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Adaptation to ileal diversion
Volume 129
Number 2
SURGERY FEBRUARY
2001
Surgical research review Adaptation to ileal diversion David I. Soybel, MD, Boston and West Roxbury, Mass
From the Department of Surgery, Brigham and Women’s Hospital and Boston VA Healthcare System, West Roxbury Division, Harvard Medical School, Boston and West Roxbury, Mass
FOR MOST PATIENTS the early period after establishment of an ileostomy is marked by salt and water depletion. For most patients the fluid and electrolyte imbalances become manageable within a few days; however, a small proportion of patients maintain outputs of ileal fluid that are greater than 1 L per day. In the 1960s there had been a considerable amount of investigation to characterize the clinical course of adaptation after ileostomy. Recent work has focused on identifying the systemic mechanisms by which the organism adapts to the loss of its colon. However, little has been done to clarify the mechanisms by which the upstream small intestine increases its efficiency in absorbing NaCl and H2O after ileal diversion. Here I review these prior studies and findings and outline experimental approaches that have evaluated mechanisms of salt and water absorption by upstream segments of small intestine after diversion of the ileal contents distally.
Accepted for publication April 17, 2000. Reprint requests: David I. Soybel, MD, Surgery 112, 1400 VFW Parkway, West Roxbury, MA 02132. Surgery 2001;129:123-7. Copyright © 2001 by Mosby, Inc. 0039-6060/2001/$35.00 + 0 doi:10.1067/msy.2001.107980
11/60/107980
CLINICAL CHARACTERISTICS OF ADAPTATION AFTER ILEAL DIVERSION Virtually all clinical reviews have indicated that patients with permanent ileostomies eventually have a high level of satisfaction with the function of the stoma. Of course, most of these studies have been conducted in patients who were suffering from acute symptoms of chronic ulcerative colitis before proctocolectomy and ileostomy. Thus, it has been argued that the improvements in satisfaction and quality of life indexes were no more than a comparison between states of illness and wellness. Nevertheless, a number of lessons have been learned from this group of patients (Table I).1-3 These include the following: First, the average patient empties the ileostomy bag, on average, 6 to 8 times per day.1 Second, despite the best techniques in stoma construction and care, skin excoriation affects between 30% and 40% of patients on a regular basis, and these effects are attributable to the volume and caustic nature of the ileal effluent.1,2 Third, certain foods, including those containing high levels of fat or fiber, often cause increased levels of ileostomy output.4-7 Fourth, ileostomy output is associated with insignificant or low levels of nutrient malabsorption, major vitamin deficiencies or metabolic derangements leading to anemia, mineral bone disease, gallstones or renal stones, unless it is also accompanied by resection of major portions of the small intestine.8-12 SURGERY 123
124 Soybel
Surgery February 2001 Table II. Daily steady-state fecal losses after ileostomy Normal stool Ileostomy
Water
Na+
K+
Cl–
100-150 650 ± 44
1-5 81 ± 7
5-15 6±1
1-2 34 ± 6
Volume in mL, mass in mmol. Means ± SD. Data from references 19 and 20.
PHASES OF ADAPTATION AFTER ILEAL DIVERSION
Figure. Ileostomy outputs in the early postoperative period. Data from 60 patients undergoing diverting ileostomy for a variety of indications (reference 17).
Table I. Life-style after ileostomy Reoperation Revision Intestinal obstruction Skin excoriation Problems Frequency of emptying Appliance change (per wk) Restriction in activity House Social Sexual Travel Diet
Age < 60 y
Age > 60 y
12% 8% 40% 6% 7.4 ± 0.2 1.0-2.7
6% 3% 30% 18% 6.6 ± 0.3 0.3-2.2
12% 20% 28% 25% 28%
18% 24% 24% 33% 34%
Data adapted from reference 2.
Overall, the average patient does well with an ileostomy. It is not hard to avoid dehydration or nutritional deficiencies, unless a very large amount of bowel has also been resected. If certain foods are not agreeable, they can be avoided. Traditionally, it has been said that elderly patients may have trouble with ileostomy, especially because of dehydration. However, it remains unclear whether elderly patients have increased levels of ileostomy output and there is evidence that they do not.2,13,14 It would appear that a subgroup of elderly patients have higher levels of complications and may have more difficulty responding to the expected levels of salt and water depletion.2,13,14 Thus, the elderly may be more susceptible to dehydration, even if actual ileostomy outputs are not increased over those seen in younger patients.
