Skip to main content

Rapid epithelial restitution of the superficially-damaged gastric mucosa

  • Chapter
Advances in Peptic Ulcer Pathogenesis
  • 72 Accesses

Abstract

Studies begun in the 1950s and 1960s1-5 elucidated some of the mechanisms by which extremely steep ionic gradients could be maintained across the gastric mucosa. The concept of the ‘gastric mucosal barrier’ was developed during this time from physiological experiments which showed that luminally-applied agents such as bile acids, various alcohols, hypertonic solutions and salicylates increased gastric mucosal permeability but also often resulted in frank bleeding into the gastric lumen6-8. Under these conditions which broke the barrier, there was a rapid back diffusion of hydrogen ions from the gastric lumen into the tissue and a concomitant loss of tissue sodium ions. From these studies, a feed forward loop was hypothesized which suggested that acid back diffusion not only resulted in tissue damage but indirectly stimulated parietal cells to secrete more acid into the lumen which initiated additional cycles of this loop9. While there is substantial experimental evidence to verify each component of this model, the cause and effect relationship between breaks in the gastric mucosal barrier and the development of gastric erosions is not understood6. Until recently there has not been sufficient data from which to postulate a mechanism by which this feed forward cycle (acid back diffusion, tissue damage, parietal cell stimulation, acid secretion) could be terminated. This in turn has put emphasis on the prophylactic aspects of gastric mucosal defence while little attention has been focused on the reparative aspects of the damaged barrier.

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

Access this chapter

Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 39.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 54.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Davenport, H.W. (1964). Gastric mucosal injury by fatty and acetylsalicylic acids. Gastroenterology, 46, 245–53

    PubMed  CAS  Google Scholar 

  2. Davenport, H.W., Warner, H.A. and Code, C.F. (1964). Functional significance of gastric mucosal barrier to sodium. Gastroenterology, 47, 142–52

    PubMed  CAS  Google Scholar 

  3. Code, C.F., Scholer, J.F. and Orvis, A.L. (1955). Barrier offered by gastric mucosa to absorption of sodium. Am. J. Physiol., 183, 604

    Google Scholar 

  4. Davenport, H.W. (1965). Damage to the gastric mucosa: effects of salicylate and stimulation. Gastroenterology, 49, 189–96

    PubMed  CAS  Google Scholar 

  5. Davenport, H.W. (1967). Ethanol damage to canine oxyntic glandular mucosa. Soc. Exp. Biol. Med., 126, 657–62

    CAS  Google Scholar 

  6. Fromm, D. (1981). Gastric mucosal barrier: In Johnson, L.R. (ed.) Physiology of the Gastrointestinal Tract, pp. 733–48. (New York: Raven Press)

    Google Scholar 

  7. Davenport, H.W. (1970). Backdiffusion of acid through the gastric mucosa and its physiological consequences. In Glass, G.B.J. (ed.) Progress in Gastroenterology, p. 48. (New York: Grune and Stratton)

    Google Scholar 

  8. Davenport, H.W. (1974). Plasma protein shedding by the canine oxyntic glandular mucosa induced by topical application of snake venom and ethanol. Gastroenterology, 67, 264–70

    PubMed  CAS  Google Scholar 

  9. Davenport, H.W. (1966). Fluid produced by the gastric mucosa during damage by acetic and salicylic acids. Gastroenterology, 50, 487–99

    PubMed  CAS  Google Scholar 

  10. Robert, A. (1975). Antisecretory, anti-ulcer, cytoprotective and diarrheogenic properties of prostaglandins. Adv. Prostaglandin Thromboxane Res., 2, 507–20

    Google Scholar 

  11. Robert, A. (1979). Cytoprotection by prostaglandins. Gastroenterology, 77, 761–7

    PubMed  CAS  Google Scholar 

  12. Robert, A., Nezamis, J.E., Lancaster, C. and Hanchar, A.J. (1979). Cytoprotection by prostaglandins in rats. Prevention of gastric necrosis produced by alcohol, HC1, NaOH, hypertonic NaCl and thermal injury. Gastroenterology, 77, 433–43

    PubMed  CAS  Google Scholar 

  13. Miller, T.A. (1983). Protective effects of prostaglandins against gastric mucosal damage: current knowledge and proposed mechanisms. Am. J. Physiol., 245, G601–23

    PubMed  CAS  Google Scholar 

  14. Lacy, E.R. and Ito, S. (1982). Microscopic analysis of ethanol damage to rat gastric mucosa after treatment with a prostaglandin. Gastroenterology, 83, 619–25

    PubMed  CAS  Google Scholar 

  15. Lacy, E.R. and Ito, S. (1984). Ethanol-induced insult to the superficial rat gastric epithelium: a study of damage and rapid repair. In Allen, A., Flemstróm, G., Garner, A., Silen W. and Turnberg, L.A. (eds) Mechanisms of Mucosal Protection in the Upper Gastrointestinal Tract, pp. 49–56. (New York: Raven Press)

