. J ' Des Dyspepsies/ p. 144, Paris, 1857. 22 ACID DYSPEPSIA terms " la dyspepsie acide grave," in which, it would almost seem as if the whole body turned acid. The disease apparently commences like an ordinary attack of gastric catarrh, but so severe are the symptoms that the patient speedily becomes prostrate and has to keep his bed. There is frequent vomiting of acid matter tinged with yellow-coloured bile, the saliva is acid, and the sourness of the breath so marked that the air of the chamber becomes tainted with it. There is obstinate constipation. After a time the character of the vomit changes from yellow to green bile, which, after persisting a considerable number of days, moderates, the pulse, however, increasing in frequency, with usually a con- siderable elevation of temperature. At this period cer- tain nervous symptoms develop, headache accompanied by hallucinations, passing gradually into coma, in which in the majority of cases the patient dies. The duration of the disease was from thirty to forty days. Chomel first noticed the affection after the cholera epidemic of 1832, but since then he has repeatedly seen cases. Dr Wilson Fox* also relates that during the cholera out- break in London in 1866, he was struck with the fre- quency of subacute inflammatory affections correspond- ing in their symptoms to those of " embarras gastrique," and he also noticed a similar frequency during the autumn of 1871, a year in which cholera was prevalent in Europe but not in England. Last autumn I saw a case which ran a course very similar to those described by Chomel, and, as it presents features of interest, I briefly summarise some of its characteristic details. A gentleman, about fifty years of age, a bon vivant, and of robust habit, and who at the time his illness com- menced was in good health, was seized one night (Oct. * ' Diseases of the Stomach,' p. 100, 3rd edit., 1872. ACID DYSPEPSIA 23 16th), after dining out, with a feeling of weight and oppression at the chest, which gradually increased till it became unbearable; he then began to vomit, and brought up a large quantity of undigested food and acid fluid. This vomiting was encouraged, and a dose of calomel, followed by some sulphate of magnesia, was ordered. This had no effect, although it was repeated, and other purgatives tried besides, and enemas adminis- tered night and morning ; it was not till the seventh day that the bowels were opened, and then only to a slight extent. Throughout the illness the bowels re- mained obstinately constipated, and were only relieved by the action of medicine. The urine was scanty, of a cherry colour, clear, and deposited no urates or uric acid, free from albumen, but highly acid. The vomit- ing continued almost incessantly for four days, and then gradually ceased, during which time he took only iced Appolinaris water with milk, a tablespoonful at a time. On the fifth day he was able to take a little beef tea, and by the end of the week a little minced chicken. He went on satisfactorily for two or three days after this, when he was seized with a most persistent and troublesome hiccough, which lasted about thirty-six hours, then he began to bring up a small quantity of acid fluid whenever he took nutriment, which consisted of teaspoonful doses of Brand's essence of beef and milk with Appolinaris water. About this time the pulse became very rapid in its action and irregular. The urine still scanty, excessively acid, and highly coloured. Bowels obstinately constipated. Almost every remedy was tried to check the sickness, and some seemed to succeed for a short time and then lost their effect. Equal parts of champagne and Appolinaris water iced stayed with him best. A sixth of a grain of 24 ACID DYSPEPSIA morphia was given three times a day. He went on in this state for a fortnight or three weeks from the com- mencement of the illness, during which time he had heen quite sensible ; on the twenty-first day, however, his nurse reported that he had passed a restless night, and in the morning during her absence he got out of bed and was unable to get back again. On her return she found him talking excitedly and fancying there were people in the room, &c. For some reason or other the usual dose of morphia had been withheld the pre- ceding night. On giving him this he became quieter, and with a second dose he became quite rational. The vomiting, which up to this time had been glairy and colourless, only sometimes tinged with bile, now became darker, and by the twenty-fourth day distinctly con- tained blood. The abdomen was flat, not tender on moderate pressure, nor was pain at all complained of. The emaciation was considerable ; the skin harsh and dry and of a yellow-brownish hue ; temperature usually below 98° F., but occasionally towards evening running up to 100° F. or 101° F. The amount of vomit dis- charged during the twenty-four hours nearly filled a good sized washhand basin. Turpentine was now given, and after a few doses the blood disappeared from the vomit and the sickness gradually diminished, the tongue became cleaner, the urine more plentiful. On Nov. 20th, the thirty-fourth day of the illness, he was able to sit up for a few hours, and had not been sick for five days. He was still kept on milk diet, and the turpen- tine mixture given once or twice a day. From this he continued to make satisfactory progress, and when seen six months afterwards was in very good health. In this case it is difficult to determine precisely the condition which led to this prolonged attack of acid ACID DYSPEPSIA 25 vomiting. During the first week of the illness the patient seemed to be suffering simply from an attack of acute gastric catarrh. After the relapse of the tenth day the character of the vomit was entirely different to what was noticed at first, and there seemed to be more constitutional disturbance. Whilst the case was in progress I thought that possibly the severe attacks of gastric catarrh had evoked some latent organic mischief, and that the irritation of the nerve centres in the walls of the stomach was the cause of the discharge of acid. The complete recovery of the patient negatived this hypothesis. It seems therefore the attack may be referred to a " gouty condition," or an outburst of an over-acid state of the system. Vomiting of acid fluid sometimes occurs in persons who have been exposed to the influence of malaria, even after other evidences of malarial poisoning have passed away. Dr Fenwick,* who was the first precisely to note this condition, remarks that the vomiting at first only troubles the patient early in the morning, but by degrees it becomes more constant, occurring directly after every meal. In these cases the appetite is always bad, there is loss of flesh, the skin sallow, and the lips bloodless ; when jthe nature of the malady is recognised, it will be found to yield to quinine or arsenic. A case that I saw for the late Dr Murchison, in 1877, may be referred to this cause. An American lady, staying at the Langham Hotel, was seized one morning with a rigor, whieh was speedily followed by sweating ; concurrently with the onset of the sweating she complained of intense pain in the epigastrium and the retching of an extremely acid fluid whenever she * ' On Atrophy of the Stomach and Nervous Affections of the Digestive Organs,' p. 173. Churchill, 1880. 26 ACID DYSPEPSIA moved in bed, or attempted to take food or drink. There was no evidence of either biliary or renal colic. As the pain was severe, a sixth of a grain of morphia was injected subcutaneously. This relieved the pain, and in a few hours the vomiting ceased. The next day quinine was prescribed, and there was no recurrence of the pain or vomiting. She informed me she had had similar attacks before, that they were always ushered in by fit of shivering, followed by sweating, and that in the States she had suffered from severe attacks of pronounced intermittent fever. The vomiting of an acid fluid is usually a distressing accompaniment of cancer and ulceration of the stomach. It is derived apparently from two sources : one from hypersecretion of the gastric juice (hydrochloric acid) from direct irritation of the nerve centres of the stomach, the other from acid derived from fermentative changes occurring in that organ (lactic acid). Both acids are usually present together, but sometimes one pre- ponderates more at one time than another. Thus, Dr G-olding Bird* states that in a case of scirrhous pylorus he found at one time a quantity of free hydrochloric acid in one pint of vomit equal to twenty-two grains of the pharmaceutical acid, with an organic acid sufficient in quantity to neutralise seven grains of pure potash. At another time the hydrochloric acid had nearly disap- peared, and the quantity of. organic acid in each pint required for saturation nearly seventeen grains of the alkali. Nausea or vomiting generally arises at some period during pregnancy. Most frequently it occurs of a morning, or immediately after taking food, but in some cases, in addition to this disturbance in the morning or » < Urinary Deposits,' p. 162. Fifth edition, 1857. ACID DYSPEPSIA 27 at meal times, there is more or less heartburn and flatulence throughout the day, and in severe cases the vomiting becomes incessant. When the sickness occurs only in the morning, or comes on when an attempt is made to take food, the vomit usually consists of mucus and acid fluid, evidently derived from hypersecretion of the gastric juice. When the vomiting is more frequent, and there is much flatulence, lactic acid derived from fermentative changes will also be present. Similar disturbance of the gastric function, the effect of reflex nervous influence, is met with in organic disease of the uterus and other organs. In phthisis, vomiting of sour fluid, accompanied with more or less pain, not infre- quently occurs towards the end of the disease. In these cases the walls of the stomach seem to have undergone atrophic changes, and the vomiting has been attributed to this condition, but, as Dr Budd* pointed out, one circumstance incompatible with the idea that the vomiting is altogether due to these changes, is that the changes of structure found after death do not neces- sarily correspond in degree with the severity or duration of the gastric symptoms. Many forms of kidney disease, such as chronic interstitial nephritis, tubular nephritis, and suppurative nephritis, are frequently attended with nausea, if not actual vomiting. In these cases, as in phthisis, there are usually changes to be found in the mucous membrane of the stomach, which some authors consider sufficient to account for this symptom. It must be borne in mind, however, that nausea and vomiting when present are often quite early symptoms and disappear for long intervals, perhaps only to be observed again towards the termi- * ' Organic and Functional Disorders of the Stomach,' p. 187, 1855. 28 ACID DYSPEPSIA nation of the case. The acid of the vomit thrown up during the sickness caused by the passage of biliary and renal calculi, has been shown by many observers to be hydrochloric acid, the acid of the gastric juice, and my friend Mr M. Beck has informed me that patients suffering from chronic bladder affections are frequently troubled with so-called " bilious attacks." Eeflex vomiting of an acid fluid is very common in children in whom irregular secretion of the gastric juice seems very readily excited when teething or suffer- ing from intestinal worms, and Budd* has pointed out that young children with tuberculous disease of the lung, or with inflammation of the brain, suffer from this gastric disorder more frequently than grown-up persons labouring under the same diseases. Other forms of nervous disturbance have a powerful influence on the secretion of the gastric juice, among which may be mentioned sudden emotions of grief, fear, or anxiety, overwork, intellectual or physical, or the exhaustion consequent on too prolonged fasting, hyste- rical conditions, &c. In these cases we have often to deal apparently at onetime with a condition of increased at another time of diminished secretion. It is perhaps this irregular performance of the gastric function that accounts for the anomalous dyspeptic symptoms these cases so frequently present. In typical cases, when the symptoms are well defined, there is usually no difficulty in determining whether the " acidity " arises from excessive or irregular secre- tion of the gastric juice, or from fermentative changes taking place in the alimentary canal. Professor Wilson Poxf has very concisely stated the chief points of dis- * Op. cit., p. 199. t ' Diseases of the Stomach,' p. 22. Third edition, 1872. ACID DYSPEPSIA 29 tinction between them in relation to flatulence, pain, and vomiting. Thus, in hypersecretion little or no flatulence is complained of, whilst in acidity arising from fermenta- tive changes it is a distinctive symptom. Pain, too, is less urgent in the latter condition than it is in the former, ■when it is often so severe as to give rise to the suspicion of the existence of organic mischief. It differs also in character. In hypersecretion it occurs on an empty stomach, and is generally relieved by taking food ; it varies in intensity from a feeling of craving or gnawing to an intense continued burning sensation behind the sternum. In fermentative dyspepsia the discomfort sets in some time after a meal, and is characterised more by a feeling of distension and weight than actual pain ; when pain is felt it is generally of a colicky nature, and referred to the intestines rather than the stomach.* Actual vomiting of acid fluid is common in cases of hypersecretion, whilst in acidity arising from fermentation only a slight regurgitation usually occurs. If, however, vomiting does take place, the matters ejected will be found to contain a considerable quantity of organic acid, chiefly lactic acid, and occasionally torulae and sarcinse, and it will occur some time after a meal. In hypersecretion, on the other hand, the vomiting often takes place on a completely empty stomach, or is provoked when only a small quantity of food is taken. * It is probable that the presence for a short time of even a considerable quantity of acid in the stomach does not cause pain. Since, as Dr Bence Jones has shown, when 81 grains or even 162 grains of dry tartaric acid are taken in four or six ounces of water the acid hurts the mouth and upper part of the food tube, and then ceases to be felt for three hours or more, when it gives rise to griping and colicky pain. The pain attendant on hypersecretion seems to originate in the nerve centres themselves and precedes apparently the discharge of acid. 30 ACID DYSPEPSIA This acid pyrosis must not, however, be confounded with that form of pyrosis or " water-brash," in which the fluid poured out is neutral or alkaline, and which is probably derived from excessive secretion by the salivary glands. Both forms of pyrosis, however, may be present together, the patient complaining of the discharge of watery fluid at one time and of acid at another. The reaction of the urine, too, exhibits different cha- racters in the two conditions. In acidity arising from fermentative changes the natural reaction of the urine is diminished, or may even become alkaline, with a ten- dency to deposit oxalates or phosphates. In hyper- secretion, however, the general character of the twenty- four hours' urine is to increased acidity and the deposi- tion of uric acid and urates. If, however, individual samples of the urine be examined, it will be found that great variations in the reaction takes place within short periods of time — the urine at one time being intensely acid, and at another neutral or alkaline, the latter con- dition being frequently accompanied by considerable diuresis. Thus, in a lady who suffers severely from attacks of megrim, accompanied by the vomiting of a glairy acid fluid, I have frequently noticed, after an attack has just passed off, the urine to be alkaline and deposit phosphates, whilst urine secreted before and during the attacks will be highly acid and turbid with urates. Similarly, in a gentleman, who suffers from frequent attacks of paroxysmal sciatica, each attack last- ing from two to three hours, a similar variation in the reaction of the urine is frequently noticed. It has already been observed that irregular secretion of the gastric juice is very readily excited in children (p. 28) ; so we also find the reaction of their urine undergoes frequent changes in the character of its reaction, even ACID DYSPEPSIA 31 under conditions when the child may be considered healthy. This temporary alkaline condition of the urine in all probability depends on the withdrawal of acid from the secretion during its discharge elsewhere, since in dogs we find that, after powerfully exciting the gastric secretion and mating them vomit, the urine becomes decidedly alkaline. In this respect the temporary alka- linity noticed in hypersecretion differs from the dimi- nution of acidity noticed in cases of fermentative dys- pepsia, where, as I shall endeavour to show when speak- ing of that condition, the alkaline tendency is not caused by any withdrawal of acid, but by the entrance of the organic acids the result of fermentative changes passing into the blood, and by oxidation appearing as carbo- nates of the alkaline oxides in the urine. Although the secondary and remote effects resulting from hypersecretion are not so marked as is the case in persons suffering from fermentative acidity, where the continued absorption of lactic acid and other vitiated products of digestion gives rise to considerable constitu- tional disturbance, still this kind of gastric disturbance does occasion derangement of other organs ; whilst the so called " bilious attacks " seem particularly associated with it. Thus, a person, after complaining for some hours of frontal headache and nausea, begins to suffer from uneasiness and pain at the pit of the stomach, and shortly after vomits, and continues to do so for some hours, bringing up at first a glairy acid fluid, which becomes more and more tinged with bile, till the patient declares he brings up nothing but " pure bile." After a time the irritability of the stomach subsides, the vomit- ing ceases, and the next day the patient will be found slightly