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L E C T U E S ROBERT SAUNDBY Ml ) EDIN F ELI 0\V O F THE ROY A L C O LLE GE O F ' PHYSICI ANS LON DON ; E ME RI TUS SE NIOR PRESI DE N T O F THE ROYA L ME DI CAL SOCIETY ; F F LLO \V O F THE ROYAL ME DICO -CHI RURGICA L SO CIETY ; M EM BE R O F THE P AT II O LO GIC A L S OCIE TY O F LON DON ; PHYSICIA N T O THE G E N ER A L H OSPI TA L ; CONS ULTI N G PHYSICIAN T O T H E EY I I HOSPITAL ; A N D CONSULTI N G PHYSICI A N TO THE HOSPITA L FO R DISE ASES O F \VOM EN B I RMI NG IIA H IVI TH FI F T Y ILL US TB A TI ON S 514733 I 1 5 0 L ON DON : HAM ILTON A DAM S CO B R I STO L : JOHN \VR IGH T C O PATER N O STER R OW 1889

JOH N W RI GH T A N D co P RI N TERS A N D P UBLISHER S B R IST O I

P R E F A C E IN p r es entin g t hi s work for the i ndul g ent con sideration of m y p rof essional r eade rs I wo uld disclaim all p r et en sion t o have said the last word on the man y v exed q u esti ons with which i ts sub j ec t m att er i s encu mbered I h av e endeav o u red t o ex p l ain within a modest com p ass the p r esent state of cont em p o rar y knowled g e makin g su ch additions and su gg es tions as hav e resulted from thirteen y e ars cli ni cal and p atholo g i cal stud y of B ri g ht s Di sease Some of th e mat erial for this book h as be en p revio u sl y p ubli sh ed but ever y cha p ter has been re - written ev er y p oint h as been thou g h t out a g a in and I n e ed offer n o a p olo g y f or su ch alteratio n s of o p i nion as ma y b e p erce p tib le i n th ese p a g e s Exce p t wher e th e sour ce i s ackn owl ed g ed all th e fi g ures have been drawn b y m y self from p re p a ration s in m y p o s session I desire to e x p r ess

vi PR EFA C E m y i ndebtedness t o Dr G F C R O O K E Patholo g ist t o th e Gen eral Ho s p ita l for m an y be autiful micro sco p i cal p re p a rations ; to Dr M ACMUN N and Mr EA L ES fo r kindl y o v erlookin g p o r tions of the p r o of - she ets ; t o th e p ub lish ers of LA N D O IS and ST IR LI N G S Ph y siolo gy for p er mission t o u se ce rtain illustrations of the An ato m y of the Kidne y ; and t o all p r ecedi n g writers on Uri nar y Disease amon g wh om I desire t o m entio n SIR W I L LI A M R OB ERTS who se wo rk o n Urin ar y a nd R enal Diseases must remain for all time a n ever failin g sou r ce of sound clini cal informatio n BIRMIN GH AM Februar y 1 889

Secti on I G ENERAL PA THOL OGY Secti on [L C LINICAL EXAMINA TION OF THE URINE C O NT E N T S CHAP I ALBUMINURIA 11 T HE PATHOLO GY OF DROPSY 111 PATHOL OGICAL R ELATIONS OF TUBE CASTS Iv CARDIO -VASCULAR C HAN GES v PATHOLO GY OF POLYURIA v1 PATHOLOGY OF URZEM IA VII RETINAL CHANGES VIII THE URINE IN HEALTH AND DISEASE 9 7 14 6 Secti on I I I B RIGH T S DI SEA SE IX HISTORY CLASSIFICATION ETIOLO GY GENERAL ANATOMY OF T HE KIDNEY XI FEBRILE NEPHRITIS XII LI THZEM I C NEPHRITIS XIII OBSTRUCTIVE NEPHRITIS XIV C OMPLICATIONS OF CHRONIC BRIGHT S DISEASE XV TREATMENT OF LI THZEM I C NEPHRITIS GENERAL INDEX 283 2 90

L E C TUR E S ON B R I GH T S D I SE A SE SECTI O N I GEN ERAL PATHOLOGY ALBUMINURIA Y ALBUMINURIA we mean the presence in the urine of an albumin ous b ody which is c oagulated by heat o r precipitated by neutralisation Serum albumen is the substance ordinarily found in albumin ous urine It is s oluble in water c oagulable by heat at from 73 to 75 C and precipitated by acids ; it is readily s oluble in strong nitric acid and not pre ci p i tated by common salt carb onates Of the alkalies or ver y dilute acids S y ntoni n or acid albumen is formed from serum albumen in the presence of a free acid ; alkali - albumen is a similar modification caused by the presence of a free alkali ; these b odies are not c oagulated by heat but are precipitated by neutralisation Syntonin may be formed by the careless use Of a test tube c ontaining traces of nitric acid Alkali - albumen is often present in putrid urine Serum g lobuli n is insoluble in distilled water but dissolves readily in the presence of c ommon salt and is then c oagulable like serum albumen at ' 73 to 75 C

2 BEIGHT S DISEASE It may be precipitated from its solutions by carb onic acid gas or by saturation with c omm on salt or mag n esi um sulphate It differs m oreover from serum albumen in its m ore ready diffusibility through animal membranes It is always present in albumin ous urine In the blood the prop ortion Of serum globulin to serum albumen is as 2 to 3 but in urine owing to its higher rate of diffusion this proportion may be reversed It has been more than once suggested that it is the b ody present in functional albuminuria or after paroxysmal h aemoglobinuria but this does n ot appear to be the case Out Of 16 cases of functional albuminuria examined this purpose the albuminous b ody was for pure gl obulin in only case and a second one on examination serum albumen was present with It it has been n oted to be in excess in cantharides p oison ing in chronic ephritis with waxy degeneration in the n early stage Of scarlatinal nephritis in the albuminuria associated with dyspepsia in phthisis Werner &c found globulin only present in a case of acute nephritis and attributed i t (following SENAT OR ) to the destruction of the renal epithelium which c ontains seven or eight times more globulin than serum albumen Hermann found globulin to be chiefly present in a case of eclampsia of pregnancy with albuminuria Retractile albumen ( BOUCHARD) was the name given to albumen which on boiling falls d own in dense flakes it was held to be characteristic of Bright s disease It is worth mentioning in order to note that this has b een abundantly proved to be a mistake this peculiar behaviour being dependent up on the a ci di t y of the urine (L EPINE ) P e p tone is best known to us as the product of the digestive action of the gastric or pancreatic j uices on albuminous food but of late years it has been Observed to be present in the urine in many acute and chronic

