- Email: [email protected]
ROLE OF THE COLON IN ILEAL-RESECTION DIARRHŒA
344
parisons between groups." Although we found that the slope of the regressions of plasma-urea, plasmacreatinine, and diastolic and systolic blood-pressures i
steeper in the analgesic group, and their age-adjusted renal concentrating power was lower, none of these differences was statistically significant. Bengtsson 16 has stressed that poor concentrating ability is a prominent sign in analgesic nephropathy. No case of frank analgesic nephropathy was identified in this survey. on
age
at necropsy found that 48 out of 59 cases who were known to have taken analgesics containing more than 2 kg. of phenacetin had definite kidney abnormalities. The average lifelong consumption of phenacetin in the analgesic group in this study was estimated as 3-6 kg., and 6 women were thought to have taken over 6 kg. of phenacetin. In these 6 women the mean plasmaurea was 25-6 mg. per 100 ml. (range 17-34) and the mean plasma-creatinine was 0-82 mg. per 100 ml. (range 0-7-0-95) - none of the 6 had significant bacteriuria or impaired concentrating ability.
Epidemiological studies are unlikely to be large enough to obtain accurate figures for the prevalence of any analgesic syndrome. Our survey, however, does suggest that many individuals can consume comparatively large amounts of analgesics, including phenacetin, without obvious kidney damage. Such individuals in data based on go unrecognised patients in but in are of importance any unbiased hospital, assessment of the dangers of kidney damage from
analgesics. We thank Prof. A. L. Cochrane and other members of the M.R.C. Epidemiology Unit, and Dr John Henry Jones, Miss Margaret Hopkins, and Mrs Susan Chick, of the Cardiff Royal Infirmary, for their help. Requests for reprints should be addressed to W. E. W.
REFERENCES
3. 4. 5. 6. 7.
Spühler, O., Zollinger, H. U. Helv. med Acta, 1950, 17, 564. Gault, M. H., Rudwal, T. C., Engles, W. D., Dossetor, J. B. Ann. intern. Med. 1968, 68, 906. Levin, N. W. J. chron. Dis. 1969, 21, 527. Koutsaimanis, K. G., de Wardener, H. E. Br. med. J. 1970, iv, 131. Kincaid-Smith, P. Lancet, 1967, i, 859. Sorensen, A. W. S. Nephron, 1966, 3, 366. Dubach, U. C., Levy, P. S., Minder, F. Helv. med. Acta, 1968, 34,
8.
Dubach,
297. U.
C., Levy, P. S., Muller,
A. Am.
J. Epidem. 1971, 93,
425. 9. 10. 11. 12. 13. 14. 15. 16. 17.
18.
J.
was
The analgesic consumptions of individuals in the analgesic group in this community study and those reported from hospitals with analgesic nephropathy should be compared. In Australia each of 20 patients with a total analgesic consumption of 1-5 kg. showed some degree of chronic renal failure. 17 Also Burry 18
1. 2.
ROLE OF THE COLON IN ILEAL-RESECTION DIARRHŒA
Purnell, J., Burry, A. F. Med. J. Aust. 1967, ii, 389. Waters, W. E. Br. J. prev. soc. Med. 1969, 23, 263. Waters, W. E., Elwood, P. C., Asscher, A. W., Abernethy, M. Br. med. J. 1970, ii, 754. Prescott, L. F. Lancet, 1966, ii, 1143. Rawnsley, K. J. psychosom. Res. 1966, 10, 84. Waters, W. E., O’Connor, P. J. J. Neurol. Neurosurg. Psychiat. 1971, 34, 148. Waters, W. E. Br. J. prev. soc. Med. 1971, 25, 162. Bengtsson, U. Acta med. scand. 1962, suppl. no. 388. Steele, T. W., Gyory, A. Z., Edwards, K. D. G. Br. med. J. 1969, ii, 213. Burry, A F. Nephron, 1967, 5, 185.
H. CUMMINGS W. P. T. H. S. WIGGINS
JAMES
Medical Research Council Gastroenterology Unit, Central Middlesex Hospital, Park Royal, London NW10 7NS
The diarrhœa that follows ileal resection has been studied in nine patients on identical diets in order to identify the factors responsible. The severity of the diarrhœa, as expressed by the fæcal weight, increased as the length of any associated colonic resection increased, and was much less influenced by the length of ileal resection. Fæcalfat output increased as the length of ileal resection increased, but did not correlate with fæcal weight.