    Google Scholar 

  16. Guth, P.H., Paulsen, G. and Nagata, H. (1984). Histologic and microcirculatory changes in alcohol-induced gastric lesions in the rat: effect of prostaglandin cytoprotection. Gastroenterology, 87, 1083–90

    PubMed  CAS  Google Scholar 

  17. Wallace, J.L., Morris, G.P., Krausse, E.J. and Greaves, S.E. (1982). Reduction by cytoprotective agents of ethanol-induced damage to the rat gastric mucosa: a correlated morphological and physiological study. Can. J. Physiol. Pharmacol., 60, 1688–99

    Article  Google Scholar 

  18. Ohno, T., Ohtsuki, H. and Okabe, S. (1985). Effect of 16, 16-dimethyl prostaglandin E2 on ethanol-induced and aspirin-induced gastric damage in the rat. Scanning electron microscopic study. Gastroenterology, 88, 353–61

    PubMed  CAS  Google Scholar 

  19. Tarnawski, A., Hollander, D., Stachura, J., Krause, W.J. and Gergely, H. (1985). Prostaglandin protection of the gastric mucosa against alcohol injury — a dynamic time-related process. Gastroenterology, 88, 334–52

    PubMed  CAS  Google Scholar 

  20. Whittle, B.J.R. and Steel, G. (1985). Evaluation of the protection of rat gastric mucosa by a prostaglandin analogue using cellular enzyme markers and histologic techniques. Gastroenterology, 88, 315–27

    PubMed  CAS  Google Scholar 

  21. Grant, R. (1945). Rate of replacement of the surface epithelial cells of the gastric mucosa. Anat. Rec., 91, 175–85

    Article  Google Scholar 

  22. Lacy, E.R. (1985). Prostaglandins and histological changes in the gastric mucosa. Dig. Dis. Sci., 30, 83S-94S

    Article  PubMed  CAS  Google Scholar 

  23. Duchateau, A., Thiefin, G., Zeithoun, P. and Barzaghi, F. (1983). Hémolyse intra-muqueuse dans la lésion nécrotique gastrique par alcool absolu chez le rat. Gastroenterol. Clin. Biol., 7, 150–7

    PubMed  CAS  Google Scholar 

  24. Lev, R., Kawashima, K. and Glass G.B.J. (1976). Morphological features and healing of stress ulcers induced by alcohol and restraint. Arch. Pathol. Lab. Med., 100, 554–8

    PubMed  CAS  Google Scholar 

  25. Helander, H.F. (1983). Morphological studies on the margin of gastric corpus wounds in the rat. J. Submicrosc. Cytol., 15, 627–43

    PubMed  CAS  Google Scholar 

  26. Blom, H. and Helander, H.F. (1981). Quantitative ultrastructural studies on parietal cell regeneration in experimental ulcers in rat gastric mucosa. Gastroenterology, 80, 334–43

    PubMed  CAS  Google Scholar 

  27. Ito, S. and Lacy, E.R. (1985). Morphology of rat gastric mucosal damage, defense, and restitution in the presence of luminal ethanol. Gastroenterology, 88, 250–60

    PubMed  CAS  Google Scholar 

  28. Ito, S. and Lacy E.R. (1984). Characteristics of ethanol induced lesions in rat gastric mucosa. In Allen, A., Flemstrôm, G., Garner, A., Silen, W. and Turnberg, L.A. (eds) Mechanisms of Mucosal Protection in the Upper Gastrointestinal Tract, pp. 57–63. (New York: Raven Press)

    Google Scholar 

  29. Lacy, E.R. (1986). Effects of absolute ethanol, misoprostol, cimetidine, and phosphate buffer on the morphology of rat gastric mucosae. Dig. Dis. Sci., 31, 101S–7S

    Article  PubMed  CAS  Google Scholar 

  30. Morris, G.P. and Wallace, J.L. (1981). The roles of ethanol and of acid in the production of gastric mucosal erosions in rats. Virchow’s Arch. (Cell Pathol.)., 38, 23–38

    Article  CAS  Google Scholar 

  31. Townsend, S.F. (1961). Regeneration of the gastric mucosa in rats. Am. J. Anat., 109, 133–47

    Article  PubMed  CAS  Google Scholar 

  32. Helpap, B., Hattori, T. and Gedigk, P. (1981). Repair of gastric ulcer. A cell kinetic study. Virchow’s Arch. (Pathol Anat.), 392, 159–70

    Article  CAS  Google Scholar 

  33. Yeomans, N.D. (1976). Electron microscopic study of the repair of aspirin-induced gastric lesions. Dig. Dis. Sci., 21, 533–41