sallow, which usually quickly passes off. If the attacks are frequent, however, the sallowness never quite 32 ACID DYSPEPSIA disappears, and the patient always looks " bilious." In this form of biliousness the liver is probably not con- cerned. The copious discharge of bile does not arise from its excessive secretion, but simply from the empty- ing of the gall bladder induced by frequent vomiting — the sallowness or slight jaundice being the result of duodenal catarrh, excited partly by the acid and partly by the straining in the act of retching. In forming an opinion as to which form of acidity we have to deal with in a given case we must remember that the one is very likely to produce the other. Thus, if irritation caused by hypersecretion is long continued, conditions arise which, by impeding the digestion of food, favour fermentative changes ; indeed the over-acidity of the gastric juice itself is sufficient to arrest the digestion* of albuminous substances, whilst the irritation caused by the frequent pouring out of a highly acid secretion, and the presence of undigested albuminous food, produces at length catarrh of the mucous membrane of stomach — one of the most potent factors in the production of fermentative dyspepsia. On the other hand, if the * That the presence of too much acid, or neutralisation, arrests the action of the gastric juice can be shown by a very simple ex- periment. Place some finely minced muscle, or boiled fibrin, about as much as will lie on a threepenny-piece, in three test tubes, a, b, c. Fill each tube two thirds full of artificial gastric juice (0 - l per cent, acidity). Add to a a few drops of strong hydrochloric acid. Neu- tralise b with sodium carbonate solution, 1 per cent. Leave c unal- tered. Place the three tubes in water, both at temp. 40° C ; digestion will alone proceed in test tube o. (N.B. — If the mixture in test tube a, acidified by the addition of hydrochloric acid, be diluted with water, and if the contents of test tube b he again rendered of the same acidity they were before neutralisation, digestion will proceed, showing digestion has only been arrested, not destroyed, by the pre- sence of too much acid, or by neutralisation.) ACID DYSPEPSIA 33 acidity in the first instance is due to fermentative changes brought about by impeded digestion, hyper- secretion of gastric juice will at last often be evoked, from the disturbance of the nerve centres of the stomach produced by the irritation of the products of fermen- tative change. In these mixed cases it is often very difficult to decide which is the originating condition, a point, however, which it is important to determine if we wish to do more than palliate the more urgent symptoms. We should, therefore, in all cases determine the nature of the acid present in the vomit. This can be done either by chemical analysis, a lengthy and tedious process, or by having recourse to Eichet's method of separating the acids by ether and determining their co- efficient of partage. If this is high we may be sure that hydrochloric acid is predominant, if low that the acidity is due to the presence of organic acids. If the patient does not vomit, or at the most is only troubled with sour risings, the acidity is probably chiefly caused by fermen- tative changes. For the relief of the pain and vomiting which result from the acidity of hypersecretion, opium or mophia are the chief remedies. When the disorder seems to arise from direct irritation of the nerve centres of the stomach itself, four or five drops of liquor opii, or an equal quantity of liquor morphise administered with bismuth on an empty stomach, generally succeeds in calming and regulating the digestive functions before many doses are taken. When the disturbance is the result of reflex irritation an injection of morphia (^th grain) is more efficacious than the administration of the drug by the mouth. When the hypersecretion seems to depend upon the accumulation of acid in the system, a gouty state, malaria, &c, morphia or opium should be given 3 34 ACID DYSPEPSIA to check the immediate urgency of the symptoms, whilst appropriate steps should he taken to relieve the system of the cause of the disturbance. In the vomiting of pregnancy Kinger* recommends the administration of drop doses of ipecacuanha wine every hour or three times a day. Ipecacuanha, too, he remarks, is some- times effective in checking the vomiting from cancer of the stomach, and succeeds sometimes after more com- monly used remedies have failed. Tincture of bella- donna in twenty-drop doses three times a day, has also been found serviceable in the vomiting of pregnancy. Liquor arsenicalis in drop doses on an empty stomach, often proves very serviceable in the late vomiting of phthisis. In a patient of mine in whom it was tried, after other remedies had failed, the relief that speedily followed its administration was very marked. Oxide of zinc, oxalate of cerium, .and nitro-glycerine are remedies often used in sympathetic vomiting, their action, however, is uncertain ; when administered they may be advantageously combined with belladonna. The application of a mustard plaster over the epi- gastrium has often a magical effect in stopping the retching and vomiting. When the excessive or irregular secretion of gastric juice seems to depend on minor forms of nervous disturbance, such as the exhaustion dependent on overwork, hysteria, &c, great benefit will often be derived from the use of the douche, especially of sea water, or a course of brine baths at Droitwitch or at Soden. The application of a cold compress at night over the abdomen has also a wonderful effect in regu- lating and calming functional disturbance both of the stomach and liver. The diet should be nutritious, easy of digestion ; an indigestible meal or even a single tough * ' Handbook of Therapeutics.' Eighth Edition, p. 409, 1880. ACID DYSPEPSIA 35 morsel often exciting a severe attack of pain and vomiting. The intervals between the meals should not be too prolonged, nor should the stomach be over- loaded at any meal. A little food should be taken the last thing at night, and immediately on waking in the morning. Alcohol and coffee as articles of diet are to be avoided, though iced champagne with Apollinaris water or a cup of strong coffee will often " stay the stomach" when the vomiting is severe. Considerable benefit is often obtained by the use of alkaline mineral waters between the attacks by persons who suffer from this form of acidity. CHAPTEE m DYSPEPSIA USUALLY ASSOCIATED WITH A NEUTRAL Or ALKALINE CONDITION OF UEINE (FLATULENT DYS- PEPSIA) As Frerichs* has well observed, though yeast fungi are continually heing taken with the food, as in bad beer or bread, and are thus brought in contact with the saccharine and albuminous matters of the food, which are capable of fermenting in the stomach, fermentation does not occur unless another condition is added. The ferment must have time and opportunity for developing itself. Under ordinary circumstances, it is so rapidly removed from the stomach, together with fermentable material, that the process has no time to commence. The conditions, therefore, that favour the development of fermentation are those which retard digestion either by mechanically obstructing the onward passage of the food, or from an abnormal condition of the digestive secretions, or the indigestible nature of the food itself. Prom experiments, we learn that under normal circumstances the gases found in the stomach consist of oxygen, nitrogen, and carbonic acid, but no hydrogen, which we would expect to find if the gases of the stomach in health were formed by lactic acid f ermen- * " Eep. Clin. Lect.," 'Med. Times and Gazette,' 1861, vol. ii, p. 410. FLATULENT DYSPEPSIA 37 tation. It is probable, therefore, that of the gases obtained from the stomach under normal conditions, the first two are derived from the air swallowed with the food, whilst the latter is derived by diffusion from the blood. In the small intestine, however, acetic and lactic acid fermentation commences, as is shown by the preponderance of carbonic acid gas, and the presence of hydrogen.* The steps that occur in this process of fermentation are well shown in the following table taken from Professor Ewald's work on ' Digestion :' C s H 12 6 Sugar. 2(Cj}H 6 0) Alcohol +2C0 2 . 2 (C 3 H 6 3 ) Lactic Acid. C 2 H 6 + 0=C 2 H 4 (Aide- H 2 OC 4 H 8 2 +2C0 2 +H 4 hyde). (Butyric Acid) . C 2 H 4 +0=C 2 H 4 0(4cefec Acid). The occurrence of this lactic and butyric acid fer- mentation in the small intestines in health, suggests a way in which the carbo-hydrate constituents of the food * The following table gives the result of Planer's analysis of the gases of stomach and small intestine respectively (' Wiener Sitzgber. Mathem. naturwiss. Classe,' Bd. xlii, 1860). Stomach. a • Small intestine. Gas. Meat. Bread. Meat, Vegetable diet. C0 2 N H 25-20 68-68 6-12 Nil 32-91 66-30 •79 Nil 401 45-5 Trace 13-86 47-34 3-97 48-69 38 FLATULENT DYSPEPSIA may become converted into fat ; for, by this lactic and butyric acid fermentation, the sugar is converted into members of the fatty acid series. The extent, however, to which this fermentation is carried in health is probably small, since if it occurred largely in the intes- tine we should, as Professor Foster* observes, have a large quantity of free hydrogen excreted by the lungs or bowels, which is not the case. The fermentative changes reach their highest point in the large intestine, so much so as to render its contents acid, in spite of the alkaline character of the secretion from its walls. Here, in addition to hydrogen, we have a considerable quantity of marsh gas (CH 4 ) developed with sul- phuretted hydrogen (H 2 S), from the decomposition of the albuminous and other sulphur-yielding elements of the food. In disease, however, excessive fermentative changes of the food may occur, leading to the production of enormous quantities of gas and the formation of various intermediate products, as we have seen, such as alcohol, aldehyde, and acetic acid on the one hand, and of lactic and butyric acid on the other. Sometimes it is a large quantity of gas that is formed, at another time an excess of, acid. Thus, Bwaldf speaks of a patient who pithily observed that " there was sometimes a vinegar factory and sometimes a gas works in his inside," in fact, at one time alcoholic fermentation led to the formation of acetic acid, at another, the butyric acid fermentation produced hydrogen and carbonic acid. It is often difficult to distinguish clinically between the different forms of flatulent distension which arise, * 'Text Book of Physiology,' p. 242. Macmillan & Co. + 'Lectures on Digestion/ Prof. C. A. Ewald. Translated by Dr. E. Saundby. Williams & Norgate. 1881. FLATULENT DYSPEPSIA 39 but we receive considerable aid if we are careful to discriminate between those forms where flatulence is the only symptom and those where it is associated with acidity, and also by taking into consideration the period with regard to digestion at which these symptoms develop. Thus, there are some persons, chiefly females, who, immediately on taking food, complain of flatulent distension without acidity, the wind they bring up is inodorous ; in these cases the gas does not apparently result from fermentative changes, but is probably derived by diffusion from the blood under nervous influences. When the flatulency is accompanied by a slight degree of acidity, and sets in about an hour after food, and the risings are simply acid, and the eructations comparatively inodorous, acetic and carbonic acid fermentation of the amylaceous and saccharine materials of the food is indicated. When the risings are dis- tinctly rancid, it is evidence that lactic acid fermentation of the nitrogenous principles is progressing. This form of fermentation is usually the most obstinate and severe, since, as Budd* has pointed out, it may continue inde- pendently of food by the decomposition of the mucus in the stomach and intestinal canal, so that flatulence may persist even when the stomach is kept empty. Among the conditions most active in producing fermentative changes in the alimentary canal, that caused by a state of general debility must be accounted as holding the foremost place. In these cases the propulsive action of the muscular walls is feeble, so that the onward passage of the food in different parts of the digestive tract is slow. In addition, the secretion con- cerned in the solution of the various constituents of the food are generally defective in quality if not in quantity, * Op. cit., p. 322. 40 FLATULENT DYSPEPSIA so that food remains undigested for a considerable time. As atonic dyspepsia is the most frequent of all forms of indigestion, so it is the most easily recognised. The broad, flabby tongue, thinly covered with white fur, with its edges indented by the pressure of the teeth ; the feeble action of the heart, the loss of appetite, and feeling of weight and distension, hardly ever amounting to actual pain, generally referred to the chest rather than the epigastrium, and experienced shortly after taking food ; the sour risings and eructa- tions from the stomach, occurring from two to three hours after a meal, whilst flatulent distension of the bowels is more or less constantly present, giving rise to sensations of weight, tightness, and soreness over the whole abdomen, but more especially distressing in the right and left hypochondriac regions, form a collection of symptoms with which we are only too familiar. Conditions of the nervous system, as is well known, have a powerful influence on the digestive process. It is, therefore, not surprising to find when innervation is impaired that dyspepsia frequently results. In some instances, nervous disturbance hastens the passage of aliment through the intestines, so that in this form of dyspepsia we have diarrhoea shortly after food instead of acid eructations, flatulence, and vomiting. In the majority of cases, however, the process of digestion is retarded and fermentative changes ensue. As a rule, the flatulent dyspepsia arising from nervous influences is less pronounced and more variable than in atonic dyspepsia, though if the disturbance be long continued, especially if caused by exhaustion from undue mental strain or depressing moral influences, a condition of general debility will in time be induced. A point of interest to be observed in the dyspepsias arising directly FLATULENT DYSPEPSIA 41 from disturbance of the nervous system is the rapidity with which the tongue often becomes coated with dense fur, and as rapidly cleans on the subsidence of the exciting cause. Flatulent distension of the stomach and intestines often arise in nervous states of the system, apparently quite independently of any fermentative changes occurring in the alimentary canal. Indeed, it is quite impossible to account for the enormous quantity of gas, which consists largely of carbonic acid, often discharged through the mouth on a perfectly empty stomach by hysterical and hypochondriacal patients, except on the supposition that it is diffused from the blood. Certain neuroses of the vaso-motor system leading to sudden increase of the salivary, gastric, and intestinal secretions, which are discharged by vomiting and purg- ing, must not be confounded with acid eructations and yeasty diarrhoea resulting from fermentative changes of the food. Such discharges are observed in the crises gastriques which are associated with ataxic phenomena ; and in pyrosis or water-brash, in which the fluid, the reaction of which is neutral or alkaline, is poured out by the salivary glands, or from the mucous surface of the stomach, probably both. As a rule, however, dyspepsias arising from disturbances of the nervous system are dependent generally on a condition of hyper- secretion, and the fermentative changes arise secondarily out of that condition. In organic disease of the stomach, acid fermentatiou is always present in greater or less degree, according to the situation of the lesion. Thus, in disease affecting the body or cardiac end of the organ, the food may be returned so quickly that fermentative changes have not time to take place, whilst in cases where the obstruction exists at the pyloric orifice, the most severe forms of the 42 FLATULENT DYSPEPSIA affection are met with, and the quantity of acid matters returned from the stomach are often enormous. Thus, Quincke* relates a case of a woman suffering from dilatation of the stomach the result of stricture of the pylorus, in whom the strong acid vomit amounted to 3000 cc. (about 5 pints) in the twenty-four hours. In catarrhal states of the stomach, whilst the process of digestion is impeded by the scanty secretion of the gastric juice, an unhealthy mucus is poured out which rapidly decomposes and itself undergoing fermentative changes, and which is often ejected from the stomach. This, however, must be distinguished from the insipid fluid retched up in the morning in catarrhal conditions resulting from alcohol. This fluid, as Frerichs has shown, is not formed in the stomach, but is due to the increased secretion from the salivary glands, and the saliva swallowed during the night is simply hawked up in the morning, converted, however, into stringy masses by the action of the acetic acid formed by fermentation, on the mucin contained in the saliva. Another cause giving rise to fermentative changes is an anomalous condition of the digestive secretions. Thus in the case of the gastric juice, it has been shown that too much acid though it hinders lactic acid fermentation furthers the development of yeast fungi and alcoholic and acetic acid fermentation. Fermentative changes may also com- mence in the mouth ; this usually depends upon an acid fermentation of the buccal and oral mucus, but in some cases appears to be due to actual acidity of the parotid saliva, f The influence that diminution or increase in the secretion of saliva has on the general health cannot * ' Correspondenzblatt f. schweiz Aerate,' 1874, Jahrg. 