ALBUMINURIA 3 diseases generally in association with serum albuminuria It must not be assumed that it is necessarily food peptone excreted by the kidneys Peptone after absor p tion rapidly disappears and seem s to act as a p oison if injected into the circulation ; while it is said on good authority ( GRHTZ N EE) that digestive ferments are present in the Accordin to urine g M and Belfanti trypsin y a the normal proteolytic ferment of the urine is replaced by pepsin in Bright s disease but either would be ; capable of effecting the c onversion of albumen into peptone a process which is probably favoured by eleva tion of the b ody tem p ei' ature in fever and by the retention of the urine for a certain time in the bladder Peptones are not coagulable by heat or precipitated by neutralisation ; they are thrown down by several of the tests recommended of late years for albumen e g picric acid metaphosphoric acid Tanret s test (potassio mercuric iodide ) & c but the characteristic reaction is a pink or rose violet c olour with Fehling s solution in the c old Albumen in the process Of conversion int o peptone becomes in the first instance a substance similar to or identical with syntonin and subsequently it is changed int o a body called p ro p e p t one or hemi - albumose bef o re its final c onversion into peptone This p ro p e p to ne or hemi - albumose is nearly allied' to the substance known as Bence J ones s albumen or par - albumen It is prob able that there are several closely related b odies f o rming a group as the reactions given differ in vari us o details Pro p e p t according Salkowski remains clear one to on boiling it is precipitated addin acetic acid and ; on g ommon c salt s olution but clears up heating to be on thrown d own again on cooling With pure nitric acid it is precipitated on heating it dissolves with the develop ment of an intense yellow c olour and on cooling c omes d own again Treated with caustic soda and cautiously

4 BRIGHT S DISEASE with copper sulphate it gives a purple violet which is lost if excess Of copper sulphate is used With p h os p h oro tungstic acid tannic acid acetic acid and ferro -cyanide of p otassium it is precipitated but the last reaction does not occur in the presence of ammonia Heated with a drop of Millon s reagent ( acid nitrate of mercury ) it gives a deep red c olour and precipitate but this reaction fails when much common salt is present Bence J ones described the albumin ous b ody in his case as affording the following reactions ; he wrote The urine that c ontained it did n ot give a precipitate i m mediately by nitric acid and when hea ted it did not coagulate and nitric acid when added the boiling to urine did n ot give a If after b oiling the precipitate urine was c ooled then the precipitate fell but was i m mediately rediss olved by heat The difference between this and the reactions of p ro p e p t given ab ove is one that it was not precipitated by nitric Th orm'ahlen acid has described a form Of albumen which differed from p ro peptone in the precipitate caused by nitric acid not re diss olving On heating and by the s olution when cleared by heating remaining clear on c ooling The urine of J oseph B a patient in the General Hospital gave a similar reaction on one occasion In the urine of a case of pernicious an aemia I found an albumin ous body which presented m ost of the re actions Of but b oiling there was a dense p ro p e p to n e on cloud which adding acetic acid disappeared while on the wh ole fluid became gelatinised that the test tube so c ould be turned upside Nitric acid gave a pre down ci p i but it diss olved heating with out any yellow tate on c oloration Acetic acid and ferro - cyanide of p otassium Q 0 gave n o reaction but this may have been due to the presence of salts of amm onia Posner has found p ro p e p to n e together with traces of peptone in human semen as well as in the urine of

ALBUMINURIA 5 spermatorrhoea and after p ollutions It has been n oticed in many diseases m ollities ossium ( BEN CE JONES ) syphilitic cachexia diphtheria cancer of oes ophagus muscular atrophy (SENATOR ) petroleum inunction ( LASSAR ) chronic nephritis (HOPPE- SEYLER ) and there fore has n o special clinical significance Albuminuria once regarded as diagn ostic of Bright s disease has lost this primitive meaning The number and variety of the pathol ogical relations under which albumen may appear in the urine c ompel us to regard it as dependent not only up on i nfl amma tion grave congestions and other c oarse organic ch anges but up on slight variations in the mechanical c onditions of the circulation in the kidney Excluding accidental admixtures of blood or pus from the bladder or urethra albuminuria is met with n ot onl y in acute and chronic Bright s disease but in diseases of the heart lungs and liver in peritonitis pregnancy abdominal tum ours In most febrile and inflammatory diseases in many cases of p oisoning in cancer tubercle and syphilis in lard disease in an aemia debility dyspepsia purpura aceou s scurv after paroxysmal y h eemo g l obi n uri in gout in a delirium tremens in various diseases Of the brain and spinal c ord in epilepsy in certain skin diseases as well as in apparently healthy pers ons after bathing exercise etc All these states are capable of being arranged under the following groups 1 Con g esti ons o f t he ki dne y A cti ve or arterial congestion may result from a chill to the skin as in bathing ( MAHOMED JOHNSON) from ex p osu re to c old from elimination of s ome irritant through the kidneys such as alcoh ol uric acid ph osphorus lead cantharides &c ; from the direct action on the kidneys of a m orbid p oison derived fr om the blood such as the virus of scarlatina diphtheria typhoid &c a c ondition

