Skip to main content

Advertisement

Log in

How to Make a Barrett Esophagus: Pathophysiology of Columnar Metaplasia of the Esophagus

  • Review Article
  • Published:
Digestive Diseases and Sciences Aims and scope Submit manuscript

Abstract

Barrett esophagus is defined as a specialized intestinal replacing the squamous epithelium of the esophageal mucosa in response to gastroesophageal reflux. Barrett metaplasia is a healing process that develops to protect the esophagus from further damage. Although mechanisms by which Barrett metaplasia evolves toward dysplasia and adenocarcinoma have been extensively studied, the process by which squamous epithelium is replaced by specialized intestinal metaplasia is poorly understood. Barrett esophagus develops when defense mechanisms in the esophageal mucosa (luminal secretion of mucus, bicarbonate, growth factors, etc.) are overwhelmed by an ongoing cycle of mucosal injury and repair. Hydrogen ion, pepsin, trypsin, and bile acids are considered harmful agents that synergistically invade the esophageal mucosa. Areas of destroyed squamous epithelium are then progressively reepithelized by a columnar epithelium that may originate from multipotent stem cells located within the basal layer of the normal esophageal mucosa or in the ducts of submucosal glands.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  1. Barrett NR: Chronic peptic ulcer of the oesophagus and oesophagitis. Br J Surg 38:175–182, 1950

    Article  PubMed  CAS  Google Scholar 

  2. Lortat-Jacob JL: L’endobrachyoesophage. Ann Chir 11:1247–1254, 1957

    Google Scholar 

  3. Hameeteman W, Tytgat GN, Houthoff HJ, van den Tweel JG: Barrett’s esophagus: development of dysplasia and adenocarcinoma. Gastroenterology 96:1249–1256, 1989

    PubMed  CAS  Google Scholar 

  4. Weinstein WM, Ippoliti AF: The diagnosis of Barrett’s esophagus: goblets, goblets, goblets. Gastrointest Endosc 44:91–95, 1996

    Article  CAS  PubMed  Google Scholar 

  5. Barrett NR: Benign stricture in the lower esophagus. J Thorac Cardiovasc Surg 43:703–708, 1962

    Google Scholar 

  6. Snyder JD, Goldman H: Barrett’s esophagus in children and young adults. Frequent association with mental retardation. Dig Dis Sci 35:1185–1189, 1990

    Article  PubMed  CAS  Google Scholar 

  7. Jochem VJ, Fuerst PA, Fromkes JJ: Familial Barrett’s esophagus associated with adenocarcinoma. Gastroenterology 102:1400–1402, 1992

    PubMed  CAS  Google Scholar 

  8. Hassall E, Israel DM, Davidson AG, Wong LT: Barrett’s esophagus in children with cystic fibrosis: not a coincidental association. Am J Gastroenterol 88:1934–1938, 1993

    CAS  PubMed  Google Scholar 

  9. Winters C Jr, Spurling TJ, Chobanian SJ, et al.: Barrett’s esophagus. A prevalent, occult complication of gastroesophageal reflux disease. Gastroenterology 92:118–124, 1987

    PubMed  Google Scholar 

  10. Jankowski JA, Wright NA, Meltzer SJ, Triadafilopoulos G, Geboes K, Casson AG, Kerr D, Young LS: Molecular evolution of the metaplasia-dysplasia-adenocarcinoma sequence in the esophagus. Am J Pathol 154:965–973, 1999

    CAS  PubMed  Google Scholar 

  11. DeMeester TR, Attwood SE, Smyrk TC, Therkildsen DH, Hinder RA: Surgical therapy in Barrett’s esophagus. Ann Surg 212:528–540; discussion 540–522, 1990

    Article  PubMed  CAS  Google Scholar 

  12. Stein HJ, Hoeft S, DeMeester TR: Functional foregut abnormalities in Barrett’s esophagus. J Thorac Cardiovasc Surg 105:107–111, 1993