During the initial postoperative period after ileostomy, there appear to be 3 distinct phases of adaptation. Initially, just after the ileostomy is formed, there is a period of 1 to 3 days after surgery in which output increases. In the second phase, which begins between days 3 to 5, outputs stabilize or decline only slightly. In the third phase, which begins between days 4 to 7, outputs decline continuously, reaching steady levels between 40 to 60 days (6 to 8 weeks). Compared with the drawn-out periods of adaptation after massive enteral resection,15,16 the phases of adaptation after simple ileal diversion are brief. The variability of individual patient responses during phases 1 and 2 is illustrated in the Figure. As shown in the Figure, taken from data published in a recent report by Tang et al,17 ileostomy outputs may vary between 300 and 3500 mL per day. It should be noted that ileal outputs of volume are closely correlated to the output of sodium ion, Na+, and chloride ion, Cl–. Ultimately, most patients have cumulative outputs of about 600 to 700 mL per day.11,12,17,18 On the basis of the data provided in Table II, it can be calculated that about 120 mEq Na+ and 50 mEq Cl– are lost with each liter of ileostomy effluent. Losses of potassium ion are not closely correlated to ileostomy output. It has been said that both normal individuals and ileostomy patients lose about 9 mEq K+ each day, regardless of the magnitude of the output of feces or ileostomy effluent.19,20 FACTORS INFLUENCING ILEOSTOMY OUTPUT Ileostomy output is influenced by several factors, some physiologic and some pathologic. Physiologic factors include body size, composition and complexity of diet, and contributions of secretions from upstream segments of the gastrointestinal tract. The single most important pathologic factor contributing to the magnitude of ileostomy output is the amount of uninjured intestine proximally. Output of volume increases with body mass, so that outputs of 300 to 400 mL/day would be
Surgery Volume 129, Number 2
expected from individuals weighing 40 kg and 800 mL/day would not be unreasonable for individuals weighing 80 kg.21 With respect to diet, it is curious that water intake itself plays virtually no role in determining the magnitude of ileostomy output. Dehydration certainly decreases outputs, but excessive levels of water consumption do not appear to alter stomal losses. With respect to individual dietary components, prior studies have shown that patients with well-established ileostomies respond to elemental diet with decreases in volume and concentrations of digestive enzymes and bile acids in the ileostomy effluent.22 High fat (long-chain triglycerides) content has been associated with higher losses through the stoma, up to 20% above baseline levels.7,23,24 The effects of fat have been evaluated in some detail. Of note, high fat diets did not elicit changes in intestinal transit, arguing against a role for gastrointestinal motility in mediating the increase in ileostomy output.7,23 Thus, it has been suggested that the fat-induced increases in output are due to absorptive inhibition or possibly secretory stimulation of the intestinal mucosa by bile salt, which are not efficiently absorbed after loss of the most terminal region of the ileum.23-25 The failure to absorb bile acids, in turn, would then lead to retention of Na+—and thus water—in the lumen. In addition, it is possible that bile acids stimulate a secretory response in the intestinal mucosa, thereby leading to further losses of salt and water. Increases in fiber content also appear to increase ileostomy output by as much as 20% to 25% when dietary bran supplementation exceeds 16 g/day.6,26 The increase in ileostomy output is accompanied by a decrease in overall water content of the effluent, reflecting the increase in stool bulk. However, there is still a net increase in water loss through the stoma. Corresponding to the increase in ileostomy volume, losses of nutrients such as carbohydrate and protein are also increased with diets high in fiber or fat. Although increased fiber content appears to have unpleasant consequences (increased stool volume, frequency, and flatus), it does not lead to dehydration or nutritional deficiencies.6,26 In addition to dietary factors, it has been postulated that overproduction of gastric acid contributes to the volume of ileostomy output. Hypergastrinemia and gastric hypersecretion are well-recognized, if inconsistent, complications of short gut syndrome, especially during the first 6 weeks after massive small bowel resection.11,12 However, it is not clear that ileostomy, in the absence of enteral resection, is associated with gastric
Soybel 125
hypersecretion or hypergastrinemia.27 In a recent study Jeppeson et al28 observed that ileostomy outputs did decrease when patients received gastric antisecretory agents such as omeprazole. However, the benefit was seen only in patients with ileostomy outputs of 2.6 L per day or more, and these were all patients with significant amounts of small bowel having been resected. Thus, gastric hypersecretion is not likely to influence the patient with an ileostomy but otherwise intact small intestine. Apart from pathologic processes such as enteric infection or inflammatory bowel disease, the single most important factor affecting ileostomy output is the amount of upstream intestine that remains. Ileostomy output is susceptible to the loss of as little as 9 cm of terminal ileum, and salt and water absorption are progressively impaired as the extent of resection increases.29 Patients with ileostomy diarrhea are not necessarily suffering from water losses due to malabsorption of organic nutrients or vitamins. It would appear that, in the absence of a colon, the terminal segment of the ileum ultimately does contribute to the organism’s ability to conserve salt and water. However, the contribution of the terminal ileum may not arise so much from the loss of especially efficient absorptive processes for Na+ or Cl–. On the contrary, it is likely that the salt and water losses are due to increased levels of bile acids in the ileal