6 BRIGHT S D ISEASE very liable to pass on to acute nephritis ; or finally from vaso - motor paralysis after inj uries to the spinal cord and in some other nervous affections P assi ve or venous congestion may result from cardiac pulmonary or liver disease peritonitis pregnancy abdominal tumours the hyp ostatic c ongestion of p ro longed illness failure of the circulation from enfeebled heart in fever in an aemia in ex0 p h th almi c goitre and fatigue or after v iolent exertion e g epilepsy 2 I n fi amm ati on acute or chronic in many i nflam mator y zymotic and septic diseases in gout in chronic lead p oisoning &c 3 N ew g rowths Cancer tubercle or syphilitic dep osits in the kidney 4 De g enem t i ons Lardaceous degeneration of the renal arterioles 5 A ltem ti ons i n the com p osi ti on o f the blood as in purpura or scurvy and after attacks of paroxysmal h aem oglobinuria L ooked at in this way the difficulties which have beset the discussion of the significance of albumin i uria melt awa y ; this result is attained by the abso lute surrender f the doctrine that albuminuria sig o ' ni Bright s disease and the acceptance fies of the view that it is simply the admixture of albumen derived from the blood serum with the It is a fact beyond urine dispute that albumen may be present in the urine of pers ons apparently in good It is even con health tended by s ome that there is a trace of albumen in the ' urine which is physiological Posner found an albumi n ous b ody precipitated by ferro - cyanide of potassium in every one of seventy experiments on the urine of N healthy persons and Chateaubourg using potassio mercuric iodide found albumen in 592 out of 701 ex ami n ati on s of urine in healthy I do n ot care persons c ontend that there is to n ot s ome departure in these

ALBUMINURIA 7 cases from the n ormal mechanism of the renal circula tion but it is certain that neither this lesion the ; n or l oss of albumen gives rise any derangement of health to which impairs the working capacity of the individual or tends sh orten his life in other words there are cases to of albuminuria which n ot only do n ot re uire medical q treatment companies but may be safely accepted by life assurance In these cases the urine is normal in every other respect there are n o tube casts the am ount of s olid matter excreted is sufficient and there are n o signs of cardiac hypertrophy of high arterial t ension no retinal changes and n o oedema Leube examined the morning urine of 119 healthy s oldiers of ninety once of twenty - three twice and of Si x three times Al bumen was found six times in the urine of five di flerent s oldiers five times only a trace once a distinct cloud The latter uri ne was that of a soldier wh ose m orn ing urine was examined twice and c ontained once a distinct cloud the other time only a trace The mid day urine of 119 s oldiers was examined especially that passed after a five hours march or many hours parade in the m onths of June July and August The five s oldiers wh ose m orning urine c ontained albumen also had albumen in their mid - day urine three times a trace three times m ore distinctly Moreover in 148 observa tions albumen was found eighteen times in the urine of s oldiers wh ose m orning urine was quite free from albu men i eight distinctly in ten only a faint The n trace results were that per of the s oldiers had albu cent men in their m orning urine and sixteen per had cent albumen in their mid-day casts blood No or urine corpuscles were All the cases in which albumi found nuria appeared were carefully examined and urethral discharges as well as signs of Bright s disease were carefully n oted to be absent The test used was b oiling and acetic acid but the albuminous b ody was separated

8 BRIGHT S DISEASE and tested by Millon s reagent sulphate of co pp e r ferr o cyanide of potassium &c Grainger Stewart examined the urine of 505 p resum ably healthy individuals c omprising 205 soldiers of the Seaforth Highlanders 100 heal thy male adults in civil employment 150 h ealth y i nmates of Crai g lockhart Poor house ( 100 adults over sixty and 50 children ) and 50 children in the Orphan h ospital of these 166 or 32 8 had tlbumi n uri a Of the 205 s oldiers 77 or 37 56 per cent h ad ' albuminuria ; of 100healthy male adults 10 only of 100 inmates of Crai g lockh ar t about or ab ove sixty years of age 62 h ad albuminuria and of 100 children it was pre sent i n 17 Dr Stirling examined 461 healthy pers ons of wh om 369 were b oys and of these 118 had albu mi nuri a o f wh om 77 were b o ys giving for adults 44 per cent for boys 20 per cent In Leube s cases the albu mi nu ri a was found in the mid-day urine four times m ore frequently than in the m orning urine that is the urine passed immediately on rising Stirling found the erect pos ture was the great determining factor in the production of albuminuria in his cases The same fact is attested by Senat or s experience wh o found that the urine of himself and three clinical assistants at the Augusta h ospital in Berlin repeatedly con tai n ed albumen between 11 a m and Bull has published a case in which the albumen was always absent when the patient was in Marcacci could produce bed albuminuria in himself by making r otatory m ovements with his arms fifteen for B ut this is trespassing minutes anoth er part on of the subj ect and it is sufficient to state here that this form of albuminuria in healthy persons seem s depend essentially up on s ome m to ech ani cal condition connected with the erect position and exerci se From his figures Grainger Stewart concludes that albuminuria is m ore c omm on in health as life advances

c ALBUMINURIA 9 but this is doubtful Hi s elderly people Sh ow a high percenta g e but there is n o evidence that care was taken to eliminate prostatic and vesical catarrh or even latent Bri g ht s idisease all very c omm on onditions at that age Other observers have met with functional albuminuria m ost c ommonly in young men But there are other cases in which s ome departure from health is present for exam p le atonic dyspepsia with oxaluria or lithuria an aemia perhaps n ot very marked or the patient is an overgrown weakly person with a tendency to varic os e veins in the l ower ex tremi ti es In 1876 Moxon described two forms of latent albu mi nuri a he called the albumi nuri a o f ad olescence One It occurs in youths and y oung men ; the patients are languid perhaps have headache ; s ome slight derange ment of the digestive sys tem is often present ; there is no evidence of organic disease and if the urine were not examined the cases would be regarded as debility with out any tangible signs of lesion Albumen is usually found in the urine passed after breakfast and is nearly surely present in s ome specimen of the urine collected for a period of forty - eight h ours A few hyaline casts and oxalates are Often to be found he called r emi tte f nt albi uni n ari a In the other form which the albumen is present in g reater quantity usually after breakfast but there is a remission at s ome period of the day nearly al ways in the early morning so that n o albumen is present in the urine passed on risin g after a night s rest These cases have been lately re - named c y c li cal albumi nuri a by Dr Pavy but their relation to the erect p osture is n ow ad mi tted It seems as if in the early part of the da y the circulation in the kidney c ould n ot establish a pr oper e q uilibrium but that after a certain number of hours this is attained and no m ore albumen is lost until after rising th next m ornin e g