Sum ary
Fæcal-electrolyte composition
was
more
closely
re-
lated to the amount of residual colon than to the amount of residual ileum, and transit-time was slower in patients in whom more colon had been preserved. Ileal resection may increase the load delivered to the colon, resulting in diarrhœa when the absorptive capacity of the colon is reduced by disease or resection. It is important to preserve as much colon as possible at operation, since this will contribute significantly to the future wellbeing of the patient. Introduction
DiARRHCEA is a well-recognised complication of ileal resection and has been attributed to several factors. Steatorrhoea commonly follows the resection and may contribute to the diarrhoea, especially when the fat output exceeds 20 g. per day.1 Steatorrhoea is associated with the production of hydroxy fatty acids2 which may be cathartic, 3,4as may be the fatty acids themselves4 or their soaps.5 Bile-salts, which are malabsorbed after ileal resection, 6 are also thought to contribute to the diarrhoea.’ The role of the ileocaecal sphincter, which is often disrupted in these circumstances,has received little attention. Removal of the terminal ileum is often accompanied by resection of part or whole of the right colon. The possible effects which the colonic resection may have on the diarrhoea are usually ignored. We report our observations in patients with diarrhoea after ileal resection, and assess the role that colonic resection plays in determining the severity of the diarrhoea. Patients Ten studies were carried out in nine patients, patient 1 being studied before and after reconstructive surgery. All the patients complained of diarrhoea and all had undergone ileal resections (table i). Seven also had an associated colonic resection. In two of the three patients who had had an ileal resection only, the ileo-cæcal valve had been retained (patients 1 and 3). Patient 1 was first studied 8 years after a road accident which damaged his ileum and necessitated resection of 46 cm. of damaged bowel: the ileum was anastomosed to the transverse colon, bypassing the ileo-caecal area and right colon. Barium studies did not show any filling of the bypassed segment in patient 1. Subsequently the continuity of the ileum was restored and he was re-studied 6 months later. In six patients the ileal resection had been performed
345 TABLE I-CLINICAL DATA ON PATIENTS STUDIED
to the sites at which the ileo-colonic anastomoses made. The length of colon resected is expressed as a percentage of the total.
mately were
Methods The studies
were
conducted in
a
metabolic ward.
All
patients received the same diet of 2400 calories, consisting of protein 83 g., fat 85 g., and carbohydrate 344 g. 70 g. of the fat was given as olive-oil suitably mixed into each meal. Three 1-day menus with the above composition were designed and served in rotation, water intake being kept constant.
After first
operation. † After re-operation.
for Crohn’s disease and all of them had had part of the colon removed as well. In two of these (patients 8 and 9) the resected colon was also affected by the disease as judged by the histopathology of the specimen. All six studies were done at least 1 year after the last operation and none of the patients had been treated with steroids, sulphasalazine, or immunosuppressants within 6 months of the study. Only one patient was anaemic (patient 9, Hb 11 -7 g.) and none of them was losing weight, or was febrile, or had abdominal pain. Barium studies demonstrated that a short length of small bowel adjacent to the anastomosis with the colon was involved by recurrent disease in two subjects (patients 6 and 8), but the rest were normal. We concluded that all six patients were in remission. No patient received any medication during the study. Accurate assessment of the amount of bowel resected is always difficult. For the ileal resection we have relied on the estimate of the surgeon, recorded in his operation notes, and have used the pathologist’s measurement of the formalinfixed specimen for confirmation. The length of resected small bowel is expressed in centimetres. To estimate the amount of colon removed we compared its configuration on a postoperative barium enema with the surgeon’s and pathologist’s estimate of the amount resected. Because the length of the colon varies so much we have arbitrarily divided it into seven sections (fig. 1) and have assumed each section to be of equal length: each part thus represents 14°. of the large bowel. These divisions correspond approxi-
Continuous collections of fxces and urine
were
made, facilities for this being available in the patient’s room. Each faecal specimen was collected separately into a plastic bag held in a modified commode. The patient removed the bag with the specimen, sealed it, recorded the time, and placed it in a nearby deep freeze at -20°C. The urine was collected separately. At the start of the diet, 25 radioopaque pellets of barium-impregnated polyethylene were given. Each stool passed was X-rayed and the appearance of 80% of the pellets in the stool was taken to indicate the end of the transit-time.9 After an equilibration period of at least twice the mouth-to-anus transit-time, a 3-day fsecal collection was made. Each stool was weighed and all the fseces passed in this period (5-50 specimens) were allowed TABLE II-FÆCAL
WEIGHT, FÆCAL COMPOSITION,
AND TRANSIT-TIME
* After first operation. After re-operation. to thaw and were then homogenised whilst still cold. Water was added if necessary. Duplicate volumes were analysed for fat by a modification 10of the method of Van der Kamer et al.,llfor sodium and potassium by flame photometry, for chloride by potentiometric titration, and for volatile fatty acids (v.F.A.) by steam distillation and titration.
Results
Fig. 1—Division of the colon into senting t4°o of the whole.
seven
sections each repre-
Although there are no accepted criteria for defining diarrhoea, the daily faecal weight is probably the single most useful index of its severity (table II). On the diet used in the present study the mean daily faecal weight varied from 162 to 1528 g. per day in the patients studied, whilst three healthy volunteers on an identical diet had fxcal weights of from 29 to 113 g. Faecal weight increased strikingly as the per day. amount of colon resected increased (fig. 2), and it correlated significantly with the extent of the colonic resection, but not with the length of ileum resected. The three patients with an ileal resection only (patients 1 [after re-operation], 2, and 3), although complaining of diarrhoea, had amongst the smallest fxcal outputs (238-281 g. per day) despite quite large resections.
