Postgrad Med J: first published as 10.1136/pgmj.4.38.19 on 1 November 1928. Downloaded from

THE P T5T GIAD UFITED; D0 0 S1MjEDICAL jou1

VOL. IV. NOVEMBER, 1928. No. 38.

CONTENTS PAGE

ALBUAMINURIA AND ...... 19 By ADOLPHE ABRAHAMS, M.D. A POST-GRADUATE CLINICAL AND PATHOLOGICAL DEMONSTRATION . ... 23 By ZACHARY COPE, M.D., M.S.Lond., F.R.C.S.Eng.

AMENTIA IN RELATION TO CEREBRAL DISEASE AND ABNORMALITY ...... 29 copyright. By E. W. NEILL HOBHOUSE, M.D., M.R.C.P.

CORRESPONDENCE ...... 34

POST-GRADUATE NEWS ...... 34 FELLOWSHIP OF MEDICINE AND POST-GRADUATE MEDICAL ASSOCIATION.-

SPECIAL COURSES ...... ;jj http://pmj.bmj.com/

ALBUMINURIA AND the condition from wlhich the patienlt is sufferinlg or the complaint he advances; and GLYCOSURIA. although I make nlo pretence to advance any A lOST-GRADUATE LECTURE DELIVERED AT WESThIINSTER new information, and can only claim the HOSPITAL, SEPTEMBER 18, 1928. attempt to provide a convenient summary, on September 26, 2021 by guest. Protected Dy ADOLPHE ABRAHAMS, there is no need to apologize for the elemen- MI.D., tary char-acter of my subject. This is logi- Physiciani to Out-Patients, Westminster Hospital; cally considered under two heads: the Physician to Hampstead General Hospital. identification of albumin or sugar in the ; and secondly, the significance, of their THERE cannot be one practitioner who at presence. some period or other of his caireer has not ALBUMINURIA means thie passage into the found reason to regret the omission to per- urine of protein that is coagulable on boiling. form the elementary tests for albumin and The pr-otein substanices that may be en- sugar in the urine ; and he is fortunate countered ar-e serum proteins - serumn indeed if the omission occurs on a relatively albumin and globulin; compound proteins, unimportant occasion. This examination is nucleo-albumin and mucinis; and proteo- in fact a fundamental precaution, whatever lytic products-albumoses. Postgrad Med J: first published as 10.1136/pgmj.4.38.19 on 1 November 1928. Downloaded from

20 ALBUMINURIA AND GLYCOSURIA The familiar tests which have successfully 2. The actual loss to the body is therefore withstood the attempted introduction of of little importance and is easily replaced. others, perhaps more delicate and less equi- It is the significance which is of conse- vQcal, are the application of heat and the quence. It may at once be said that the addition of nitric acid, or, as they are presence of albumin is not necessarily patho- popularly termed, the coagulation and the logical, still less is it an indication of nitric acid tests. A urine with turbidity due diseased kidneys. It is convenient to speak to urates becomes clear on being heated; a of pathological and non-pathological albu- cloudy precipitate which may subsequently minuria; the latter may conveniently, if form will be due to earthy phosphates or to perhaps unscientifically, be called physio- coagulated albumin. The former is at once logical. dissolved by a few drops of acetic acid, the Pathological albuminuria occurs in latter becomes denser. It is well to add a nephritis, in other diseases of the , few drops of acetic acid to the urine before e.g., tuberculosis and new growth, in sup- boiling to ensure sufficient acidity. This purative conditions of the lower urinary precaution is in itself a test, as a precipitate tract-cystitis, urethritis; in haemorrhage which forms with acetic acid in the cold, as from any part of the urinary tract; in damage it is termed, is identified as nucleo-protein, to the renal epithelium by toxins, exogenous which may be mistaken for albumin, but is or autogenotls; this category will naturally of no pathological significance. A final include a very large number of conditions, precaution is to recognize an unusual e.g., alcoholism, burns, , gout, lead, copyright. phenomenon, a precipitate which appears at mercury and arsenic poisoning, syphilis, a comparatively low temperature and dis- foetal products in pregnancy. Albuminuria appears on further heating. This is the occurs in many of the acute specific fevers, Bence Jones albumose, wliich is an accom- particularly scarlet, diphtheria, variola, ery- paniment of multiple myelomata, and is also sipelas, also in pneumonia and typhoid, found in some cases of leukaemia. It may less so in influenza and measles. In certain be said that the average onset of coagulation nervous disorders, apoplexy and convulsions; http://pmj.bmj.com/ of albumin is 75° C.; the Bence Jones in circulatory disturbances, whether due to body begins to precipitate out at 5° C., heart or lung disease, or to pressure on or at 58° C. it is well developed, at 70° C. obstruction of the inferior vena cava; ascites, clearing has already begun, and on boiling ovarian tutlours or cysts may be mentioned the liquid sliould again be nearly if not in this category. It is clear that a variety quite clear. It is a rare phenomenon, but it of causes be for the