    Article  CAS  Google Scholar 

  34. Hingson, D.J. and Ito, S. (1971). Effect of aspirin and related compounds on the fine structure of mouse gastric mucosa. Gastroenterology, 61, 156–77

    PubMed  CAS  Google Scholar 

  35. Yeomans, N.D., St. John D.J.B. and de Boer, W.G.R.M. (1973). Regeneration of gastric mucosa after aspirin-induced injury in the rat. Dig. Dis. Sci., 18, 773–80

    CAS  Google Scholar 

  36. Ferguson, A.R. (1928). A cytological study of the regeneration of gastric glands following the experimental removal of large areas of mucosa. Am. J. Anat., 42, 403–41

    Article  Google Scholar 

  37. Lacy, E.R. and Ito, S. (1984). Rapid epithelial restitution of the rat gastric mucosa after ethanol injury. Lab. Invest., 51(5), 573–83

    PubMed  CAS  Google Scholar 

  38. Dinoso, V.P., Ming, S. and McNiff, J. (1976). Ultrastructural changes of the canine gastric mucosa after topical application of graded concentrations of ethanol. Am. J. Dig. Dis., 21, 626–32

    Article  PubMed  CAS  Google Scholar 

  39. Rutten, M.J. and Ito, S. (1983). Morphology and electrophysiology of guinea pig gastric mucosal repair in vitro. Am. J. Physiol., 244, G171–81

    PubMed  CAS  Google Scholar 

  40. Ito, S., Lacy, E.R., Rutten, M.J., Critchlow, J. and Silen, W. (1984). Rapid repair of injured gastric mucosa. Scand. J. Gastroenterol., (Suppl. 101), 87–95

    Google Scholar 

  41. Svanes, K., Ito, S., Takeuchi, K. and Silen, W. (1982). Restitution of the surface epithelium of in vitro frog gastric mucosa after damage with hyperosmolar sodium chloride: morphologic and physiologic characteristics. Gastroenterology, 82, 1409–26

    PubMed  CAS  Google Scholar 

  42. Critchlow, J., Magee, D., Ito, S., Takeuchi, K. and Silen, W. (1985). Requirements for restitution of the surface epithelium of frog stomach after mucosal injury. Gastroenterology, 88, 237–49

    PubMed  CAS  Google Scholar 

  43. Eastwood, G.L. and Kirchner, J.P. (1974). Changes in the fine structure of mouse gastric epithelium produced by ethanol and urea. Gastroenterology, 67, 71–84

    PubMed  CAS  Google Scholar 

  44. Szabo, S., Trier, J.S., Brown, A. and Schnoor, J. (1985). Early vascular injury and increased vascular permeability in gastric mucosal injury caused by ethanol in the rat. Gastroenterology, 88, 228–36

    PubMed  CAS  Google Scholar 

  45. Wallace, J.L. and Whittle, B.J.R. (1986). Role of mucus in the repair of gastric epithelial damage in the rat. Inhibition of epithelial recovery by mucolytic agents. Gastroenterology, 91, 603–11

    PubMed  CAS  Google Scholar 

  46. Svanes, K., Critchlow, J., Takeuchi, K., Magee, D., Ito, S. and Silen, W. (1984). Factors influencing reconstitution of frog gastric mucosa: role of prostaglandins. In Allen, A., Flemstrom, G., Garner, A., Silen, W. and Turnberg, L.A. (eds) Mechanisms of Mucosal Protection in the Upper Gastrointestinal Tract, pp. 33–9. (New York: Raven Press)

    Google Scholar 

  47. Dinoso, V.P., Chey, W.Y., Siplet, H. and Lorder, S.H. (1970). Effects of ethanol on the gastric mucosa of the Heidenhain pouch of dogs. Dig. Dis. Sci., 15, 809–19

    Article  CAS  Google Scholar 

  48. Biggerstaff, R.J. and Leitch, G.J. (1977). Effects of ethanol on electrical parameters of the in vivo rat stomach. Dig. Dis. Sci., 22, 1064–8

    Article  CAS  Google Scholar 

  49. Shanbour, L.L. (1980). Effects of alcohol on acid secretion and ion transport in the gastric mucosa. Alcohol and the gastrointestinal tract. INSERM, 95, 390–404

    Google Scholar 

  50. Dipasquale, A. (1975). Locomotion of epithelial cells: factors involved in extension of the leading edge. Exp. Cell Res., 95, 425–39.