346
Fig. 2-Fæcal weight and faecal-fat output correlated with the amount
of ileum and colon resected.
N.S. =not
significant. Fig. 4-Fæcal-electrolyte concentrations correlated with the percentage of colon resected.
patients had comparable ileal resections, patient 3 and patient 1 (after first operation), or patient 1 (after re-operation) and patient 6, the one with the additional colonic resection had a much higher Where such as
faecal output. Transit-time through the gut was also affected by the colonic resection: the more extensive the colonic resection the more rapid was transit (fig. 3). Fxcal weight showed a similar relation to transit-time, the shortest transit-time being found in those patients with the greatest faecal weight. All seven patients with a colonic resection had abnormally rapid transit of less than 24 hours, whilst the three with only an ileal resection had normal transit-times. The length of the ileal resection did not correlate with transit-time (r=0°12, P>0°1). Faecal-electrolyte composition changed with the severity of the diarrhoea (fig. 4). Sodium and chloride concentrations in the stool rose with increasing colonic
resection and greater faecal weight, whereas potassium and V.F.A. concentrations fell. When no colon had been resected the diarrhoea was slight and potassium concentrations ranged from 49-130 meq. per litre, with V.F.A. as the major anion; a situation very similar to that found in normal people.12 With increasing colonic resection the electrolyte concentrations approached ileostomy values,13 whilst the V.F.A. fell to low levels. Fat output in these patients was the only variable measured which correlated with the amount of ileum resected and not with the colonic resection (fig. 2). It follows from this and the previous data that fat output does not correlate with the faecal weight in these patients (r=0°21).
The variation in faecal weight from day to day was small (coefficient of variation 22°8°), and so a 3-day faecal collection was judged to be adequate for the assessment of fxcal output in these patients with diarrhoea. Discussion
Fig. 3-Transit-time (mouth-to-anus) centage of colon resected.
correlated with the per-
The present studies indicate that the proportion of colon removed is more important in determining the severity of the diarrhoea than the length of ileum resected. Although this has not been previously reported, it may be deduced from studies in which patients have had faecal outputs and intestinal resections recorded quantitatively as part of other investigations, such as those into bile-salt kinetics.14,15 In the groups of patients with intestinal resection studied by Miettinen 1’ and Woodbury and Kern 15 the greatest faecal weight was recorded in those with less than half the colon remaining. The exact outputs are not directly
347
comparable with
ours because of differences in the and this also diets, applies to fxcal-fat outputS.16 The severity of the diarrhoea is probably related to both the ileal and colonic resection. The absence of a significant correlation between ileal resection and faecal weight indicates that in our group of patients the effect of the ileal resection is small enough to be masked by that of the colonic resection. The relative contributions of the different resections can be calculated by multiple regression analysis,1’ which gives the equation : y=ll’94xi+3-19x2—l-07, where y = fxcal weight, Xi==% colon resected, and x2=cm. ileum resected. Analysis of variance indicates that both regression coefficients are significant: colonic resection, ileal resection, .F=7-81, p<0’05. F=28’4, p<0’005; Thus both the ileal and colonic resection contribute to the increased faecal weight, but the latter is the more important of the two factors. The exact mechanism whereby ileal resection causes diarrhoea remains to be elucidated. Bile-salts, which are absorbed mainly in the terminal ileum in man,18 may be partly responsible, since they cause secretion of water and electrolytes when perfused through the colon. 19 The effect of unabsorbed bilesalts on the colon is thought to be responsible for the cholerrhceic enteropathy " that follows ileal resection. 7,19 In our study, faecal weight increased as the amount of colon resected increased, which suggests that the diarrhoea results more from a loss of the normal colonic absorptive function than from a net secretion induced by bile-salts or fatty acids. Another effect of ileal resection is to reduce the surface area available in the small intestine for water Miettinen and Peltoand electrolyte absorption. kallio 20 have demonstrated an increase in ileostomy output in patients with ileostomies who took bilesalts, suggesting that unabsorbed bile-salts may determine the amount of fluid leaving the ileum. In patients with an ileal resection a greater load of fluid and electrolytes may be delivered to the colon and if colonic function is impaired by disease or resection its absorptive capacity will be more easily overwhelmed. The colon has been shown to absorb salt and water, whilst secreting potassium. 21 If the volume and composition of normal stool 12 is compared to that of ileostomy fluid, 13then salt and water absorption would seem to be a major function of the colon. Removal of part of the colon would reduce its capacity to absorb water and electrolytes, resulting in an increased water output in the stools-i.e., diarrhoea-and increased sodium and chloride concentrations with a fall in potassium excretion. The fxcal-electrolyte data in our patients conform to this pattern of higher sodium and chloride, with lower potassium concentrations as the severity of the diarrhoea increases,and suggest that loss of colonic absorptive function plays a major role in causing the diarrhoea. The V.F.A. represent the major fraction (50-60%) of the titratable organic anion in normal fxces 2’Z and in diarrhoea.23 Fernandez et al. 24 noted that organic-anion output correlated closely with faecal output, and it has been suggested 25 that organic anion may play an important role in determining faecal bulk. This is not the case in our group of patients, and it "
improbable that the v.F.A. are acting as nonabsorbable osmotic cathartics here as they do in the diarrhoea of sugar malabsorption 26, 11 and some The observed fall in forms of infant diarrhoea.28 with V.F.A. concentrations increasing faecal weight and colonic resection (fig. 4) may be related to the faster transit-time in our patients. The v.F.A. are the products of bacterial metabolism of unabsorbed dietary components and are present in smaller quantities when rapid transit reduces the time available for their seems
production. Our observations have important implications both and to those investigating the diarrhoea that follows ileal resection. Ileal resection may indeed lead to diarrhoea, but this will become much more severe if there is any associated colonic resection. This factor must be taken into account when suggesting mechanisms for diarrhoea after ileal resection. At operation, care should be taken to preserve as much colon as possible, since this will contribute to the future wellbeing of the patient.