may responsible on September 26, 2021 by guest. Protected is peculiarly striking. I once identified it albuminuria of pregnancy, pressure of the in a routine examination of a medical man, uterus on veins, excessive strain on the who believed himself to be in perfect health placental circulation, the direct action of and in whom three months later symptoms foetal products on the kidneys, not to first appeared. mention the possibility of contamination of The nitric acid test is, in my opinion, less the urine by small haemorrhages or vaginal convenient. An excess of urates may be discharges. precipitated, and so may nucleo-protein. It will be evident that the significance of There are also other fallacies, e.g., precipita- albuminuria in any one of these numerous tion of copaiba resin, if the patient is taking conditions will depend upon the recogni- this drug, and urea itself may be precipitated tion of a cause which is primarily as the nitrate. responsible. In some instances a clinical As regards genuine albuminuria, the per- examination suffices, in others a micro- cntage is usually below I and rarely exceeds scopical examination revealing the presence Postgrad Med J: first published as 10.1136/pgmj.4.38.19 on 1 November 1928. Downloaded from

ALBUMINURIA AND GLYCOSURIA 21 of casts, blood-cells, pus, organisms, will is to recognize the innocence of the condi- indicate the line along which further in- tion, and not to restrict the subject's activities vestigation should extend. It is impossible or in any way to prejudice him. This cir- to consider such a vast subject even super- cumstance acquires particular importance in ficially, nor for the present purpose is it relation to exercise. The albumin which so necessary. commonly results after exertion is now re- To turn now to the condition regarded as garded as negligible. It is found to be invari- non-pathological albuminuria. Some idea of able in oarsmen and in boys after any form of its uncertain .etiology is afforded by the exercise; in my experience it is less common extensive terminology attached to it-physio- in adults who indulge in track athletics. logical, adolescent, intermittent, remittent, As casts and blood are sometimes found cyclical, postural, functional, alimentary, the with albumin, it is, perhaps, going too far albuminuria of exercise. to include these circumstances as functional In many instances there is a high per- only, but any nephritis which results would centage of globulin or eiglobulin, and pre- appear to be of the most trivial character. cipitation by acetic acid in the cold may be There appears to be no evidence that a so- produced. In some instances the albumin called alimentary albuininuria ever occurs may be detected only at certain lhours of as a leakage when an excess of protein, e.g., the day, being usually absent during re- eggs, has been taken. the active hours cumbency, to appear during GLYCOSURIA. of the day. It is associated therefore with copyright. the erect attitude and also with exercise. In That glycosuria is not diabetes is nowa- some cases there is also a paroxysmal hamo- days an elementary truism. Our eminent globinuria. In some cases the albuminuria predecessors, notwithstanding the lack of is induced by a cold bath or even a surface assistance from blood-sugar estimations, chill. All kinds of explanations are forth- which are a comparatively recent introduc- coming. That posture has a distinct effect tion, realized the existence of several condi-

is indubitable, and it appears that lordosis tions in which glycosuria was a transitory and http://pmj.bmj.com/ of the spine is of consequence, as this exerts trivial phenomenon, and even of conditions its influence when the subject is erect. The in which sugar was excreted in compara- left renal vein is then compressed between tively large quantities, yet without the usual the spine and the aorta, and it has been pathological accompaniments of diabetes shown on occasion that such albuminuria mellitus. To the latter the term diabetes be derived from the left innocens was sometimes applied, a term