effluent.23-25 SYSTEMIC RESPONSES TO STOMAL SALT AND WATER LOSSES As early as 1966, Kramer30 observed that variations in dietary Na+ do not markedly influence the Na+ content of the stomal effluent. However, systemic salt and water depletion associated with ileostomy are accompanied by profound changes in urine volume, osmolality, and Na+ content. These observations are consistent with more recent studies that indicate that, after ileostomy, the kidneys promote systemic conservation of salt and water through the release of mineral corticoids and their precursors. Thus, after ileostomy, urine volume and sodium ion concentrations ([Na+]) fall, accompanied by increases in [H+] and [K+].18,31,32 Early on, there may be disturbances in total body water and [K+] stores.33 Subsequently, when the patient has achieved a steady state, the chronic stimulation of endogenous mineral corticoid secretion is sufficient to restore body water and ion composition.18,33 The well-recognized tendency for patients with ileostomy to form renal stones8,12,34 is, in part, a consequence of this compensated but chronic state of mild dehydration.
126 Soybel
EXPERIMENTAL OBSERVATIONS AND MODELS OF ILEOSTOMY ADAPTATION Although there has been considerable interest in evaluating motility, mucosal function, and bacteriology of ileal reservoirs (J-pouch, S-pouch), surprisingly little is known about the effects of ileal diversion on the adjacent terminal ileum or segments of small intestine that are farther upstream. In the few studies that have been conducted, one of the more striking observations has been that the immediately adjacent ileum may not have greatly enhanced capacity for absorption of salt and water. Initially, studies by Wright et al35 suggested that such adaptation was easily discernible, because it seemed to be associated with improvements in fluid and electrolyte balance. In addition, Wright et al also observed that these physiologic changes were accompanied by changes in villus length of the small intestine adjacent to the stoma. Thus, it appeared that adaptation would be attributable to changes in morphology and function of regions of intestine that were immediately upstream from the stoma. Subsequently, however, Hawker et al36 used in vivo and in vitro techniques in patients with wellestablished ileostomies to evaluate electrophysiologic properties of ileal mucosa just upstream from the stoma. In this study the investigators found that the transmucosal potential difference was lower and transmucosal resistance higher in samples from ileostomy patients than in samples from control specimens taken in the operating room. The transmucosal short-circuit current was also reduced, although there were no discernible differences in absorption of Na+ or Cl– ions. These findings were consistent with “tightening” of the intercellular pathways and tight junctions but provided no evidence for increased efficiency of absorption of the terminal ileum. The authors thus concluded that ileostomy does not necessarily lead to enhanced salt and water absorption in immediately adjacent regions of upstream intestine. At first glance, these observations might seem to contradict clinical information that suggests that, over time, salt and water absorption from the lumen are enhanced. In addition to clinical observations, a number of studies have also suggested that, compared with patients without ileostomy, the ileostomy effluent tends to be more concentrated (hyperosmolar), has lower levels of Na+, and has higher levels of K+ and H+.18,23,31,32 How could the composition of the ileostomy effluent be altered when the active, electrogenic Na+ and Cl– transport properties of the ileal mucosa seem unchanged?
Surgery February 2001
To reconcile these observations, at least 2 hypotheses might be entertained: first, absorption may be mediated by electroneutral Na+/H+ exchange processes, located in the intestinal brush border; second, and not necessarily in competition with the first hypothesis, it is possible that the region in which adaptation occurs is not the ileum adjacent to the stoma but in regions of small intestine that are farther upstream. In our laboratory, preliminary data obtained in a rat model of ileostomy would suggest that distal ileal diversion is accompanied by significant alterations in expression of different isoforms of Na+/H+ exchange37,38 in the intestinal mucosa of diverted segments. This was true especially for the isoform NHE-3, which has been localized to the apical membranes and brush borders of the enterocyte and is thought to mediate water-coupled Na+ absorption from the lumen.39,40 In addition, at least at the level of gene expression, increases in mRNA encoding NHE-3 have been observed in very proximal regions of the small intestine.37 If it turns out that these changes in mRNA content are accompanied by compatible differences in levels of protein expression or perhaps in localization, NHE-3 or other specific Na+ transporters may become useful targets for therapies aimed at improving Na + absorption in patients with high outputs from ileostomies, ileal pouches, or short bowel syndromes. CLOSING COMMENTS There is relatively little information regarding mechanisms that promote adaptation of upstream intestine after diversion of the distal ileum. Such adaptation almost certainly does occur, as evidenced by the observation that stomal outputs of salt and water normally decrease over time in humans and experimental animal models. However, the specific transport mechanisms that mediate improvements in transepithelial Na+ and H2O movements have not been identified with certainty. Moreover, the role of systemic, neurohormonal pathways in promoting intestinal absorption have not been evaluated systematically. Considerably more work is required to persuasively identify the molecular targets of the adaptive response and to understand how best to enhance their region-specific expression. These studies should have direct bearing on understanding not only the adaptive response to ileostomy, but also responses to more severe forms of intestinal dysfunction, resection or reconstruction.