    CAS  PubMed  Google Scholar 

  13. Stein HJ, Barlow AP, DeMeester TR, Hinder RA: Complications of gastroesophageal reflux disease. Role of the lower esophageal sphincter, esophageal acid and acid/alkaline exposure, and duodenogastric reflux. Ann Surg 216:35–43, 1992

    Article  CAS  PubMed  Google Scholar 

  14. Mulholland MW, Reid BJ, Levine DS, Rubin CE: Elevated gastric acid secretion in patients with Barrett’s metaplastic epithelium. Dig Dis Sci 34:1329–1334, 1989

    Article  PubMed  CAS  Google Scholar 

  15. Guillem P, Billeret V, Buisine MP, Flejou JF, Lecomte-Houcke M, Degand P, Aubert JP, Triboulet JP, Porchet N: Mucin gene expression and cell differentiation in human normal, premalignant and malignant esophagus. Int J Cancer 88:856–861, 2000

    Article  PubMed  CAS  Google Scholar 

  16. Namiot Z, Sarosiek J, Marcinkiewicz M, Edmunds MC, McCallum RW: Declined human esophageal mucin secretion in patients with severe reflux esophagitis. Dig Dis Sci 39:2523–2529, 1994

    Article  PubMed  CAS  Google Scholar 

  17. Brown CM, Snowdon CF, Slee B, Sandle LN, Rees WD: Effect of topical oesophageal acidification on human salivary and oesophageal alkali secretion. Gut 36:649–653, 1995

    Article  PubMed  CAS  Google Scholar 

  18. Gray MR, Donnelly RJ, Kingsnorth AN: Role of salivary epidermal growth factor in the pathogenesis of Barrett’s columnar lined oesophagus. Br J Surg 78:1461–1466, 1991

    Article  PubMed  CAS  Google Scholar 

  19. Filipe MI, Jankowski J: Growth factors and oncogenes in Barrett’s oesophagus and gastric metaplasia. Endoscopy 25:637–641, 1993

    Article  PubMed  CAS  Google Scholar 

  20. Namiot Z, Yu ZJ, Piascik R, Hetzel DP, McCallum RW, Sarosiek J: Modulatory effect of esophageal intraluminal mechanical and chemical stressors on salivary prostaglandin E2 in humans. Am J Med Sci 313:90–98, 1997

    Article  PubMed  CAS  Google Scholar 

  21. Tobey NA, Reddy SP, Khalbuss WE, Silvers SM, Cragoe EJ, Jr., Orlando RC: Na(+)-dependent and -independent Cl/HCO3 exchangers in cultured rabbit esophageal epithelial cells. Gastroenterology 104:185–195, 1993

    PubMed  CAS  Google Scholar 

  22. Hollwarth ME, Smith M, Kvietys PR, Granger DN: Esophageal blood flow in the cat. Normal distribution and effects of acid perfusion. Gastroenterology 90:622–627, 1986

    PubMed  CAS  Google Scholar 

  23. Bremner CG, Lynch VP, Ellis FH, Jr.: Barrett’s esophagus: Congenital or acquired? An experimental study of esophageal mucosal regeneration in the dog. Surgery 68:209–216, 1970

    PubMed  CAS  Google Scholar 

  24. Khalbuss WE, Marousis CG, Subramanyam M, Orlando RC: Effect of HCl on transmembrane potentials and intracellular pH in rabbit esophageal epithelium. Gastroenterology 108:662–672, 1995

    Article  PubMed  CAS  Google Scholar 

  25. Carney CN, Orlando RC, Powell DW, Dotson MM: Morphologic alterations in early acid-induced epithelial injury of the rabbit esophagus. Lab Invest 45:198–208, 1981

    PubMed  CAS  Google Scholar 

  26. Tobey NA, Reddy SP, Keku TO, Cragoe EJ, Jr., Orlando RC: Mechanisms of HCl-induced lowering of intracellular pH in rabbit esophageal epithelial cells. Gastroenterology 105:1035–1044, 1993