of the heart is m ore forcible and frequent than normal 10 BRIGHT S DISEASE Some years ago I published a series of cases of albu mi n uri a in lads and y oung men all suffering from dyspepsia Case 1 T S set 15 lab ourer c om p lained of pain in the ches t and palpitation had had a cold ; all winter never had gon orrh oea had measles six ; ; years ago scarlatina twelve years ago other ; ; no serious illness he had never had He was ; dropsy a tall raw boned lad with a tendency blueness - to about the cheeks and nose His knuckles were bluish and his hands and feet were often Lungs n ormal cold except slight prolongation of Heart not expiration enlarged apex in 5th interspace 1% inches left of to sternum first sound at apex reduplicated second sound in aortic area accentuated liver dulness ; 31 } inches in vertical mammillary line appetite go od c omplained of feeling oppressed after eating b owels c onfined urine ; ; pale clear acid s p gr 1009 a little albumen no sugar or bile one or two pale hyaline casts and a few epithelial scales (on two subsequent examinations no casts were found) ; ophthalmoscopic signs negative (Mr EALES ) The pulse was not diminished by 300 grammes pressure but no satisfact ory tracing was Obtained I saw this patient ab out a year after his case was published he was looking much stronger and his urine was free from albu men I do n ot attach as much imp ortance as I did to the signs of high arterial tension These lads are ner vous and excited under examination so that the action and i n c onsequence the pulse is fuller and there may be s ome accentuation of the aortic 2nd sound ; but I am convinced that their usual condition is one tendin g rather to low arterial tension It must be admitted that all ou r kn owledge of these benign forms of albuminuria is recent and in the face of authorities who maintain that even the smallest trace

12 BRIGHT S DISEASE late years a third has been added ; these three theories may be called : the Haematogen ous ; the Parench y matous ; and the Vascular There always has been a sch ool which attributed albuminuria not to changes in the kidney but to changes in the blood and even in Bright s own day he was t old that the strue tural alterations described by him were onl y the results Of the elimination of albumen by the kidneys ; this d octrine still survives and finds a persistent defender in Semmola of Naples His argument is especially directed to the etiol ogy of Bright s disease where he contends that the blood contains albumin oids of an abnormal diffusibility so that they are found in the saliva sweat and bile a fact in which he is supp orted by Vulpian and others Tizz oni h owever found that albu men from the urine of a case of Bright s disease did n ot cause albuminuria when inj ected into the circulation of animals Semmola entirely overl ooks all that has been recently observed with regard to albuminuria apart from Bright s disease N othing can be farther from the truth than to supp ose that the elimination of albumen by the kidney is liable to set up inflammatory action for we kn ow that it may g o On for many years with out any such result But variations in the diffusibility of the albumin oids of the blood may yet acc ount for albuminuria in certain cases and there is a great tendency the part on of authorities accept such a Gl obulin diffuses more to view rapidly than serum albumen and it has been stated by L epine that al bumen found in the urine after food diffused m ore rapidly than that passed The fasting truth of the doctrine of h aemat ogen ous lbuminuria is a by means b ound up with food albuminuria that n o so it is perfectly allowable doubt the occurrence of the to latter while admitting the general probability that changes in the blood account a certain number for

that it is n ot egg albumen " (GRAINGER STEWART) albuminuria occurs ( LAUDER BRUNTON) ALBUMINURIA 13 of cases of albuminuri a for example in purpura scurvy pr ofound an aemia after h eemo g l obi nuri a etc With respect to food albuminuria we have Christison s case of th young man wh ose urine was always albu e minous after eating cheese and the experiments of Se uard Brown- q B arreswi l and others in which the urine became albumin ous a diet largely c omposed on Of B ut in the first case the albumen excreted eggs was not shown be casein in the sec ond be egg to n or to albumen while m ore recent experiments have proved and that it is only when the digestive p owers are over taxed as by swallowing many raw eggs together that Parkes was one of th e first to n otice that there was an apparent increase of albumen after food He stated that the albumen was increased after food in two cases of chronic Bright s disease alth ough it was diminished after food in a case of heart disease He inclined to the view that the increase after food was due to the passage of imperfectly digested albumen analogous to that which occurs when albumen is inj ected into the veins or to the albumen undergoing s ome m odification in the digestive process such as its c onversion into an acid albuminate by which its diffusibility would be i n creased Park es s facts do n ot seem to warrant this conclusion for while the albumen was increased after food in the two cases of Bright s disease it was diminished under similar circumstances in the case of heart disease so tha t i t is necessary to p ostulate a peculiar inability to digest albumen in the former cases which did not exist in the latter On the other hand if we re g ard albuminuria as When e gg ~ album en i s i nj e cte d i nto th e vei n s e gg alb um en i s excreted b y th e ki dn e y s

