Rapid epithelial restitution of the superficially-damaged gastric mucosa

  • E. R. Lacy
Chapter

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.

Keywords

Gastric Mucosa Basal Lamina Mucous Cell Gastric Lumen Gastric Mucus 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.
This is a preview of subscription content, log in to check access.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    Davenport, H.W. (1964). Gastric mucosal injury by fatty and acetylsalicylic acids. Gastroenterology, 46, 245–53PubMedGoogle Scholar
  2. 2.
    Davenport, H.W., Warner, H.A. and Code, C.F. (1964). Functional significance of gastric mucosal barrier to sodium. Gastroenterology, 47, 142–52PubMedGoogle Scholar
  3. 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, 604Google Scholar
  4. 4.
    Davenport, H.W. (1965). Damage to the gastric mucosa: effects of salicylate and stimulation. Gastroenterology, 49, 189–96PubMedGoogle Scholar
  5. 5.
    Davenport, H.W. (1967). Ethanol damage to canine oxyntic glandular mucosa. Soc. Exp. Biol. Med., 126, 657–62Google Scholar
  6. 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. 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. 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, 264–70PubMedGoogle Scholar
  9. 9.
    Davenport, H.W. (1966). Fluid produced by the gastric mucosa during damage by acetic and salicylic acids. Gastroenterology, 50, 487–99PubMedGoogle Scholar
  10. 10.
    Robert, A. (1975). Antisecretory, anti-ulcer, cytoprotective and diarrheogenic properties of prostaglandins. Adv. Prostaglandin Thromboxane Res., 2, 507–20Google Scholar
  11. 11.
    Robert, A. (1979). Cytoprotection by prostaglandins. Gastroenterology, 77, 761–7PubMedGoogle Scholar
  12. 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, 433–43PubMedGoogle Scholar
  13. 13.
    Miller, T.A. (1983). Protective effects of prostaglandins against gastric mucosal damage: current knowledge and proposed mechanisms. Am. J. Physiol., 245, G601–23PubMedGoogle Scholar
  14. 14.
    Lacy, E.R. and Ito, S. (1982). Microscopic analysis of ethanol damage to rat gastric mucosa after treatment with a prostaglandin. Gastroenterology, 83, 619–25PubMedGoogle Scholar
  15. 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. 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, 1083–90PubMedGoogle Scholar
  17. 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, 1688–99CrossRefGoogle Scholar
  18. 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, 353–61PubMedGoogle Scholar
  19. 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, 334–52PubMedGoogle Scholar
  20. 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, 315–27PubMedGoogle Scholar
  21. 21.
    Grant, R. (1945). Rate of replacement of the surface epithelial cells of the gastric mucosa. Anat. Rec., 91, 175–85CrossRefGoogle Scholar
  22. 22.
    Lacy, E.R. (1985). Prostaglandins and histological changes in the gastric mucosa. Dig. Dis. Sci., 30, 83S-94SPubMedCrossRefGoogle Scholar
  23. 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, 150–7PubMedGoogle Scholar
  24. 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, 554–8PubMedGoogle Scholar
  25. 25.
    Helander, H.F. (1983). Morphological studies on the margin of gastric corpus wounds in the rat. J. Submicrosc. Cytol., 15, 627–43PubMedGoogle Scholar
  26. 26.
    Blom, H. and Helander, H.F. (1981). Quantitative ultrastructural studies on parietal cell regeneration in experimental ulcers in rat gastric mucosa. Gastroenterology, 80, 334–43PubMedGoogle Scholar
  27. 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, 250–60PubMedGoogle Scholar
  28. 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. 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–7SPubMedCrossRefGoogle Scholar
  30. 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, 23–38CrossRefGoogle Scholar
  31. 31.
    Townsend, S.F. (1961). Regeneration of the gastric mucosa in rats. Am. J. Anat., 109, 133–47PubMedCrossRefGoogle Scholar
  32. 32.
    Helpap, B., Hattori, T. and Gedigk, P. (1981). Repair of gastric ulcer. A cell kinetic study. Virchow’s Arch. (Pathol Anat.), 392, 159–70CrossRefGoogle Scholar