    PubMed  CAS  Google Scholar 

  27. Snow JC, Goldstein JL, Schmidt LN, Lisitza P, Layden TJ: Rabbit esophageal cells show regulatory volume decrease: ionic basis and effect of pH. Gastroenterology 105:102–110, 1993

    PubMed  CAS  Google Scholar 

  28. Tobey NA, Cragoe EJ Jr., Orlando RC: HCl-induced cell edema in rabbit esophageal epithelium: A bumetanide-sensitive process. Gastroenterology 109:414–421, 1995

    Article  PubMed  CAS  Google Scholar 

  29. Orlando RC, Bryson JC, Powell DW: Mechanisms of H+ injury in rabbit esophageal epithelium. Am J Physiol 246:G718–G724, 1984

    PubMed  CAS  Google Scholar 

  30. De Backer A, Haentjens P, Willems G: Hydrochloric acid. A trigger of cell proliferation in the esophagus of dogs. Dig Dis Sci 30:884–890, 1985

    Article  PubMed  CAS  Google Scholar 

  31. Sandler AD, Schmidt C, Richardson K, Murray J, Maher JW: Regulation of distal esophageal mucosal blood flow: the roles of nitric oxide and substance P. Surgery 114:285–293; discussion 293–284, 1993

    PubMed  CAS  Google Scholar 

  32. Gillen P, Keeling P, Byrne PJ, West AB, Hennessy TP: Experimental columnar metaplasia in the canine oesophagus. Br J Surg 75:113–115, 1988

    Article  PubMed  CAS  Google Scholar 

  33. Fitzgerald RC, Omary MB, Triadafilopoulos G: Dynamic effects of acid on Barrett’s esophagus. An ex vivo proliferation and differentiation model. J Clin Invest 98:2120–2128, 1996

    Article  PubMed  CAS  Google Scholar 

  34. Safaie-Shirazi S: Effect of pepsin on ionic permeability of canine esophageal mucosa. J Surg Res 22:5–8, 1977

    Article  PubMed  CAS  Google Scholar 

  35. Lillemoe KD, Johnson LF, Harmon JW: Alkaline esophagitis: a comparison of the ability of components of gastroduodenal contents to injure the rabbit esophagus. Gastroenterology 85:621–628, 1983

    PubMed  CAS  Google Scholar 

  36. Lillemoe KD, Johnson LF, Harmon JW: Role of the components of the gastroduodenal contents in experimental acid esophagitis. Surgery 92:276–284, 1982

    PubMed  CAS  Google Scholar 

  37. Meyer W, Vollmar F, Bar W: Barrett-esophagus following total gastrectomy. A contribution to its pathogenesis. Endoscopy 11:121–126, 1979

    Article  PubMed  CAS  Google Scholar 

  38. Seto Y, Kobori O: Role of reflux oesophagitis and acid in the development of columnar epithelium in the rat oesophagus. Br J Surg 80:467–470, 1993

    Article  PubMed  CAS  Google Scholar 

  39. Orlando RC, Powell DW, Carney CN: Pathophysiology of acute acid injury in rabbit esophageal epithelium. J Clin Invest 68:286–293, 1981

    Article  PubMed  CAS  Google Scholar 

  40. Kauer WK, Peters JH, DeMeester TR, Ireland AP, Bremner CG, Hagen JA: Mixed reflux of gastric and duodenal juices is more harmful to the esophagus than gastric juice alone. The need for surgical therapy re-emphasized. Ann Surg 222:525–531, 1995

    CAS  PubMed  Google Scholar 

  41. Fein M, Ireland AP, Ritter MP, Peters JH, Hagen JA, Bremner CG, DeMeester TR: Duodenogastric reflux potentiates the injurious effects of gastroesophageal reflux. J Gastrointest Surg 1:27–33, 1997

    Article  PubMed  CAS  Google Scholar 

  42. Safaie-Shirazi S, DenBesten L, Zike WL: Effect of bile salts on the ionic permeability of the esophageal mucosa and their role in the production of esophagitis. Gastroenterology 68:728–733, 1975