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Surgery Volume 129, Number 2
REFERENCES 1. Morowitz DA, Kirsner JB. Ileostomy in UC: a questionnaire study of 1803 patients. Am J Surg 1981;141:370-5. 2. Stryker SJ, Pemberton JH, Zinsmeister AR. Long-term results of ileostomy in older patients. Dis Colon Rectum 1985;28:844-6. 3. McLeod RS, Lavery IC, Leatherman JR, Maryland PA, Fazio VW, Jagelman DG, et al. Patient evaluation of the conventional ileostomy. Dis Colon Rectum 1985;28:152-4. 4. Gazzard BG, Saunders B, Dawson AM. Diets and stoma function. Br J Surg 1977;65:642-4. 5. Kramer P. Effect of specific foods, beverages, and spices on amount of ileostomy output in human subjects. Am Gastroenterol 1987;82:327–32. 6. Steinhart AH, Jenkins DJA, Mitchell S, Cuff D, Prokipchuk EJ. Effect of dietary fiber on total carbohydrate losses in ileostomy effluent. Am J Gastroenterol 1992;87:48-54. 7. Higham SE, Read NW. Effect of ingestion of fat on ileostomy effluent. Gut 1990;31:435-8. 8. Balmbach CP, Robertson WG, Peacock M, Hill GL. Effect of intestinal surgery on the risk of urinary stone formation. Gut 1981;22:257-63. 9. Hill GL, Mair WS, Goligher JC. Gallstones after ileostomy and ileal resection. Gut 1975;16:932-6. 10. M’Koma AE. Follow-up results of hematology data before and after restorative proctocolectomy. Dis Colon Rectum 1994;37:932-7. 11. Metcalf AM, Phillips SF. Ileostomy diarrhea. Clin Gastroenterol 1986;15:705-22. 12. Christl SU, Schepach W. Metabolic consequences of total colectomy. Scand J Gastroenterol 1997;32(suppl 222):20-4. 13. Nugent KP, Dabiels P, Stewart B, Patankar R, Johnson CD. Quality of life in stoma patients. Dis Colon Rectum 1999;42:1569-74. 14. Park JJ, Del Pino A, Orsay CP, Nelson RI, Pearl RK, Cintron JR, et al. Stoma complications: the Cook County experience. Dis Colon Rectum 1999;42:1575-80. 15. Tilson MD. Pathophysiology and treatment of short bowel syndrome. Surg Clin North Am 1980;60:1273-84. 16. Shanbhogue LK, Molenaar JC. Short bowel syndrome: metabolic and surgical management. Br J Surg 1994;81:48699. 17. Tang CL, Yunos A, Leong APK, Seow-Choen F, Goh HS. Ileostomy output in the early post-operative period. Br J Surg 1998;82:607-8. 18. Huber F-X, Stern J, Hinz U, Werle E, Haack D, Kienle P, et al. Effects of restorative proctocolectomy on renal and adrenal function. Dis Colon Rectum 1999;42:1318-24. 19. Kelly DG, Branon ME, Phillips SF, Kelly KA. Diarrhoea after continent ileostomy. Gut 1980;21:711-6. 20. Taylor BM, Cranley B, Kelly KA, Phillips SF, Beart RW Jr, Dozois RR. A clinicophysiological comparison of ileal pouch-anal and straight ileoanal anastomosis. Ann Surg 1983;198:462-8. 21. Hill GL, Millward SF, King RFGJ, Smith RC. Normal ileostomy output: close relation to body size. Br Med J 1979;2:831-2. 22. Hill GL, Mair WSJ, Edwards JP, Morgan DB, Goligher JC. Effect of a chemically defined liquid elemental diet on composition and volume of ileal fistula drainage. Gastroenterology 1975;68:676-82. 23. Ladas SD, Isaacs PE, Murphy GM, Sladen GE. Fasting and
24.