clinically
We thank Sir Francis Avery Jones, Dr T. D. Kellock, and Dr J. J. Misiewicz for allowing us to study patients under their care; Mrs Mottram and the staff of the diet kitchen for carefully controlling the diets; the Sister and staff who supervise the metabolic patients; Mr A. G. Booker for the illustrations; Mrs 1. M. Prentice for the drawings; and Mrs Wendy Lamble and Mr Raymond Sapsford for help with the chemical determinations. W. P. T. J. was in receipt of a grant from the Wellcome
Trust.
Requests for reprints should be addressed
to
J. H. C.
REFERENCES 1. 2.
3. 4. 5. 6. 7. 8. 9. 10. 11. 12.
13. 14. 15. 16.
Hofmann, A. F., Poley, J. R. Gastroenterology, 1972, 62, 918. Kellock, T. D., Pearson, J. R., Russell, R. I., Walker, J. G., Wiggins, H. S. Gut, 1969, 10, 1055. James, A. T., Webb, J. P. W., Kellock, T. D. Biochem. J. 1961, 78, 333. Ammon, H. V., Phillips, S. F. Gastroenterology, 1972, 62, 717. Leveen, H. H., Borek, B., Axelrod, D. R., Johnson, A. Surgery Gynec. Obstet. 1967, 124, 766. Austad, W. I., Lack, L., Tyor, M. P. Gastroenterology, 1967, 52, 638. Hofmann, A. F. ibid. p. 752. Gazet, J. C. Ann. R. Coll. Surg. 1968, 43, 19. Hinton, J. M., Lennard-Jones, J. E., Young, A. C. Gut, 1969, 10, 842. Jover, A., Gordon, R. S. J. Lab. clin. Med. 1962, 59, 878. Van der Kamer, J. H., Huinink, H. Ten B., Weyers, H. A. J. biol. Chem. 1949, 177, 347. Wrong, O., Metcalfe-Gibson, A., Morrison, R. B. I., Ng, S. T., Howard, A. V. Clin. Sci. 1965, 28, 357. Kanaghinis, T., Lubran, M., Coghill, N. F. Gut, 1963, 4, 322. Miettinen, T. A. Eur. J. clin. Invest. 1971, 1, 452. Woodbury, J. F., Kern, F. J. clin. Invest. 1971, 50, 2531. Hofmann, A. F., Poley, J. R. New Engl. J. Med. 1969, 281, 397.
Snedecor, G. W., Cochran, W. G. Statistical Methods; p. 381. Ames, Iowa, 1967. 18. Borgstrom, B., Lundh, G., Hofmann, A. F. Gastroenterology, 1963, 45, 229. 19. Mekhjian, H. S., Phillips, S. F., Hofmann, A. F. J. clin. Invest. 1971, 50, 1569. 20. Miettinen, T. A., Peltokallio, P. Scand. J. Gastroenterol. 1971, 6, 17.
543.
21. 22.
Levitan, R., Fordtran, J. S., Burrows, B. A., Ingelfinger, F. J. J. clin. Invest. 1962, 41, 1754. Rubinstein, R., Howard, A. V., Wrong, O. M. Clin. Sci. 1969, 37, 549.
