403 BIOCHEMICAL DISTURBANCES AFTER TRANSPLANTATION OF THE URETERS By A. W. WILKINSON, Ch.M., F.R.C.S. (Edin.) Senior Lecturer in Surgery, University of Aberdeen Complete diversion of the urinary flow to the large bowel was first deliberately achieved in 185I by Simon, who pr'oduced fistulae between the lower ends of the ureters and the rectum in a boy aged I3 years who had extroversion of the bladder, the patient survived for io months and died of the effects of infection; accidental fistulous con- nection between the bladder and bowel may not have been uncommon before this time following perineal lithotomy. During the ensuing ioo years thousands of patients have had their ureters trans- planted by more than 8o different techniques, the chief indications being congenital anomalies such as extroversion of the urinary bladder, some forms of vesical fistulae and tuberculosis or carcinoma of the bladder. The reduction of infective complications fol- lowing the introduction of the sulphonamide and antibiotic drugs and improvements in anaesthesia, blood transfusion and other types of fluid therapy led to a marked reduction in the early mortality and morbidity following this operation. It was recognized many years ago that patients who sur- vived the operation for more than six months or a year were liable to suffer from recurrent bouts of fever with loss of appetite, nausea and tiredness. It has become increasingly evident that such dis- turbances cannot always be ascribed to ascending infection and pyelonephritis and that a significant part of the late post-operative disturbances have a chemical basis. Until recently indirect anastomosis by either the Coffey (I9II) or Stiles (i9ii) method was by far the commonest procedure; in this a length of ureter is laid in a tunnel made in the wall of the pelvic colon with the distal end of the ureter pro- jecting into the lumen of the colon. This results in a valvular formation, but the lower end of the ureter is liable to stenosis and the formation of calculi and concretions, with hydronephrosis and dilatation of the ureter. During the'last six years a direct anastomosis of the Nesbit (1949) type, in which the mucosa of the ureter is sutured to that of the colon, has been employed more fre- quently. The disadvantage of this method is that there may be reflux of gas and faecal fluid from the colon up the ureter. After transplantation all the urine is discharged into the colon and for up to a week after operation the bowel is drained through an indwelling rectal tube; most patients become continent soon after removal of this tube. Subsequently they are able to distinguish between fluid and solid contents and they empty the bowel at varying intervals of from 2 to 5 hours during the day and rise once or twice during the night. The combined output of water in urine and faeces is increased after this operation and the daily consumption of water rises. The typical biochemical disturbance is usually found in continent patients after complete diver- sion of their urine to the colon; it may come on at any time after operation, but appears to become commoner the longer the patient survives opera- tion and when renal function is impaired. The commonest type of disturbance is an elevation of the plasma chloride concentration which is usually accompanied by depression of the plasma, bicar- bonate concentration, the so-called ' hyperchlo- raemic acidosis'. Flocks (I949) found mild to moderate acidosis in 62 per cent. of patients'after bilateral ureterosigmoidostomy. Ferris and Odel (1950) reviewed I41 patients and found that in 79 per cent. the plasma chloride concentration was above normal, and that in 75 per cent. this had occurred within a year of operation; in 8o per cent. plasma bicarbonate was below the normal range and this had occurred within a year of operation in 77 per cent. Two-stage transplan- tations were done in i6 of their patients, the plasma chloride concentration was raised in two and' bicarbonate was lowered in five patients after only one ureter had been transplanted. Jacobs and Stirling (1952) found that six months or more' after bilateral ureterosigmoidostomy there was depression of plasma concentrations of bicar- bonate in 8i per cent. and of potassium in 30 per cent., and elevation of plasma concentrations of chloride in 48 per cent., urea in 76 per cent., and sodium in less than io per cent. of the patients on by copyright. on August 6, 2020 by guest. Protected http://pmj.bmj.com/ Postgrad Med J: first published as 10.1136/pgmj.30.346.405 on 1 August 1954. Downloaded from
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403
BIOCHEMICAL DISTURBANCES AFTERTRANSPLANTATION OF THE URETERS
By A. W. WILKINSON, Ch.M., F.R.C.S. (Edin.)Senior Lecturer in Surgery, University of Aberdeen