4, No. 1. + Astuschawsky, "Keaction des Parotis Speichel bei gesamden Menschen." * Centralblatt f. d. Med. Wiss.,' 1878, 257. FLATULENT DYSPEPSIA 43 be stated with certainty, but if, as it has been stated, the alkaline saliya is a powerful stimuli for the secre- tion of the gastric juice, then a deficiency in its quantity, or perversion in its quality and its reaction, are probably not without influence on the secretion of the latter fluid ; whilst such alterations must result in imperfect con- version of the amylaceous principles into sugar, and thus lead to acidity and flatulence. Bile exercises an un- doubted anti- fermentative action, whilst also it induces increased peristalsis of the intestinal walls. Diminution of the secretion would therefore allow fermentative changes to take place more readily than would be other- wise the case. Dogs in whom biliary fistulse have been established, pass much offensive flatus. The effect that disease of the pancreas or derangement of its secretion has in the production of disorders connected with digestion has yet to be studied ; there can be no doubt, however, that any disturbance of secretion of an organ which has such a powerful action on starch, fats, and albumins, must make itself felt. There is one point, however, concerning the pancreatic juice we must notice, and that is, its prolonged action on albuminous matters leads to the formation of putrefactive products. Thus, " trypsin," by its action on albuminous matters, converts them into two forms of peptone — anti-peptone and hemi-peptone.* The former undergoes no further change, but the other, after a longer or shorter time, breaks up into other bodies, such as leucin and tyrosin, &c, and by prolonged action in neutral or feebly alkaline solutions, into ammonia, sulphuretted hydrogen, hydrogen, and carbonic acid. So that if the peptones are retained for too long a time unabsorbed in the * Kiihne und Lea, " Ueber die Absonderung des Pancreas." ' Heidelb. Natural Medio. Verhandlungen,' i, Hft. 5. 44 FLATULENT DYSPEPSIA upper part of the small intestines, flatulence may be caused by the continued action of the pancreatic juice. Among the causes leading to fermentative changes must be mentioned the diet of the individual. In many cases food is taken in such excess that it is not absorbed, and it then undergoes putrefactive changes in the alimentary canal. As much as thirty pounds of a half putrid mass has been got rid of by purgatives. Parkes instances a case of this kind as occurring among some convicts in Australia, who received from seven and a quarter to seven and a half pounds of food daily ; dyspepsia, obstinate constipation, diarrhcea, skin dis- eases, and ophthalmia were the result. That a too free consumption of saccharine and amylaceous articles of diet will induce this form of dyspepsia there can be no doubt, since simple abstinence from such articles of diet is often sufficient to remove the disorder. Milk, containing as it does the very element for lactic acid fermentation is a frequent cause of this form of dyspepsia. Inordinate tea drinkers also suffer greatly from flatulent dyspepsia ; this is caused partly by its influence through the nervous system on digestion, partly by the dilution of the digestive secretions by an ingestion of an over-abundance of fluid, by the action of its tannin on the albuminous principles, and, lastly, though not least, by its being a vehicle for a considerable quantity of milk and sugar. Alcohol, likewise, by inducing gastric catarrh, is one of the most active factors in the production of this form of dyspepsia. Food of a bad quality, itself undergoing fermentative changes at the time of ingestion, such as bad bread, bad beer, and the like, introduced into the stomach, is a cause not to be overlooked. Whilst, in relation to food, FLATULENT DYSPEPSIA 45 we must insist upon its sufficient mastication and upon regular and well-arranged meal times. A sufficient time being allowed between each meal for its proper digestion, but not so far prolonged as to induce exhaus- tion. Lastly, climate is an important consideration in these cases, patients suffering from flatulent dyspepsia being greatly benefited by residence on dry soil and in sheltered situations. Thus Prout has observed that certain seasons and certain malarious districts more than others aggravate the tendency towards saccharine mal-assimilation, probably by the induction of a catar- rhal state of the digestive organs. Some of the most severe and obstinate forms of this disorder I have met with have been in patients who have resided in malarious districts, and at some time or other have suffered from its influence. Since fermentative changes give rise to the develop- ment of flatus and acid, the disturbances we meet with in this form of dyspepsia are caused by the presence of these abnormal products of digestion and the efforts made to expel them. In the majority of instances almost immediately on taking food a sense of weight and fulness is experienced. Then the feeling of weight is exchanged for tearing, twisting sensations, and cramp- like colicky pains. Severe pain, however, and tenderness on pressure, are not complained of, unless there is also organic disease of the stomach. The heartburn is accompanied by eructations of gas and risings of sour acid fluid, and undigested portions of food ; actual vomiting is rare, except in cases of pyloric obstruction. So great occasionally is the acidity of these regurgitated matters, that they set the teeth on edge like the sharpest lemon juice, and as Trousseau observes will often cover copper vessels into which they are placed with 46 FLATULENT DYSPEPSIA a coating of lactate or acetate of copper. In ordinary cases of flatulent dyspepsia the gas is usually carbonic acid, and the sour risings will be found to contain both lactic and acetic acid, one or other predominating according to the nature of the case. In severe cases of catarrh, especially when much unwholesome mucus is secreted by the walls of the stomach, the lactic acid fermentation is carried on to the production of butyric acid, which being volatile , imparts its peculiar rancid odour to the breath ; this is particularly noticeable in the catarrhal condition induced by alcoholism. Inter- mediate products of acetic acid fermentation are also frequently found in the ejected matters, such as alcohol, aldehyde, and acetone. In the cases in which these products are observed, an algoid growth known by the name of sareina, is generally met with. This growth, however, has no effect in producing those abnormal decompositions of the contents of the stomach, and its presence merely indicates that conditions favorable for its development exists in the stomach. The disturbances caused by fermentative changes in the stomach are not limited to that organ. The acid products formed in it, together with the undigested residue of the food, pass on into the intestines and excites more or less pain and diarrhoea. Again, fer- mentative changes may occur chiefly in the intestines and only a slight degree in the stomach. In this case, which is associated with a greater or less degree of chronic intestinal catarrh, a constipated condition of the bowels generally exists ; for though there may be frequent loose, slimy, and offensive discharges from the bowels, yet a purge never fails to bring away accumu- lated masses of faecal matter. The whole of the intes- tinal tract may be affected, or only part of it. Some ' FLATtTLBNT DYSPEPSIA 47 writers have asserted that the evil effects of fermenta- tive changes are more felt in the small intestines than in the large, and that catarrh of the small intestines is generally associated with oxaluria. The flatulence may distend the whole intestinal tract, hut one part of it is generally distended more than another; and circum- scribed swellings occur, chiefly in the right and left hypochondriac regions, causing pain over the region of the liver and stomach, spleen, or kidneys, and leading the patient to suspect disease of these organs. But the mischief resulting from excessive formation of acid in the stomach and bowels is not limited to mere dis- turbance of digestion, injurious effects making them- selves manifest on the system and on the general nutrition of the body when the morbid condition has been present for some time. These evils, as Dr Wilson Fox has pointed out, are more marked in cases of acidity arising from fermentative change than from the acidity of hypersecretion. The highly acid fluid con- taining the imperfectly digested products of gastric digestion passing into the duodenum excites more or less catarrh of that portion of the intestine, and the discharge of bile is interfered with, hence persons suffering with flatulent dyspepsia have usually sallow complexions, complain of pain in the hepatic region, and suffer frequently from so-called "bilious attacks." The absorption of the vitiated products of digestion, together with some of the free acid, produce many general and remote disorders of nutrition, so that a condition of debility and exhaustion is speedily induced. The urine in cases of flatulent dyspepsia has its natural acidity, as a rule, considerably decreased, that is, it becomes neutral or even alkaline ; and in severe cases * Op. cit. 48 FLATULENT DYSPEPSIA a persistent deposit of oxalates, associated with peculiar train of nervous symptoms, is generally met with (see Chapter V). This condition of diminished acidity of the urine cannot, I think, he accounted for by Dr Bence Jones's* hypothesis that when the contents of the stomach are most acid the reaction of the urine is least acid, because in these cases the acid is not with- drawn from the system but is formed in the stomach itself. Nor can I accept Dr Roberts' s view, endorsed by Dr Wilson Pox, that the alkalinity is due to the addition to the blood of the alkaline bases of the food, since in these cases there is no evidence that more food contain- ing alkaline bases is either ingested or absorbed than in a healthy condition. Indeed, so far from there being any evidence that more solid matters are passing into the system, the opposite is generally observed. One point that I have noticed with regard to these urines is, that they effervesce strongly on addition of acetic or nitric acid, denoting the presence of carbonates. These carbonates are those of the fixed alkalies, potash and soda, since the blue reaction given to red litmus paper is persistent and not evanescent, as would be the case if alkalescence was caused by ammonium carbonate. The alkaline condition, therefore, of the urine in cases of flatulent dyspepsia I believe to be due entirely to the excessive elimination of the carbonates of soda and potash, and this excessive elimination is brought about by three conditions — (a) general debility and the feebleness with which the respiratory act is performed, leading to the accumulation of carbonic acid in the system. With regard to this point, it is interesting to note that urine alkaline from the presence of carbonates * " On the Alkalescence of Urine from Fixed Alkali in some cases of Diseased Stomach." 'Med.-Chir. Trans.,' vol. xxxv, p. 41. FLATULENT DYSPEPSIA 49 of the fixed alkalies is frequently met with in patients convalescing from acute diseases. (6.) Diminished secretion of bile, which is the frequent result of the duodenal catarrh produced by the irritation of the acid contents of the stomach being poured into the intestines, gives rise to an accumulation of alkaline carbonates in the blood, the bile being the chief secretion by which alkaline salts are removed from the body ; for though a portion of them are undoubtedly reabsorbed into the blood from the intestines, a considerable proportion of them are discharged with the faeces. Obstruction, therefore, to the discharge of bile leads to their retention in the blood, and consequently being eliminated in greater quantity by the kidney, (c.) The acids formed by fermentative changes being of the fatty acid series ; these on entering the system are oxidised into carbonic acid, and this uniting with the bases of the alkaline oxides form carbonates of these bodies, and by increasing the alkalescence of the blood will diminish the natural acidity of the urine and even render it alkaline. The irridescent film, consisting of crystals of ammo- nium magnesium phosphate, often found on the surface of urine of persons suffering from flatulent dyspepsia, is due apparently to the passage of urine alkaline from fixed alkali into a dirty chamber-pot, and has no special clinical significance. For if we take a sample of normal urine of acid reaction and divide it into two portions and place them both in beakers, each of which contains a drop of stale urine, and then render the portion in one of the beakers alkaline with liquor potass®, ureal decomposition will set in very much earlier in the beaker containing the alkalised urine than in the one permitted to retain its normal acid reaction, and crystals of triple phosphate speedily form. 4 50 FLATULENT DYSPEPSIA Cases of flatulent dyspepsia associated with alkaline condition of mine. Case 1. — A gentleman, aged 60, consulted me during Dr Murchison's absence from town (August, 1874). He stated that during the past four months he had lost flesh and had suffered considerably from muscular pains, especially in the thighs, with a sense of inde- scribable weariness. General appearance worn ; com- plexion sallow ; conjunctivae slightly yellow. Complains of palpitation of the heart and shortness of breath. Bowels constipated ; much flatulent distension ; troubled with frequent micturition, and is frequently awoke early in the morning for this purpose. Physical exami- nation elicited that there was no disease of the heart and lungs. The liver was of normal dimension, and there was no pain in the epigastric or right hypo- chondriac region. The urine was clear, slightly acid when passed, but became alkaline on boiling, and threw down a filmy cloud of phosphates, which redissolved with considerable effervescence on the addition of dilute acetic acid. The specific gravity was normal, 1020, no albumen, no sugar, and there was no excess of either alkaline or earthy phosphates, nor any trace of ammonia. The alkalescence was thus solely due to the presence of carbonates of potash and soda. He was ordered two- drachm doses of Carlsbad salts twice a week, and to take a mixture containing ten drops each of dilute hydrochloric acid and tincture of nux vomica. On August 23rd he called, and said that shortly after com- mencing the treatment he began to feel better. He has lost the worn expression of countenance, and his complexion is clearer. The sense of weariness, backache) and muscular pain have disappeared, and he has regained FLATULENT DYSPEPSIA 51 some of his lost weight. His urine is normal in all respects, and the tendency to frequent micturition has quite subsided. He considers himself quite well. Advised him to continue the use of the Carlsbad salts for some time longer, but to leave off the acid mixture. Saw him four years afterwards ; he had been free from the symptoms ever since. Case 2. — A lady, aged thirty-six, the wife of a school- master. Has lately been very anxious about her hus- band's health and that of her only child. Has lost flesh considerably of late, Suffers much from muscular pain, and especially in the legs; much backache. Bowels constipated; suffers much from flatulence. Worn, anxious appearance ; complexion sallow, but conjunctivae clear. No enlargement or tenderness in the epigastric or right hypochondriac region. Heart and lungs healthy. Urine neutral in reaction; the quantity passed in twenty-four hours amounts to 800 centimetres ; specific gravity 1020. The phosphoric acid about normal in quantity, being 2'2 grammes ; uric acid - 32 gramme. No ammonia present. There was no sugar ; no albumen. Phosphates were thrown down on boiling, but were redissolved with violent effervescence by the addition of dilute acetic acid. The patient was ordered two-drachm doses twice a week of Carlsbad salts and a mixture containing ten-minim doses of dilute hydrochloric acid and tincture of nux vomica. The patient improved materially under this treatment, but not so rapidly as did Case 1. It was not till she was able to leave home with its cares and anxieties for a while that the improvement in her condition became permanent. Case 3. — A Cambridge graduate, aged thirty-five, 52 FLATULENT DYSPEPSIA fellow of his college, who for some months previously had been engaged in arduous mathematical studies. Had suffered for six weeks from despondency, and a sense of indescribable weariness, backache, and muscular pains, chiefly in the legs. Has lost flesh. Bowels con- stipated ; suffers much from flatulence. Micturition frequent ; is roused often in the night time to pass water. Fears that he is suffering from diabetes. On physical examination his organs were found healthy. Urine normal in appearance, slightly alkaline in reaction, throwing down on boiling a cloud of phosphates, which cleared up with considerable effervescence on the addition of dilute acid. Phosphoric acid normal in quantity. No albumen, no sugar. No carbonate of ammonia. Ordered two drachms of Carlsbad salts two mornings in the week and a mixture with ten-minim doses of dilute hydrochloric acid and nux vomica. In three weeks' time he reported himself quite well. Case 4. — A gentleman, aged sixty, whom I saw during Dr Murchison's absence from town. Had spent many years of his life in India, in a Civil Service appointment. Has lately been losing flesh, and suffering much from weariness, with muscular pains in limbs. Bowels con- stipated, with considerable flatulence. Sallow com- plexion, micturition frequent. Urine alkaline; phos- phates normal, no sugar, no albumen, no carbonate of ammonia. On boiling, the urine deposited phosphates, which cleared up with effervescence on the addition of dilute hydrochloric acid. Ordered Carlsbad salts and a mixture with dilute hydrochloric acid and nux vomica. A fortnight afterwards he reported himself as much better, and in a month he wrote to say he was quite well. FLATULENT DYSPEPSIA 53 I have also noticed similar conditions in six other cases, but as they all present the same features it is unnecessary to quote them in detail. There was loss of weight, weariness, constipation, flatulence, frequent micturition, more or less sallowness of complexion. Urine alkaline, neutral or faintly 'acid, effervescing on the addition of dilute acid, with no increased elimination of phosphates nor any trace of ammonia or ammonium