Wiggins, H. S., Cummings, J. H. Unpublished. Fernandez, L. B., Gonzalez, E., Marzi, A., Paolo, M. I. L. de. New Engl. J. Med. 1971, 284, 295. 25. Fordtran, J. S. ibid. p. 329. 26. Weijers, H. A., Van der Kamer, J. H. Acta pædiat. Stockh. 1963, 52, 329. 27. Launiala, K. Acta pædiat. scand. 1968, 57, 425. 28. Torres-Pinedo, R., Lavistida, M., Rivera, C. L., Rodriguez, H., Ortiz, A. J. clin. Invest. 1966, 45, 469. 23. 24.
parisons between groups." Although we found that the slope of the regressions of plasma-urea, plasmacreatinine, and diastolic and systolic blood-pressures i
steeper in the analgesic group, and their age-adjusted renal concentrating power was lower, none of these differences was statistically significant. Bengtsson 16 has stressed that poor concentrating ability is a prominent sign in analgesic nephropathy. No case of frank analgesic nephropathy was identified in this survey. on
age
at necropsy found that 48 out of 59 cases who were known to have taken analgesics containing more than 2 kg. of phenacetin had definite kidney abnormalities. The average lifelong consumption of phenacetin in the analgesic group in this study was estimated as 3-6 kg., and 6 women were thought to have taken over 6 kg. of phenacetin. In these 6 women the mean plasmaurea was 25-6 mg. per 100 ml. (range 17-34) and the mean plasma-creatinine was 0-82 mg. per 100 ml. (range 0-7-0-95) - none of the 6 had significant bacteriuria or impaired concentrating ability.
Epidemiological studies are unlikely to be large enough to obtain accurate figures for the prevalence of any analgesic syndrome. Our survey, however, does suggest that many individuals can consume comparatively large amounts of analgesics, including phenacetin, without obvious kidney damage. Such individuals in data based on go unrecognised patients in but in are of importance any unbiased hospital, assessment of the dangers of kidney damage from
analgesics. We thank Prof. A. L. Cochrane and other members of the M.R.C. Epidemiology Unit, and Dr John Henry Jones, Miss Margaret Hopkins, and Mrs Susan Chick, of the Cardiff Royal Infirmary, for their help. Requests for reprints should be addressed to W. E. W.
REFERENCES
3. 4. 5. 6. 7.
Spühler, O., Zollinger, H. U. Helv. med Acta, 1950, 17, 564. Gault, M. H., Rudwal, T. C., Engles, W. D., Dossetor, J. B. Ann. intern. Med. 1968, 68, 906. Levin, N. W. J. chron. Dis. 1969, 21, 527. Koutsaimanis, K. G., de Wardener, H. E. Br. med. J. 1970, iv, 131. Kincaid-Smith, P. Lancet, 1967, i, 859. Sorensen, A. W. S. Nephron, 1966, 3, 366. Dubach, U. C., Levy, P. S., Minder, F. Helv. med. Acta, 1968, 34,
8.
Dubach,
297. U.
C., Levy, P. S., Muller,
A. Am.
J. Epidem. 1971, 93,
425. 9. 10. 11. 12. 13. 14. 15. 16. 17.
18.
J.
was
The analgesic consumptions of individuals in the analgesic group in this community study and those reported from hospitals with analgesic nephropathy should be compared. In Australia each of 20 patients with a total analgesic consumption of 1-5 kg. showed some degree of chronic renal failure. 17 Also Burry 18
1. 2.
ROLE OF THE COLON IN ILEAL-RESECTION DIARRHŒA
Purnell, J., Burry, A. F. Med. J. Aust. 1967, ii, 389. Waters, W. E. Br. J. prev. soc. Med. 1969, 23, 263. Waters, W. E., Elwood, P. C., Asscher, A. W., Abernethy, M. Br. med. J. 1970, ii, 754. Prescott, L. F. Lancet, 1966, ii, 1143. Rawnsley, K. J. psychosom. Res. 1966, 10, 84. Waters, W. E., O’Connor, P. J. J. Neurol. Neurosurg. Psychiat. 1971, 34, 148. Waters, W. E. Br. J. prev. soc. Med. 1971, 25, 162. Bengtsson, U. Acta med. scand. 1962, suppl. no. 388. Steele, T. W., Gyory, A. Z., Edwards, K. D. G. Br. med. J. 1969, ii, 213. Burry, A F. Nephron, 1967, 5, 185.
H. CUMMINGS W. P. T. H. S. WIGGINS
JAMES
Medical Research Council Gastroenterology Unit, Central Middlesex Hospital, Park Royal, London NW10 7NS
The diarrhœa that follows ileal resection has been studied in nine patients on identical diets in order to identify the factors responsible. The severity of the diarrhœa, as expressed by the fæcal weight, increased as the length of any associated colonic resection increased, and was much less influenced by the length of ileal resection. Fæcalfat output increased as the length of ileal resection increased, but did not correlate with fæcal weight.