Complete diversion of the urinary flow to thelarge bowel was first deliberately achieved in 185Iby Simon, who pr'oduced fistulae between thelower ends of the ureters and the rectum in a boyaged I3 years who had extroversion of the bladder,the patient survived for io months and died ofthe effects of infection; accidental fistulous con-nection between the bladder and bowel may nothave been uncommon before this time followingperineal lithotomy. During the ensuing ioo yearsthousands of patients have had their ureters trans-planted by more than 8o different techniques, thechief indications being congenital anomalies suchas extroversion of the urinary bladder, some formsof vesical fistulae and tuberculosis or carcinomaof the bladder.The reduction of infective complications fol-
lowing the introduction of the sulphonamide andantibiotic drugs and improvements in anaesthesia,blood transfusion and other types of fluid therapyled to a marked reduction in the early mortalityand morbidity following this operation. It wasrecognized many years ago that patients who sur-vived the operation for more than six months ora year were liable to suffer from recurrent boutsof fever with loss of appetite, nausea and tiredness.It has become increasingly evident that such dis-turbances cannot always be ascribed to ascendinginfection and pyelonephritis and that a significantpart of the late post-operative disturbances have achemical basis.
Until recently indirect anastomosis by eitherthe Coffey (I9II) or Stiles (i9ii) method was byfar the commonest procedure; in this a length ofureter is laid in a tunnel made in the wall of thepelvic colon with the distal end of the ureter pro-jecting into the lumen of the colon. This resultsin a valvular formation, but the lower end of theureter is liable to stenosis and the formation ofcalculi and concretions, with hydronephrosis anddilatation of the ureter. During the'last six yearsa direct anastomosis of the Nesbit (1949) type,in which the mucosa of the ureter is sutured tothat of the colon, has been employed more fre-quently. The disadvantage of this method is that
there may be reflux of gas and faecal fluid fromthe colon up the ureter.
After transplantation all the urine is dischargedinto the colon and for up to a week after operationthe bowel is drained through an indwelling rectaltube; most patients become continent soon afterremoval of this tube. Subsequently they are ableto distinguish between fluid and solid contentsand they empty the bowel at varying intervalsof from 2 to 5 hours during the day and rise onceor twice during the night. The combined outputof water in urine and faeces is increased after thisoperation and the daily consumption of waterrises.The typical biochemical disturbance is usually
found in continent patients after complete diver-sion of their urine to the colon; it may come onat any time after operation, but appears to becomecommoner the longer the patient survives opera-tion and when renal function is impaired. Thecommonest type of disturbance is an elevation ofthe plasma chloride concentration which is usuallyaccompanied by depression of the plasma, bicar-bonate concentration, the so-called ' hyperchlo-raemic acidosis'. Flocks (I949) found mild tomoderate acidosis in 62 per cent. of patients'afterbilateral ureterosigmoidostomy. Ferris and Odel(1950) reviewed I41 patients and found that in79 per cent. the plasma chloride concentrationwas above normal, and that in 75 per cent. thishad occurred within a year of operation; in 8oper cent. plasma bicarbonate was below thenormal range and this had occurred within a yearof operation in 77 per cent. Two-stage transplan-tations were done in i6 of their patients, theplasma chloride concentration was raised in twoand' bicarbonate was lowered in five patients afteronly one ureter had been transplanted. Jacobsand Stirling (1952) found that six months ormore' after bilateral ureterosigmoidostomy therewas depression of plasma concentrations of bicar-bonate in 8i per cent. and of potassium in 30 percent., and elevation of plasma concentrations ofchloride in 48 per cent., urea in 76 per cent., andsodium in less than io per cent. of the patients on
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ed J: first published as 10.1136/pgmj.30.346.405 on 1 A
whom these observations were made. Contraryto the belief of Flocks-and of Foster, Drew andWiss that the tendency to acidosis disappears aftersix months from operation, Jacobs and'Stirlingfound that there was a progressive increase in theincidence and severity of the abnormality of thebicarbonate, chloride and urea concentrations astime elapsed, and that acidosis and retention ofurea were more common in patients whose renalfunction was poor.Most of the patients show similar clinical
features. At first they are easily tired or feelweak and their appetite becomes poor; later theremay be nausea with revulsion for food andvomiting, irritability and increasing drowsiness.From an early stage they notice a salty taste intheir mouths, later thirst becomes progressivelymore severe. Most of them experience rectalurgency and frequency and the rectal fluid isunusually watery and its volume is increased.Not all conform to this pattern and it is note-worthy that some patients may show severe dis-tortion of their blood chemistry without experi-encing any symptoms or alteration in fluid intakeor output.