  33. 33.
    Yeomans, N.D. (1976). Electron microscopic study of the repair of aspirin-induced gastric lesions. Dig. Dis. Sci., 21, 533–41CrossRefGoogle Scholar
  34. 34.
    Hingson, D.J. and Ito, S. (1971). Effect of aspirin and related compounds on the fine structure of mouse gastric mucosa. Gastroenterology, 61, 156–77PubMedGoogle Scholar
  35. 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, 773–80Google Scholar
  36. 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, 403–41CrossRefGoogle Scholar
  37. 37.
    Lacy, E.R. and Ito, S. (1984). Rapid epithelial restitution of the rat gastric mucosa after ethanol injury. Lab. Invest., 51(5), 573–83PubMedGoogle Scholar
  38. 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, 626–32PubMedCrossRefGoogle Scholar
  39. 39.
    Rutten, M.J. and Ito, S. (1983). Morphology and electrophysiology of guinea pig gastric mucosal repair in vitro. Am. J. Physiol., 244, G171–81PubMedGoogle Scholar
  40. 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), 87–95Google Scholar
  41. 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, 1409–26PubMedGoogle Scholar
  42. 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, 237–49PubMedGoogle Scholar
  43. 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, 71–84PubMedGoogle Scholar
  44. 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, 228–36PubMedGoogle Scholar
  45. 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, 603–11PubMedGoogle Scholar
  46. 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. 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, 809–19CrossRefGoogle Scholar
  48. 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, 1064–8CrossRefGoogle Scholar
  49. 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, 390–404Google Scholar
  50. 50.
    Dipasquale, A. (1975). Locomotion of epithelial cells: factors involved in extension of the leading edge. Exp. Cell Res., 95, 425–39.PubMedCrossRefGoogle Scholar
  51. 51.
    Allen, R.D. (1981). Cell motility. J. Cell Biol., 91 (suppl.), 148S-55SPubMedCrossRefGoogle Scholar
  52. 52.
    Lacy, E.R. (1987). Gastric mucosal defense after superficial injury. Clin. Invest. Med., 10, 189–200PubMedGoogle Scholar
  53. 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, 104aGoogle Scholar
  54. 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, 837–42Google Scholar
  55. 55.
    Miller, T.A. and Henagan, J.M. (1984). Indomethacin decreases resistance of gastric barrier to disruption by alcohol. Dig. Dis. Sci., 29, 141–9PubMedCrossRefGoogle Scholar
  56. 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, 970–80PubMedGoogle Scholar
  57. 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, 922–32PubMedGoogle Scholar
  58. 58.
    Deregnaucourt, J. and Code, C.F. (1979). Increased resistance of the gastric mucosal barrier to barrier breakers in the rat. Gastroenterology, 77, 309–12PubMedGoogle Scholar
  59. 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, 251–6PubMedCrossRefGoogle Scholar
  60. 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, 881–6CrossRefGoogle Scholar
  61. 61.
    Lacy, E.R. (1985). Gastric mucosal resistance to a repeated ethanol insult. Scand. J. Gastroenterol., 20 (Suppl. 110), 63–72CrossRefGoogle Scholar
  62. 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. 63.
    Kivilaakso, E. and Flemstrom, G. (1984). Surface pH gradient in gastroduodenal mucosa. Scand. J. Gastroenterol., 19 (Suppl. 105), 50–2Google Scholar
  64. 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, 713–8PubMedGoogle Scholar
  65. 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, 331–40PubMedGoogle Scholar
  66. 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, 299–304PubMedGoogle Scholar
  67. 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, 239–51CrossRefGoogle Scholar
  68. 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, 993–1000PubMedCrossRefGoogle Scholar
  69. 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, 494–500PubMedGoogle Scholar

Copyright information

© MTP Press Limited 1988

Authors and Affiliations

  • E. R. Lacy

There are no affiliations available

Personalised recommendations