Sum ary
Fæcal-electrolyte composition
was
more
closely
re-
lated to the amount of residual colon than to the amount of residual ileum, and transit-time was slower in patients in whom more colon had been preserved. Ileal resection may increase the load delivered to the colon, resulting in diarrhœa when the absorptive capacity of the colon is reduced by disease or resection. It is important to preserve as much colon as possible at operation, since this will contribute significantly to the future wellbeing of the patient. Introduction
DiARRHCEA is a well-recognised complication of ileal resection and has been attributed to several factors. Steatorrhoea commonly follows the resection and may contribute to the diarrhoea, especially when the fat output exceeds 20 g. per day.1 Steatorrhoea is associated with the production of hydroxy fatty acids2 which may be cathartic, 3,4as may be the fatty acids themselves4 or their soaps.5 Bile-salts, which are malabsorbed after ileal resection, 6 are also thought to contribute to the diarrhoea.’ The role of the ileocaecal sphincter, which is often disrupted in these circumstances,has received little attention. Removal of the terminal ileum is often accompanied by resection of part or whole of the right colon. The possible effects which the colonic resection may have on the diarrhoea are usually ignored. We report our observations in patients with diarrhoea after ileal resection, and assess the role that colonic resection plays in determining the severity of the diarrhoea. Patients Ten studies were carried out in nine patients, patient 1 being studied before and after reconstructive surgery. All the patients complained of diarrhoea and all had undergone ileal resections (table i). Seven also had an associated colonic resection. In two of the three patients who had had an ileal resection only, the ileo-cæcal valve had been retained (patients 1 and 3). Patient 1 was first studied 8 years after a road accident which damaged his ileum and necessitated resection of 46 cm. of damaged bowel: the ileum was anastomosed to the transverse colon, bypassing the ileo-caecal area and right colon. Barium studies did not show any filling of the bypassed segment in patient 1. Subsequently the continuity of the ileum was restored and he was re-studied 6 months later. In six patients the ileal resection had been performed
345 TABLE I-CLINICAL DATA ON PATIENTS STUDIED
to the sites at which the ileo-colonic anastomoses made. The length of colon resected is expressed as a percentage of the total.
mately were
Methods The studies
were
conducted in
a
metabolic ward.
All
patients received the same diet of 2400 calories, consisting of protein 83 g., fat 85 g., and carbohydrate 344 g. 70 g. of the fat was given as olive-oil suitably mixed into each meal. Three 1-day menus with the above composition were designed and served in rotation, water intake being kept constant.
After first
operation. † After re-operation.
for Crohn’s disease and all of them had had part of the colon removed as well. In two of these (patients 8 and 9) the resected colon was also affected by the disease as judged by the histopathology of the specimen. All six studies were done at least 1 year after the last operation and none of the patients had been treated with steroids, sulphasalazine, or immunosuppressants within 6 months of the study. Only one patient was anaemic (patient 9, Hb 11 -7 g.) and none of them was losing weight, or was febrile, or had abdominal pain. Barium studies demonstrated that a short length of small bowel adjacent to the anastomosis with the colon was involved by recurrent disease in two subjects (patients 6 and 8), but the rest were normal. We concluded that all six patients were in remission. No patient received any medication during the study. Accurate assessment of the amount of bowel resected is always difficult. For the ileal resection we have relied on the estimate of the surgeon, recorded in his operation notes, and have used the pathologist’s measurement of the formalinfixed specimen for confirmation. The length of resected small bowel is expressed in centimetres. To estimate the amount of colon removed we compared its configuration on a postoperative barium enema with the surgeon’s and pathologist’s estimate of the amount resected. Because the length of the colon varies so much we have arbitrarily divided it into seven sections (fig. 1) and have assumed each section to be of equal length: each part thus represents 14°. of the large bowel. These divisions correspond approxi-
Continuous collections of fxces and urine
were
made, facilities for this being available in the patient’s room. Each faecal specimen was collected separately into a plastic bag held in a modified commode. The patient removed the bag with the specimen, sealed it, recorded the time, and placed it in a nearby deep freeze at -20°C. The urine was collected separately. At the start of the diet, 25 radioopaque pellets of barium-impregnated polyethylene were given. Each stool passed was X-rayed and the appearance of 80% of the pellets in the stool was taken to indicate the end of the transit-time.9 After an equilibration period of at least twice the mouth-to-anus transit-time, a 3-day fsecal collection was made. Each stool was weighed and all the fseces passed in this period (5-50 specimens) were allowed TABLE II-FÆCAL
WEIGHT, FÆCAL COMPOSITION,
AND TRANSIT-TIME
* After first operation. After re-operation. to thaw and were then homogenised whilst still cold. Water was added if necessary. Duplicate volumes were analysed for fat by a modification 10of the method of Van der Kamer et al.,llfor sodium and potassium by flame photometry, for chloride by potentiometric titration, and for volatile fatty acids (v.F.A.) by steam distillation and titration.
Results
Fig. 1—Division of the colon into senting t4°o of the whole.
seven
sections each repre-
Although there are no accepted criteria for defining diarrhoea, the daily faecal weight is probably the single most useful index of its severity (table II). On the diet used in the present study the mean daily faecal weight varied from 162 to 1528 g. per day in the patients studied, whilst three healthy volunteers on an identical diet had fxcal weights of from 29 to 113 g. Faecal weight increased strikingly as the per day. amount of colon resected increased (fig. 2), and it correlated significantly with the extent of the colonic resection, but not with the length of ileum resected. The three patients with an ileal resection only (patients 1 [after re-operation], 2, and 3), although complaining of diarrhoea, had amongst the smallest fxcal outputs (238-281 g. per day) despite quite large resections.