Diefenbach, Fisk and Gibson (95i) drewattention to the possible importance of potassiumdeficiency in this syndrome when they reportedthe case of a man whose presenting feature was acomplete flaccid quadriplegia with an associatedlow serum potassium concentration sixteen monthsafter bilateral transplantation of the ureters tothe colon; in this case there was little alterationin plasma bicarbonate, chloride or urea concen-trations and there was a rapid response to theintravenous administration of Darrow's solution.Foster, Drew and Wiss (r95o) had already re-ported a patient of theirs who, following twopremonitory disturbances marked by hiccup andacidosis, was admitted after rigors, anorexia andweakness in a semi-conscious state with a lowserum potassium concentration. Further cases ofsevere potassium deficiency complicating acidosishave been reported by Wilkinson (1952), Parsonset al. (I952) and Creevy (I953). Amongst thesepatients both the morbidity and mortality ratesare higher; Ieven when the potassium deficiencyis recognized and specially treated, recovery isslower and complications are more common.
Anuria is not a common feature of the chemicaldistuirbances after ureterosigmoidostomy and isusually associated with severely damaged kidneys(Parsons et al., 1952) or with advanced potassiumdeficiency'(Wilkinson, 1952).
In the majority of patients rapid relief of symp-.toms follows such siimple measures as continuousdrainage of the rectum by an indwelling tube orwashing out the large bowel repeatedly with water
combined with the consumption of a normal fulldiet (Ferris and Odel, 1950). Even the disorderedblood chemistry returns to within normal limitsin most cases if rectal drainage is continued forfour or five days. Relief has also been obtainedafter unilateral nephrostomy or by caecostomy.Intravenous therapy seems seldom to have beennecessary, except in cases complicated by severepotassium deficiency, but when patients are semi-conscious or comatose, prompt relief usuallydepends on the early intravenous administrationof potassium salts. In most cases it is enough toincrease the fluid intake by persuading the patientsto drink up to six pints each day.
Prevention of the disturbance has been attemp-ted by various measures and it is difficult to judgehow effective some of these have been. The mostimportant single measure is generally believed tobe the regular emptying of the bowel at shortintervals of from two to three hours by day andon one or two occasions during the night; thishas been recommended regardless of whether theauthor believed in selective absorption of chloride,or back pressure and renal damage, or both, asthe cause of the acidosis. Regardless of surgicalbelief, this advice seems to be good. There isfairly wide agreement, too, that the daily intake ofchloride should be restricted, some advocatemerely avoiding the addition of salt to the foodon the plate, while others advise the full rigoursof a ' salt-free ' diet. Those who have had themisfortune to encounter patients with advancedpotassium deficiency in addition to acidosisnaturally advocate the regular prophylactic ad-ministration of potassium citrate, in addition tosome form of chloride restriction. Because theirdaily output of water is increased most patientsdrink more after operation and this natural inclina-tion should be strongly encouraged.