25.
26.
27.
28.
29.
30.
31.
32.
33.
34.
35.
36.
37.
38.
39.
40.
post-prandial ileal function in adapted ileostomates and normal subjects. Gut 1986;27:906-12. Hallgren T, Oresland T, Andersson H, Hulten L. Ileostomy output and bile acid excretion after intraduodenal administration of oleic acid. Scand J Gastroenterol 1994;29:101723. MacGregor IL, Wiley ZD, Sleisenger MH. The role of bile acids in determining ileal flow rates in normal subjects and following ileostomy. Digestion 1978;18:192-200. Sandberg A-S, Andersson H, Hallgren B, Hasselblad K, Isaksson B. Experimental model for in vivo determination of dietary fiber and its effect on absorption of nutrients in the small intestine. Br J Nutr 1981;45:283-94. Greenberg GR, Buchan AM, McLeod RS, Preston P, Cohen Z. Gut hormone responses after reconstructive surgery for ulcerative colitis. Gut 1989;30:1721-30. Jeppeson PB, Staun M, Tjellesen L, Mortensen PB. Effect of intravenous ranitidine and omeprazole on intestinal absorption of water, sodium, and macronutrients in patients with intestinal resection. Gut 1998;43:763-9. Hill GL, Mair WSJ, Goligher JC. Cause and management of high volume output salt-depleting ileostomy. Br J Surg 1975;62:720-6. Kramer P. The effect of varying sodium loads on the ileal excreta of human ileostomized subjects. J Clin Invest 1966;45:1710-8. Kennedy HJ, Al-Dujaili EAS, Edwards CRW, Truelove SC. Water and electrolyte balance in subjects with a permanent ileostomy. Gut 1983;24:702-5. Svaninger G, Nordgren S, Palselius IRN, Fasth S, Hulten L. Sodium and potassium excretion in patients with ileostomies. Eur J Surg 1992;157:601-5. Christie PM, Knight GS, Hill GL. Metabolism of body water and electrolytes after surgery for ulcerative colitis. Br J Surg 1990;77:149-51. Christie PM, Knight GS, Hill GL. Comparison of relative risks of urinary stone formation after surgery for ulcerative colitis. Dis Colon Rectum 1996;39:50-4. Wright HK, Cleveland JC, Tilson MD, Herskovic T. Morphology and absorptive capacity of the ileum after ileostomy in man. Am J Surg 1969;117:242-5. Hawker PC, Morris AI, McKay J, Turnberg LA. Study of ion transport across biopsies of ileostomy in vitro: search for evidence of intestinal ‘adaptation’ after colectomy. Gut 1980;21:146-50. Cima RR, Purdy J, Doble MA, Zinner MJ, Soybel DI. Regionspecific changes in levels of mRNAs encoding Na+/H+ exchangers in intestinal mucosa after distal ileal diversion. Surg Forum 1998;48:126-8. Doble MA, Tola VB, Cima RR, Zinner MJ, Soybel DI. Luminal osmolarity downregulates gene expression of Na+/H+ exchanger (NHE3) in rat colon mucosa. J Gastrointest Surg 2000;4:531-5. Bookstein C, DePaoli AM, Xie Y, Niu P, Musch MW, Rao MC, et al. Na/H exchangers, NHE1 and NHE3 of rat intestine (expression and localization). J Clin Invest 1994;93:106-13. Brant SR, Yun CHC, Donowitz M, Tse CM. Cloning, tissue distribution, and functional analysis of the human Na/H exchanger isoform, NHE3. Am J Physiol 1995;269:C198204.
Number 2
SURGERY FEBRUARY
2001
Surgical research review Adaptation to ileal diversion David I. Soybel, MD, Boston and West Roxbury, Mass
From the Department of Surgery, Brigham and Women’s Hospital and Boston VA Healthcare System, West Roxbury Division, Harvard Medical School, Boston and West Roxbury, Mass
FOR MOST PATIENTS the early period after establishment of an ileostomy is marked by salt and water depletion. For most patients the fluid and electrolyte imbalances become manageable within a few days; however, a small proportion of patients maintain outputs of ileal fluid that are greater than 1 L per day. In the 1960s there had been a considerable amount of investigation to characterize the clinical course of adaptation after ileostomy. Recent work has focused on identifying the systemic mechanisms by which the organism adapts to the loss of its colon. However, little has been done to clarify the mechanisms by which the upstream small intestine increases its efficiency in absorbing NaCl and H2O after ileal diversion. Here I review these prior studies and findings and outline experimental approaches that have evaluated mechanisms of salt and water absorption by upstream segments of small intestine after diversion of the ileal contents distally.
