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What sequence of pathogenetic events leads to acute ulcerative colitis?

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Diseases of the Colon & Rectum

Abstract

The etiology of ulcerative colitis remains unresolved despite new immunologic, biochemical, and microbiologic observations made in this disease. A sequence of pathogenetic events has been adduced from abnormalities reported from human and experimental colitis with the express purpose of establishing priority of factors that may lead to an attack of acute ulcerative colitis. The presence of undefined bacterial metabolites in the colonic lumen causing specific breadown of fatty acid oxidation in colonic epithelial cells is proposed to be the initiating event of the disease process that leads to an immune response and eicosanoid response perpetuating epithelial cell damage. The proposals embody the thesis that primary metabolic damage to colonocytes determines the clinical and pathologic manifestations of ulcerative colitis.

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References

  1. Maratka Z. Pathogenesis and aetiology of inflammatory bowel disease. In: De Dombal FT, Myren J, Bouchier IA, Watkinson G, eds. Inflammatory bowel disease: some international data and reflections. New York: Oxford University Press, 1986:29–65.

    Google Scholar 

  2. Fiocchi C. Etiology of mucosal ulcerative colitis. In: Jagelman DG, ed. Mucosal ulcerative colitis. Mt Kisco: Futura Publishing, 1986:1–35.

    Google Scholar 

  3. Hill MJ. Bacteria and inflammatory bowel disease. In: Hill MJ, ed. Microbial metabolism in the digestive tract. Boca Raton: CRC Press, 1986:211–20.

    Google Scholar 

  4. Jewell DP, Rhodes JM. Immunology of ulcerative colitis. In: Allan RN, Keighley MR, Alexander-Williams J, Hawkins C, eds. Inflammatory bowel diseases. New York: Churchill Livingstone, 1983:154–70.

    Google Scholar 

  5. Emery ES Jr. Concerning the etiology of “peptic” ulcer (editorial). Gastroenrerology 1943;1:431–2.

    Google Scholar 

  6. WCA. William Prout, the discoverer of hydrochloric acid in the gastric juice (editorial) Gastroenterology 1948;11:133–4.

    Google Scholar 

  7. Van Kruiningen HJ, Stephenson EH, Thayer WR Jr. A negative search for four infectious agents in inflammatory bowel disease. J Clin Gastroenterol 1986;8:255–7.

    Article  PubMed  Google Scholar 

  8. Gorbach SL, Nahas L, Plaut AG, Weinstein L, Patterson JF, Levitan R. Studies of intestinal microflora. V. Fecal microbial ecology in ulcerative colitis and regional enteritis: relationship to severity of disease and chemotherapy. Gastroenterology 1968;54:575–87.

    PubMed  CAS  Google Scholar 

  9. Van der Wiel-Korstanje JA, Winkler KC. The faecal flora in ulcerative colitis. J Med Microbiol 1975;8:491–501.

    Article  PubMed  Google Scholar 

  10. Dickinson RJ, Varian SA, Axon AT, Cooke EM. Increased incidence of faecal coliforms within vitro adhesive and invasive properties in patients with ulcerative colitis. Gut 1980;21:787–92.

    PubMed  CAS  Google Scholar 

  11. DeGraaf FK, Mooi FR. The fimbrial adhesins ofEscherichia coli. Adv Microb Physiol 1986;28:65–143.

    CAS  Google Scholar 

  12. Chadwick V, Mellor DM, Myers DB, Selden AC, Keshavarzian A, Broom MF. Production of peptides inducing chemotaxis and lysosomal enzyme release in human neutrophils by intestinal bacteriain vitro andin vivo (abst). Aust NZ J Med 1986;16:601.

    Google Scholar 

  13. Selby WS, Janossy G, Bofill M, Jewell DP. Intestinal lymphocyte subpopulations in inflammatory bowel disease: an analysis by immunohistological and cell isolation techniques. Gut 1984; 25:32–40.

    PubMed  CAS  Google Scholar 

  14. Bookman MA, Bull DM. Characteristics of isolated intestinal mucosal lymphoid cells in inflammatory bowel disease. Gastroenterology 1979;77:503–10.

    PubMed  CAS  Google Scholar 

  15. Tanner AR, Arthur MJ, Wright R. Macrophage activation, chronic inflammation and gastrointestinal disease. Gut 1984;25: 760–83.

    PubMed  CAS  Google Scholar 

  16. Kane SP, Vincenti AC. Mucosal enzymes in human inflammatory bowel disease with reference to neutrophil granulocytes as mediators of tissue injury. Clin Sci 1979;57:295–303.

