Current Gastroenterologic Aspects of Pernicious Anemia

  • D. Cattan
  • A. M. Roucayrol
  • J. Belaïche

Abstract

It is generally recognized that a patient suffering from atrophic gastritis of the fundic portion of the stomach becomes successively deficient in hydrochloric acid secretion, pepsin, and then intrinsic factor (IF). The atrophic gastritis observed in pernicious anemia causes failure of gastric secretion. The most direct consequences of this process include microbial overgrowth in the stomach (which is generally well tolerated), increased levels of serum gastrin secreted by the antrum (a relatively constant reaction to increased gastric pH when the antrum is spared), and vitamin B12 deficiency.

Keywords

Anemia Nitrite Assimilation Histamine Folate 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    Alumets J, Sundler F, Falkmer J, Jungberg O, Hakanson R, Martensson H et al. (1983) Neurohormonal peptides in endocrine tumors of the pancreas, stomach and upper small intestine. Immunohistochemical study of 24 cases. Ultrastruct Pathol 5:55–72PubMedCrossRefGoogle Scholar
  2. 2.
    Amin S, Spinks T, Ranicar A, Short MD, Hoffbrand AB (1980) Long-term clearance of (57 Co)-cyanocobalamin in vegans and pernicious anaemia. Clin Sci 58:101–103PubMedGoogle Scholar
  3. 3.
    Ardeman S, Chanarin I (1986) Intrinsic factor secretion in gastric atrophy. Gut 7:99–101CrossRefGoogle Scholar
  4. 4.
    Ardeman S, Chanarin I, Berry V (1965) Studies on human gastric intrinsic factor. Observations on its possible absorption and enterohepatic circulation. Br J Haematol 11:11–14PubMedCrossRefGoogle Scholar
  5. 5.
    Aures D, Akanson R, Schauer A (1968) Histidine decarboxylase and dopa decarboxylase in the rat stomach. Properties and cellular localization. Eur. J. Pharmacol 3:217–234PubMedCrossRefGoogle Scholar
  6. 6.
    Black WC, Haffner HE (1968) Diffuse hyperplasia of gastric argyrophil cells and multiple carcinoid tumors. Cancer 21:1080–1099PubMedCrossRefGoogle Scholar
  7. 7.
    Blackburn EK, Callender ST, Dacie JV et al (1968) Possible association between anemia and leukemia: a prospective study of 1,625 patients with a note on the very high incidence of stomach cancer. Int. J. Cancer 3:163–170PubMedCrossRefGoogle Scholar
  8. 8.
    Borch K (1986) Epidemiologic, clinicopathologic and economic aspects of gastroscopic screening of patients with pernicious anemia. Scand J. Gastroenterol 21:21–30PubMedCrossRefGoogle Scholar
  9. 9.
    Borch K, Ren vail H, Liedberg G (1985) Gastric endocrine cell hyperplasia and carcinoid tumors in pernicious anemia. Gastroenterology 88:638–648PubMedGoogle Scholar
  10. 10.
    Bordi C, Costa A, Missale G (1975) ECL cell proliferation and gastrin levels. Gastroenterology 68:205–206PubMedGoogle Scholar
  11. 11.
    Bordi C, Gabrielli M, Missale G (1978) Pathological changes of endocrine cells in chronic atrophic gastritis. An ultrastructural study on peroral gastric biopsy specimens. Arch. Pathol. Lab. Med 102:129–135PubMedGoogle Scholar
  12. 12.
    Bordi C, Ravazzola M, De Vita O (1983) Pathology of endocrine cells in gastric mucosa. Ann. Pathol 3:19–28PubMedGoogle Scholar
  13. 13.
    Boriello SP, Reed PJ, Dolby JM, Barclay FE, Webster ADB (1985) Microbiologic and metabolic profile of achlorhydric stomach: comparison of pernicious anaemia and hypogam- maglobulinaemai. J. Clin. Pathol 38:946–953CrossRefGoogle Scholar
  14. 14.