    PubMed  CAS  Google Scholar 

  43. Chung RS, Johnson GM, Denbesten L: Effect of sodium taurocholate and ethanol on hydrogen ion absorption in rabbit esophagus. Am J Dig Dis 22:582–588, 1977

    Article  PubMed  CAS  Google Scholar 

  44. Harmon JW, Johnson LF, Maydonovitch CL: Effects of acid and bile salts on the rabbit esophageal mucosa. Dig Dis Sci 26:65–72, 1981

    Article  PubMed  CAS  Google Scholar 

  45. Kivilaakso E, Fromm D, Silen W: Effect of bile salts and related compounds on isolated esophageal mucosa. Surgery 87:280–285, 1980

    PubMed  CAS  Google Scholar 

  46. Attwood SE, Ball CS, Barlow AP, Jenkinson L, Norris TL, Watson A: Role of intragastric and intraoesophageal alkalinisation in the genesis of complications in Barrett’s columnar lined lower oesophagus. Gut 34:11–15, 1993

    Article  PubMed  CAS  Google Scholar 

  47. Vaezi MF, Lacamera RG, Richter JE: Validation studies of Bilitec 2000: an ambulatory duodenogastric reflux monitoring system. Am J Physiol 267:G1050–G1057, 1994

    PubMed  CAS  Google Scholar 

  48. Vaezi MF, Richter JE: Role of acid and duodenogastroesophageal reflux in gastroesophageal reflux disease. Gastroenterology 111: 1192–1199, 1996

    Article  CAS  PubMed  Google Scholar 

  49. Van Deenen LL, De Haas GH, Heensherk CH: Hydrolysis of synthetic mixed acid phospholipids by phospholipase A from human pancreas. Biochim Biophys Acta 67:295–297, 1963

    Article  PubMed  CAS  Google Scholar 

  50. Nehra D, Howell P, Williams CP, Pye JK, Beynon J: Toxic bile acids in gastro-oesophageal reflux disease: Influence of gastric acidity. Gut 44:598–602, 1999

    Article  CAS  PubMed  Google Scholar 

  51. Tanaka K, Fromm D: Effects of bile acid and salicylate on isolated surface and glandular cells of rabbit stomach. Surgery 93:660–663, 1983

    PubMed  CAS  Google Scholar 

  52. Schweitzer EJ, Bass BL, Batzri S, Young PM, Huesken J, Harmon JW: Lipid solubilization during bile salt-induced esophageal mucosal barrier disruption in the rabbit. J Lab Clin Med 110:172–179, 1987

    PubMed  CAS  Google Scholar 

  53. Batzri S, Harmon JW, Schweitzer EJ, Toles R: Bile acid accumulation in gastric mucosal cells. Proc Soc Exp Biol Med 197:393–399, 1991

    PubMed  CAS  Google Scholar 

  54. Schweitzer EJ, Bass BL, Batzri S, Harmon JW: Bile acid accumulation by rabbit esophageal mucosa. Dig Dis Sci 31:1105–1113, 1986

    Article  PubMed  CAS  Google Scholar 

  55. Makishima M, Okamoto AY, Repa JJ, Tu H, Learned RM, Luk A, Hull MV, Lustig KD, Mangelsdorf DJ, Shan B: identification of a nuclear receptor for bile acids. Science 284:1362–1365, 1999

    Article  PubMed  CAS  Google Scholar 

  56. Xie W, Radominska-Pandya A, Shi Y, Simon CM, Nelson MC, Ong ES, Waxman DJ, Evans RM: An essential role for nuclear receptors SXR/PXR in detoxification of cholestatic bile acids. Proc Natl Acad Sci USA 98:3375–3380, 2001

    Article  PubMed  CAS  Google Scholar 

  57. Goodwin B, Gauthier KC, Umetani M, Watson MA, Lochansky MI, Collins JL, Leitersdorf E, Mangelsdorf DJ, Kliewer SA, Repa JJ: Identification of bile acid precursors as endogenous ligands for the nuclear xenobiotic pregnane X receptor. Proc Natl Acad Sci USA 100:223–228, 2003