Accepted for publication April 17, 2000. Reprint requests: David I. Soybel, MD, Surgery 112, 1400 VFW Parkway, West Roxbury, MA 02132. Surgery 2001;129:123-7. Copyright © 2001 by Mosby, Inc. 0039-6060/2001/$35.00 + 0 doi:10.1067/msy.2001.107980
11/60/107980
CLINICAL CHARACTERISTICS OF ADAPTATION AFTER ILEAL DIVERSION Virtually all clinical reviews have indicated that patients with permanent ileostomies eventually have a high level of satisfaction with the function of the stoma. Of course, most of these studies have been conducted in patients who were suffering from acute symptoms of chronic ulcerative colitis before proctocolectomy and ileostomy. Thus, it has been argued that the improvements in satisfaction and quality of life indexes were no more than a comparison between states of illness and wellness. Nevertheless, a number of lessons have been learned from this group of patients (Table I).1-3 These include the following: First, the average patient empties the ileostomy bag, on average, 6 to 8 times per day.1 Second, despite the best techniques in stoma construction and care, skin excoriation affects between 30% and 40% of patients on a regular basis, and these effects are attributable to the volume and caustic nature of the ileal effluent.1,2 Third, certain foods, including those containing high levels of fat or fiber, often cause increased levels of ileostomy output.4-7 Fourth, ileostomy output is associated with insignificant or low levels of nutrient malabsorption, major vitamin deficiencies or metabolic derangements leading to anemia, mineral bone disease, gallstones or renal stones, unless it is also accompanied by resection of major portions of the small intestine.8-12 SURGERY 123
124 Soybel
Surgery February 2001 Table II. Daily steady-state fecal losses after ileostomy Normal stool Ileostomy
Water
Na+
K+
Cl–
100-150 650 ± 44
1-5 81 ± 7
5-15 6±1
1-2 34 ± 6
Volume in mL, mass in mmol. Means ± SD. Data from references 19 and 20.
PHASES OF ADAPTATION AFTER ILEAL DIVERSION
Figure. Ileostomy outputs in the early postoperative period. Data from 60 patients undergoing diverting ileostomy for a variety of indications (reference 17).
Table I. Life-style after ileostomy Reoperation Revision Intestinal obstruction Skin excoriation Problems Frequency of emptying Appliance change (per wk) Restriction in activity House Social Sexual Travel Diet
Age < 60 y
Age > 60 y
12% 8% 40% 6% 7.4 ± 0.2 1.0-2.7
6% 3% 30% 18% 6.6 ± 0.3 0.3-2.2
12% 20% 28% 25% 28%
18% 24% 24% 33% 34%
Data adapted from reference 2.
Overall, the average patient does well with an ileostomy. It is not hard to avoid dehydration or nutritional deficiencies, unless a very large amount of bowel has also been resected. If certain foods are not agreeable, they can be avoided. Traditionally, it has been said that elderly patients may have trouble with ileostomy, especially because of dehydration. However, it remains unclear whether elderly patients have increased levels of ileostomy output and there is evidence that they do not.2,13,14 It would appear that a subgroup of elderly patients have higher levels of complications and may have more difficulty responding to the expected levels of salt and water depletion.2,13,14 Thus, the elderly may be more susceptible to dehydration, even if actual ileostomy outputs are not increased over those seen in younger patients.