14 B RIGHT s DISEASE p otato e s bre ad and water a result of c ongestion of the kidney we can easily under stand why i n the cases of chronic Bright s disease the stimulus to the circulation increased the albuminuria in already inflamed organs while it diminished it in the case of heart disease where the transudation was due to pas sive engorgement of the renal capillaries and veins Parkee s views have been adopted by many writers B ut Pavy supports Parkes by giving a table of the amounts of albu men excreted before and after breakfast in six ex p e ri ments all showing a marked Pavy further increase adopted Park View that this might be due the es s i to n creased diffusibility of the albumen and supported it by sh owing that in some urines it is highly diffusible ; but he did not attempt prove that the albumen to passed after food was more diffusible than that passed before food or to indicate to what circumstances this i n creased diffusibility might be due Most physiologists deny that unchanged albumen is abs orbed the blood and the only piece into of direct evidence I know the c ontrary is the statement to of Brucke that he has found c oagulable albumen in the lacteals I endeavoured in the first place to determine whether this apparent increase of albumen after food really t ook place and the following observations were made on a case of Bright s disease in the Queen s Hospital under the care of Dr Carter The patient had been on milk diet previous to this experiment but on March l 0th 1880 he was p ut on the following diet B re akfast 5 a m two slices of bre ad and butte r with te a Lunch 10 a m ad two Slice s Of bre and butter with one pint of Dinn er 1 p m four ounce s of cooked me at ei g ht ounce s of T e a 6 p m th e s am e as bre akfast Suppe r 7 p m h alf -pint of milk

ALBUMINURIA 15 and He took walkin g exe rcis e twice dai l y for h alf an h our at Date Peri od Q uanti t y Albumen i n of Uri ne 40 ccms March 10 7 R M to 5 A M 1620 cc 008 g rm s 5 A M to 1 P M 150 cc ' 016 1 P M to 5 P M 180 cc ' 01 5 R M to 7 P M 120 cc 008 7 R M to 5 A M 870 cc ' 0069 5 A M to 1 R M 180 c c ' 0 17 1 R M to 5 R M 180 c c ' 014 1 5 R M to 7 R M 150 C O ' 009 7 R M to 5 A M 1410 c c 0 155 5 A M to 1 R M 180 c c ' 020 1 R M to 5 R M 180 cc 0166 5 P M to 7 P M 12 0 cc ' 015 On each day the relatively greatest quantity of albu men was excreted between breakfast and dinner The quantity each day fell as the day advanced in spite of the meat eaten at dinner and the exercise taken in the aftern oon The t otal q uantity of albumen excreted rose steadily under the influence of meat diet being three times greater on the fourth day than on the first One b ottle containing the urine of part of March 1l th g ot br oken that day s record was The so incomplete analyses were performed by MacMunn Dr This experiment is opposed to the doctrine of Parkes that unassimilated albumen is excreted b y the kidneys But it has been suggested that after food there may be a m ore rapidly diffusible albumen present in the blood That there should be such differences is uite probable q as Graham long a g o p ointed o ut that an acid solution of albumen diffuses readily while an alkaline s olution scarcely diffuses at all that differences in the ; so alkalinity of the blood serum may determine variations in the amount of albumen excreted Pavy Sh owed

16 BRIGHT S DISEASE using pericardium as a membrane that egg albumen di ffuses more readily than serum albumen and L epine has filled up the gap left by Pavy by observing that albu men i n the urine after food diffused m ore rapidly than that passed fasting The following experiments appear to Sh ow that the results may depend up on variations in acidity etc and n ot up on any primary difference in the albumen itself The septum used was vegetable parchment ; and the time allowed was twenty - four h ours in each case The following experiments were made on the urine of the same case E x p e I ri ment B e fore breakfast : In bed Urine faintly acid ; third on e - of a c olumn of albumen ; albumen in no A f t er breakfast : diffusate In bed Urine acid ; four fifths of a c olumn of albumen ; a trace of albumen in diffusate Ex p er i ment II B efore br eakfast : In bed Urine neu tral a trace of albumen in diffusate After break f ast In Urine acid a trace in bed diffusate III E x p er i ment B In Urine efore breakfast : bed faintly acid third ; one - of a c olumn of albumen a faint ; trace in diffusate A In Urine acid fter breakfast : bed two - thirds of a c olumn a trace in diffusate E x p er i ment IV B efore breakfas t : In bed Urine faintly acid one - third of a c olumn of albumen a trace in diffusate After breakf ast : In bed Urine acid two thirds of a column of albumen a trace in diffusate Ex p er i ment V B efore di n ner : U p Urine neutral a distinct cloud in diffusate After di nn er : U p Urine acid a distinct cloud in diffusate but less than before dinner E x p eri m ent VI - B efore di nner : U p Urine acid half a column of albumen ; a cloud in diffusate After di n : n er : Up Urine strongly acid a wh ole c olumn of albumen ; a dense cloud in diffusate

ALBUMINURIA 17 E x p er i ment VII B efore di nn er : U p Urine acid ; half a c olumn of albumen ; a faint trace in diffusate After di nn er : U p Urine faintly acid ; one - third of a c olumn of albumen ; a faint trace i n diffusate As a rule the albumen appeared to diffuse in propor tion to the acidity of the urine The diffusate b ore n o relation to the q uantity of albumen present in the urine While it is fully admitted that m ore carefully con ducted experiments might determine differences in diffusibility due as suggested to alterations in the salts of the blood or the alkalinity of the blood serum there is no evidence that undigested albumen is ever excreted by the kidneys and in this shape the doctrine of food albuminuria must be abandoned The parenchymatous theory ascribes the albuminuria to the destruction of the epithelial lining Of the renal tubules but there are several hyp otheses which are strongly opp osed to on e another One of the most interesting that of Von Wittich adopted bv Ludwig and lately revived in Glasgow is that albumen is p h y si olo g i /Cally transuded thr ough th Malpighian tufts but re e abs orbed by the epithelium oi the When the tubules parenchyma is diseased this reabs orption is m ore less or hindered and albuminuria This theory attrae results tive as it is is disp osed of by the experiments of Posner and Ribbert wh o proved by b oiling freshly excised kid neys and hardening them in alcoh ol that there is no albumen present in the capsular space around the Malpighian tuft in healthy kidneys th ough it can be easily dem onstrated in albuminuric kidneys even when the epithelium is intact Another form of the parenchymatous hyp othesis is that when the parenchyma has been shed from th e tubules the basement membrane permits the tran suda tion of albumen This theory has never been disproved and it is in its favour that kidneys prepared by the b oil 2