    Brunet M, Berlie J, Janin ML, Zimmerman B, Hucher M, Ducourneau R (1979) Mortalité par cancer de l’estomac de 1954 à 1974. Nouv. Presse Méd. 21:1743–1744Google Scholar
  15. 15.
    Callender ST, Retief FP, Witts LJ (1960) The augmented histamine test with special reference to achlorhydria. Gut 1:326–336PubMedPubMedCentralCrossRefGoogle Scholar
  16. 16.
    Capella C, Polak JM, Timson CM, Frigerio B, Solcia E (1980) Gastric carcinoids of argyro- phil cells. Ultrastruct Pathol 1:411–418PubMedCrossRefGoogle Scholar
  17. 17.
    Carmel R, Johnson CS (1978) Racial patterns in pernicious anemia. N. Engl. J. Med 298:647–650PubMedCrossRefGoogle Scholar
  18. 18.
    Carney JA, Go VL, Fairbanks VF, Moore SB, Alport EC, Nora FE (1983) The syndrome of gastric argyrophil carcinoid tumors and non-antral gastric atrophy. Ann. Intern Med 99:761–766PubMedCrossRefGoogle Scholar
  19. 19.
    Caruso MP, Beardwoodd, Maxwell R, Wagner C (1984) Gastric atrophy and carcinoid tumors. Ann. Intern Med 100:459PubMedCrossRefGoogle Scholar
  20. 20.
    Cattan D, Belaïche J, Zittoun J. Yvart J, Chagnon P, Nurit Y (1982) Rôle de la carence en facteur intrinsèque dans la malabsorption de la vitamin B12 liée aux protéines dans les achlorhydries. Gastroentérol. Clin Biol 6:570–575PubMedGoogle Scholar
  21. 21.
    Cattan D, Roucayrol AM, Launay JM, Callebert J (1986) Histamine et activité histidine décarboxylase de la muqueuse fundique dans les gastrites atrophiques fundiques avec et sans hyperplasie des cellules ECL. Gastroentérol. Clin Biol 10(2bis):138AGoogle Scholar
  22. 22.
    Cattan D, Roucayrol AM, Launay JM, Callebert T (1989) Circulating gastrin endocrine cells hystamine content and histidine decarboxylase activity in atrophie gastritis. Gastroenterology, to be published.Google Scholar
  23. 23.
    Cattan R, Nallet J, Libeskind M, Habib R, Pariente P (1955) Carcinoide de l’estomac et anémie de Biermer. Arch. Mal. Appar Dig. 1955; 44:922–8Google Scholar
  24. 24.
    Charnarin I, James D (1974) Humoral and cell-mediated intrinsic factor. Lancet 1:1078–1083CrossRefGoogle Scholar
  25. 25.
    Chanarin I (1979) Megaloblastic anaemia, 2nd edn. Blackwell, OxfordGoogle Scholar
  26. 26.
    Deschner EE, Winawer SJ, Lipkin M (1972) Patterns of nucleic acid and protein synthesis in normal human gastric mucosa and atrophic gastritis. J Natl. Cancer Inst 48:1567–1574PubMedGoogle Scholar
  27. 27.
    Dolby JM, Webster ADB, Boriello SP, Barclay FE, Bartholomew BA, Hill MJ (1984) Bacterial colonization and nitrite concentration in the achlorhydric stomachs of patients with primary hypogammaglobulinemia or classical pernicious anaemia. Scand. J. Gastroenterol 19:105–110Google Scholar
  28. 28.
    Doscherholmen A, Swaim WR (1973) Impaired assimilation of egg 57 Co-vitamin B12 in patients with hypochlorhydria and achlorhydria, and after gastric resection. Gastroenterology 64:913–919PubMedGoogle Scholar
  29. 29.
    Doscherholmen A, McMahon J, Ripley D (1976) Inhibitory effect of eggs on vitamin B12 absorption: description of a simple ovalbumin 57 Co-vitamin B12 absorption test. Br. J. Haematol 33:261–272PubMedCrossRefGoogle Scholar
  30. 30.