During the initial postoperative period after ileostomy, there appear to be 3 distinct phases of adaptation. Initially, just after the ileostomy is formed, there is a period of 1 to 3 days after surgery in which output increases. In the second phase, which begins between days 3 to 5, outputs stabilize or decline only slightly. In the third phase, which begins between days 4 to 7, outputs decline continuously, reaching steady levels between 40 to 60 days (6 to 8 weeks). Compared with the drawn-out periods of adaptation after massive enteral resection,15,16 the phases of adaptation after simple ileal diversion are brief. The variability of individual patient responses during phases 1 and 2 is illustrated in the Figure. As shown in the Figure, taken from data published in a recent report by Tang et al,17 ileostomy outputs may vary between 300 and 3500 mL per day. It should be noted that ileal outputs of volume are closely correlated to the output of sodium ion, Na+, and chloride ion, Cl–. Ultimately, most patients have cumulative outputs of about 600 to 700 mL per day.11,12,17,18 On the basis of the data provided in Table II, it can be calculated that about 120 mEq Na+ and 50 mEq Cl– are lost with each liter of ileostomy effluent. Losses of potassium ion are not closely correlated to ileostomy output. It has been said that both normal individuals and ileostomy patients lose about 9 mEq K+ each day, regardless of the magnitude of the output of feces or ileostomy effluent.19,20 FACTORS INFLUENCING ILEOSTOMY OUTPUT Ileostomy output is influenced by several factors, some physiologic and some pathologic. Physiologic factors include body size, composition and complexity of diet, and contributions of secretions from upstream segments of the gastrointestinal tract. The single most important pathologic factor contributing to the magnitude of ileostomy output is the amount of uninjured intestine proximally. Output of volume increases with body mass, so that outputs of 300 to 400 mL/day would be
Surgery Volume 129, Number 2
expected from individuals weighing 40 kg and 800 mL/day would not be unreasonable for individuals weighing 80 kg.21 With respect to diet, it is curious that water intake itself plays virtually no role in determining the magnitude of ileostomy output. Dehydration certainly decreases outputs, but excessive levels of water consumption do not appear to alter stomal losses. With respect to individual dietary components, prior studies have shown that patients with well-established ileostomies respond to elemental diet with decreases in volume and concentrations of digestive enzymes and bile acids in the ileostomy effluent.22 High fat (long-chain triglycerides) content has been associated with higher losses through the stoma, up to 20% above baseline levels.7,23,24 The effects of fat have been evaluated in some detail. Of note, high fat diets did not elicit changes in intestinal transit, arguing against a role for gastrointestinal motility in mediating the increase in ileostomy output.7,23 Thus, it has been suggested that the fat-induced increases in output are due to absorptive inhibition or possibly secretory stimulation of the intestinal mucosa by bile salt, which are not efficiently absorbed after loss of the most terminal region of the ileum.23-25 The failure to absorb bile acids, in turn, would then lead to retention of Na+—and thus water—in the lumen. In addition, it is possible that bile acids stimulate a secretory response in the intestinal mucosa, thereby leading to further losses of salt and water. Increases in fiber content also appear to increase ileostomy output by as much as 20% to 25% when dietary bran supplementation exceeds 16 g/day.6,26 The increase in ileostomy output is accompanied by a decrease in overall water content of the effluent, reflecting the increase in stool bulk. However, there is still a net increase in water loss through the stoma. Corresponding to the increase in ileostomy volume, losses of nutrients such as carbohydrate and protein are also increased with diets high in fiber or fat. Although increased fiber content appears to have unpleasant consequences (increased stool volume, frequency, and flatus), it does not lead to dehydration or nutritional deficiencies.6,26 In addition to dietary factors, it has been postulated that overproduction of gastric acid contributes to the volume of ileostomy output. Hypergastrinemia and gastric hypersecretion are well-recognized, if inconsistent, complications of short gut syndrome, especially during the first 6 weeks after massive small bowel resection.11,12 However, it is not clear that ileostomy, in the absence of enteral resection, is associated with gastric
Soybel 125
hypersecretion or hypergastrinemia.27 In a recent study Jeppeson et al28 observed that ileostomy outputs did decrease when patients received gastric antisecretory agents such as omeprazole. However, the benefit was seen only in patients with ileostomy outputs of 2.6 L per day or more, and these were all patients with significant amounts of small bowel having been resected. Thus, gastric hypersecretion is not likely to influence the patient with an ileostomy but otherwise intact small intestine. Apart from pathologic processes such as enteric infection or inflammatory bowel disease, the single most important factor affecting ileostomy output is the amount of upstream intestine that remains. Ileostomy output is susceptible to the loss of as little as 9 cm of terminal ileum, and salt and water absorption are progressively impaired as the extent of resection increases.29 Patients with ileostomy diarrhea are not necessarily suffering from water losses due to malabsorption of organic nutrients or vitamins. It would appear that, in the absence of a colon, the terminal segment of the ileum ultimately does contribute to the organism’s ability to conserve salt and water. However, the contribution of the terminal ileum may not arise so much from the loss of especially efficient absorptive processes for Na+ or Cl–. On the contrary, it is likely that the salt and water losses are due to increased levels of bile acids in the ileal effluent.23-25 SYSTEMIC RESPONSES TO STOMAL SALT AND WATER LOSSES As early as 1966, Kramer30 observed that variations in dietary Na+ do not markedly influence the Na+ content of the stomal effluent. However, systemic salt and water depletion associated with ileostomy are accompanied by profound changes in urine volume, osmolality, and Na+ content. These observations are consistent with more recent studies that indicate that, after ileostomy, the kidneys promote systemic conservation of salt and water through the release of mineral corticoids and their precursors. Thus, after ileostomy, urine volume and sodium ion concentrations ([Na+]) fall, accompanied by increases in [H+] and [K+].18,31,32 Early on, there may be disturbances in total body water and [K+] stores.33 Subsequently, when the patient has achieved a steady state, the chronic stimulation of endogenous mineral corticoid secretion is sufficient to restore body water and ion composition.18,33 The well-recognized tendency for patients with ileostomy to form renal stones8,12,34 is, in part, a consequence of this compensated but chronic state of mild dehydration.