18 ERI GHT S DISEASE i n g and alcoh ol meth od showed albumen in the straight tubes ten minutes after ligature of the renal vein A third suggestion made by Senator is that the destruction Of the renal epithelium itself furnishes a sensible amount of In the early stage of albumen nephritis the epithelial cells shed their protoplasmic con tents the lumina of the This would only into tubules apply to cases of irritative or inflammatory albuminuria Lastly there is the vascular theory The ordinary seat of the transudation of albumen has been shown by Posner to be the Malpighian tufts as was suggested by an experiment of Nussbaum s In frogs the veins of the p osterior extremities divide in the pelvis i nto two branches on e of which passes to the kidney like a portal vein while the other j oins its fell ow of the opposite side to form the vena abd ominalis anterior The blood in the other branch passes through the kidneys and the li ver into the vena cava inferior to reach the right side of the heart The renal gl omeruli receive their blood from the renal arteries and the vasa efferentia pass into the same capillary network as that supplied by the renal p ortal veins so that by tying the renal arteries in frogs the renal circulation is n ot brought to a stand - still as it is in mammalia T aking advantage of this anatomical fact Nussbaum tied the renal arteries and then inj ected a five per cent s olution of egg albumen or a ten per cent s olution of peptone int o the anterior abdominal vein with out causing albuminuria although when the renal arteries were n ot tied a smaller quantity sufficed to produce albuminuria It is therefore proved that in frogs an albumin uric dyscrasia causes transudation of albumen only through the glomeruli and it is probable that this is true also in man ; taken together with Posner s ob servati on s we may regard the p oint as practically deter mined i n that sense The question is what causes the transudation? Is

20 BRIGHT S DISEASE Senator accepts this View and h olds that the higher the pressure th e m ore water but the less albumen Bamberger also believes the albumen to be diminished as the pressure rises L'Obi sch and R okitansky caused albuminuria in healthy persons by lowering the blood pressure with There can b e d oubt n o pilocarpine that increased venous pressure leads albuminuria to as is seen clinically in cases of heart lung and liver disease pregnancy ab dominal tum our and pr obably too in many cases of debility an aemia and in the hypos tatic c ongestion of fevers pneumonia &c In ligature Of the renal vein albuminuria occurs rapidl y and has been proved by Senator to take place by direct tran suda tion into the tubules probably from the lymphatics Charc ot and Bamberger attach much imp ortance to the influence of slowing the current which is sh own by physical experiment to fav our the filtration of albumen Isch aemia of the kidney by experimental narr owing of the renal artery leads to albuminuria probably by slow n the current and reducing the pressure Claude Bernard s puncture and experimental lesions of the spinal c ord give rise to albuminuria by vas e -m otor paralysis the kidneys bei ng deeply c ongested (SCHIP F) Many of the cases which have been regarded as neurotic albuminuria are susceptible of a more simple explana tion has been already suggested for epilepsy and a s tetanus ; and it will be admitted that other c onditions are present in ex0 p h th almi c goitre besides the nervous dis turbance sufficient to account for albuminuria though this may be due in part to altered vascular innervation We may usefully summarise the teachings of this lecture i the following c onclusions n 1 A lbuminuria is defined as the presence in the urine of serum albumen serum globulin or or their modifications syntonin and alkali albumen 2 Al buminuria may be present in healthy persons and

to alterations in the diffusibility of the blood albumin oids li ni t y of the blood serum ; but albuminuria is never due ALBUMINURIA 2 1 persist for long periods with out causing any derangement of the g eneral health or of the structure of the kidneys 3 A lbuminuria p er se sh ould not be regarded as an insuperable obj ection life to insurance Albuminuria may occur i ndyspeptic people and 4 in weakly over - grown pers ons without being an indica tion of actual or p oten tial renal disease 5 Al buminuria may depend up on many causes grouped under three headings : Haemat ogenous : due owing to changes in the salts of the blood or the alka as has been asserted to the excretion of undigested or partly digested albumen taken as food Parenchyma t ous : inflammat ory changes in the epithelium give rise in the first instance to an albumin ous exudate which must be present in the urine and secondly by destroying the cell layer and altering the basement membrane allow direct transudation from the lymphatic vessels into the tubules Vascular : the walls of the glomeruli probably undergo alterations of their permeability fr om the effects of p ois ons inflammation and vas e -m otor paralysis while lowering of the blood pressure and sl owing of the bl ood current favour filtration of albumen through them In ven ous obstruction there is ( edema of the whole organ and transudation of albumin ous fluid direct from the lymphatic spaces into the tubules in inflammation and vas e -m otor paralysis a Similar oedema is likely to occur with identical results BIB LIOGRAPH Y BAMBERGER ( VON) Ueber h amato g e n e Albuminuri e Wien e r M ed 188 1 N OS 6 and 7 Albumi nu ri latent Sk rum BULL p n y re N M ord ed A rk i v 1885 Ed XVII N o 2 5 CHARC OT ( J C o ndi tion s Path o g é ni q u e s d e l Albumi nuri e Le Pro g r és Med Tome IX 1881 p 55