    Doscherholmen A, McMahon J, Ripley D (1978) Vitamin B12 assimilation from chicken meat. Am. J. Clin. Nutr 31:825–830PubMedGoogle Scholar
  31. 31.
    Doscherholmen A, McMahon J, Ripley D (1978) Physiologic role of gastric acid and pepsin in the assimilation of vitamin B12 from food. Clin. Res. 26:661 AGoogle Scholar
  32. 32.
    Doscherholmen A, McMahon J, Economon P (1981) Vitamin B12 absorption from fish. Proc. Soc. Exp. Biol. Med 167:480–484PubMedCrossRefGoogle Scholar
  33. 33.
    Elsborg L, Mosbech J (1979) Pernicious anaemia as a risk factor in gastric cancer. Acta. Med Scand 208:315–318Google Scholar
  34. 34.
    Eriksson S, Clase L, Moquist-Olsson I (1981) Pernicious anaemia as a risk factor in gastric cancer. Acta. Med. Scand 210:481–484PubMedCrossRefGoogle Scholar
  35. 35.
    Fairbanks VF, Lennon VA, Kokmen E, Howard FM (1983) Test for pernicious anemia: serum intrinsic factor blocking antibody. Mayo Clin. Proc. 58:203–204PubMedGoogle Scholar
  36. 36.
    Ganguli PC, Cullen DR, Irvine NJ (1971) Radioimmunoassay of plasma gastrin in pernicious anemia achlorhydria, without pernicious anemia-hypochlorhydria and in controls. Lancet 1:155–158PubMedCrossRefGoogle Scholar
  37. 37.
    Glass GB, Pirchumoni CS (1975) Atrophic gastritis. Hum. Pathol 6:219–250CrossRefGoogle Scholar
  38. 38.
    Glass GB, Speer FD, Nierburgs HE et al. (1960) Gastric atrophy, atrophic gastritis and gastric secretory failure. Correlative study by suction biopsy and exfoliative cytology of gastric mucosa, paper electrophoretic and secretory assay of gastric secretion and measurements of intestinal absorption and blood levels of vitamin B12. Gastroenterology 39:429–453PubMedGoogle Scholar
  39. 39.
    Godwin J (1975) Carcinoid tumors. An analysis of 2,837 cases. Cancer 36:560–569PubMedCrossRefGoogle Scholar
  40. 40.
    Goldman H, French S, Burbridge E (1981) Cell hyperplasia and multiple metastasizing carcinoids of the stomach. Cancer 47:2620–2626PubMedCrossRefGoogle Scholar
  41. 41.
    Grasbeck R, Nyberg W, Reinzenstein P (1958) Biliary and fecal vitamin B12 excretion in man. An isotope study. Proc. Soc. Exp. Biol. Med 97:780–784PubMedCrossRefGoogle Scholar
  42. 42.
    Green R, Jacobsen DW, Van Tonder SV, Kew MC, Metz J (1982) Enterohepatic circulation of cobalamin in the non-human primate. Gastroenterology 61:773–776Google Scholar
  43. 43.
    Gueant JL, Monin B, Gaucher P, Nicolas JP (1984) Biliary excretion of cobalamin and cobalamin analogues in the human. Digestion 30:151–157PubMedCrossRefGoogle Scholar
  44. 44.
    Haentjens P. Williams G (1984) Precancerous lesions in the stomach. Acta. Clin. Belg 84:277–282Google Scholar
  45. 45.
    Hakanson R, Larsson JI, Liedberg G (1976) Effects of antrectomy and porto-caval shunting on the histamine-storing endocrine-like cells in oxyntic mucosa of the rat stomach. J Physiol (Lond) 259:785–800Google Scholar
  46. 46.
    Hastrup-Svendsen J, Dahl C, Bosvendsen L, Christiansen (1986) Gastric cancer risk in aehlorhydric patients. A long term follow-up study. Scand. J. Gastroenterol 21:16–20CrossRefGoogle Scholar
  47. 47.