carbonate. They all rapidly improved under the same treatment. In the ten cases under my observation the alkalescence of the urine was clearly due to the presence in excess of the carbonates of soda and potash, and to no other cause, since the blue colour on the litmus paper remained permanent and there was no ammoniacal odour ; and the inference may fairly be drawn that the dyspeptic symptoms, in the absence of any other determinable condition, were connected with the presence of these salts in abnormal quantities in the blood. With regard to treatment, the chief object is to prevent the decomposition of the organic matters of the food in the alimentary canal. Thus, when the disorder occurs in delicate people with feeble digestions, we, endeavour, by stimulating the gastric secretion and by giving tone to the muscular walls of the digestive tract, to ensure the solution of the albuminous constituents and the onward propulsion of the food generally before fermentative changes can occur. The former indication is probably best effected in the majority of cases by the administration of an alkali before meals, since Claude Bernard has shown that small amounts of diluted alkali introduced into the empty stomach will provoke a discharge of gastric juice more than sufficient to neutralise it. In the case of liquor potass®, it is 54 FLATULENT DYSPEPSIA probable the alkali acts simply as a direct stimulus to the mucous membrane, but when the alkaline bicar- bonates are taken, in addition to this action it is probable they add to the acidity of the system, being themselves acid salts, and so improve the quality of the gastric secretion. This action of the alkaline bicar- bonates is not, however, based solely upon a considera- tion of their chemical constitution, but from the effect their administration has on the reaction of the urine. Thus, Dr Bence Jones, in a paper read before the Eoyal Society, 1850, showed conclusively, from a series of observations, that large doses of sesquicarbonate of ammonia not only did not diminish the acidity of the urine, but actually increased it, as he found that the day when most sesquicarbonate of ammonia* was taken the acidity was higher than it had been any previous day, and that the acidity was still very high on the day following its discontinuance. Four years later a similar observation was made by Dr. W. F. Benekef with regard to the effect of bicarbonate of soda. And, lastly, Professor ParkesJ instances a case of rheumatic fever in which the acidity of the urine on the day following the administration of bicarbonate of potash was con- siderably higher than on the day before it was taken. As the question is of considerable importance with regard to treatment, especially of those affections which are under our consideration, I will briefly give the * Sesquicarbonate of ammonia is half acid carbonate. It con- tains the elements of one molecule of normal carbonate and two molecules of acid carbonate. By exposure to air it decomposes and is converted wholly into acid carbonate. t ' Archiv deB Wissenschaftlichen Heilkunde,' 1854 ; ' Studien zur Urologie,' p. 444. J ' Composition of the Urine in Health and Disease,' p. 297, 1860. FLATULENT DYSPEPSIA 55 results of some observations* made by myself on tlie subject (the details of the experiments are appended at the end of the volume), which show that the effect of bicarbonate of potash, taken after food, on the acidity of the urine is different from that when it is adminis- tered on an empty stomach. For when taken before meals the acidity of the urine on the day of adminis- tration was found only slightly depressed, whilst on the day following the acidity was considerably higher than it was the day the salt was taken. But when adminis- tered during the process of digestion the acidity of the urine entirely disappeared, being on two occasions neutral and on one alkaline, whilst on succeeding days there was no marked increase in the acidity of the urine as compared with that of the days preceding the experiment. And the same difference was observable in the hourly variations of the urine, for when the bicarbonate was taken before meals the effect of the alkali passed of at the end of two hours, and the amount of acid passed in the succeeding three hours was nearly equal to what was passed on the day no medicine was taken; whilst when the salt was taken after meals the urine remained alkaline up to the end of four hours after the dose was taken, and no recovery of acidity was noticeable. The result of these observations tends, therefore, to establish the fact that the administration of an alkaline bicarbonate on an empty stomach increases the acidity of the system, whilst its administration after a meal diminishes it. But how is it that these alkaline bicarbonates have such opposite effects ? The explana- tion that has occurred to me as the most probable, and by which the variable effect of these salts on the acidity * " Effect of Bicarbonate of Potash on the Acidity of Urine," ' Lancet,' Nov. 9, 1878. 56 FLATULENT DYSPEPSIA of the urine can be best accounted for, lies, as I have already stated, in their chemical constitution, the alkaline bicarbonates being acid salts. Now, the acid reaction of the urine is generally considered due to the decomposition that occurs between an acid or an acid salt and the neutral phosphate of sodium in the blood, acid sodium phosphate being formed, which passes out with the urine. Now, one of the chief acid salts of the blood is undoubtedly bicarbonate of potash or soda an acid salt ■with an alkaline reaction. The decomposition which results between these two salts may be represented as follows : Acid Neutral Normal Acid Carbonate. Phosphate. Carbonate. Phosphate. —A NaH 2 C0 3 + Na 2 HPO^ = NajHCO^ + NaH 2 PO^ "We therefore need not be surprised to find the administration of an acid salt, if it passes unaltered from the stomach into the blood, causing an increase in the acidity of the urine. And this is, indeed, what happens when a dose of bicarbonate of potash and soda is taken into the stomach before meals, for then, the mucous membrane under normal conditions being either neutral or alkaline, the bicarbonate is absorbed nnde- composed into the blood, and causes that increase in the acidity of the urine which has been noted. On the other hand, when the salt is taken during digestion, the acid contents of the stomach decompose it, carbonic acid is liberated, which escapes by the mouth, whilst the alkaline bases pass into the system and render it, and consequently the urine, more alkaline. With the alkali is generally associated some vegetable bitter. Nux vomica or its alkaloid strychnia is the one PLATXTLEH'T DYSPEPSIA 57 usually selected ; serviceable in almost every form of indigestion, it is particularly valuable in the flatulent dyspepsia arising from a state of general weakness and debility. Its extremely bitter taste excites the excretion of saliva, and thus aids in the conversion of the starchy matter of the food. It also possesses antiseptic pro- perties. By its action through the nervous system it gives tone to the muscular walls of the digestive tract, and thus ensures the onward propulsion of the food before fermentative changes occur. The increased muscular contractility it imparts aids in overcoming the attendant constipation and in expelling flatus. Nux vomica is usually well borne, but it sometimes causes headache and a feeling of fulness and irritation in the stomach. In this case calumba may be advantageously substituted. Should there be much anaemia, iron must be given, though it is generally tolerated with difficulty ; the best way to administer it, so as to cause the least disturbance, is in the form of steel wine diluted with water, taken once a day at dinner time. If the adminis- tration of the alkali before meals does not excite a sufficiency of gastric juice, pepsin and hydrochloric acid should be administered during meals. The hydrochloric acid should not, however, be given in too concentrated a form. The strength of the acid solution which in artificial gastric digestion is found to be most active contains 0'2 per cent, of real hydrochloric acid. This degree of dilution can be obtained by prescribing ten drops of the dilute acid of the Pharmacopoeia to be taken in two and a half ounces of water (an ordinary wine- glass). When the dyspepsia arises from nervous disturbance and there is little or no debility, and we have no reason to suspect deficiency of the gastric secretion, acids taken 58 FLATULENT DYSPEPSIA some little time before meals are indicated. Combined with nux vomica they are particularly valuable in those cases when the patient has been long in a depressed state, has suffered much from care and anxiety, or has been over-worked. Either hydrochloric, phosphoric, and nitric acids are usually administered, some cases seeming to be more benefited by one acid than by another. Although our physiological and chemical knowledge respecting the action of acids within the body does not enable us as yet to indicate with precision the cases which will receive the most benefit from the admi- nistration of any special acid, or give a reason for its employment, still, speaking broadly, we may say hydro- chloric acid seems best suited to that class of cases in which the dyspepsia is associated with an alkaline or feebly acid state of the urine unattended with exces- sive deposition of phosphates, whilst phosphoric acid should be prescribed in those cases where with alkaline urine there is a tolerably constant deposit of phosphate of lime or triple phosphate.* Nitric or nitro-muriatic acid, on the other hand, seems most beneficial in those cases in which the urine is acid and has a tendency to deposit oxalates and urates, or in which sudden and frequent changes in its reaction occur, especially if these deposits or changes are apparently associated with any disturbance of the hepatic function. Catarrh of the stomach and intestines may be either * The value of phosphoric acid in these cases seems to depend on the fact that equal quantities of phosphoric acid have a greater effect in rendering the urine acid than either hydrochloric or nitric, probably because the two latter combine with bases to form neutral salts, whilst the former appears in the urine as an acid salt, the restoration of the normal reaction of the urine in this case pre- venting the deposition of phosphates. FLATULENT DYSPEPSIA 59 a cause or consequence of fermentative dyspepsia. For the treatment of this condition nitrate of bismuth is the most efficacious drug we possess. It should he given in large doses (twenty to thirty grains) on an empty stomach. The powder is more efficacious than the liquid preparations. It is well, especially if consti- pation exists, to give with it small doses of some aperient salt, such as sulphate of magnesia or sulphate of soda. Nitrate of potash, in five-grain doses, may also advan- tageously be added to the bismuth mixture if the gastritis be of a subacute type. Nux vomica is also very serviceable in chronic gastric catarrh, especially, as Dr Einger has pointed out, when this condition arises from mechanical obstruction to the circulation, such as occurs in chronic bronchitis, dilated heart, or cirrhosis of the liver. In these cases, as well as in chronic alco- holic catarrh, there is generally associated an abundant flux of gastric or intestinal mucus, which unless re- moved adds to the existing trouble by itself undergoing fermentative changes. For this purpose the syste- matic employment of small doses of Carlsbad salts will be found of the greatest benefit. A. teaspoonful o the salt dissolved in from ten to fifteen ounces of hot water, as hot as the patient can bear it, should be taken every other morning, an hour before breakfast. This dilute warm saline solution seems to have the power of dissolving and removing a considerable quantity of this abnormal mucus, and carrying it off by the bowels, the motions containing not only fsecal matter, but an offen- sive and glutinous-looking slime, which often adheres most tenaciously to the sides of the chamber vessel. The cold wet compress is also a powerful agent in the treatment of subacute and chronic gastric catarrh, indeed its employment is advantageous in flatulent 60 FLATULENT DYSPEPSIA dyspepsia from whatever cause it arises. It should not be applied during full digestion, but towards the end of the process, about three hours after a meal. Thus, if the principal meal of the day be taken at seven in the evening, it may be applied at half past ten or eleven o'clock, before the patient retires to rest. In the majority of cases it can be borne the whole night, patients under its influence enjoying sound repose whose rest had previously been disturbed by bad dreams or distressing restlessness. With delicate and feeble persons it is as well at first to limit the period of application to three hours. This can be done if the compress be applied the first thing in the morning, the patient's stomach being stayed with a small cup of tea and a piece of toast to prevent exhaustion. When the compress is removed the skin should be gently rubbed with a bathing glove or a soft Turkish towel. In addi- tion to relieving abdominal plethora it increases the peristaltic action of the intestines, and thus aids in expelling flatus and overcoming constipation. When fermentative changes are a consequence of obstruction to the onward passage of the food, such as results in an extreme degree from stenosis of the pyloric orifice, our treatment is of necessity limited to relieving the dis- tressing symptoms caused by the excess of acid, the development of sarcinse, and the flatulent distension. Drs Ringer and Murrell* have recently advocated the use of glycerine for the relief of flatulence and acidity. They base their recommendation on the fact that it retards some forms of fermentation and putrefaction, notably of nitrogenous substances. Experimentsf show that 2 to 3 per cent, of glycerine added to milk will * ' Lancet,' July 3, 1880. t Dr. E.Munk, Virchow's 'Archiv,' 1879. FLATULENT DYSPEPSIA 61 delay lactic acid fermentation from eighteen to twenty- four hours, and it is a well-ascertained fact that glycerine preserves meat so completely that after immersion for some months it is still fresh and can be eaten. Drs Ringer and Murrell recommend it to be taken in tea- spoonful doses either immediately before, with, or directly after food. Their observations were made on stomach flatulence, and they obtained satisfactory results, for though it only partially succeeded in some cases where other remedies at once cured, in others it speedily and completely succeeded when these failed. Owing to its solubility they do not think it influences the formation of wind in the colon except when given in large doses, when it acts as a slight laxative, and so expels the putrefying mass which forms the wind. My own experience points to the conclusion that its adminis- tration is most beneficial in cases of ordinarily delayed digestion, but that it is of little value in severe cases. Glycerine, however, is an exceedingly valuable menstruum for the administration of other medicines ; we can, there- fore use it in all cases, obtaining the benefit it un- doubtedly confers in many instances without in any way interfering with the employment of other remedies in cases where its efficacy is doubtful. Thus, bismuth may be administered before meals, pepsin during meals, and a few drops of chloroform, as an antispasmodic, after meals, in a teaspoonful of glycerine. Charcoal is useful in all cases of flatulence and acidity, and its beneficial effects are well marked in intestinal flatulence associated with offensive smelling evacuations ; thus, I have employed it with considerable success in relieving the flatulence which in some cases is a very distress- ing symptom in chronic dysentery ; it also has a marked effect in diminishing the fcetor of the stools. 