    PubMed  CAS  Google Scholar 

  17. Willoughby CP, Piris J, Truelove SC. Tissue eosinophils in ulcerative colitis. Scand J Gastroenterol 1979;14:395–9.

    PubMed  CAS  Google Scholar 

  18. Skinner JM, Whitehead R. The plasma cells in inflammatory disease of the colon: a quantitative study. J Clin Pathol 1974; 27:643–6.

    PubMed  CAS  Google Scholar 

  19. Perlmann P, Broberger O. In vitro studies of ulcerative colitis. II. Cytotoxic action of white blood cells from patients on human fetal colon cells. J Exp Med 1963;117:717–33.

    Article  PubMed  CAS  Google Scholar 

  20. Watson DW, Quigley A, Bolt RJ. The cytotoxicity of circulating lymphocytes from ulcerative colitis patients for human colon epithelial cells: disease specificity and relationship to disease activity. Gastroenterology 1966;50:886–7.

    Google Scholar 

  21. Saverymuttu SH, Chadwick VS, Hodgson HJ. Granulocyte migration in ulcerative colitis. Eur J Clin Invest 1985;15:60–3.

    Article  PubMed  CAS  Google Scholar 

  22. Fadan H, Rossi TM. Chemiluminescent response of neutrophils from patients with inflammatory bowel disease. Dig Dis Sci 1985;30:139–42.

    Article  Google Scholar 

  23. Hodgson HJ, Potter BJ, Jewell DP. C3 metabolism in ulcerative colitis and Crohn's disease. Clin Exp Immunol 1977;28:490–5.

    PubMed  CAS  Google Scholar 

  24. Doe WF, Booth CC, Brown DL. Evidence for complement-binding immune complexes in adult coeliac disease, Crohn's disease, and ulcerative colitis. Lancet 1973;1:402–3.

    Article  PubMed  CAS  Google Scholar 

  25. Shandall AA, Williams GT, Hallett MB, Young HL. Colonic healing: a role for polymorphonuclear leucocytes and oxygen radical production. Br J Surg 1986;73:225–8.

    PubMed  CAS  Google Scholar 

  26. Strober W, James SP. The immunologic basis of inflammatory bowel disease. J Clin Immunol 1986;6:415–32.

    Article  PubMed  CAS  Google Scholar 

  27. Kirsner JB, Shorter RG. Recent developments in “nonspecific” inflammatory bowel disease. N Engl J Med 1982;306:775–85; 837–48.

    Article  PubMed  CAS  Google Scholar 

  28. Rhodes JM, Black RR, Gallimore R, Savage A. Histochemical demonstration of desialation and desulphation of normal and inflammatory bowel disease rectal mucus by faecal extracts. Gut 1985;26:1312–8.

    PubMed  CAS  Google Scholar 

  29. Podolsky DK, Isselbacher KH. Glycoprotein composition of colonic mucosa: specific alterations in ulcerative colitis. Gastroenterology 1984;87:991–8.

    PubMed  CAS  Google Scholar 

  30. Boughton-Smith NK, Hawkey CJ, Whittle BJ. Biosynthesis of lipoxygenase and cyclo-oxygenase products from [14C]-arachidonic acid by human colonic mucosa. Gut 1983;24:1176–82.

    PubMed  CAS  Google Scholar 

  31. Sharon P, Stenson WF. Enhanced synthesis of leukotriene B4 by colonic mucosa in inflammatory bowel disease. Gastroenterology 1984;86:453–60.

    PubMed  CAS  Google Scholar 

  32. Rachmilewitz D, Karmeli F, Selinger Z. Increased colonic adenylate cyclase activity in active ulcerative colitis. Gastroenterology 1983;85:12–6.

    PubMed  CAS  Google Scholar 

  33. Rachmilewitz D, Karmeli F, Sharon P. Decreased colonic Na+K-ATPase activity in active ulcerative colitis. Ist J Med Sci 1984;20: 681–4.

    CAS  Google Scholar 

  34. Roediger WE. Utilization of nutrients by isolated epithelial cells of the rat colon. Gastroenterology 1982;83:424–9.

    PubMed  CAS  Google Scholar 

  35. Roediger WE. The colonic epithelium in ulcerative colitis: an energy deficiency disease. Lancet 1980;2:712–5.

    Article  PubMed  CAS  Google Scholar 

  36. Roediger WE, Lawson MJ, Kwok V, Kerr-Grant A, Pannall PR. Colonic bicarbonate output as a test of disease activity in ulcerative colitis. J Clin Pathol 1984;37:704–7.

    PubMed  CAS  Google Scholar 

  37. Kameyama J, Narui H, Inui M, Sato T. Energy level in large intestinal mucosa in patients with ulcerative colitis. Tohoku J Exp Med 1984;143:253–4.