may kidney on September 26, 2021 by guest. Protected only. Such a mechanical effect may be which has now been replaced by "renal partly responsible for the albuminuria of glycosuria," as removing any suggestion of pregnancy. a real diabetic condition and introducing a But even if posture and corresponding renal possibility, a consideration to which I circulatory disturbance play a more or less shall shortly return. indispensable part in the production of Dextrose (or glucose) is the important albuminuria, there must be an appropriate carbohydrate excreted. Its identification as condition of the blood plasma. Tlie subject a substance which reduces Fehling's solu- usually displays many manifestations of tion permits confusion with other reducing vaso-motor instability, and the albuminuria 'substances which may also be found in may often be checked by the administration urine, some of which are carbohydrates, such of calcium lactate. Certainly it may be as lactose, laevulose, maltose, and pentose. checked by no other means short of per- Lactose may be found in the urine of preg- petual recumbency, and the cliief importanlce nant or puerperal women, laevulose and Postgrad Med J: first published as 10.1136/pgmj.4.38.19 on 1 November 1928. Downloaded from

22 ALBUMINURIA AND GLYCOSURIA maltose as rare metabolic disturbances, from an abnormality present only at certain and pentose still more rare. Another sub- times of the day. stance which reduces Fehling-'s solution is If Fehling's solution is used, the two glycuronic acid, which may result from the solutions should be kept separately and administration of large doses of chloral mixed only at the time of testing, as the hydrate. In addition, an imperfectly per- mixed solution tehds to become self- formed test may result in reduction from reducing. At the time of performing the the presence of uric, hippuric, homogentisic test, equal parts are mixed and boiled, an and salicylic acids, of .creatin, creatinin, equal quantity of urine is separately boiled xanthin, and other bodies of this composi- and added, and preferably a few drops at a tion. So far as the identification of glucose time to gain some impression of the quantity is concerned, the result of fermentation with of sugar present. Prolonged boiling with yeast will exclude lactose and pentose, a rare Fehling's solution of a urine containing uric product which may occur after the ingestion acid or creatinin may lead to reduction which of certain fruits rich in arabinose, cllerries, will not occur if the reagent and the urine plums, and pears, and also spontaneously are separately boiled and then mixed. as a metabolic freak, particularly in Jews. Benedict's solution requires exactness in use. Fermentation will also exclude the large Five c.c. of the reagent must be measured, variety of non-carbohydrate substances and eight to ten drops of urine added. The above enumerated. If any doubt still re- mixture is boiled for two minutes. A green, mains as to whether glucose or some other yellow or red precipitate forms, according copyright. sugar is present, subsidiary tests may be to the quantity of sugar present. An employed, rotation of the plane of polarized important advantage is that the other sub- light, or production of appropriate osazone stances which reduce Fehling's solution give crystals. But this is really within the realm a negative result with Benedict's. of the laboratory worker and not of the Fermentation by yeast has already been clinician. As a general reduction of Fehling's mentioned as a confirmatory test of the or Benedict's solution means glycosuria, it presence of sugar. It also affords a method http://pmj.bmj.com/ will be well to spend a few moments dis- of estimating the quantity. The rationale cussing the perfomance of these tests. of the test is that owing to decomposition of First of all, it should be remembered that the sugar the specific gravity falls; every glucose is present normally in urine in degree of specific gravity lost represents one perhaps o'oi per cent., that Fehling's test grain of sugar per ounce. will detect and Benedict's the existence of 0'02 per cent., Now, admitting glyco- on September 26, 2021 by guest. Protected considerably less. The delicacy of the last- suria, let us turn to the circumstances in named is indeed an objection to its clinical which it occurs. In the majority of subjects application, although it is immune to falla- sugar appears in the urine as soon as the cies. As a rule, a urine containing an blood-sugar exceeds about o'I7 per cent., appreciable quantity of sugar has a specific and if an opportunity is afforded to estimate gravity above I025, but discovery of a lower the percentage of sugar in the blood, the specific gravity must not be interpreted as comparative, importance of glycosuria be- evidence that glycosuria is absent. It has comes known. For, on the one hand, we been shown that i per cent. glucose may be may find in an establistied diabetic that the present in a urine of specific gravity 1007, blood-sugar is substantially above o'I7 per and even I003. Another practical con- cent., and yet sugar does not appear in the sideration is the advantage of employing a urine, so that a dangerous degree of hyper- twenty-four hours' specimen for examina- glycemia may be overlooked because tion, since an isolated specimen may be free glycosuria is not present. On the other Postgrad Med J: first published as 10.1136/pgmj.4.38.19 on 1 November 1928. Downloaded from