    Article  PubMed  CAS  Google Scholar 

  58. Halvorsen JF, Semb BK: The “Barrett syndrome” (the columnar-lined lower oesophagus): an acquired condition secondary to reflux oesophagitis. A case report with discussion of pathogenesis. Acta Chir Scand 141:683–687, 1975

    CAS  Google Scholar 

  59. Li H, Walsh TN, O’Dowd G, Gillen P, Byrne PJ, Hennessy TP: Mechanisms of columnar metaplasia and squamous regeneration in experimental Barrett’s esophagus. Surgery 115:176–181, 1994

    PubMed  CAS  Google Scholar 

  60. Hamilton SR, Yardley JH: Regnerative of cardiac type mucosa and acquisition of Barrett mucosa after esophagogastrostomy. Gastroenterology 72:669–675, 1977

    PubMed  CAS  Google Scholar 

  61. Levine DS, Rubin CE, Reid BJ, Haggitt RC: Specialized metaplastic columnar epithelium in Barrett’s esophagus. A comparative transmission electron microscopic study. Lab Invest 60:418–432, 1989

    PubMed  CAS  Google Scholar 

  62. Johns BAE: Developmental changes in the oesophageal epithelium in man. J Anat 86:431–439, 1952

    PubMed  CAS  Google Scholar 

  63. Jabbari M, Goresky CA, Lough J, Yaffe C, Daly D, Cote C: The inlet patch: heterotopic gastric mucosa in the upper esophagus. Gastroenterology 89:352–356, 1985

    PubMed  CAS  Google Scholar 

  64. Wright NA: Migration of the ductular elements of gut-associated glands gives clues to the histogenesis of structures associated with responses to acid hypersecretory state: the origins of “gastric metaplasia” in the duodenum of the specialized mucosa of barrett’s esophagus and of pseudopyloric metaplasia. Yale J Biol Med 69:147–153, 1996

    PubMed  CAS  Google Scholar 

  65. Herbst JJ, Berenson MM, McCloskey DW, Wiser WC: Cell proliferation in esophageal columnar epithelium (Barrett’s esophagus). Gastroenterology 75:683–687, 1978

    PubMed  CAS  Google Scholar 

  66. Glickman JN, Chen YY, Wang HH, Antonioli DA, Odze RD: Phenotypic characteristics of a distinctive multilayered epithelium suggests that it is a precursor in the development of Barrett’s esophagus. Am J Surg Pathol 25:569–578, 2001

    Article  PubMed  CAS  Google Scholar 

  67. Shields HM, Zwas F, Antonioli DA, Doos WG, Kim S, Spechler SJ: Detection by scanning electron microscopy of a distinctive esophageal surface cell at the junction of squamous and Barrett’s epithelium. Dig Dis Sci 38:97–108, 1993

    Article  PubMed  CAS  Google Scholar 

  68. Sawhney RA, Shields HM, Allan CH, Boch JA, Trier JS, Antonioli DA: Morphological characterization of the squamocolumnar junction of the esophagus in patients with and without Barrett’s epithelium. Dig Dis Sci 41:1088–1098, 1996

    Article  PubMed  CAS  Google Scholar 

  69. Boch JA, Shields HM, Antonioli DA, Zwas F, Sawhney RA, Trier JS: Distribution of cytokeratin markers in Barrett’s specialized columnar epithelium. Gastroenterology 112:760–765, 1997

    Article  PubMed  CAS  Google Scholar 

  70. Eda A, Osawa H, Satoh K, Yanaka I, Kihira K, Ishino Y, Mutoh H, Sugano K: Aberrant expression of CDX2 in Barrett’s epithelium and inflammatory esophageal mucosa. J Gastroenterol 38:14–22, 2003

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Philippe G. Guillem MD, PhD.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Guillem, P.G. How to Make a Barrett Esophagus: Pathophysiology of Columnar Metaplasia of the Esophagus. Dig Dis Sci 50, 415–424 (2005). https://doi.org/10.1007/s10620-005-2451-x

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10620-005-2451-x

Keywords:

Navigation