346
Fig. 2-Fæcal weight and faecal-fat output correlated with the amount
of ileum and colon resected.
N.S. =not
significant. Fig. 4-Fæcal-electrolyte concentrations correlated with the percentage of colon resected.
patients had comparable ileal resections, patient 3 and patient 1 (after first operation), or patient 1 (after re-operation) and patient 6, the one with the additional colonic resection had a much higher Where such as
faecal output. Transit-time through the gut was also affected by the colonic resection: the more extensive the colonic resection the more rapid was transit (fig. 3). Fxcal weight showed a similar relation to transit-time, the shortest transit-time being found in those patients with the greatest faecal weight. All seven patients with a colonic resection had abnormally rapid transit of less than 24 hours, whilst the three with only an ileal resection had normal transit-times. The length of the ileal resection did not correlate with transit-time (r=0°12, P>0°1). Faecal-electrolyte composition changed with the severity of the diarrhoea (fig. 4). Sodium and chloride concentrations in the stool rose with increasing colonic
resection and greater faecal weight, whereas potassium and V.F.A. concentrations fell. When no colon had been resected the diarrhoea was slight and potassium concentrations ranged from 49-130 meq. per litre, with V.F.A. as the major anion; a situation very similar to that found in normal people.12 With increasing colonic resection the electrolyte concentrations approached ileostomy values,13 whilst the V.F.A. fell to low levels. Fat output in these patients was the only variable measured which correlated with the amount of ileum resected and not with the colonic resection (fig. 2). It follows from this and the previous data that fat output does not correlate with the faecal weight in these patients (r=0°21).
The variation in faecal weight from day to day was small (coefficient of variation 22°8°), and so a 3-day faecal collection was judged to be adequate for the assessment of fxcal output in these patients with diarrhoea. Discussion
Fig. 3-Transit-time (mouth-to-anus) centage of colon resected.
correlated with the per-
The present studies indicate that the proportion of colon removed is more important in determining the severity of the diarrhoea than the length of ileum resected. Although this has not been previously reported, it may be deduced from studies in which patients have had faecal outputs and intestinal resections recorded quantitatively as part of other investigations, such as those into bile-salt kinetics.14,15 In the groups of patients with intestinal resection studied by Miettinen 1’ and Woodbury and Kern 15 the greatest faecal weight was recorded in those with less than half the colon remaining. The exact outputs are not directly
347
comparable with
ours because of differences in the and this also diets, applies to fxcal-fat outputS.16 The severity of the diarrhoea is probably related to both the ileal and colonic resection. The absence of a significant correlation between ileal resection and faecal weight indicates that in our group of patients the effect of the ileal resection is small enough to be masked by that of the colonic resection. The relative contributions of the different resections can be calculated by multiple regression analysis,1’ which gives the equation : y=ll’94xi+3-19x2—l-07, where y = fxcal weight, Xi==% colon resected, and x2=cm. ileum resected. Analysis of variance indicates that both regression coefficients are significant: colonic resection, ileal resection, .F=7-81, p<0’05. F=28’4, p<0’005; Thus both the ileal and colonic resection contribute to the increased faecal weight, but the latter is the more important of the two factors. The exact mechanism whereby ileal resection causes diarrhoea remains to be elucidated. Bile-salts, which are absorbed mainly in the terminal ileum in man,18 may be partly responsible, since they cause secretion of water and electrolytes when perfused through the colon. 19 The effect of unabsorbed bilesalts on the colon is thought to be responsible for the cholerrhceic enteropathy " that follows ileal resection. 7,19 In our study, faecal weight increased as the amount of colon resected increased, which suggests that the diarrhoea results more from a loss of the normal colonic absorptive function than from a net secretion induced by bile-salts or fatty acids. Another effect of ileal resection is to reduce the surface area available in the small intestine for water Miettinen and Peltoand electrolyte absorption. kallio 20 have demonstrated an increase in ileostomy output in patients with ileostomies who took bilesalts, suggesting that unabsorbed bile-salts may determine the amount of fluid leaving the ileum. In patients with an ileal resection a greater load of fluid and electrolytes may be delivered to the colon and if colonic function is impaired by disease or resection its absorptive capacity will be more easily overwhelmed. The colon has been shown to absorb salt and water, whilst secreting potassium. 21 If the volume and composition of normal stool 12 is compared to that of ileostomy fluid, 13then salt and water absorption would seem to be a major function of the colon. Removal of part of the colon would reduce its capacity to absorb water and electrolytes, resulting in an increased water output in the stools-i.e., diarrhoea-and increased sodium and chloride concentrations with a fall in potassium excretion. The fxcal-electrolyte data in our patients conform to this pattern of higher sodium and chloride, with lower potassium concentrations as the severity of the diarrhoea increases,and suggest that loss of colonic absorptive function plays a major role in causing the diarrhoea. The V.F.A. represent the major fraction (50-60%) of the titratable organic anion in normal fxces 2’Z and in diarrhoea.23 Fernandez et al. 24 noted that organic-anion output correlated closely with faecal output, and it has been suggested 25 that organic anion may play an important role in determining faecal bulk. This is not the case in our group of patients, and it "
improbable that the v.F.A. are acting as nonabsorbable osmotic cathartics here as they do in the diarrhoea of sugar malabsorption 26, 11 and some The observed fall in forms of infant diarrhoea.28 with V.F.A. concentrations increasing faecal weight and colonic resection (fig. 4) may be related to the faster transit-time in our patients. The v.F.A. are the products of bacterial metabolism of unabsorbed dietary components and are present in smaller quantities when rapid transit reduces the time available for their seems
production. Our observations have important implications both and to those investigating the diarrhoea that follows ileal resection. Ileal resection may indeed lead to diarrhoea, but this will become much more severe if there is any associated colonic resection. This factor must be taken into account when suggesting mechanisms for diarrhoea after ileal resection. At operation, care should be taken to preserve as much colon as possible, since this will contribute to the future wellbeing of the patient.