62 FLATULENT DYSPEPSIA Vegetable charcoal is undoubtedly more efficacious than animal, and it is best administered in a dry state in the ■ form of powder. A convenient mode of administering it in this form is to strew a teaspoonful thickly on the centre of a slice of very thin bread and butter, then rolling this up tightly, compressing the edges to prevent the escape of the charcoal, and swallowing it with as little mastication as possible. When the flatulence chiefly occurs in the stomach the charcoal should be taken immediately before food ; in intestinal flatulence immediately after. Creasote and carbolic acid are often employed for the relief of flatulence. Dr Sansom, who has intro- duced the use of sulpho-carbolates, has shown that they effectually arrest fermentation ; ten or fifteen grains of sulpho-carbolate of soda may be administered either immediately before or after food. Dr Einger has pointed out that the sulpho-carbolates may be advantageously employed in cases when the patient complains of pain, often most marked on one side of the abdomen, generally the left side, under the ribs. This pain, which is temporarily relieved by the eructa- tion of a little wind, soon returns, and may endure many hours. This pain, Dr Einger thinks, is of neu- ralgic character, and is excited by flatulency. In severe cases of flatulence and acidity I have found considerable benefit result from the use of turpentine in from ten to fifteen drop doses, taken shortly after food. By acting as a stimulant to the mucous membrane of the stomach and intestines it increases the quantity and improves the quality of the secretion, and diminishes the catarrh of those organs. It checks the formation of sarcinse. In the majority of cases it has a laxative effect, and thus relieves constipation without recourse being FLATULENT DYSPEPSIA 63 had to other remedies. The best mode of prescribing it is as follows : — Ten drops of spirits of turpentine are suspended in four drachms of acacia mixture ; to this is added a drachm of glycerine, containing five drops of pure chloroform in solution, twenty grains of bicar- bonate of soda, and cinnamon water to one ounce. Opium and its alkaloids are contra-indicated in flatu- lent dyspepsia, since they tend to diminish the digestive secretions and the contractile movement of the stomach and intestines. Five drops of chloroform dissolved in a teaspoonful of glycerine affords considerable relief to cramp and spasm. For the relief of acidity the alkaline bicarbonates must be administered from two to three hours after meals. Purgative medicines are to be avoided as much as possible. When absolutely required to remove accu- mulations, &c, dilute warm solutions of Carlsbad salts or small quantities of Fredrickshall, Pullna, or Hunyadi Janos water, should be employed in preference to drugs. With regard to the diet of persons suffering from flatulent dyspepsia, it is important to insist on the food being well masticated before swallowed, as well as being tender, easy of digestion, and well cooked. The meals should be taken regularly, and the intervals between them not too prolonged ; a weak and delicate person should take food at least every four hours. A small quantity of food should be taken on going to bed and on first rising in the morning, care, however, being taken not to overload the stomach at any one meal. With the avoidance of notoriously indigestible or flatu- lent articles of diet the patient need not be placed on too rigorous a dietary. Cream should be used instead of milk for tea or coffee; these, however, should be indulged in sparingly. Alcohol is borne badly by 64 FLATULENT DYSPEPSIA persons suffering from this form of dyspepsia, and they are often particularly susceptible to its influence, whilst from a purely medical point of view they are distinctly better without it. In eases, however, where there is a considerable degree of atony a tablespoonful of brandy, diluted with two table3poonfuls of water, may be given with advantage at the principal meal of the day, since dilute alcohol in moderate quantity is, as Bernard, has shown, a very efficient stimulant of the gastric juice. Only a small quantity of fluid should by taken at meal times, and, therefore, the same benefit is not derived from the employment of " table waters " as is obtained from their use in cases of dyspepsia arising from undue secretion of acid ; a small tumbler, however, of Appoli- naris water taken with dinner is often of distinct service, probably from the fact of the considerable proportion of chloride of sodium it contains. Fluids are best taken about two hours after food, when they dilute the acid that may be formed, and help to remove the products of digestion from the stomach. For this purpose the natural effervescent alkaline waters may be employed. They are, however, most beneficial in cases when the flatulence is limited to the stomach, and are of little use in relieving intestinal flatulence, whilst in those cases of intestinal dyspepsia which are associated with oxaluria they are distrinctly injurious. Flatulent patients are decidedly worse in wet, cold, and raw weather, or when they change from a dry soil to a damp situation. Those residing on wet clay soil or in marshy districts should, therefore, particularly attend to the subsoil drainage of their houses, and the use of the cold compress whenever the weather changes from fine to wet will protect them from being over-sensitive to cli- matic vicissitudes. UEIC ACID 65 CHAPTEE IV DERANGEMENTS ASSOCIATED WITH DEPOSITS OF UEKJ ACID Although, prior to the discovery of uric acid by Scheele in 1776, many physicians* taught that gout was produced by a morbific matter resulting from the " coctions " being imperfectly performed in the primes vim and in the secondary assimilating processes, still it was not till twenty years later that the probability of there being a connection between uric acid and gout was even hinted at. Indeed, at first uric acid was solely regarded as a " concreting " acid formed in the kidney, which bound together the earthy matters of the urine, and so engendered stone. This view was expressed by the term lithic acid — a term which is still employed clinically, though its chemical composition and relation- ship is best expressed by the title uric acid. In 1793, however, Mr Murray Forbesf pointed out that this substance was deposited in other parts of the body besides the urinary passages, and this, he thought, showed that it was contained in the general fluids of the body, and not merely formed in the kidneys. But though this observation was shortly afterwards confirmed * Thomas Sydenham, ' Treatise on Gout,' 1685. t ' Treatise upon Gravel and upon Gout, with an Examination of Austin's Theory of Stone, and Dissertation on Bile and on Solvents,' 1793. 5 66 TTEIC ACID by the analyses of Woolaston, in 1797, of gouty tophi, which he found composed of urate of soda, it was not till Dr Garrod, in 1848, brought forward before the Eoyal Medical and Chirurgical Society the result of his observations, based on chemical analysis of blood and urine in gout and rheumatism, that the fact that in true gout an excess of uric acid exists in the blood prior to and at the period of the attack was first demonstrated. The facts then brought for- ward have been since fully confirmed as to their accu- racy, and although Dr Garrod does not maintain they are in themselves sufficient to explain all the pheno- mena of gout, still his researches have thrown consider- able light on the pathology of the disease. Since Dr Garrod's observations have been published there has, however, been a tendency on the part of some writers to extend Dr Garrod's guarded statements with regard to uric acid, and they have assigned to it a place in patho- logy which is not yet warranted by physiological and chemical observation, nor even, I venture to think, by clinical experience. Already a reaction has set in against the doctrines enunciated by the most advanced members of this school of humoral pathology, and which, like most reactions, may in turn become extreme, and ignore many important points in connection with the pathological relations of uric acid which have been fairly established. Prom the circumstance that uric acid is a di-ureide, that is, by oxidation a molecule of uric acid can be split up into a molecule of a non-nitrogenous acid and two molecules of urea, it has been assumed that when the process of oxidation is imperfectly performed within the body uric acid will be found in excess in the blood ; and this assumption has been further strengthened by the URIC ACID 67 supposition that uric acid is one of the substances through which each particle of albumen passes before it is thrown out of the body. Now, whilst uric acid may fairly be spoken of as a less oxidised product of proteid metabolism than urea, yet there is no evidence, as Pro- fessor Poster* points out, to show that it is a necessary antecedent of the latter. Indeed, we have increasing evidence to show that the probable antecedents of the urea in the blood are partly the kreatin formed in muscle and elsewhere, and partly the leucin and other like bodies formed in the alimentary canal. The phy- siological variation, too, of the quantity of uric acid, so far as we can judge from its excretion by the urine, depends less on the nature of the food than upon special conditions of the internal organs than is the case with urea ; and this also points to an origin slightly divergent from that body. Thus, Professor Parkesf found, after four days of non-nitrogenous diet, that traces of uric acid could always be found in the urine, which seems an additional argument against the origin of urea from uric acid. For why, Professor Parkes observes, when all the nitrogen was cut off, and consequently the oxy- gen was in relative excess, should not all the uric acid have been converted into urea if that was its usual origin in the body ? It is not, however, so converted, but passes off pari passu with the urea as if furnished by special cells. Professor Parkes has also pointed out J that the comparative constancy in the amount of uric acid excreted, within narrow limits, and the want of connexion between its changes and the changes in the urea, in health and disease, seem to offer extremely * 'Text Book of Physiology,' p. 353. Macmillan, 1878. t ' Lancet,' vol. i, p. 722, 1874. J ' Composition of the Urine,' p. 29. Churchill, 1860. 68 T/RIC ACID strong arguments against the supposition that the latter body is largely derived from the former. Again, the fact that in birds and reptiles uric acid replaces urea has been urged in support of the insufficient oxidation theory, since it has been urged that both have to economise oxygen — the bird for the due performance of its active vital functions, the reptile on account of the structural imperfections of the respiratory apparatus. With regard' to birds, however, we have no proof whatever of their need to economise oxygen ; indeed, the fact of the richness of their blood in red corpuscles points to an opposite conclusion. The final causes of the divergence in these cases Professor Forster seems to think are to be sought rather in the fact that urea is the form best adapted to a fluid, and uric acid to a solid excrement. Lastly, it must be borne in mind that uric acid and its salts are by far the most insoluble of all the organic products met with in the body, so that unless some special provision was sup- plied for its prompt removal, as is the case with birds and reptiles, by their voluminous kidneys, any consider- able temporary excess would, especially if the excess was attributed to imperfect oxidation, lead to deposition in the textures of the body. These considerations certainly do not give support to those who have given to uric acid an undue prominence in humoral pathology, and who have based their hypo- theses on the supposition that uric acid is one of the substances through which every particle of albumen passes before it is thrown out of the body, and that when oxidation is imperfectly performed there is a pro- duction of insoluble uric acid and urates instead of urea. Indeed, they point rather to an opposite conclu- sion, that uric acid in the human body in health, and URIC ACID 69 even in disease, is formed in only very minute quanti- ties, and that when it is deposited from the urine or in the tissues the fact of the occurrence of such deposit may be generally referred to its insolubility rather than to its excessive production in the system. Thus, in the majority of cases where frequent and even persistent deposits of uric acid and urates are met with in the urine, we are often unable to show that they are in absolute excess ; whilst, on the other hand, it has been repeatedly demonstrated that no absolute increase does occur in a very large proportion of cases, and that the precipitation depends solely upon changes in the cha- racter of the urine, such as increase of its density or acidity, or both combined, the result of some derange- ment of the digestive organs, or from catarrhal or other morbid conditions of the urinary passages. Whilst in those cases in which a considerable quantity of uric acid is suddenly discharged we generally have sufficient evi- dence to show that the deposit has been accumulating for some time previously in the urinary passages, and does not represent the amount separated from the system within a period of twenty-four hours. Again, in those cases where an absolute increase of uric acid excreted in the twenty-four hours' urine does occur, it will be generally found on inquiry that other urinary consti- tuents are likewise being eliminated in excess, notably the urea and phosphoric acid. The circumstances under which this elimination occurs have received but little attention ; they seem to depend in many cases on dis- turbing influences, which apparently have a more pro- found origin than mere disturbance of the hepatic func- tions to which they are generally referred. In cases where the condition is temporary the increased elimina- tion may often be referred to disturbance of the nitro- 70 TTBIC ACID genous equilibrium, induced by the employment of a too highly animalised diet, by nervous influences, or temporary disturbances in some function of the organism. These cases in their general characters correspond to the condition described by Murchison under the term lithwmia, though increased elimination of uric acid is not the sole urinary characteristic, nor functional derangement of the liver necessarily the sole cause of the disorder. In cases, however, where the discharge of uric acid in excess is more or less persistent in a urine of high average specific gravity, whilst the urinary secre- tion is not diminished in quantity, it is to be feared that the condition is a prelude to some serious organic mischief— often phthisis, and, as Prout pointed out, of uterine cancer. It is a condition which is often found preceding or alternating with saccharine diabetes, and attention has recently been drawn to the considerable increase of phosphoric acid discharged daily with the urine in these cases.* Considerable clinical importance has been attached to the fact of uric acid deposits thus alternating with sugar, as indicating an alliance of this form of diabetes with the gouty state. Without deny- ing that such is the case in some instances, I would, however, point out that these deposits of uric acid are often more apparent than real, and depend rather on the changes in the urinary secretion itself than on any chemical transformation within the body. Thus, when sugar is abundant there is usually a corresponding increase in the quantity of water discharged, so that the relative quantity (per cent.) of uric acid is lessened ; if, however, the quantity of sugar becomes diminished, the the discharge of water from the body is generally pro- * J. L. Tessier, ' Du Diabete Phosphatique,' Paris, 187?: Also paper by author, ' Lancet,' March 12th, 1881. URIC ACID 71 portionately reduced, whilst the acidity of the urine is relatively, if not- absolutely, increased, so that the uric acid becomes relatively in excess, and is deposited partly on that account and partly from the increase in the acidity of the urine. Indeed, it is not improbable that an accumulation of acid salts in the blood may be a cause of some of the intermitting forms of diabetes ; since Dr Pavy* has found that the introduction of an acid into the system produces saccharine urine, this effect has followed the injection of phosphoric acid into the general venous system and also its introduction into the intestinal canal. There is, again, a tendency among many physicians at the present time to consider certain anomalous symptoms, which are not, however, recognised as distinct diseases, as connected with the " gouty diathesis " or due to " uric acid tendencies.'' Whilst admitting that these symptoms are met with frequently in patients who suffer from gout, or who are predisposed to the disease, it is important to remember that these symptoms also occur in persons in whom it is difficult by the Utmost stretch of' the imagination to suppose to be under the influence of the gouty diathesis, but who frequently develop at a subsequent period some other marked constitutional taint. Among the premonitory signs of scurvy are many which are also considered sure indications of the gouty state.f There are the same fugitive and erratic pains in the limbs, tenderness of the joints, attacks of dyspnoea more or less paroxysmal in character, severe attacks of pain over the region of the heart, weak and intermittent pulse, irregular discharges of urine, some- * ' Diabetes,' p. 82. t Sydenham, ' Opera universa,' Sect. 6, cap. 5, de Rheumatismo, 1685. Garrod ' On Gout,' p. 473, 1876. 72 raic acid times profuse and of low specific gravity, at other times scanty and concentrated, &c, and yet scurvy and gout are, when developed, distinct diseases. Now, although true scurvy has almost disappeared from civil practice, and is only occasionally met with among the sailors of our mercantile marine, still, as Dr Eade* and others have shown, incompletely developed forms of it are hy no means of rare occurrence, though, as Dr Buzzardf has pointed out, the true nature of the ailment is very often overlooked. Among the class of persons who form the bulk of the out-patients of our hospitals and dispensaries mild scorbutic manifestations may be frequently noted. At the London Hospital, where, from a. habit acquired at the Dreadnought, I make it a rule to examine the gums of all patients at the time I examine the tongue, a visit seldom passes without a case presenting itself exhibiting sufficiently characteristic scorbutic symptoms. This manifestation of a scorbutic condition is not, however, by any means confined to our poorer patients, since we find it deve- loping from time to time among those of a better class.. Here it frequently supervenes on some chronic affec- tion ; thus, for instance, a patient with a weak and feeble digestion is afraid of taking sugar because it turns acid, and vegetables, particularly potatoes, because they cause flatulence, so fruit, potatoes, and green vegetables are avoided. Absolute deprivation of vegetable food, how- ever, is not required to produce a tendency to scurvy, some persons being naturally predisposed towards the disease, and are more readily and speedily affected by a temporary withdrawal or a diminished supply than others; these persons have what the older writers * ' Lancet,' June, 1880; ' Brit. Med. Journal,' Nov. 19th, 1881. t Reynolds' 'System of Medicine,' Article "Scurvy," p. 745. URIC ACID 73 termed the " scorbutic constitution." In many instances that have come under my observation of persons sup- posed to be " gouty," I have suspected them to be really suffering from an incompletely developed form of scurvy, and have noticed an almost immediate alleviation of the symptoms by recourse to lemon juice.