    Article  PubMed  CAS  Google Scholar 

  38. Monsen U, Broström O, Nordenvall B, Sörstad J, Hellers G. Prevalence of inflammatory bowel disease among relatives of patients with ulcerative colitis. Scand J Gastroenterol 1987; 22:214–8.

    PubMed  CAS  Google Scholar 

  39. Nunn WD. A molecular view of fatty acid catabolism inEscherichia coli. Microbiol Rev 1986;50:179–92.

    PubMed  CAS  Google Scholar 

  40. Kirsner JB, Elchlepp JG, Goldgraber MB, Ablaza J, Ford H. Production of an experimental ulcerative “colitis” in rabbits. Arch Pathol 1959;68:392–408.

    PubMed  CAS  Google Scholar 

  41. Bicks RO, Rosenberg EW. A chronic delayed hypersensitivity reaction in the guinea pig colon. Gastroenterology 1964;46:543–9.

    PubMed  CAS  Google Scholar 

  42. MacPherson BR, Pfeiffer CJ. Experimental production of diffuse colitis in rats. Digestion 1978;17:135–50.

    PubMed  CAS  Google Scholar 

  43. LeVeen HH, Falk G, Schatman B. Experimental ulcerative colitis produced by anticolon sera. Ann Surg 1961;154:275–80.

    PubMed  CAS  Google Scholar 

  44. Chester JF, Ross JS, Malt RA, Weitzman SA. Acute colitis produced by chemotactic peptides in rats and mice. Am J Pathol 1985;121:284–90.

    PubMed  CAS  Google Scholar 

  45. Sharon P, Stenson WF. Metabolism of arachidonic acid in acetic acid colitis in rats: similarity to human inflammatory bowel disease. Gastroenterology 1985;88:55–63.

    PubMed  CAS  Google Scholar 

  46. Hodgson HJ, Potter BJ, Skinner J, Jewell DP. Immune-complex mediated colitis in rabbits: an experimental model. Gut 1978;19: 225–32.

    PubMed  CAS  Google Scholar 

  47. Roediger WE, Nance S. Metabolic induction of experimental ulcerative colitis by inhibition of fatty acid oxidation. Br J Exp Pathol 1986;67:773–82.

    PubMed  CAS  Google Scholar 

  48. Kraft SC, Fitch FW, Kirsner JB. Histologic and immunohistochemical features of Auer “colitis” in rabbits. Am J Pathol 1963;43:913–27.

    PubMed  CAS  Google Scholar 

  49. Goldgraber MB, Kirsner JB. The Arthus phenomenon in the colon of rabbits: a serial histological study. Arch Pathol 1959;67:556–71.

    CAS  Google Scholar 

  50. Watt J, Marcus R. Experimental ulcerative disease of the colon in animals. Gut 1973;14:506–10.

    PubMed  CAS  Google Scholar 

  51. Perlmann P, Hammarström S, Lagercrantz R, Gustafsson BE. Antigen from colon of germfree rats and antibodies in human ulcerative colitis. Ann NY Acad Sci 1965;124:377–94.

    Article  PubMed  CAS  Google Scholar 

  52. Thayer WR Jr, Brown M, Sangree MH, Katz J, Hersh T.Escherichia coli O:14 and colon hemagglutinating antibodies in inflammatory bowel disease. Gastroenterology 1969;57:311–8.

    PubMed  Google Scholar 

  53. Anand BS, Malhotra V, Bhattacharya SK, et al. Rectal histology in acute bacillary dysentery. Gastroenterology 1986;90:654–60.

    PubMed  CAS  Google Scholar 

  54. Powell DW. Barrier function of epithelia. Am J Physiol 1981;241: G275–88.

    PubMed  CAS  Google Scholar 

  55. Wijesinha SS, Steer HW. Studies of the immunoglobulin-producing cells of the human intestine: the defunctioned bowel. Gut 1982;23:211–4.

    PubMed  CAS  Google Scholar 

  56. Hoel PG. Probability. In: Elementary statistics. 2nd ed. New York: John Wiley & Sons, 1966:45–77.

    Google Scholar 

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Authors and Affiliations

  1. Department of Surgery, The University of Adelaide at The Queen Elizabeth Hospital, Adelaide, Australia

    W. E. W. Roediger M.B., B.Ch., M.Sc., D.Phil. (Oxon), F.R.A.C.S.

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  1. W. E. W. Roediger M.B., B.Ch., M.Sc., D.Phil. (Oxon), F.R.A.C.S.
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Roediger, W.E.W. What sequence of pathogenetic events leads to acute ulcerative colitis?. Dis Colon Rectum 31, 482–487 (1988). https://doi.org/10.1007/BF02552623

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  • DOI: https://doi.org/10.1007/BF02552623

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