    Article  PubMed  CAS  Google Scholar 

  51. Allen, R.D. (1981). Cell motility. J. Cell Biol., 91 (suppl.), 148S-55S

    Article  PubMed  CAS  Google Scholar 

  52. Lacy, E.R. (1987). Gastric mucosal defense after superficial injury. Clin. Invest. Med., 10, 189–200

    PubMed  CAS  Google Scholar 

  53. Lacy, E.R., Rutten, M.J. and Ito, S. (1983). The role of the basal lamina in gastric mucosa reepithelization after surface cell destruction. Anal. Rec., 205, 104a

    Google Scholar 

  54. Wallace, J.L. and Whittle, B.J.R. (1985). Acceleration of recovery of gastric epithelial integrity by 16, 16-dimethyl prostaglandin E2. Br. J. Pharmac., 86, 837–42

    CAS  Google Scholar 

  55. Miller, T.A. and Henagan, J.M. (1984). Indomethacin decreases resistance of gastric barrier to disruption by alcohol. Dig. Dis. Sci., 29, 141–9

    Article  PubMed  CAS  Google Scholar 

  56. Lev, R., Siegel, H.I. and Glass, G.B.J. (1972). Effects of salicylates on the canine stomach: a morphological and histochemical study. Gastroenterology, 62, 970–80

    PubMed  CAS  Google Scholar 

  57. Ivey, K.J., Tarnawski, A., Stachura, J., Werner, H., Mach, T. and Burks, M. (1980). The induction of gastric mucosal tolerance to alcohol by chronic administration. J. Lab. Clin. Med., 96, 922–32

    PubMed  CAS  Google Scholar 

  58. Deregnaucourt, J. and Code, C.F. (1979). Increased resistance of the gastric mucosal barrier to barrier breakers in the rat. Gastroenterology, 77, 309–12

    PubMed  CAS  Google Scholar 

  59. Bolton, J.P. and Cohen, M.M. (1977). Effect of repeated aspirin administration on the gastric mucosal barrier and cell turnover. J. Surg. Res., 23, 251–6

    Article  PubMed  CAS  Google Scholar 

  60. St. John, D.J.B., Yeomans, N.D., McDermott, F.T. and de Boer, W.G.R.M. (1973). Adaptation of the gastric mucosa to repeated administration of aspirin in the rat. Dig. Dis. Sci., 18, 881–6

    Article  Google Scholar 

  61. Lacy, E.R. (1985). Gastric mucosal resistance to a repeated ethanol insult. Scand. J. Gastroenterol., 20 (Suppl. 110), 63–72

    Article  Google Scholar 

  62. Allen, A. (1981). Structure and function of gastrointestinal mucus. In Johnson, L.R. (ed.) Physiology of the Gastrointestinal Tract, pp. 617–39. (Raven Press: New York)

    Google Scholar 

  63. Kivilaakso, E. and Flemstrom, G. (1984). Surface pH gradient in gastroduodenal mucosa. Scand. J. Gastroenterol., 19 (Suppl. 105), 50–2

    Google Scholar 

  64. Ross, I.N., Bahari, H.M.M. and Turnberg, L.A. (1981). The pH gradient across mucus adherent to rat fundic mucosa in vivo and the effect of potential damaging agents. Gastroenterology, 81, 713–8

    PubMed  CAS  Google Scholar 

  65. Takeuchi, K.M., Magee, J., Critchlow, J., Matthews, J. and Silen, W. (1983). Studies of the pH gradient and thickness of frog gastric mucus gel. Gastroenterology, 84, 331–40

    PubMed  CAS  Google Scholar 

  66. Williams, S.E. and Turnberg, L.A. (1980). Retardation of acid diffusion by pig gastric mucus: a potential role in mucosal protection. Gastroenterology, 79, 299–304

    PubMed  CAS  Google Scholar 

  67. Morris, G.P., Harding, R.K. and Wallace, J.L. (1984). A functional model for extracellular gastric mucus in the rat. Virchow’s Arch. (Cell Pathol.), 46, 239–51

    Article  CAS  Google Scholar 

  68. Takeuchi, K. and Okabe, S. (1983). Role of luminal alkalinization in repair process of ethanol-induced mucosal damage in rat stomach. Dig. Dis. Sci., 28, 993–1000

    Article  PubMed  CAS  Google Scholar 

  69. Svanes, K., Takeuchi, K., Ito, S. and Silen, W. (1983). Effect of luminal pH and nutrient bicarbonate concentration on restitution after gastric surface cell injury. Surgery, 94, 494–500

    PubMed  CAS  Google Scholar 

Download references

Authors

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 1988 MTP Press Limited

About this chapter

Cite this chapter

Lacy, E.R. (1988). Rapid epithelial restitution of the superficially-damaged gastric mucosa. In: Rees, W.D.W. (eds) Advances in Peptic Ulcer Pathogenesis. Springer, Dordrecht. https://doi.org/10.1007/978-94-009-1245-8_8

Download citation

  • DOI: https://doi.org/10.1007/978-94-009-1245-8_8

  • Publisher Name: Springer, Dordrecht

  • Print ISBN: 978-94-010-7052-2

  • Online ISBN: 978-94-009-1245-8

  • eBook Packages: Springer Book Archive

Publish with us

Policies and ethics