p 613 22 B RIGHT s DISEASE JONES ( BENCE ) Anim al Chemistr y i n i t s Application to Stomach and Ren al Di se ase s L ondon 1850 LEPINE Q u elque s travaux rel atifs al Alb um i nuri e et a l a P a th o l o g i e rén al e Revue d e T ome II 1882 LEUB E (W U e b er di e Au s scheidu n g v on Eiweiss i m H arn d e s g e sun d e n M e n sch en Virchow s B d LXXII Heft 2 MARCACCI Di un n u ovo c aso di Albuminuria fisi olo g i c a C omment Clin d M al d Or g Gen - urin Pis a 1884 I M OXON On Chronic Intermittent Albuminu ria Gu y s Ho sp Reports 3rd vol S XXIII NU S SBAU M F ort g e s etzt e Untersuchun g e n u e b er di e Secre ti o n d er Niere Pfl ii g er s B d XVII 1878 p 580 PAVY (F Gul stoni an L ecture s On th e Assimil ation and th e influence of i ts defects on th e U rine L ancet 1862 II ; 1863 461 POSNER Studien u eb er p ath olo gisch en Exudatsbi ldun g e n Vi r ch ow s B d LXXIX p 311 U e ber p atholo gisch e Albuminurie B erl Klin B d XXII 1885 p 654 R IEB ER T U eber di e Ei wei ssau sch ei dun g d urch di e Nieren C ent f d M ed Wis s 1879 p 47 and 188 1 p 17 ROBINSON Rese arch es into th e conn ection exi stin g betwe en an unn atural de g r e e of c ompre ssi on of th e bl ood contain ed i n th e ren al ve ssels and th e pre s ence of certain abnorm al m atte rs i n th e u rin e M ed Chir T ran s 2 nd Vol S VIII 1843 p 51 RUNEBERG (J U ebe r di e p ath olo gi sch en B edin g u n g e n d e r Albuminurie D Arch fiir Klin B d XXIII p 41 SEM M OLA Nuove Contribuzioni all a Patolo gia ed alla cura d el Morbo di B ri g ht M ed C ontemp N ap oli 1886 III pp 449 to 467 Also s ee Le Pr o g r és Médical 1883 T om e XL p 471 SENATOR Di e Albuminu ri e i m g e su nden und kranken Z ustande B erlin : A Hirschwald 1882 STEWART ( G RAINGER ) Clinical L ectur e s on important s y mpto ms Fasc II Albuminuria Edinbur gh : B ell and B radfute 1888 STIRLING ( A Albuminuria i n th e apparentl health y y L ancet 1887 II p 1157 TH OMA Z ur Kenntni ss d e r Ci rculati ons storun g i n den Nie ren b ei chronischer interstitieller Nephritis Virchow s A rchiv B d LXXI Heft 1 and 2 TH ORMAHLEN U eber ein e ei g enth umli ch e Ei wei s sart i m men schliche n U rin Virchow s B d CVIII p 322 TI Z Z ONI Alcuni e sp erim enti into rno alla p ato g e n s d ell Alb uminu ri a Gaz d e g O spit Mi lan o 1885 VI 12 W ITTICH U eb e r H arn s e creti on und Albuminu rie Virchow s Archi v Bd X p 32 5

out of a hundred cases seen in the out -patient department CHAPTER II THE PATHOL OGY OF DROPSY DROPSY is certainl y the m ost striking symptom of Bright s disease and the one that commonly first attracts the patient s attention Frerichs found it absent in only on e out of 6 97 cases Rosenstein in only one out of 80 ; but the proportion varies in the different form s of Bright s disease It is usually present in acute nephritis but it may be very slight or altogether absent Thus i t is c omm onl y absent in cases of acute nephritis su p e rven ing in the course of pneumonia diphtheria typh oid fever &c though the state of the urine pr oves incontestabl y that acute nephritis exists In subacute nephritis and i n large white kidney dropsy is ver y c ommon being absent in only eight or ten per cent In the c ontractin g form it is much less c omm on in the earlier stages it is generally absent but later on it is more frequent Thus I found dropsy present in ten per cent only while in the b odies of pers ons wh o had died with c ontracting kidney I found the prop ortion as high as twenty - five per cent This variation is fully explained by the cause of the dropsy which in contracting kidney must for the most part be attributed to heart failure So l ong as the hyper trophied heart can do its work all goes on fairly well ; but when this organ at last breaks down drops y appears along with other signs of th e c ollapse of the wh ole s y stem Like ordinary cardiac dropsy it is first seen in the legs and ankles increasing after risin g or getting ab out and must be regarded as of g rave pro g nosis indicating failure of the heart to maintain the struggle an y longer The fluid in renal dr opsy varies in different Situations being poorer in albumen and s olids in the subcutaneous

of dropsy radicles as fast as it is poured out 2 4 BRIGHT S DISEASE tissue than in the serous sacs The following table taken from Bartels gives the comp osition in the various seats W ater Soli ds A lbumen B l ood Serum P eri cardi al fl ui d 1009 6 9 9 78 62 2 P eri ton e al 1009 6 3 9843 1 Sub cutan eou s 10076 5 988 30 Schmidt gives the following figures Subcutaneous tissue albumen Meninges ; 06 to 08 Peritoneum and Pleura Urea has been found in it by many observers and Bartels quotes the following figures from Edlefsen Subcutaneous tissue Peritoneum 02 8 to Pericardium 1 What is dropsy 2 Dropsy c onsists in an accumulation of watery fluid in the lymph spaces of the subcutaneous cellular tissue and in the ser ous cavities of the b ody This fluid or lymph is derived from the capillaries and under n ormal circumstances is p oured out int o these spaces but taken up again by the ven ous and lymphatic For the production of dropsy the equilibrium of this arrangement must be upset by either ( a ) an increase in the out - flow of fluid or ( b) a failure on the part of the veins and lymphatics to take up the effused fluid An increase in the out - flow of lymph from the ca p i l i lari es i s caused experimentally by section of the vas e m otor nerves and occurs in disease when their function is paralysed ; it may als o be due the oretically to i n creased permeability of the vascular walls and to changes in the bl ood serum We shall afterwards see what share to assi g n to each of these factors