    Heysell RM, Bozian RC, Darby WJ, Bell MC (1966) Vitamin B12 turnover in man. The assimilation of vitamin B]2 from natural foodstuff by man and estimates of minimal daily dietary requirements. Am. J. Clin. Nutr. 18:176–184Google Scholar
  48. 48.
    Hodges JR, Isaacson P, Wright R (1981) Diffuse enterochromaffin-like (ECL) cell hyperplasia and multiple gastric carcinoids: a complication of pernicious anemia. Gut 22:237–241PubMedPubMedCentralCrossRefGoogle Scholar
  49. 49.
    Hoffman NR (1970) The relationship between pernicious anemia and cancer of the stomach. Geriatrics 25:90–95PubMedGoogle Scholar
  50. 50.
    Imai T, Kubo T, Watanabe H (1971) Chronic gastritis in Japanese with reference to high incidence of gastric carcinoma. J. Natl. Cancer. Inst. 47:179–195PubMedGoogle Scholar
  51. 51.
    Irvine WJ, Davies SH, Haynes RC (1965) Secretion of intrinsic factor in response to histamine and to gastrin in the diagnosis of addisonian pernicious anaemia. Lancet 1:397–401CrossRefGoogle Scholar
  52. 52.
    Irvine WJ, Cullen DR, Scarth L, Simpson JD (1968) Intrinsic factor secretion assessed by direct radioimmunoassay and by total body counting in patients with achlorhydria and in acid secretors. Lancet 1:184–188CrossRefGoogle Scholar
  53. 53.
    Itsumo M, Watanabe H, Iwafuchi M, Yanahihara N, Ito S, Uwo J (1983) Multiple gastric carcinoids occurring in atrophic fundic mucosa. Gan No Rinsho 29:915–922Google Scholar
  54. 54.
    Kanazawa S, Herbert V, Herzlich B, Brivas G, Manusselis C (1983) Removal of cobalamin analogue in bile by enterohepatic circulation of vitamin B12. Lancet 1:707–708PubMedCrossRefGoogle Scholar
  55. 55.
    Kapadia CR, Mathan VI, Baker SJ (1976) Free intrinsic factor in the small intestine in man. Gastroenterology 70:704–706PubMedGoogle Scholar
  56. 56.
    King CE, Liebach J, Toskes PP (1979) Clinically significant vitamin B12 deficiency secondary to malabsorption of protein-bound vitamin B12 Dig. Dis. Sci 24:397–402CrossRefGoogle Scholar
  57. 57.
    Kittang E, Hamborg B, Schonsby H (1985) Absorption of food cobalamin assessed by the double isotope method in healthy volunteers and in patients with chronic diarrhea. Scand. J. Gastroenterol 20:500–507PubMedCrossRefGoogle Scholar
  58. 58.
    Larsson LI, Rehfeld JF, Stockbruegger R et al (1978) Mixed endocrine gastric tumors associated with hypergastrinemia of antral origin. Am. J. Pathol 93:53–68PubMedPubMedCentralGoogle Scholar
  59. 59.
    Larsson H, Carlsson E, Mattson H et al (1986) Plasma gastrin enterochromaffln-like cell activation and proliferation: studies with omeprazole and ranitidine in intact and antrec- tomized rats. Gastroenterology 90:391–399PubMedGoogle Scholar
  60. 60.
    Lattes R, Grossi C (1956) Carcinoid tumors of the stomach. Cancer 9:698–711PubMedCrossRefGoogle Scholar
  61. 61.
    Laxen F (1984) Gastric carcinoma and pernicious anemia in long-term endoscopic follow- up of subjects with gastric polyps. Scand. J Gastroenterol 19:515–540Google Scholar
  62. 62.
    Lehtola J, Karttunen T, Krekela I, Niemela S, Rasanen O (1985) Gastric carcinoids with minimal or no macroscopic lesion in patients with pernicious anemia. Hepatogastroenterology 32:72–76PubMedGoogle Scholar
  63. 63.
    Lindenbaum J (1983) Status of laboratory testing in the diagnosis of megaloblastic anemia. Blood 61:624–627PubMedGoogle Scholar
  64. 64.