* So also with persons who have had syphilis, but who at the time they come under observation are free from any apparent manifestations of the disease, and who often complain of symptoms that closely resemble those experienced by gouty subjects ; so that if our patient's memory is short, or there are difficulties in the way of direct inquiries, we may readily fall into error. Thus, in the case of a lady who was sent to me in the spring of last year, supposed to be suffering from some "gouty trouble," her chief symptoms were periodical attacks of jaundice, though not of very severe character, fol- lowed by urticaria, with dyspnoea, irregular and weak action of the heart, shooting pains in the limbs, r Tessier have come under my observation, although in none of them were the symptoms so marked or- the excretion of phosphoric acid so considerable as in those described by him, I- give a brief account of them^ since they may be of some service in illustrating this in- teresting and obscure point in urinary pathology. Case 1. Polyv/ria with increased excretion of phosphoric acid and urea; nervous-symptoms. — J. H. — , aged sixteen, was admitted into the Seamen's Hospital July, 1876, in a stupid, semi-comatose condition, extremely feeble, and emaciated. Weight under 9 st. y no great thirst ; pass- ing large quantities of urine of medium specific gravity with trace of albumen ; no sugar. No history of syphi- lis or injury to the head. Analysis of the twenty-four hours' urine gave the following result r Quantity 29.00 c.c Specific gravity ... ... 1010 Earths \ , ■. t, • • ^ ( 2-3 } K „ ( (P aos P norlc aei< i) ) 9.9 t grammes. Urea ... ... ... ... SI* grammes. The lad remained in bed for several days in a dull, stupid condition, and then gradually brightened. The diuresis continued excessive during the whole period of 122 PHOSPHORIC ACID his stay in hospital, the specific gravity ranging from 1010 to 1015. He was treated successively with large doses of valerian, with small doses of opium, with cod- liver oil and quinine. He improved greatly under treatment with regard to his general condition, but he was still polyuric when discharged. In this case the quantity of urine passed was about three times, the solids about double (calculated from the specific gravity), the phosphoric acid more than treble, and the urea rather more than double the normal for a lad of his age. In this case there was a decided increase of tissue metamorphosis, as evidenced by excessive excre- tion of urea and phosphoric acid, the latter especially. It comes under Dr Parkes' third definition, and corre- sponds with the first group of Dr Tessier. Case 2. Polyuria; increased elimination of phosphoric acid ; death ; small syphilitic gumma at base of brain. — T. G — , aged twenty-four, a patient of the late Dr Mur- chison, came under my observation on August 24th, 1878, during Dr Murchison's absence from town. The patient, a slight man weighing about 9 st., had been ailing four or five months ; sight failing for a month, but has got rapidly worse during the last week ; cannot now read or count fingers when held up. Passing large quantities of water ; syphilis five years ago. Ophthal- moscopic examination only revealed slight fulness of veins. He was instructed to collect and measure urine and bring some for analysis next visit. August 28th. — Patient much worse ; complains of violent pain in head. Quantity of urine passed in the last twenty-four hours 9500 c.c.; reaction neutral ; sp. gr. 1004; phosphoric acid 6 grammes. August 30th. — Violent pain in head ; now quite blind ; as he required more care and attention PHOSPHORIC ACID 123 than he could in his circumstances receive at home he was taken to St. Thomas's Hospital. Here, shortly- after admission, he became delirious, and then comatose, and died on September 2nd. I am indebted to the courtesy of the then house-physician for a note with regard to the condition of the brain as found at the post-mortem examination: — " A small syphilitic gumma, about half the size of a small hazel-nut, situate in the middle line under the floor of the third ventricle, ob- structing some of the vessels at the base ; some softening of the brain substance."* Case 3. — Polyuria moderate; increased elimination of phosphoric acid ; hypochondriasis ; rheumatic pains in loins ; emaciation. — Out-patient, under my care at the London Hospital. First seen September 16th, 1880. A small but well-built man, aged twenty-five, weighing about 9 st., employed on the East London Railway ; attributes his illness to over-work. No history of syphilis. Temperate habits. Has a pale, anxious, haggard expression. States that he has been ailing some months, has lost flesh, and complains of a feeling of extreme nervousness and exhaustion, with frequent fits of trembling. Constant tearing pains in loins, often shooting round the pelvic region, with cramp-like spasms in lower parts of abdomen. No lightning pains, patellar reflex unimpaired. Vision perfectly distinct. * This case was plainly one of hydruria, or diabetes insipidus, without increased tissue metaphorphosis, the diuresis being a consequence of the cerebral lesion. The increase of the phos- phoric acid (nearly treble the normal) is, I think, sufficiently accounted for by the large quantities of milk and beef -tea taken to quench thirst at that period of the illness when the analysis was made, and also to some extent to the washing out of the tissues by the drainage going on through the body. 124 PHOSPHORIC ACID No apparent disease of abdominal or thoracic viscera. Digestion fairly good ; bowels constipated. Urine pale, whey- like, of medium specific gravity ; alkaline reaction ; no sugar; no albumen. States that he passes more urine than he should, and is frequently disturbed at night to pass it. Instructed how to collect and measure it, and to bring, a sample of the mixed twenty-four hours' urine at the next visit. The- patient, however, did not comply with all the conditions necessary for accurate measurement; and it was not till Oct. 21st that I was satisfied that my instructions had- been- carefully carried out. By that time he had been five weeks under treatment (mineral acids and'nux vomica), and'had im- proved to some extent. Analysis of twenty-four hours' urine : Oct. 21st. — Quantity 2300 c.c. ; sp. gr. 1015 ; reaction alkaline. Phosphoric acid 7~Q grms., treble what it should be for a man of his weight. Ordered codeia pill, one third of" graih, and a mixture with bromide of potassium and nux vomica. Nov. 18th. — Very much improved 1 ; is gaining Weight, feels stronger, has nearly lost the pains, discharge of urine still more abundant than it should be. To collect and measure it as before and' bring a sample at next visit. To continue mixtures but to discontinue the codeia. Nov. 25th. — Analysis of urine : quantity 2300 ; sp. gr; 1015 ; reaction alkaline. Phosphoric acid 5 - 8 grms. ; urea 335 grms. Continued to attend off and on as an out-patient till November, 1881. His general condition was then much improved, and he resumed regular work. Case 4. Excessive elimination of phosphoric acid ; no polyuria ; hypochondriasis ; enormous quantities of calcium oxalate in urine. — A gentleman's servant, aged twenty- seven. First came under observation Sept. 28th, 1880. PHOSPHORIC ACID 125 He is a thin spare man, weighing about eight and a half stone ; of sallow, haggard complexion. No history of syphilis ; habits temperate. Complains of aching pains, especially in the loins, shooting down the hips, and occasionally affecting the bladder and testicles. Alleged loss of virile power. Abdominal and thoracic organs apparently healthy. Digestion fair, bowels constipated. Peels very wretched and depressed. Urine passed at the time of visit (11 a.m.) acid ; specific gravity 1028, containing 8 grms. of phosphoric acid in 1000 c.c. The secretion of urine, he said, was not excessive ; he was rarely troubled during the day, but frequently at night, with calls to* micturate. (He was requested to collect and measure the urine for a few days, and send a note with regard to the quantity passed in the twenty-four hours ; this proved to be just under two pints, or about 1100 c.c.) The urine he passed in my presence deposited in a few hours an enormous quantity of oxalate of lime ; no sugar ; no albumen. Ordered codeia pill, a quarter of a grain, at night, and a mixture of hydrochloric acid in nux vomica and cod-liver oil. Nov. 18th. — Is much better. Less pain in loins. Not so despondent, though still fears he is impotent ; confesses, however, to occasional manifest- ations of " his nature." To discontinue codeia and take phosphorus pills, one sixtieth of a grain, instead. To collect urine for twenty-four hours and send it for examination. Dec. 1st. — Quantity 1520 c.c; sp. gr. 1022 ; urea 41*2 grms. ; phosphoric acid 5'2 grms.* Case 5. Polyuria ; increased elimination of phosphoric acid, co-existing with a mild form of glycosuria. — A * This case corresponds with those originally described by Beneke of phosphaturia combined with oxaluria. ' Zur Phys. and Path, des Phosphors und Oxalsaure,' Kalkes, 1850. 126 PHOSPHORIC ACID gentleman, aged thirty-seven, who for the last eighteen months has suffered intermittently from a mild form of glycosuria, which did not apparently affect bis general health, began in the autumn of the present year (1880) to suffer from constant aching, boring pains in the loins, shooting round the pelvic regions, with occasional cramp-like sensations in the bladder, and a tired, sore feeling in the muscles of the thighs and calves of the legs. He also became dispirited and hypochondriacal ; began to lose weight and flesh. The amount of sugar passed had never been excessive, and had always been controlled by restricted diet. At this time he was certainly not passing more sugar than he had done in the earlier stage of his illness, and it again disappeared when he placed himself on restricted diet for a few days. Still, however, the pains and malaise continued. On Oct. 12th the urine was collected for twenty-four hours, and subsequently on Oct. 14th and 15th, and Nov. 3rd, 21st, and 26th. On each occasion the amount of phosphoric acid present was estimated with the fol- lowing results : PhoBphoric acid. Sugar. Urea. .. 7'6 grins. ... nil. — Quantity. Sp. gr Oct. 12th 2020 C.C. . . 1018 » 14th 2300 c.c. . . 1015 „ 15th 1520 c.c. . . 1020 Nov . 3rd 2500 c.c. . . 1012 tr 21st 2350 c.c. . . 1019 » 26th 2300 c.c. . . 1018 6-9 57 7-5 8-2 4-6t nil. nil. considerable 69 grms. The patient began taking codeia in half-grain doses at bedtime on the night of Oct. 12th, and continued to take it till Oct. 25th ; it was then discontinued, as he was feeling better. On Nov. 3rd the pains, however, f Phosphoric acid in combination with the earths, 2-1 grms.; with the alkalies, 2°5 grms. PHOSFHOKIC ACID 127 returned with considerable severity, and the codeia was resumed, but it was only taken occasionally up to Nov. 20th. Sugar also reappeared in the urine in more considerable amount than had been previously noted, and continued till the patient left town. No special reason could be assigned for the reappearance of the sugar, as the diet was in no way different on the days of its reappearance than it had been during the period immediately preceding. That is to say, the diet had been restricted, with the exception of a small quantity of crust of bread taken with each meal. Grain doses of extract of opium were now given at bedtime till Dec. 4th, when the patient left town for a month's rest. During that time he took no medicine. Most of the holiday was spent at watering-places, where he bathed daily and made use of tepid saline douches ; he also took a considerable amount of walking exercise. He returned to town feeling better in every respect. He has regained his lost weight, and is now bright, cheerful, and hopeful. The pains in the loins and thighs still, however, trouble him occasionally. The urine (Jan. 15th) on examination gave the following result. Quan- tity 1900 c.c. ; sp. gr. 1020 ; urea 66 grms. ; phosphoric acid 3 - 8 grms. ; no sugar. Since the last note up to Feb. 14th, 1882, the patient's health, with the exception of temporary attacks of glycosuria, has continued to improve. Case 6. Polyuria ; excessive elimination of phosphoric acid and urea. — J. G- — , aged twenty, was admitted into the Seamen's Hospital on Nov. 13th, 1877, suffering from extreme debility and prostration, and complaining of pain in all his limbs, and especially across the loins. His face was somewhat flushed and the eyes bright, but 128 PHOSFHOBIC ACID the temperature was normal ; the pulse weak and feeble ; chest sounds natural, with the exception of some coarse rales in the large bronchial tubes. Urine clear, acid ; no albumen ; no sugar. He says the present illness com- menced three weeks previous to admission, but he had otherwise always enjoyed good health. During this attack he had lost eighteen pounds in weight. He has a spinal curvature, the seventh and eighth dorsal vertebra being the bones affected, and he has also a strumous appearance generally. On Nov. 19th, seven days after admission, the mucous rales in the chest had cleared up, and he was not so prostrate. The pulse was stronger, and the temperature had remained normal during the time he had been in the hospital. Still the patient, in the absence of any definite symptoms, was extremely feeble and weak. Although no sugar had been found in the urine, it was thought advisable to collect the urine for twenty-four hours, and then test for that sub- stance in the whole quantity. Nov. 20th. — The urine collected during the last twenty-four hours measured 4600 c.c, and had a specific gravity of 1010, but gave no reaction with Fehling's solution. Nov. 21st. — The quantity of urine collected in twenty-four hours mea- sured 1400 c.c, a nearly normal quantity, but the specific gravity had risen to 1029, so that the relationship between the solids excreted on each day was tolerably constant, and exceeded by a third the normal excretion. The urine was collected, measured, and the specific gravity taken subsequently each day during the patient's stay in the hospital ; but it will be sufficient here to state that the average quantity passed by the patient each day for a month was 3263 c.c, with a specific gravity of 1017. Taking the healthy excretion of an adult so be at the outside 1500 c.c, with a specific gravity of 1020, PHOSPHORIC ACID 129 the patient was passing more than twice the normal quantity of urine, and excreting one third more than the ordinary quantity of urinary solids. The urea and phosphoric acid were determined quanti- tatively on several occasions by the house-physician, Dr Murphy, with the following result : Date, Dec, e. 3rd . Quantity of Urine. C.c. ... 4476 ... Sp. gr. 1011 ., Urea. Grma, ,. 67 . Phosp. Acid. Grms. .. 5-3 4th ... 4800 ... 1016 . .. 116 . .. 96 5th ... 4100 ... 1018 ., ,. 103 . .. 90 7th ... 3050 ... 1017 . .. 61 . .. 4-28 On the 13th of December I made a quantitative esti- mation of the urea and the earthy and alkaline phos- phates, with standard solutions distinct from those used by Dr Murphy, and my results closely corresponded with his — viz. quantity 2700 c.c, total urinary solids 108 grms., urea 89 grms. Phosphoric acid in combi- nation with lime and magnesia 1*8 grms. ; phosphoric acid in combination with the alkaline oxides 3'7 grms. ; total phosphoric acid 5'5 grms. Diet : 4 oz. wine, milk 2 pints, strong beef-tea 1 pint, bread 12 oz. The patient remained in hospital till the 20th December, when he was removed by his friends. His condition was mate- rially improved, and he had regained 15 lbs. of his lost weight, but the urinary secretion was not diminished. During his stay in hospital the patient suffered greatly from boils. The patient had no dimness of sight, nor any appearance of cataract. At no time could even minute traces of sugar be discovered in the urine. This may be considered as a typical case of diabetes insipidus, accompanied with increased metamorphosis of tissue. Jt resembles Willis and Prout's cases of azoturia, and also corresponds to Tessier's fourth group. 9 130 PHOSPHORIC ACID The particulars of the six foregoing cases may thus be briefly summarised : Case 1. Age. .16.. Approximate weight. . 8 st. 7 lb.. Quantity. ..2900 C.C Sp.gr. ..1010. ..5-2 Pho»p. Acid. grins. Urea. ..51-0 grms ., 2. .24.. . 9 st. ..9500 „ . ..1004. .6-0 n — „ 3. „ 4. .25.. .27.. . 9 st. . 8 st. 71b.. ..2300 „ . ..1520 „ . .1015. ..1022. .7-8 .5-2 ,.33'5 grms ..41-2 „ „ 5. „ 6*. .37.. .20.. .12 st. 7 lb.. . 9 st. .2020 „ . .3825 „ . .1018. .1016. .76 .6-7 ..87 - 2 grms. In all the increase of phosphoric acid over the normal excretion was considerable. If we except Case 2, they differ from the ordinary hydruric forms of diabetes insipidus, in that the discharge of urine, though con- siderably more than normal, in no way approached the enormous superflux met with in that form of the disease. f On the other hand, the cases in many respects resemble those related by Prout and Willis, and to which those authors gave ;the title azoturia. As, however, these observers did not estimate the phosphoric acid excreted as well as the urea, it is impossible to say in their cases whether it was increased or not. Dr Parkes,J however, quotes a case of Vogel's, which seems closely to corre- spond with the instances I have given, and in which the following amounts were passed in two periods of twenty- four hours respectively : Quantity 2800 c.c. and 3600 c.c. ; urea 40"6 grms. and 47 grms. ; phosphoric acid 4*1 grms. and 8 # 3 grms. In this case the urea as well as the * Average of five observations. t It may be as well to mention that, though reference is only made to the quantity qf urine and the specific gravity on those days when an estimation of phosphoric acid was made, yet obser- vations on this point were frequently made in each individual case, and the relationship was found to be pretty constant. % Op. cit., pp. 10, '367. PHOSPHORIC ACID 131 phosphoric acid was increased, though the proportionate increase of the latter over the former in the second analysis is prodigious. This is what Dr Tessier contends for when he gives the distinctive title " phosphatic diabetes" to this form of diuresis accompanied with increased elimination of phosphoric acid; for though urea in some of his cases was in excess, it was not so ii^ all; and this, he says, is the point that distinguishes between azoturia and phosphaturia. Of my cases, in Case 1 and Case 4 the urea was about one third in excess, whilst the phosphoric acid was more than double the normal excretion. In Case 6 the urea was more than double, and the phosphoric acid treble, the normal. In Case 3 the amount of urea was normal, whilst more than double the usual amount of phosphoric acid was excreted.