Broadly speaking, two explanations of hyper-chloraemic acidosis have been proposed. Thefirst ascribes it to selective absorption by thecolonic mucosa of chloride from the urine in thecolon. The second explanation invokes impair-ment of renal function, particularly that of thedistal tubules, either by hydronephrosis and back-pressure, especially after the indirect type ofanastomosis, or by pyelonephritis and ascendinginfection, especially after the direct type of anasto-mosis. Much conflicting evidence has beenadduced in support of each of these explanationsand of combinations of them with other possiblemechanisms. As well as the more recent workon the ;effects of transplantation of the ureters indogs and man it seemed worthwhile consideringsome of the earlier experimental and clinicalwork, both on transplantation and on intestinalabsorption.'
August 1954 WILKINSON: Biochemical Disturbances after Transplantation of the Ureters
Jacobs and Stirling found that acidosis followedeither type of anastomosis, but was rather morecommon after the direct (45.5 per cent.) than theindirect type (32.5 per cent.); this rather smalldifference in the incidence of acidosis does notseem to implicate particularly either technicalprocedure. Yet after the direct type of anasto-mosis 50 per cent. of cases show reflux of air and30 per cent. reflux of opaque medium from thebowel, whereas after indirect anastomosis therewas no evidence of reflux of opaque medium, andof air in only io per cent. of cases. If backpressure and infection are as important primaryfactors in the production of acidosis as manyauthors have claimed, acidosis should be muchmore common after the direct anastomosis whichallows such free access of faeces and gas to therenal pelvis. As there is so little difference in theincidence of acidosis after direct or indirect typesof anastomosis, which produce such differentorganic unions between the ureters and colon, itseems reasonable to conclude that the commonprimary cause of acidosis lies elsewhere and thatabsorption from the colon is a more importantfactor.
It is a general finding that even a short timeafter transplantation evidence of pyelonephritiscan be found in the kidneys and when some yearshave elapsed there is almost invariably abundantevidence of chronic inflammation and infection ofthe kidney, often with signs of hydronephrosis aswell (Poole and Cook, 1950; Graves and Bud-dington, i95o). Lapides (1952) has observedpyelographic changes in 77 per cent. of his patientswhich were often intermittent and improvedspontaneously, as were the bouts of acidosis fromwhich his patients suffered. Harvard and Thomp-son (195i) reviewed I98 patients whose ureterswere transplanted for extrophy of the bladder, ofwhom 52 per cent. survived 20 years; they attri-buted 67.5 per cent. of the late deaths to pyelone-phritis. Grey Turner (I943) reviewed ninepatients between i6 and 30 years after trans-plantation of their ureters and concluded that afterthis operation in nearly all cases there was someevidence of ascending infection; eight of thesepatients were able to work, but five out of sixshowed marked dilation of the upper urinarytract. He remarked on the general good healthof the eight patients he was able to examine; itis difficult to judge how far this was due to theconsumption of potassium citrate. Six weeks ormore after operation Creevy (I953) found thatthe plasma chloride concentration was raised inonly 44 per cent. of patients whose blood ureaconcentration was within normal limits, but in75 per cent. when the blood urea concentrationwas above normal. In spite of the early onset of
infective lesions in the kidneys it is well establishedthat acidosis commonly occurs only intermittentlyand usually responds rapidly and completely tosimple therapeutic measures, even in patients whohave signs of moderately severe renal functionalimpair-ment.
In an attempt to avoid infection of the renaltract from the colon Baird, Scott and Spencer(1917) transplanted the ureters of dogs into theduodenum; this was apparently followed by therapid absorption of all the urine, leading to asteady rise in blood non-protein nitrogen anddeath after a few days. Bollman and Mann (1927)found that the higher they transplanted bothureters into the small intestine the more rapid wasthe rise in blood urea, although some elevationof the blood urea followed transplantation eveninto the colon; they found, however, that theconcentration of creatinine in the blood did notrise, which suggested that absorption of urinaryconstituents by the intestine might be selectiveand that such selective absorption, rather thanrenal damage, might be the cause of the death oftheir animals. Jewett (I940) observed that indogs after transplantation of the ureters to therectum the blood urea concentration rose ifemptying of the bowel was delayed; he alsosuggested that the accompanying acidosis was dueto the absorption of chloride from the bowel andcould be prevented by the restriction of the intakeof sodium chloride and by the administration ofalkali.