    Lindenbaum J, Pezzimenti JF, Shea N (1974) Small intestinal function in vitamin B12 deficiency. An Intern Med 80:326–331CrossRefGoogle Scholar
  65. 65.
    MacDonald RA (1956) Study of 356 carcinoids of the gastrointestinal tract: report of four cases of the carcinoid syndrome. Am J. Med. 21:867–878PubMedCrossRefGoogle Scholar
  66. 66.
    Martin JD, Atkins EL (1952) Carcinoid of the stomach. Surgery 27:698–704Google Scholar
  67. 67.
    Ming SC (1977) The classification and significance of gastric polyps. In: Yardley JH, Morson BS, Abell MD (eds) Intenational Academy of Pathology Monographs Williams and Wilkins Baltimore, pp 149–175Google Scholar
  68. 68.
    Morgan JE, Kaiser CW, Johnson W et al. (1983) Gastric carcinoid (gastrinoma) associated with achlorhydria (pernicious anemia). Cancer 51:2332–2340PubMedCrossRefGoogle Scholar
  69. 69.
    Mosbech J, Videbaek A (1950) Mortality from and risk of gastric carcinoma among patients with pernicious anemia. Br J 2:390–394CrossRefGoogle Scholar
  70. 70.
    Nicolas JP (1982) Le protocole classique du double test de Schilling, est-il toujours bien adapté au diagnostic des malabsorptions intestinales de la vitamine B12? Importance de la sécrétion chlorhydro-peptidique de la forme d’administration de la vitamine B12 Gastroen- térol. Clin. Biol 6:554–556Google Scholar
  71. 71.
    Okuda K, Takara I, Fujii T (1968) Absorption of liver-bound vitamin B12 in relation to intrinsic factor. Blood 32:313–323PubMedGoogle Scholar
  72. 72.
    Payne RW (1961) Pernicious anemia and gastric cancer in England and Wales. Br. Med. J 1807–1808Google Scholar
  73. 73.
    Potet E, Camilleri JP (1982) Populations à haut risque et dysplasies précancéreuses de l’estomac, définition et attitude pratique. Gastroentérol. Clin. Biol 6:454–461PubMedGoogle Scholar
  74. 74.
    Reed PI, Smith PLR, Haines K, House FR, Walters CL (1981) Gastric juice. N-nitrosamines in health and gastroduodenal disease. Lancet 11:550–552CrossRefGoogle Scholar
  75. 75.
    Rogers LW, Murphy RC (1979) Gastric carcinoid and gastric carcinoma morphological correlates of survival. Am J pathol 3:195–202CrossRefGoogle Scholar
  76. 76.
    Rotterdam H, Sommer SC (1981) Biopsy diagnosis of the digestive tract. Raven, New York, pp 96–117Google Scholar
  77. 77.
    Roucayrol AM, Cattan D (1985) Corrélation entre l’hypergastrinémie et l’hyperplasie des cellules endocrines argyrophiles non-gastrino-secrétantes du fundus gastrique au cours des gastrites chroniques atrophiques. Gastroentérol Clin Biol 9(2 bis):28AGoogle Scholar
  78. 78.
    Rubin W (1969) Proliferation of endocrine-like (enterochromaffln) cells in atrophic gastric mucosa. Gastroenterology 57:641–649Google Scholar
  79. 79.
    Rudell WS, Bone ES, Hill M, Walters CL (1978) Pathogenesis of gastric cancer in pernicious anemia. Lancet 1:521–523CrossRefGoogle Scholar
  80. 80.
    Saint-Andre JP, D’Aubigny N, Ben Gouali A, Goethals G, Simard C (1983) Gastrite chronique atrophique avec tumeur carcinoïde et “microcarcinoïdes”. An Pathol 3:235–240Google Scholar
  81. 81.
    Schafer LW, Larson DE, Melton LJ, Higgins JA, Zinsmeister AR (1985) Risk of development of gastric carcinoma in patients with PA; a population-based study in Rochester. Mayo Clin Proc 60:444–448PubMedCrossRefGoogle Scholar
  82. 82.