* In these cases, therefore, the excess in the elimination of phosphoric acid was proportionately larger than that of the urea. The question may now be asked, Whether increase of phosphoric acid is not a constant phenomenon in all cases of diuresis, or whether it may not be accounted for by the increased ingestion of food and by the washing out of the tissues by the drain of water through them ? Analytical evidence on this point is meagre, but what evidence we have shows that the increase in the quantity of food ingested, or the drain of water through the system, does not necessarily increase the elimination of phosphoric acid. Dickinsonf and other observers} have * Throughout I have assumed the 2-5 grammes represent the normal excretion of an adult weighing from 8 to 9 stone, and 3" grammes for an adult weighing 11 to 12 stone. f W. Howship Dickinson, M.D., ' Diseases of the Kidney,' &c, Part 1, " Diabetes," pp. 173 and 208. London, 1875. J Neubauer, Boecker, Beneke, Vogel, Gaethgens, quoted iu Ziemssen's ' Cyclopaedia/ Article " Diabetes." 132 PHOSPHORIC ACID remarked an increased elimination of phosphoric acid, especially in comhination with the earths, in certain cases of diabetes mellitus, but this increase is very far from being universal, as other analyses prove (Parkes).* Again, in the cases of diabetes insipidus given by Dickin- son, though an increase is noted in some, it is not in all ; and in two cases, which I reported in the ' Lancet.'f the phosphoric acid was if anything decreased. For exam- ple, in one case in a man weighing 11£ st., the daily average secretion of urine was over 3000 c.c, whilst the phosphoric acid estimated on three occasions never exceeded 2'4 grms. In the second case the patient weighed 8-| st., the urine passed was 2400 c.c., and the phosphoric acid was only 1*6 grm. But if the ex- aggerated excretion of phosphoric acid is not a constant phenomenon of diabetes insipidus, to what are we to attribute its appearance in the exceptional cases ? And here we pass from the consideration of facts to the region of conjecture. There is no question in scientific medi- cine on which we have fewer facts to generalise from than that concerning the elimination of " phosphates in disease," and consequently there are few subjects which have yielded a richer harvest to the quack. Physiology J can only tell us that the element phosphorus is absolutely essential for the growth and nutrition of the tissues, but cannot explain its role. Whilst, therefore, our informa- tion with regard to the physiological action of phos- phorus within the body is still so scanty, it is obvious we are not yet in a position to indulge in speculations concerning the part played by it in the production of * Op. cit., p. 344. t ' The Lancet,' Feb. 26th, 1876. % 'Text-Book of Physiology/ MicUael Foster, M.D., F.R.S., p. 366. Loud™, 1878. PHOSPHORIC ACID 133 certain pathological phenomena with which it has been associated. It is satisfactory, however, to know that the attention of scientific workers* has been called to this subject, and we may hope that shortly a sufficient number of trustworthy facts may be collected, which will enable us to gain a clearer insight into the part played by this important element with respect to the nutritive changes with which it is concerned within the body. Nor is clinical observation in this instance much in advance of our physiological and pathological know- ledge. Excessive elimination of phosphoric acid has been noticed in acute inflammation of the membranes of the brain (Bence Jones), in the acute paroxysms of certain forms of mania (Sutherland and Beale) , and after injuries to the head (George Harley). And the late Dr Golding Bird attributed some of the cases of phosphaturia that came under his observation to spinal lesions, probably functional in character. But whether in these conditions it is due to increased metamorphosis of the nervous matter or to the. irritation of a still hypo- thetical " coordinating chemical centre," or to the in- fluence of a disturbed condition of the nervous system upon nutrition generally, it is at present impossible to decide. Increased elimination of phosphoric acid, again, Benekef has considered in some cases to be due to excessive formation of acid in the tissues, dissolving out the earthy phosphates ; in these cases oxalates and * W. Zulzer, ' Ueber das Verhaltniss der Phosphorsaure zum Stickstoff in Urin," ' Centralblatt fur die Med. Wissenscbaft,' 1876, p. 474. Von Prof. Dr. Edlessen in Kiel, " Ueber das Verhaltniss der Phosphorsaure zum Stickstoff in Urin," ' Centralblatt f. d. Med. Wissensehaft,' 20 Julii, 1878. Eniilie Lehmus, " Ueber der Rela- tiven Wert der Phosphorsaure in Urin bei Kiudern,'' ' Cbl. f. Kinderheilk.,' No. 19, 1878. t Dr. P. W. Beneke, ' Archiv des Vereins,' p. 450. 1854. 134 PHOSPHORIC ACID phosphates of lime will both be found in excess in the urine. Similarly in certain cases of dyspepsia associated with excessive formation of lactic acid in the stomach and intestines, more phosphate of lime may be rendered soluble and absorbed into the system, and thus pass out by the urine instead of by the bowel. Marcet* has shown from analyses of pulmonary tissue in consumption that a considerable reduction of phosphoric acid and potash takes place, both in the insoluble tissue and nutritive material, as compared with healthy lung tissue. And Edlessenf has shown that the excretion of phosphoric acid is increased in cases of anaemia, espe- cially pernicious anaemia. The observations of the authors I have quoted are, however, too limited to draw definite conclusions from as yet. All that we are warranted in assuming from them is, that increased excretion of phosphoric acid is met with in those states of the system which we characterise as " nervous," and that it is often met with accompanying or preceding diseases in which disorder of nutrition is usually well marted.J * W. Marcet, M.D., F.R.S., 'Experimental Inquiry into the Nutrition of Animal Tissues,' p. 47. London, 1874. t Op. cit. J It will be observed that I have not included rickets among the diseases in which an increased elimination of phosphoric acid is noticed. The truth is that the fact of there being an increase is by no means established. Professor Gamgee, in his recent work on ' Physiological Chemistry,' states that no reliable analysis has yet been made to prove it. Whilst Dr Seeman who has analysed the urine of sixteen rachitic children, has actually found a dimi- nution, which was most marked when the disease was at its height. Dr Seeman regards the bone changes in rickets to be due to lime starvation, the salts of that base not being introduced in sufficient quantity into the system, owing to the catarrhal condition PHOSPHOEIC ACID 135 With regard to the treatment of the form of disease under consideration, the main indications are rest and an endeavour to promote nutrition generally. To attain this end opium or codeia should he given in full doses, when the patient first comes under ohservation. As soon, however, as the nervous system is quieted, and the rheumatic and neuralgic pains are less severe, it should be discontinued, lest it interfere with digestion . General tonics, such as iron, phosphorus, quinine, nux vomica, hydrochloric acid, and cod-liver oil, should be persevered with. When there is a history of syphilis iodide of potassium should be combined with these remedies. Warm baths, followed by^tepid douches, give great relief to the neuralgic pains, and also soothe the nervous system. The soluble phosphates may be admi- nistered; but their utility in these cases is questionable. There appears to be no lack of these constituents in the system ; the difficulty seems rather to lie in the want of power of the tissues to retain them. The food should be light and nutritious, and milk one of the chief con- stituents. Alcohol should be avoided; it invariably, even in small quantities, increases the diuresis. The same may be said of coffee. Change to dry bracing air should be obtained if possible.* • The clothing should of the mucous membrane of the intestines hindering their ab- sorption. (" Zur Pathogenese und Btiologie der Bachifcis," von Dr Seeman, ' Virchow's Archiv/ Ixxvii, 1879.) * By strictly carrying out the above plan of treatment, by ex- changing his residence from London to Brighton, a gentleman who consulted me in the autumn of last year has succeeded in reducing the daily urinary flux from 90 ounces, with a specific gravity of 1015; to 60 — 70 ounces, with a specific gravity of 1015 — 16, whilst the excessive elimination of phosphoric acid is pro- portionately reduced. The improvement in his urinary symptoms, only became definite since his removal to Brighton. 136 PHOSPHORIC ACID be warm, and the patient carefully guarded against cold, since in these cases a reduction of bodily tempe- rature is always noted. When, in spite of the pursuance of these therapeutic and hygienic conditions, the diuresis and excretion of phosphoric acid continues, though the general condition of the patient may temporarily im- prove, there is reason to fear that phthisis will super- vene, or that the disease may assume the features of saccharine diabetes. APPENDIX EFFECT OF BICARBONATE OF POTASH ON THE ACIDITY OF URINE Thirty-two years ago Dr Bence Jones, in a paper read before the Royal Society,* showed conclusively, from a series of observations, that large doses of sesqui- carbonate of ammonia not only did not diminish the acidity of the urine, but actually increased it ; as he found that the day when most carbonate of ammonia was taken the acidity was higher than it had been any previous day, and that the acidity of the urine was still very high on the day following its discontinuance. Four years later a similar observation was made by Dr W. P. Benekef with regard to the effect of bicarbonate of soda. And lastly, Professor Parkes,J in his work on the ' Urine,' published in 1860, instances a case of rheu- matic fever in which the acidity of the urine on the day following the administration of bicarbonate of potash was considerably higher than on the day before it was taken. It is strange that observations made by authorities so * ' Philosophical Transactions,' 1850, part ii, p. 673. t ' Archiv des Wissenschaftlichen Heilkunde,' 1854. ' Studien zur Urologie,' p. 444. + ' Composition of tne Urine in Health and Disease,' p. 297. Churchill, 1860. 138 APPENDIX eminent and trustworthy, tending to controvert the generally received opinion as to the action of these alkaline bicarbonates as antacids, and establishing the contrary proposition that they increase rather than diminish the acidity of urine, should have attracted so little the attention of writers on therapeutics or urinary pathology in this country or abroad. As the question is of considerable importance with regard to treatment especially of those affections which are caused by the excessive formation of acid within the system, I have thought an account of some obser- vations made by myself on the action of one of these carbonates — the bicarbonate of potash — would be of service, not merely in calling attention to an important therapeutic fact, but also in determining the circum- stances that induce this apparently anomalous action, and in endeavouring to explain the paradox of these alkaline salts increasing instead of diminishing the acid reaction of the urine. The first series of observations were made to test the effect of bicarbonate of potash on the reaction of the urine when taken before meals. The quantity of the salt taken was two drachms in the twenty-four hours — namely, one drachm at 12 p.m. (one hour before dinner) , and one drachm at 8 p.m. (one hour before supper). The physiological conditions of food, rest and work were kept as equal as possible. Observation 1.— Sept. 7th, 8th, 9th, 1876. Quantity. Acidity. Uric acid. Cub. cent. Grm. Gnn. Day before . . . 1730 ... 1-4 ... 0-41 Day, with 2 drs. of bicarbonate . 2080 ... 078 ... 0-66 Day after . . . 1750 ... 23 ... 0-70 APPENDIX 139 Observation 2.— Aug. 10th, 11th, 12th, 1877. Quantity. Acidity. Uric acid Cub. cent. Orm. Grm. Day before . 1442 .. 25 ... 1-05 Day, with 2 dra. of bicarbonate . 1720 .. 1-2 ... 0-75 Day after . 1230 .. 39 ... 17 Observation 3. — May 12th, 13th 14th, 1878. Quantity. Acidity. Uric acid. Cub. cent. Grin. Grm. Day before . 2050 .. 1-9 ... 1-05 Day, with 2 drs. of bicarbonate . 2190 ... 1-2 ... 1-6 Day after . 1650 ... 2-4 ... 13 In order to determine the effect o£ bicarbonate of potash on the hourly variations in the reaction of the urine, when taken before meals, two observations were made. In each instance, for the purpose of comparison, the variations of the acidity of the preceding day, when no bicarbonate was taken, are given. Observation 1. Day preceding experiment — Aug. 10th 1877. Quantity. Acidity. Uric acid Cub. cent. Grm. Grm. Water passed from 12 p.m. to 1 p.m. 58 . . 0-9 .. -04 » „ 1 p.m. to 2 p.m. 55 . . -08 .. -03 i> „ 2 p.m. to 3 p.m. 90 . . -08 .. -06 » 3 p.m. to 4 p.m. 35 .. . -07 . .. -09 »» „ 4 p.m. to 5 p.m. 104 .. . -17 .. -09- Total , . . 342 .. . 0-39 . .. 0-31 140 APPENDIX Day of experiment- -Aug. 11th, 1877. Quantity. Acidity. Uric acid Cub. cent. Grm. Grm. Water passed from 12 a.m. to 1 p. m. 72 .. .Alkaline.. . -05 » j> 1 p.m. to 2 p. m. 45 . , . 33 . -04 »» „ 2 p.m. to 3 p. ,m. 40 .. ,. -05 .. . -08 » 3 p.m. to 4 p, m. 70 . .. -09 .. . -08 >» it 4 p.m. to 5 p. ,m. 90 . .. -09 .. . -07 Total 317 0-23 0-32 Observation 2. Day preceding experiment — Nov. 6th, 1877. Water passed Quantity. Acidity. Uric ac Cub. cent. Grm. Grm. from 12 a.m. to 1 p.m. 34 ... •046 .. •04 „ 1 p.m. to 2 p.m. 43 ... •094 ... . -06 „ 2 p.m. to 3 p.m. 41 .. . -096 .. •03 „ 3 p.m. to 4 p.m. 50 ... , -065 .. , -04 „ 4 p.m. to 5 p.m. 60 .., . -075 ... , -03 Total 228 0-376 0-20 Day of experiment— Nov. 7th, 1877. Quantity. Cub. cent. Water passed from 12 p.m. to 1 p.m. 82 .. „ „ 1 p.m. to 2 p.m. 60 .. „ „ 2 p.m. to 3 p.m. 98 .. „ „ 3 p.m. to 4 p.m. 150 .. „ „ 4 p.m. to 5 p.m. 310 .. Total 700 Acidity. Uric acid Grm Grm. Alkaline ., . -07 *» *- . -06 011 .. . -04 0-13 .. . -05 011 .. . '07 0-35 0-29 It will be gathered from these observations that though the acidity of the urine was depressed on the . days the bicarbonate was taken, yet on the days following there was in each instance a considerable increase as APPENDIX 141 compared with the day preceding the experiment. Be- sides, the actual depression of the acidity on the days when the salt was taken is much less than might he expected, when we consider the neutralising effect such a quantity of an alkaline salt would have, and it is evi- • dent that a considerable quantity of free acid must have been passed into the urine after the immediate effect of the alkali had passed off, in order to have maintained this degree of acidity. How quickly the urine recovers its acidity is shown by the subsequent observations on the hourly variations of the reaction of the urine when the salt was taken before meals ; the reaction in both instances never remaining alkaline more than two hours, whilst the acid passed in the remaining three hours amounts to little less than the acid excreted in the five hours on the day preceding the experiment. It will also be observed that the excretion of uric acid was increased on the days the bicarbonate of potash was taken. A second series of observations were made to test the effect of bicarbonate of potash when taken after meals. The quantity of the salt taken was two drachms in twenty-four hours — viz. one drachm at 2 p.m. (one hour after dinner), and one drachm at 9 p.m. (one hour after supper). The physiological conditions of food, rest, and work were kept as equal as possible. Observation 1.— Feb. 20th, 21st, 22nd, 1877. Quantity. Acidity. Uric acid. Cub. cent. Grm. Grm. Day before . , . 1480 ... 1-6 ... 0'69 Day, with 2 drs. of bicarbonate . 1720 ...Neutral... 076 Dav after . . . 2540 ... 1'5 ... 0"91 142 APPENDIX Observation 2.— May 2nd, 3rd, 4th, 1877. Day before Day, with 2 drs. of bicarbonate Day after Observation 3. — M Day before Day, with 2 drs. of bicarbonate , Day after The effect also of bicarbonate of potash on the hourly variation of the reaction of the urine was determined on two occasions ; and for the purpose of comparison the variations of the acidity of the day preceding, when no bicarbonate was taken, are given. Observation 1. Day preceding experiment — Jan. 25th, 1878. • Quantity. Acidity. Uric acid. Cub. cent. Gim. Grin. 2600 ... 2-4 .. 1-04 1900 ... Neutral .. 0-95 2300 .... 1-3 .. . 1-15 T 21st, 22nd, 23rd. Quantity. Acidity. Uric acid. Cub. cent. Grin. Grin. 1290 ... 1-3 :. i-7 2600 ... Alkaline .. 21 1480 ... 17 .. 1-8 Quantity. Acidity. Uric acid 3ub. cent. Grm. Grm. er passed from 1 p.m. to 2 p.m. 53 . . -06 . . 0-12 » s> 2 p.m. to 3 p.m 55 . . -15 . .. 0-12 J' 33 3 p.m. to 4 p.m 41 . . -11 . .. 011 » » 4 p.m. to 5 p.m 60 . . -04 . .. 0-07 » 33 5 p.m. to 6 p.m 61 . . -02 . .. 0-12 Total 270 . .. -38 . .. 0-54 Daj of experiment — Jan. 26th, 1878. Quantity. Acidity. Uric acid Dub. cent. Grm. Grm. er passed from 1 p.m. to 2 p.m. 47 . . 11 . .. 0-6 » *> 2 p.m. to 3 p.m 83 . . Neutral . .. 06 » » 3 p.m. to 4 p.m 103 . . Alkaline . .. 0-7 .. jj 4 p.m. to 5 p.m 105 . • » ... ' 0-3 ■ ,» w 5 p.m. to 6 p.m. 110 . • >» • .. >-o-7 Total 448 . ..\0-29. APPENDIX 143 Observation 2. Day preceding experiment — Feb. 20th, 1878. Quantity. Acidity. Uric acid. Cub. cent. Grm. Grm. Water passed from 1 p.m. to 2 p.m. 55 . . -11 . . 009 » it 2 p.m. to 3 p.m. 34 . . -02 . . 004 »» » 3 p.m. to 4 p.m. 94 . . Alkaline . . 0-10 »» ii 4 p.m. to 5 p.m. 50 . . '02 . . 0-08 }> M 5 p.m. to 6 p.m 306 . . -08 . . 006 Total 539 . . '23 . . 037 Day of experiment— Feb. 21st, 1878. Quantity. Acidity. Uric acid. , 3ub. cent. Grm. Grm. Water passed fi ran 1 p.m. to 2 p.m 15 . . -08 . . -04 j» « 2 p.m. to 3 p.m 92 . . Alkaline . . -03 w » 3 p.m. to 4 p.m 45 , ■ _. »» . -09 ii » 4 p.m. to 5 p.m 65 . .. )t . . -07 » « 5 p.m. to 6 p.m 105 . . „ . -06 Total 322 . . 