clinically
We thank Sir Francis Avery Jones, Dr T. D. Kellock, and Dr J. J. Misiewicz for allowing us to study patients under their care; Mrs Mottram and the staff of the diet kitchen for carefully controlling the diets; the Sister and staff who supervise the metabolic patients; Mr A. G. Booker for the illustrations; Mrs 1. M. Prentice for the drawings; and Mrs Wendy Lamble and Mr Raymond Sapsford for help with the chemical determinations. W. P. T. J. was in receipt of a grant from the Wellcome
Trust.
Requests for reprints should be addressed
to
J. H. C.
REFERENCES 1. 2.
3. 4. 5. 6. 7. 8. 9. 10. 11. 12.
13. 14. 15. 16.
Hofmann, A. F., Poley, J. R. Gastroenterology, 1972, 62, 918. Kellock, T. D., Pearson, J. R., Russell, R. I., Walker, J. G., Wiggins, H. S. Gut, 1969, 10, 1055. James, A. T., Webb, J. P. W., Kellock, T. D. Biochem. J. 1961, 78, 333. Ammon, H. V., Phillips, S. F. Gastroenterology, 1972, 62, 717. Leveen, H. H., Borek, B., Axelrod, D. R., Johnson, A. Surgery Gynec. Obstet. 1967, 124, 766. Austad, W. I., Lack, L., Tyor, M. P. Gastroenterology, 1967, 52, 638. Hofmann, A. F. ibid. p. 752. Gazet, J. C. Ann. R. Coll. Surg. 1968, 43, 19. Hinton, J. M., Lennard-Jones, J. E., Young, A. C. Gut, 1969, 10, 842. Jover, A., Gordon, R. S. J. Lab. clin. Med. 1962, 59, 878. Van der Kamer, J. H., Huinink, H. Ten B., Weyers, H. A. J. biol. Chem. 1949, 177, 347. Wrong, O., Metcalfe-Gibson, A., Morrison, R. B. I., Ng, S. T., Howard, A. V. Clin. Sci. 1965, 28, 357. Kanaghinis, T., Lubran, M., Coghill, N. F. Gut, 1963, 4, 322. Miettinen, T. A. Eur. J. clin. Invest. 1971, 1, 452. Woodbury, J. F., Kern, F. J. clin. Invest. 1971, 50, 2531. Hofmann, A. F., Poley, J. R. New Engl. J. Med. 1969, 281, 397.
Snedecor, G. W., Cochran, W. G. Statistical Methods; p. 381. Ames, Iowa, 1967. 18. Borgstrom, B., Lundh, G., Hofmann, A. F. Gastroenterology, 1963, 45, 229. 19. Mekhjian, H. S., Phillips, S. F., Hofmann, A. F. J. clin. Invest. 1971, 50, 1569. 20. Miettinen, T. A., Peltokallio, P. Scand. J. Gastroenterol. 1971, 6, 17.
543.
21. 22.
Levitan, R., Fordtran, J. S., Burrows, B. A., Ingelfinger, F. J. J. clin. Invest. 1962, 41, 1754. Rubinstein, R., Howard, A. V., Wrong, O. M. Clin. Sci. 1969, 37, 549.
Wiggins, H. S., Cummings, J. H. Unpublished. Fernandez, L. B., Gonzalez, E., Marzi, A., Paolo, M. I. L. de. New Engl. J. Med. 1971, 284, 295. 25. Fordtran, J. S. ibid. p. 329. 26. Weijers, H. A., Van der Kamer, J. H. Acta pædiat. Stockh. 1963, 52, 329. 27. Launiala, K. Acta pædiat. scand. 1968, 57, 425. 28. Torres-Pinedo, R., Lavistida, M., Rivera, C. L., Rodriguez, H., Ortiz, A. J. clin. Invest. 1966, 45, 469. 23. 24.