    Schlag P, Bockler R, Peter M (1982) Nitrite and nitrosamines in gastric juice: risk factors for gastric cancer. Scand J Gastroenterol 17:145–150PubMedCrossRefGoogle Scholar
  83. 83.
    Siurala M, Eramaa E, Nyberg W (1960) pernicious anemia and atrophic gastritis Acta Med Scand 166:213–223CrossRefGoogle Scholar
  84. 84.
    Slingerland DW, Cardarelli JA, Belton AB, Miller A (1984) The utility of serum gastrin levels in assessing the significance of low serum vitamin B12 levels. Arch. Intern. Med 144:1167–1168PubMedCrossRefGoogle Scholar
  85. 85.
    Solcia E, Capella C, Vasallo G (1971) Endocrine cells of the stomach and pancreas in states of gastric hypersecretion. Rendic. Gastroentereology 2:147–158Google Scholar
  86. 86.
    Solcia E, Capella C, Vassalo G, Buffa R (1975) Endocrine cells of the gastric mucosa. Int Rev. Cytol 42:223–286PubMedCrossRefGoogle Scholar
  87. 87.
    Stockbruegger RW, Menon GG, Beilby JOW, Mason RR, Cotton PB (1983) Gastroscopic screening in 80 patients with pernicious anemia. Gut 24:1141–1147CrossRefGoogle Scholar
  88. 88.
    Stockbruegger RW, Cotton PB, Menon GG et al. (1984) Pernicious anemia, intragastric bacterial overgrowth and possible consequences. Scand J Gastroenterol 19:355–364PubMedGoogle Scholar
  89. 89.
    Streeter AM, Shum HY, Duncombe VM, Hewson JW, Thrope MEC (1976) Vitamin B12 malabsorption associated with a normal Schilling test result. Med J Aust 1:54–55PubMedGoogle Scholar
  90. 90.
    Tannenbaum SR (1983) N-nitrosocompounds: a perspective on human exposure. Lancet 1:629–631PubMedCrossRefGoogle Scholar
  91. 91.
    Walker IR, Strickland RG, Ungar B, Mackay IR (1971) Simple atrophic gastritis and gastric carcinoma. Gut 12:906–911PubMedPubMedCentralCrossRefGoogle Scholar
  92. 92.
    Waterhouse J, Muir C, Shanmuguratnam K, Powell J (1982) Cancer incidence in four continents, vol IV. International Agency for Research on Cancer Lyons IARC scientific publication no 42Google Scholar
  93. 93.
    Whiteside MG, Mollin DL, Cognill NF, Williams AW, Anderson B (1964) The absorption of radioactive vitamin B12 and the secretion of hydrochloric acid in patients with atrophic gastritis. Gut 5:385–399PubMedPubMedCentralCrossRefGoogle Scholar
  94. 94.
    Wilander E, Grimelius L, Lundquist G, Skoog V (1979) Polypeptide hormones in argentaffin and argyrophil gastroduodenal endocrine tumors. Am J Pathol 96:519–530PubMedPubMedCentralGoogle Scholar
  95. 95.
    Wilander E, El-Salhy M, Pitakanen P (1984) Histopathology of gastric carcinoids: a survey of 42 cases. Histopathology 8:183–193PubMedCrossRefGoogle Scholar
  96. 96.
    Willems G (1979) Cell population kinetics in the mucosa in the gastrointestinal tract. In: Duthie HL, Wormsley KG (eds) Scientific basis of gastroenterology. Churchill Livingstone, EdinbourgGoogle Scholar
  97. 97.
    Zamchek N, Grable E, Ley A, Norman L (1955) Occurrence of gastric cancer among patients with pernicious anemia at the Boston City Hospital. N Engl. J. Med 252:1103–1110CrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 1989

Authors and Affiliations

  • D. Cattan
  • A. M. Roucayrol
  • J. Belaïche

There are no affiliations available

Personalised recommendations