126 Soybel
EXPERIMENTAL OBSERVATIONS AND MODELS OF ILEOSTOMY ADAPTATION Although there has been considerable interest in evaluating motility, mucosal function, and bacteriology of ileal reservoirs (J-pouch, S-pouch), surprisingly little is known about the effects of ileal diversion on the adjacent terminal ileum or segments of small intestine that are farther upstream. In the few studies that have been conducted, one of the more striking observations has been that the immediately adjacent ileum may not have greatly enhanced capacity for absorption of salt and water. Initially, studies by Wright et al35 suggested that such adaptation was easily discernible, because it seemed to be associated with improvements in fluid and electrolyte balance. In addition, Wright et al also observed that these physiologic changes were accompanied by changes in villus length of the small intestine adjacent to the stoma. Thus, it appeared that adaptation would be attributable to changes in morphology and function of regions of intestine that were immediately upstream from the stoma. Subsequently, however, Hawker et al36 used in vivo and in vitro techniques in patients with wellestablished ileostomies to evaluate electrophysiologic properties of ileal mucosa just upstream from the stoma. In this study the investigators found that the transmucosal potential difference was lower and transmucosal resistance higher in samples from ileostomy patients than in samples from control specimens taken in the operating room. The transmucosal short-circuit current was also reduced, although there were no discernible differences in absorption of Na+ or Cl– ions. These findings were consistent with “tightening” of the intercellular pathways and tight junctions but provided no evidence for increased efficiency of absorption of the terminal ileum. The authors thus concluded that ileostomy does not necessarily lead to enhanced salt and water absorption in immediately adjacent regions of upstream intestine. At first glance, these observations might seem to contradict clinical information that suggests that, over time, salt and water absorption from the lumen are enhanced. In addition to clinical observations, a number of studies have also suggested that, compared with patients without ileostomy, the ileostomy effluent tends to be more concentrated (hyperosmolar), has lower levels of Na+, and has higher levels of K+ and H+.18,23,31,32 How could the composition of the ileostomy effluent be altered when the active, electrogenic Na+ and Cl– transport properties of the ileal mucosa seem unchanged?
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To reconcile these observations, at least 2 hypotheses might be entertained: first, absorption may be mediated by electroneutral Na+/H+ exchange processes, located in the intestinal brush border; second, and not necessarily in competition with the first hypothesis, it is possible that the region in which adaptation occurs is not the ileum adjacent to the stoma but in regions of small intestine that are farther upstream. In our laboratory, preliminary data obtained in a rat model of ileostomy would suggest that distal ileal diversion is accompanied by significant alterations in expression of different isoforms of Na+/H+ exchange37,38 in the intestinal mucosa of diverted segments. This was true especially for the isoform NHE-3, which has been localized to the apical membranes and brush borders of the enterocyte and is thought to mediate water-coupled Na+ absorption from the lumen.39,40 In addition, at least at the level of gene expression, increases in mRNA encoding NHE-3 have been observed in very proximal regions of the small intestine.37 If it turns out that these changes in mRNA content are accompanied by compatible differences in levels of protein expression or perhaps in localization, NHE-3 or other specific Na+ transporters may become useful targets for therapies aimed at improving Na + absorption in patients with high outputs from ileostomies, ileal pouches, or short bowel syndromes. CLOSING COMMENTS There is relatively little information regarding mechanisms that promote adaptation of upstream intestine after diversion of the distal ileum. Such adaptation almost certainly does occur, as evidenced by the observation that stomal outputs of salt and water normally decrease over time in humans and experimental animal models. However, the specific transport mechanisms that mediate improvements in transepithelial Na+ and H2O movements have not been identified with certainty. Moreover, the role of systemic, neurohormonal pathways in promoting intestinal absorption have not been evaluated systematically. Considerably more work is required to persuasively identify the molecular targets of the adaptive response and to understand how best to enhance their region-specific expression. These studies should have direct bearing on understanding not only the adaptive response to ileostomy, but also responses to more severe forms of intestinal dysfunction, resection or reconstruction.
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