Boyce (I95I) has repeated some of this workand shown that the absorption of chloride andnitrogenous material is most active from thecaecum and least from the rectum; transplanta-tion of the ureters of dogs to the caecum wasassociated with a very high mortality rate. Kekwicket al. (I95i) reported that five out of I5 of theirpatients died after transplantation of the rightureter to the caecum and the left to the sigmoidcolon. They did not find any change in thechloride content of urine which they ran into acaecostomy or an ileostomy in patients withnormal kidneys, whose ureters had not beentransplanted, and concluded that absorption ofchloride from urine in the bowel was not animportant factor in the development of acidosisafter transplantation of the ureters. Theseexperiments did not reproduce the conditionsabove *a continent anal sphincter under whichacidosis arises after ureteric transplantation;indeed in one of their own patients recovery fromcoma followed the institution of a caecostomy.They attributed the acidosis to back pressure andtubular damage leading to polyuria and chlorideretention. Several observers have shown thatfollowing intravenous pyelography urine contain-
ing radio-opaque material may pass freely fromthe transplanted ureters in the sigmoid colon tothe caecum, so that even low anastomosis cannotentirely etsure that the urinary constituents arenot presented to higher segments of the colon.There is, however, good experimental evidencein support of the usual practice of transplantingthe ureters into the sigmoid colon and sufficientreason for avoiding the small intestine, caecumand right half of the colon.
Absorption from the intestine is an activeprocess and occurs even against a steep concen-tration gradient. Visscher and his group usingNa24 and Cl'9 have shown that even when chlonrdeis being absorbed from a solution containingsodium and chloride in the intestines, Cl"9 ispassing out of the blood back into the intestine.They found also that there was a high rate ofexchange of sodium between the blood and intes-tinal fluid, the equivalent of all the sodium in theplasma passing into the intestine in 83 minutes;they also found that the colon was more efficientthan the small intestine at absorbing sodium andchloride.
Goldschmidt and Dayton (i919) showed thatin a dog with a normal serum chloride concentra-tion, chloride was lost into the colon when thecolonic chloride content fell below 27.4 mEq. perlitre; at concentrations above this the quantity ofchloride which was absorbed into the plasmavaried with the concentration of chloride in thebowel. The magnitude and direction of activetransport of an ion across a barrier depends onthe balance between the rates of inward and out-ward migration of a particular ion.
In the case of the colon after bilateral trans-plantation of the ureters, the quantity of chloridewhich is absorbed from the urine discharged intothe bowel will depend on the concentration ofchloride in the original urine and in the plasma,and the length of time the urine is in contact withthe colonic mucosa. The chloride content of thebody is normally regulated by the kidneys. Whenall the urine is discharged into the colon absorp-tion of chloride from this urine returns someexcreted chloride to the whole body ' pool' ofchloride. The urinary chloride concentration is,therefore, likely to rise and unless water intake isincreased or chloride intake is reduced this willlead to a vicious circle of rising concentration ofchloride in both plasma and the rest of the extra-cellular fluid and urine.