A POST-GRADUATE CLINICAL AND PATHOLOGICAL DEMONSTRATION 23 hand, the opposite condition may be en- which, although it cannot in itself intrinsi- couiitered when glycosuria occurs, although cally produce coma, is an essenitial factor. the blood-sugar never rises even to the It is not strictly true to say that one tests normal maximum, O-I7 per cent. In this for ,8-oxybutyric acid, for direct identification case some peculiar condition of the kidnieys of this acid is very difficult. But since it is appears to be presenit, and the term leaky always accompanied by diacetic acid, the kidneys or renal glycosuria is employed. test for the latter by the simple addition of In the days which preceded blood-sugar ferric perchloride is sufficient. The only examinations, such cases wvere regarded as fallacy in this test is the close similarity diabetes and treated quite unnecessarily by afforded by a urine containing the decom- restriction or deprivation of carbohydrate. position produicts of salicvlic acid, which Their innocence was identified clinically by will be present if one of the coal-tar products astute obsersvers, who expressed their opinion has been administered. The colour is rather by employing the term diabetes innocens. different, but sufficiently like for confusion It may be added that a combination of if the possibility is forgotten. Naturally, diabetes with renial glycosuria mav occur prolonged boiling in the case of diacetic but rarely. acid, which is volatile, destroys the colour The occurrence of glycosuria in cerebral which persists in the other instance. tumours, epilepsy and nervous disturbances genierally is very familiar. Such cases are the clinical representatives of glycosuria A copyright. i-esulting from puncture of the floor of the fourth ventricle; the action is upon the POSr-GRADUATE CLINICAL sympathetic nervous system through the AND PATHOLOGICAL adrenals, anid explains the temporary glyco- suria whichi may result from excitement DEMONS'TRATION. and other emotional disturbances. Given at St.. Mary's Hospital, October 7, 1928.

Intermittent glycosuria is not infrequent By ZACHARY COPE. http://pmj.bmj.com/ in gouty subjects, and especially those .M.D., M.S.LOND., F.R.C.S.ENG. addicted to alcoholic excess. It is some- times (though not often) present in Graves' LADIES AND GENTI.EMEN,-I have en- disease, presumably from antagonism of the deavoured to bring together a series of thyroid and pancreas. For a similar reason cases and specimens as instructive as they glycosuria may occur in acromegaly. are rare and interesting. All the patients The association with boils and sepsis is before you have been operated upon, and on September 26, 2021 by guest. Protected familiar. In children glycosuria sometimes some hiave only been asked to come in order- occurs shortly after an attack of pertussis. that you may be assured of their present Apart fr-om the question of blood-sugar condition. From each case I hope we shall estimations, glycosuria acquires special im- be able to draw one or more cliniical lessons portance when associated with the presence which may prove of value in future practice. of acetone, 8-oxvbutyric and diacetic acids The first patient is a man aged 57, whom in the urine, and particuilarly the last two, 1 first saw five years ago on accoutit of a since acetonie may occur in the urine in a large hard swelling in the posterior part of large num-ber of relatively ininocent condi- the left frontal region of theskull. It was tioIns. In diabetes the percentage of sugar hard, painless and appeared one with the bears no relation to the amount of diacetic bony skull. It had been first noticed between acid excr-eted, but the presence of sugar ten and fifteen years previously, and epileptic enicouirages the test for- 8-oxybutyric aicid fits liad begunii ten yearls before I saw him,