0-29 The effect, therefore, of bicarbonate of potash, taken after food, on the acidity of the urine, is different from that when it is administered before meals. For when taken on an empty stomach we have seen that the acidity on the day of administration was only slightly depressed, whilst on the day following the acidity was considerably higher than it was the day before the salt was taken. But when it was administered during the process of digestion the acidity of the urine entirely disappeared, being on two occasions neutral, and on one alkaline, whilst on the succeeding days there was no marked increased in the acidity of the urine, as compared with that of the days preceding the experiment. And the same difference is observable in the hourly variations of 144 APPENDIX the urine, for when the bicarbonate was taken before meals the effects of the alkali passed off at the end of two hours, and the amount of acid passed in the suc- ceeding three hours was nearly equal to what was passed on the day no medicine was taken ; whilst when the salt was taken after meals the urine remained alkaline up to the end of four hours after the dose was taken, and no recovery of acidity was noticeable. The result of these observations tends to establish the fact that the administration of an alkaline bicarbonate on an empty stomach increases the acidity of the system whilst its administration after a meal diminishes it. The explanation as how it happens that these alkaline bicarbonates have such opposite effects will be found given at pages 55 and 56 of the text. INDEX. Acid dyspepsia .... „ excess of, whence it arises „ removal of, by what channels „ secretions, how formed from the alkaline blood Acidity, consequence of excess , „ of gastric j uice „ of urine .... Acids, mineral, how separated from organic . Action of acids within the body „ of alkaline bicarbonatea within the body Ague, a cause of acid vomiting Alcohol in gout .... „ in one gallon of different beverages . Alkaline condition of urine in dyspepsia Ammonium magnesium phosphate in urine Ansmia, increase of phosphoric acid in Beck, Marcus, vomiting in chronic bladder affections Bernard, Claude, section of vagi during digestion Bilious attacks, so-called Bismuth in catarrhal dyspepsia Blood, alkaline reaction of „ effects of diminished alkalinity Burning patches in palms and soles . Cancer, of stomach, vomiting of acid in „ uterine, uric acid deposits often precede Carlsbad salts in intestinal catarrh PAGE 20 1 5 10 17 8 12 7 58 54, 137 25 82 83 48, 117 48 117 134 . 28 21 31 59 2 3 18 26 70 59, 115 10 146 INDEX PAGE Chemical circulation in the body ... 19 Chomel, " la dyspepsie acide grave " . . . 22 Co-efficient of partage ..... 7 Colchicam in gout ... . . .96 Cold compress in flatulent dyspepsia . . .59 Diabetes insipidus ...... 119 „ temporary, may be caused by diminished alkalinity of the blood . . . . .71 „ uric acid deposits in . . . . .70 Diet in flatulent dyspepsia . . . .63 „ in gout ....... 91 „ in oxaluria ...... 115 Diuresis ....... 119 Dysentery, use of charcoal in . . . . .61 Dyspepsia, associated with acid condition of urine . . 20 „ associated with an alkaline condition of urine . 36 Elimination, defective, of alkaline „ excess of phosphoric acid „ „ of urea „ „ of uric acid Ewald, Prof., Lectures on Digestion . in scurvy 4,81 . 118 69, 131 . 69 . 37 Faces, slimy, in intestinal catarrh Fermentation, acid, of mucus . Fermentative changes in stomach and intestines Fothergill, Dr., on unrecognised syphilis Fox, Wilson, Dr., chief points of distinction between acidity from hypersecretion and from fermentative changes Free acidity of claret, porter, port wine and whiskey of urine . Functional derangement of liver ' Garrod, Dr., views on gout » i) on scurvy . Gastric juice, acidity of , Gout, nature of acid in „ relation to rheumatism and scurvy „ theories concerning 59, 115 . 109 . 37 . 73 28 83 15 69 77 80 8 82 80 77 INDEX. 147 PAGE Harley, George, Dr., increased elimination of phosphoric acid after injury to head .... Hydrochloric acid, action of, within the body Intestinal catarrh ..... „ „ a cause of oxaluria . Ipecacuanha in vomiting of pregnancy Leucin and its relation to formation of urea . Lithajmia ...... „ distinct from oxaluria Malaria, cause of acid vomiting Megrim, reaction of urine in . Mineral acids, action of, within the body Nervous influence regulating the discharge of acid . Nitric acid, action of, within the body Nitrogenous, disturbance of, equilibrium of . Noises in ears ...... Nutrition, disturbance of, a cause of uric acid deposits Opium in chronic gout .... Oxalate of lime, directly from the food from excess of acid in system from increased tissue metabolism from mucus .... indirectly from the food „ pathology of ... Oxaluria, true application of term Oxidation, complete not imperfect, required to reduce uric acid to oxalic acid .... 133 58 46 110 34 67 69 111 25 30 58 19 58 69 18 75 97 105 110 107 108 107 101 111 103 Paget, Sir James, on unrecognised syphilis . . 73 Palpitation of the heart . . . . .18 Parkes, Professor, on elimination of uric acid . . 67 „ „ on increase of acidity of urine after admin- istration of acid carbonates . 17, 136 Phosphates deposited .... . 117 „ in disease ...... 132 ,, in excess . . . . . . 1 ly 148 INDEX PAOE Phosphoric acid, action in causing diabetes . . .71 Poore, Dr., vital changes produced by electricity . . 12 Potash bicarbonate, effect on acidity of urine . . 137 „ salts in scurvy . . . . .80 Renal calculi, acid vomiting in . . . .28 Rheumatism, relation to gout and scurvy . . 80, 85 Rickets, elimination of phosphoric acid in . . 134 Ringer, Dr., use of glycerine in fermentative dyspepsia . 59 Rutherford, Professor, a section of vagi nerves during diges- tion ....... 21 Sanderson, Burdon, Dr., electrical disturbance in plants . 12 Scrofula as a cause of uric acid deposits . . .73- Scurvy, as a cause of uric acid deposits . . .71 „ pathology of . . . . 3, 80, 85 Sugar in claret, porter, port- wine, and whisky . . 83 „ effect of in gout . . . . ,84 Syphilis as a cause of nric acid deposits . . .74 Urea, increased elimination of 69, 131 Uric acid, circumstances attending its deposit . . 75 „ „ „ its excessive elimination . 76 „ views regarding its origin . . . .66 Urine, alterations in its reaction after food . . .15 „ in acid dyspepsia ... 30 „ in flatulent dyspepsia . . . . .47 PRINTED BY J. £. 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Travis "Whittakee, M.D., Clinical Demonstrator at the Eoyal Infirmary, Glasgow. With Illustrations, and 16 Plates etched on Copper. Post 8vo, 4s. 6d. MIDWIFERY. BARNES. — Lectures on Obstetric Operations, including the Treatment of Haemorrhage, and forming a Guide to the Management of Difficult Labour. By Robert Barnes, M.D,, F.B.C.P., Obstetric Physician to, and Lecturer on Diseases of "Women, &c, at St. George's Hospital. Third Edition. With 124 Engravings. 8vo, 18s. CLAY.— The Complete Handbook of Obstetric Surgery; or, Short Rules of Practice in every Emergency, from the Simplest to the most formidable Operations connected with the Science of Obstetricy. By Charles Clay, M.D., late Senior Surgeon to, and Lecturer on Midwifery at, St. Mary's Hospital, Manchester. Third Edition. With 91 Engravings. Ecap. 8vo, 6s. 6d. RAMSBOTHAM.— The Principles and Practice of Obstetric Medicine and Surgery. By Francis H. Ramsbotham, M.D., formerly Obstetric Physician to the London Hospital. Fifth Edition. With 120 Plates, forming one thick handsome volume. 8vo, 22s. REYNOLDS.— Notes on Midwifery: specially designed to assist the Student in preparing for Examination. By J. J. Reynolds, M.E.C.S. Ecap. 8vo, 4s. ROBERTS.— The Student's Guide to the Practice of Midwifery. By D. Lloyd Roberts, M.D., F.R.C.P., Physician to St. Mary's Hospital, Manchester. Second Edition. With 111 Engrav- ings. Fcap. 8vo, 7s. SGHROEDER.—A Manual of Midwifery ; includ- ing the Pathology of Pregnancy and the Puerperal State. By Karl Schboeder, M.D. , Prof essor of Midwifery in the University of Erlangen. Translated by Charles H. Carter, M.D. With Engravings. 8vo, 12s. yd. NEW BURLINQTON STREET. J. § A. Churchill's Medical Class Books. MIDWIFERY — continued. SWAYNE.— Obstetric Aphorisms for the Use of Students commencing Midwifery Practice. By Joseph G. Swayke, M.D., Lecturer on Midwifery at the Bristol School of Medicine. Seventh Edition. With Engravings. Fcap. 8vo, 3s. 6d. • MICROSCOPY. CARPENTER.— The Microscope and its Revela- tions. By William B. Caepehtee, C.B., M.D., F.K.S. Sixth Edition. With 26 Hates, a Coloured Frontispiece, and more than 500 Engravings. Crown 8vo, 16s. MARSH. — Microscopical Section-Cutting : a Practical Guide to the Preparation and Mounting of Sections for the Microscope, special prominence heing given to the subject of Animal Sections. By Dr. Sylvesteb Maesh. Second Edition. With 17 Engravings, reap. 8vo, 3s. 6d. MARTIN.— A Manual of Microscopic Mounting. By Johs H. Maktin, Member of the Society of Public Analysts, &c. Second Edition. With several Plates and 144 Engravings. 8vo, 7a. 6d. OPHTHALMOLOGY. DAGUENET.—A Manual of Ophthalmoscopy for the Use of Students. By Dr. Daguenet. Translated by C. S. Jeaffeeson, Surgeon to the Newcastle-on-Tyne Eye Infirmary. With Engravings. Ecap. 8vo, 5s. HIOGENS.— Hints on Ophthalmic Out-Patient Practice. By Charles Higgens, F.R.C.S., Ophthalmic Assistant-Sur- geon to, and Lecturer on Ophthalmology at, Guy's Hospital. Second Edition. Ecap. 8vo, 3s. JONES. — A Manual of the Principles and Practice of Ophthalmic Medicine and Surgery. By T. Whaeton Jokes, F.K.C.S.,E.B.S.,late Ophthalmic Surgeon and Professor of Ophthalmo- logy to University College Hospital. Third Edition. With 9 Coloured Plates and 173 Engravings. Fcap. 8vo, 12s. 6d. NEW BURLINGTON STREET. J. 8f A. Churchill's Medical Class Books. OPHTHALMOLOGY — continued. MACNAMARA.—K Manual of the Diseases of the Bye. By Charles Macnamara, F.R.C.S., Surgeon to "Westminster Hospital. Third Edition. With 7 Coloured Plates and 62 Engravings. Feap. 8vo, 12s. 6d. NETTLESHIP.— The Student's Guide to Diseases of the Eye. By Edward Nettleship, F.R.C.8., Ophthalmic Surgeon to, and Lecturer on Ophthalmic Surgery at, St. Thomas's Hospital. Second Edition. With Engravings. Fcap. 8vo. [In the Press. WOLFE. — On Diseases and Injuries of the Eye : a Course of Systematic and Clinical Lectures to Students and Medical Practitioners. By J. R. Wolfe, M.D., F.K.C.S.E., Senior Surgeon to the Glasgow Ophthalmic Institution, Lecturer on Ophthalmic Medicine and Surgery in Anderson's College. With 10 Coloured Plates, and 120 Wood Engravings, 8vo. PATHOLOGY. JONES AND SIEVEKING.—A Manual of Patho- logical Anatomy. By C. Handeield Jokes, M.B., F.R.S., and Edward H. Sievekinq, M.D., F.R.C.P. Second Edition. Edited, with consider- able enlargement, by J. F. Payne, M.B., Assistant-Physician and Lecturer on General Pathology at St. Thomas's Hospital. With 195 Engravings. Crown 8vo, 16s. LANCEREAUX.— Atlas of Pathological Ana- tomy. By Dr. Lancereaux. Translated by W. S. Greenfield, M.D., Professor of Pathology in the University of Edinburgh. With 70 Coloured Plates. Imperial 8vo. £5 6s. VIRGHOW. — Post-Mortem Examinations : a Description and Explanation of the Method of Performing them, with especial reference to Medico-Legal Practice. By Professor Rudolph Virchow, Berlin Charite Hospital. Translated by Dr. T. B. Smith. Second Edition, with 4 Plates. Fcap. 8vo, Ss. 6d. WILKS AND MOXON— Lectures on Pathologi- cal Anatomy. By Samuel Wilks, M.D., F.R.8., Physician to, and Lecturer on Medicine at, Guy's Hospital ; and Walter Moxon, M.D. , F.R.C.P., Physician to, and Lecturer on Clinical Medicine at, Guy's Hospital. Second Edition. With 7 Steel Plates. 8vo, 18s. NEW BURLINGTON STREET. J. 8f A. Churchill's Medical Class Books. PSYCHOLOGY. BUCKNILL AND TUKK—A Manual of Psycho- logical Medicine : containing- the Lunacy Laws, Nosology, iEtiology r Statistics, Description, Diagnosis, Pathology, and Treatment of Insanity, with an Appendix of Cases. By John C. Bucknill, M.D., F.R.8., and D. HackTukb, M.D., F.R.C.P. Fourth Edition, with 12 Platea (30 Figures). 8vo, 26s. PHYSIOLOGY. CARPENTER. — Principles of Human Physio- logy. By William B. Carpenter, C.B., M.D., F.E.8. Ninth Edition. Edited by Henry Power, M.B., F.R.C.S. "With 3 Steel Plates and 377 Wood Engravings. 8vo, 31s. 6d. DALTON. — A Treatise on Human Physiology : designed for the use of Students and Practitioners of Medicine. By John C. Dalton, M.D., Professor of Physiology and Hygiene in the College of Physicians and Surgeons, New York. Sixth Edition. With 316 Engravings. Royal 8vo, 20s. FREY. — The Histology and Histo-Chemistry of Man. A Treatise on the Elements of Composition and Structure of the Human Body. By Heinsich Frey, Professor of Medicine in Zurich. Translated by Arthur E. Barker, Assistant-Surgeon to the Uni- versity College Hospital. With 608 Engavings. 8vo, 21s. RUTHERFORD. — Outlines of Practical Histo- logy. By William Rutherford, M.D., F.R.S., Professor of the Insti- tutes of Medicine in the University of Edinburgh ; Examiner in Physiology in the University of London. Third Edition. With Engravings. Crown 8vo (with additional leaves for Notes). [In preparation. SANDERSON. — Handbook for the Physiological Laboratory : containing an Exposition of the fundamental facts of the Science, with explicit Directions for their demonstration. By J. Burdon Sandebsok, M.D., F.R.S., Jodrell Professor of Physiology in University College; E. Klein, M.D., F.E.S., Assistant-Professor in the Brown Institution; Michael Fostee, M.D., F.R.S., Prselector of Physiology at Trinity College, Cambridge ; and T. Lauder Bruntow, M.D., F.E.S., Lecturer on Materia Medica at St. Bartholomew's Hospital Medical College. 2 Vols., with 123 Plates. 8vo, 24s. NEW BURLINGTON STREET. J. 8f A. Churchill's Medical Class Books. STTBGEBY. BRYANT. — A Manual for the Practice of Surgery. By Thomas Bryant, F.R.C.S., Surgeon to, and Lecturer on Surgery at, Guy's Hospital. Third Edition. With 672 Engravings (nearly all original, many being coloured). 2 vols. Crown 8vo, 28s. BELLAMY.— The. Student's Guide to Surgical Anatomy ; a Description of the more important Surgical Regions of the Human Body, and an Introduction to Operative Surgery. By Edward Bellamy, E.R.C.S., and Member of the Board of Examiners ; Surgeon to, and Lecturer on Anatomy at, Charing Cross Hospital. Second Edition. "With 76 Engravings. Fcap. 8vo, 7s. CLARK AND JVAGSTAFFE. — Outlines of Surgery and Surgical Pathology. By F. Le Gbos Clabk, F.R.C.S., F.R.S., Consulting Surgeon to St. Thomas's Hospital. Second Edition. Revised and expanded by the Author, assisted by W. W. Wagstaffe, F.R.C.S., Assistant-Surgeon to St. Thomas's Hospital. 8vo, 10s. 6d. DRU1TT.— The Surgeon's Vade-Mecum ; a Manual of Modern Surgery. By Robert Druitt, F.R.C.S. Eleventh Edition. With 369 Engravings. Fcap. 8vo, 14s. FERGUSSON.—A System of Practical Surgery. By Sir William Feegussox, Bart., F.R.C.S., F.R.S., late Surgeon and Professor of Clinical Surgery to King's College Hospital. With 463 Engravings. Fifth Edition. 8vo, 21s. HEATH.— A Manual of Minor Surgery and Bandaging, for the use of House-Surgeons, Dressers, and Junior Practi- tioners. ByCHBisTOPHEE Heath, F.R.C.S., Holme Professor of Clinical Surgery in University College and Surgeon to the Hospital. Sixth Edition. With 115 Engravings. Fcap. 8vo. 6s. 6d. By the same Author. A Course of Operative Surgery : with Twenty Plates drawn from Nature by M. Leveille, and Coloured by hand under his direction. Large 8vo, 40s. ALSO, The Student's Guide to Surgical Diag- nosis. Fcap. 8vo, 6s. 6d. NEW BURLINGTON STREET. J. 8f A. Churchill's Medical Class Books. SURGERY— continued. MAUNDER— Operative Surgery. By Charles F. Maunder, F.R.C.S., late Surgeon to, and Lecturer on Surgery at, the London Hospital. Second Edition. "With. 164 Engravings. Post 8vo, 6s. PIRRIE — The Principles and Practice of Surgery. By William Pieeie, F.R.S.E., Professor of Surgery in the University of Aberdeen. Third Edition. With 490 Engravings. 8vo, 28s. TERMINOLOGY. DUNGLISON. — Medical Lexicon: a Dictionary of Medical Science, containing a concise Explanation of its various Subjects and Terms, with Accentuation, Etymology, Synonymes, &c. By KoBLEr Dunglison, M.D. New Edition, thoroughly revised by Richard J. Dunglison, M.D. Royal 8vo, 28s. MAYNE. — A Medical Vocabulary: being an Explanation of all Terms and Phrases used in the various Depart- ments of Medical Science and Practice, giving their Derivation, Meaning, Application, and Pronunciation. By Robeht G. Matne, M.D., LL.D., and John Matne, M.D., L.R.C.S.E. Fifth Edition,. Fcap. 8vo, 10s. 6d. WOMEN, DISEASES OP. BARNES.— A Clinical History of the Medical and Surgical Diseases of Women. By Robert Barnes, M.D., F.R.C.P., Obstetric Physician to, and Lecturer on Diseases of Women, &c, at, St. George's Hospital. Second Edition. With 181 Engravings. 8vo, 28s. DUNCAN— Clinical Lectures on the Diseases of Women. By J. Matthews Duncan, M.D., Obstetric Physician to St. Bartholomew's Hospital. 8vo, 8s. EMMET. — The Principles and Practice of Gynaecology. By Thomas Addis Emmet, M.D., Surgeon to the Woman's Hospital of the State of New York. With 130 Engravings. Royal 8vo, 24s. NEW BURLINGTON STREET. J. 8f A. Churchill's Medical < ass Books. WOMEN", DISEASES OP — continued. QALABIN— The Student's Guide to the Dis- eases of Women. By Alfred L. Galabin, M.D., F.R.C.P., Assistant Obstetric Physician and Joint Lecturer on Obstetric Medicine at Guy's- Hospital. Second Edition; With. 70 Engravings. Fcap. 8vo, 7s. 6d. REYNOLDS. — Notes on Diseases of Women. Specially designed for Students preparing for Examination. By J. J. Reynolds, M.R.C.S. Fcap. 8vo, 2s. 6d. SMITH. — Practical Gynaecology : a Handbook of the Diseases of Women. By Hetwood Smith, M.D., Physician to- the Hospital for Women and to the British Lying-in Hospital. With Engravings. Second Edition. Crown 8vo. [In preparation. WEST AND DUNCAN.— Lectures on the Dis- eases of "Women. By Charles West, M.D., F.R.C.P. Fourth Edition. Revised and in part re-written by the Author, with numerous additions, by J. Matthews Duncan, M..D., Obstetric Physician to St. Bartholomew's Hospital. 8vo, 16s. ZOOLOGY. GHAUVEAU AND FLEMING.— The Compara- tive Anatomy of the Domesticated Animals. By A. Chauveatj,. Professor at the Lyons Veterinary School ; and George Fleming, Veterinary Surgeon, Royal Engineers. With 450 Engravings. 8vo, 31s. 6d. HUXLEY.— Manual of the Anatomy of Inverte- brated Animals. By Thomas H. Huxley, LL.D., F.E.S. With 166- Engravings. Fcap. 8vo, 16s. By the same A ulhor. Manual of the Anatomy of Vertebrated Animals. With 110 Engravings. Post 8vo, 12s. WILSON— The Student's Guide to Zoology: a Manual of the Principles of Zoological Science. By Andrew Wilson,. Lecturer on Natural History, Edinburgh. With Engravings. Fcap. 8vo, 6s. 6d. NEW BURLINGTON STREET. 16