Bollman and Mann (1927) found that in dogswhen only one ureter was transplanted into thebowel chemical changes in the blood did notoccur as long as the remaining kidney retainedgood function (see also Pendleton and West, 1932;Geer and Dragstedt, 1938). This was also
observed by Ferris and Odel in surgical patients.Some interesting observations after unilateraltransplanation have recently been reported byParsons et al. (1952). In one patient three timesas much urea and 7.5 times as much chloridewere recovered in 24 hours from the bladderurine as from the rectal fluid; the creatinineclearance and volume were both about 15 percent. less for the rectal fluid compared withbladder urine, suggesting that although the totaloutput by the transplanted side was less than onthe normal side there is a compensatory increasein chloride and urea excretion by the untrans-planted side in response to absorption by the colon.In another patient one ureter was transplantedinto an artificial bladder formed by isolating thelower sigmoid colon and rectum from the remain-der of the bowel by a terminal colostomy. Theyconfirmed the well - known observation thatwhereas the rectal fluid is consistently alkaline,the bladder urine is strongly acid; there was alsomarked reduction in the urea (30 per cent.),chloride (70 per cent.) and sodium (55 per cent.)content and volume (20 per cent.), but a rise ofpotassium (I5 per cent.) content of urine placedin the artificial bladder. When Na24 and Cl"3were added to urine which was placed in theartificial bladder the Cl"' concentration of peri-pheral venous blood rose more rapidly than thatof Na24 and there was also a disproportionate risein the C138 content of bladder urine derived fromthe normal kidney and ureter. These experimentsconfirm in the human subject the work previouslydone on dogs and illustrate as well the rapidexcretory response by the normal kidney to theabsorption of C189 from the urine in the colon.In spite of the absorption of sodium from theurine elevation of the serum sodium concentra-tion is not common (io per cent., Jacobs andStirling) perhaps because, as Korenberg (I951)has suggested, the sodium is transferred into cellswhich have lost potassium.
Berglin (1952) found that in a control subjectthe intravenous administration of 5 per cent.saline caused only a slight rise in plasma chlorideconcentration with a marked increase in urinarychloride concentration and output, but that in apatient whose ureters had been transplanted therewas a rapid rise of plasma chloride concentrationwhich persisted for eight hours, that the urinarychloride concentration also was raised and bothplasma and urinary chloride concentration fellonly slowly towards the normal range. Theurinary volume was increased for three hoursafter the infusion and then fell in spite of anincreased intake by drinking. This experimentindicates the reduced capacity of the kidneys todeal with added loads of chloride after transplan-
August I954 WILKINSON: Biochemical Disturbancev after a4tsplahtation of the Ureters
tation of the uretets, but it does not distinguishbetween absorption from the colon and tenaldamage as the causes of this incapacity.The use of isolated segtnents of small or large
intestine as substitute reservoirs for urine, afterexcision of the urinary bladder (Bricker, I950;Glaser, i952), has the advantage of avoiding therisk of ascending infection and the reflux offaecal material into the ureters and renal pelves.A short segment (io in.) of ileum has been used
as a conduit from the ureters to the exterior byAnnis, Hunter and Wells (I953) and acidosis hadnot developed in any of their patients. Wilson(1953), however, reported the development ofacidosis within I5 days of such an operation whichresponded to the administration of sodium citrate;as the result of further observations on this patienthe suggested that when used in this way the ileumrapidly adapts itself to the new circumstances andthe absorption of urinary constituents is thenunlikely to occur. Eiseman and Bricker (1952)found that both chloride and urea were absorbedfrom isolated draining loops of ileum into whichthe ureters were transplanted, but think thatprovided the loop is short absorption is unlikelyto distort body chemistry. Higgins (1948) foundthat in dogs when the isolated distal stump of thecolon and rectum was used as an artificial bladderit contracted and after two years had almost com-pletely lost its capacity; such shrinkage of theexcluded rectum or colon is a well-known sequelto palliative colostomy for inoperable cancers ofthe bowel. The use of the ascending colon andcaecum as a reservoir, with the ileocaecal valve asa sphincter to control discharge of urine from anileostomy (Moore, 1953) seems unwise in view ofthe evidence which has been cited. It is too soonto judge whether the use of a short isolated seg-ment of ileum is as safe as has been claimed, therisk of absorption of urinary constituents mayhave been modified, but it is not certain that ithas been eliminated.