DROPSY 2 5 The principal source of p ower in pumping these lymph spaces d r y is the heart it is assisted by the aspirat ory acti o n of the th orax in respiration and the c ontractions of the muscles in the limbs When the heart fails to main t ain a negative pressure in theveins oedema sets in L ocalised ven ous obstruction acts with less certainty in the same wa y ; as the lymphatics which open int o the venous circulation beyond the Obstruction may carry on the work if h owever their task is added by cutting to the motor nerves and leading a greater influx vase - so to of blood the capillaries and increase in the outfl ow of to lymph dropsy sets Section of the nerves probably in has more than this simple effect but it need not c oncern us at present There are no difficulties in the way of understanding dropsy due to heart failure ; it is a break down in the central pumping apparatus and need n ot detain us longer The dropsy of greater difficulty acute nephritis presents problems of In m ost cases there can be no question of heart failure and its explanation must be s ought for in the fact ors that determine an excessive outpouring of lymph fr om the blood vessels In acute Bright s disease the urinar y secretion is very scanty and as patients con tinne to swall ow fluids the total quantity of blood mus t increase abs olutely in volume while suffering a relative diminution of its s olids ; that is to say the water is ab solutel y increased and the s olids relatively decreased inducing a state of hydraemic plethora A watery c ondition of the blood has long been regarded as a cause Of dropsy s ome auth ors seeing i it a predisp osing fact or others ascribin it still n g to greater imp Br'ucke s experiment of cutting one ortance sciatic nerve of a fro g and puttin g the animal on a piece of moist blotting paper in a large glass vessel sh owed that after s ome weeks oedema occurred in the palsied limb which disappeared on food bein g administered re

2 6 BRIGHT S DISEASE appeared in inanition and disappeared again when nutri tion was restored But there is considerable difficult y in ascertaining what are the circumstances under which h y drzemi a will produce dropsy for auth orities certainly differ as they are wont to do One of earliest experimenters Hales succeeded our in producing b oth the ascites and the anasarca in a dog by p ouring wa ter into th j ugular vein but e when we read the description it appears that the do g died during the progress of the experiment and we are not told whether these phen omena preceded death or not this is an imp ortant p oint as the retentive power of the vascular walls alters altogether after death Magendie in his sur les Le q o n Ph Physiques s énomén es de la Vie alludes this matter in several lectures he to certainly tells us that he succeeded in producing general dropsy by defibri nati n g the blood of a dog and in another experiment he produced analogous results by p ouring water the veins as Hales had But he performed into done a much m ore remarkable experiment by introducing no less than ten litres of water the veins of into a patient sufferin g from hydrophobia he had observed the wonderful calmative influence which similar inj ections had up on ferocious dogs and he h oped by this means to c ombat this fatal disease His patient lived several days and died presenting the phenomena of several p se udar th dropsical swellings roses or of j We are not oints told that oedema was absent but from the relation the story bears to the main p oint of the lecture we may feel j ustified in c oncluding that had there been any anasarca the lecturer would n ot have failed to mention it Niemeyer states I kn ow n ot on wh ose auth ority that if we abstract blood from an animal and inj ect a c orres ponding quantity of water int o its veins in its stead the animal does not become dropsical on the other hand Jaccoud says the artificial dyscrasia created by the

28 BRIGHT S DISEASE loss of albumen may take place with out any dropsy resulting if only the quantity of water passed is suffi ci entl c opious while dropsy may ensue during an y insignificant loss of albumen directly the daily urinary secretion falls below a certain minimum q uantity He quoted the observations of Rehder wh with the o view of establishing the prop ortion b orne by the quantity of water taken in drink and food towards that which afterwards appears in the urine instituted a series of experiments up on healthy pers ons living under identical external c onditions and then compared th e results with a series of analogous observations made on dropsical subj ects He subj ected five healthy pers ons to experiment and the average of the daily results extending over thirty - two days was that of every hundred parts of fluid ingested 764 parts were excreted in the urine the lowest mean in individual was one 68 per cent the highest 88 per cent Very c ontrary results were obtained by the observations on pers ons suffering from cardiac and renal dropsy A man aged fifty with cardiac disease excreted quantities of water varying from 2 9 7 to 492 per cent a youth with chr onic parenchymat ous neph ritis excreted 18 6 to 335 per cent only in a w oman with the same disease the excreted water averaged 16 per cent and never exceeded 24 4 per cent a man with the same gave an average of 28 per cent In another case the exact corresp ondence between the increase and suhsi dence of the anasarca and the diminution and increase of the urinary secretion was perfectly established Bartels held that these experiments sh ow that the dropsy of renal disease is due to the relative insufficienc y of the kidneys to eliminate water but s ome time must elapse before anasarca occurs ; in on e case in which' stoppage of both ureters was p resent one hundred and twenty - two h ours elapsed with out a trace of oedema

Cohnheim and Lichtheim directly opp ose Bartels view DROPSY 29 showing itself but this patient vomited large quantities of li q uid The cases given by Trousseau of two patients suffering from general anasarca due simply to retention of urine and whose sympt oms were c ompletely relieved by empty ing the bladder are if any be needed additional clinical illustrations of the dependence of dropsy on a free exit of water by the kidneys and they have endeavoured to show that hydr aemia p er s e cannot produce subcutaneous oedema Their experiments were made by inj ecting wi th a syringe under very or l ow c onstant pressure large quantities of a blood-warm 0 6 per solution of c ommon salt into th circulation e of cent dogs rabbits and other animals rabbits were used with ; out any preparation but dogs and the larger animals were s oothed with morphia or curarised As a preliminary proceeding they endeavoured to gain s ome idea of the quantity of fluid which might be inj ected with out killing the animal and they found that dogs c ould stand much more than rabbits the latter generally c ould support an inj ection of 46 per cent of their b ody weight before they died but dogs withstood a much greater quantity espe ci all y if the abdominal cavity were Opened 92 per cent of his b ody weight being introduced into on e do g bef ore he died In on e case the do g died of acute oedema of the lung but they were unable to acc ount for this exce p ti onal occurrence in general the animals died with sympt oms of deoxygenation of the blood paralysis of the heart and in s ome cases c onvulsions In n one of these experiments and they were very numerous e was any subcutaneous oedema or anasarca p ro duced even after the largest inj ections the subcutaneous tissue was quite free fr om water and as this is the earliest and principal seat of the so -called hydr aemic oedema it appeared from these observations that hydr aemic plethora