In the continent subject urine is secretedagainst a raised hydrostatic pressure, but it isuncertain how important this elevation of pres-sure is in the production of acidosis. Shackman(1952) has observed that the elevation of theplasma chloride, which may be associated withacute retention of urine due to prostatic obstruc-tion, subsides spontaneously when the urinaryobstruction is relieved; he suggested that tran-sient tubular damage resulted from the raisedhydrostatic tension in the urinary tract in acuteretention of urine, and that this might be a factorin the production of acidosis after ureteric trans-plantation.
It is conceivable that disturbance of tubularfunction could occur simply as the result of back
pressure, but it seems unlikely that changes inpressure of the order of a few centimetres of waterwould have much effect on secretion whichdepends on the active transport of ions acrossmembrane barriers. It seems unlikely, too, thatsimple relief of pressure would have much effecton tubular dysfunction, which was due to organicchange secondary to bacterial infection. Iftubular damage is an important factor in theproduction of acidosis after ureterosigmoidostomyit is hardly likely to respond as rapidly as is usuallythe case to relief of pressure such as is afforded bysimple drainage of only one kidney by nephro-stomy. If there is functional impairment of thedistal tubules by back pressure it will surely affectother functions than chloride excretion. Theproblem could probably be solved by the cathe-terization of both ureters after transplantation andthe subsequent complete drainage of urine to theexterior, combined with periods of instillation ofportions of this urine into the colon.
Chloride is absorbed from the lower colon inexcess of sodium, most probably in associationwith ammonium derived from the bacterial break-down of urea in the intestine. This dispropQr-tionate absorption of chloride with a ' disposable'cation like ammonium will lead to acidosis withdepression of plasma bicarbonate concentration.In these circumstances the response of the kidneyswill be similar to that in experimental acidosis inman induced by the consumption of ammoniumchloride (Sartorius et al., I949); in this statethere is a loss of fixed base (chiefly potassium)from the body accompanied by a nearly equivalentquantity of water. Mitchell and Valk (I953)found that acidosis developed in their patientsafter ureteric transplanation when renal function(as shown by G.F.R., renal blood flow andTMP.A.H.) was better than the normal minimum;they found that when acidosis was corrected theplasma non-protein nitrogen and blood ureanitrogen concentration fell also and concludedthat their elevation had been due to the acidosis,to an alteration in rather than to an impairmentof, renal function.When the kidneys attempt to play their normal
part in the regulation of chloride and bicarbonateequilibrium, by excreting chloride in the urine,they are foiled for so long as urine is allowed tocollect in the colon and rectum, the more chloridethat is excreted into the urine the more there isavailable for absorption by the colon. This viciouscircle can be broken by draining away the urinefrom the colon, thus reducing absorption ofchloride and allowing the renal tubules to excretechloride unhindered by reabsorption and to restorethe normal balance of chloride and bicarbonate.The fact that this type of acidosis is so readily and
completely relieved by continuous drainage of thebowel suggests strongly that organic damage ofthe tubules or lasting interference with the car-bonic anhydrase system in the tubular cells arenot important factors in the production of thistype of acidosis. There is little evidence ofalteration in extracellular base (mainly sodium),but in advanced stages of the hyperchloraemicacidosis there may be some elevation of serumsodium; this may be due to an actual increase inthe total quantity of extracellular sodium or merelyto an increase in concentration due to reductionin extracellular fluid volume. It is probablyunlikely, therefore, that the sum of chloride andbicarbonate is altered, the change being in theirproportions.The total body potassium is reduced as the
result of the increased daily loss from the boweland this is accompanied by a reduction in totalbody water which chiefly affects the cells sinceabout 98 per cent. of the potassium is intracellular.Disturbances -f potassium metabolism which aresufficiently severe to give rise to symptoms arenot common. They are most often found afterinfective lesions or other acute complications.The importance of severe potassium deficiencyin association with acidosis is the higher mortalityrate, which results from the combination. Althoughthe potassium and other disturbances occurtogether it is important to appreciate that themechanisms of production may be quite different.The experiments of Parsons et al (I952) haveshown clearly that the higher potassium contentof cloacal fluid as compared with that of urine asoriginally secreted is due to the addition of potas-sium in the lower sigmoid and rectum. This leadsto persistent and progressive loss of base and to achronic state of intracellular dehydration (Wilkin-son, 1952), which would account for the inabilit'yof these patients to tolerate restriction of theirwater intake (Kekwick et al., I95i), and for thechronic thirst and salty taste of which many ofthem complain.
Summary and ConclusionsThe disturbances of blood and body chemistry
after transplantation of both ureters to the colonshow marked individual variation in severity andtime of onset, and some patients appear to survivefor many years without significant disturbances.Yet the general impression which emerges froma study of the available reports is remarkablyconsistent. The commonest feature is elevationof the plasma chloride concentration in a continentpatient and this seems to be more common whenthere is impairment of renal function. It is alsoa general feature that this type of acidosis respondswell and rapidly to such simple treatment is con-
tinuous drainage of the bowel with a rectal tube.The primary change seems to be the absorption
of chloride from the colon which causes a moderateelevation of plasma and extracellular chloride con-centration; to this the kidneys respond by anincreased output of chloride in the urine, muchof which, however, may be absorbed from thecolon although the net loss from the body isincreased. This increased renal excretion is onlypartially successful in controlling the rising extra-cellular concentration of chloride, but as theurinary excretion of chloride approaches a maxi-mum there is stabilization of the plasma chlorideat a concentration which varies in any individualfrom hour to hour according to circumstancesand intake of chloride in the food. Whether thereare changes in the plasma chloride concentrationfollowing large increments to, or losses of, chloridefrom the body depends on the ability of thekidneys to respond by an increase or reduction ofchloride output, as may be required. Becausethe daily turnover of chloride through the kidneysis increased so much by absorption of urinarychloride from the bowel the capacity of the kidneyto respond to chloride loading is greatly reducedafter transplantation of the ureters to the colon,and the likelihood of elevation of plasma chlorideconcentration is increased. The renal capacity torespond to variations in chloride intake and outputmay be further reduced by functional impairmentdue to hydronephrosis or pyelonephritis; whensuch organic changes in the kidneys becomemarked the life of the individual is closely circum-scribed by his limited renal capacity and the risksof-even minor additional complications is seriouslyincreased.
Alterations in the plasma bicarbonate concen-tration are secondary to those in chloride. Thereis no direct evidence that total plasma or extra-cellular fluid base concentration is reduced, butin a small proportion of patients plasma sodiumconcentration is raised and there is evidence thatsodium as well as urea and chloride is absorbedfrom the colon. The continued daily loss ofpotassium in the bowel leads to a reduction in totalbody base and may be the cause of clinicallyevident potassium deficiency and marked intra-cellular dehydration. After transplantation ofboth ureters the daily turnover of water is increasedby absorption from the colon with other con-stituents of the urine, in the larger volume ofwater lost each day in the mixed urine and faecesand in the greater quantity drunk; these patientsdo not react well to changes in their water intakeand the more advanced the organic changes intheir kidneys the less specific and delicate' can betheir renal reaction to 'changing water andelectrolyte intake.
August 1954 WILKINSON: Biochemical Disturbances after Transplantation of the Ureters 411
These patients should be encouraged to eat afull ordinary diet without adding salt to theirfood at the table, a salt-free diet is unpalatable andunattractive. Instead of restricting their chlorideintake it is easier to prescribe a mixture of sodiumbicarbonate and potassium citrate, or simplypotassium citrate alone; this will counteract thetendency to acidosis and replace the daily loss ofpotassium in the rectal fluid. They should beadvised to drink four to six pints of fluid eachday. In ordering their daily life they should seeka dish of herbs and contentment rather than thestalled ox and strife.
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