Close
New

Medscape is available in 5 Language Editions – Choose your Edition here.

 

Achlorhydria Differential Diagnoses

  • Author: Divyanshoo Rai Kohli, MD; Chief Editor: BS Anand, MD  more...
 
Updated: Jul 15, 2016
 
 

Diagnostic ConsiderationsImportant considerations

Long-term proton pump inhibitor (PPI) therapy has been associated with two major complications. As described previously, there is an association with hip fractures in patients with achlorhydria on PPI therapy. In addition, current use of gastric acid suppressive therapy has been associated with an increased risk of community-acquired pneumonia (CAP).

Sustained achlorhydria has been observed after PPI treatment in a patient with Zollinger-Ellison syndrome (ZES), starting soon after treatment began and becoming complete within 6 months.

Gastric resection, leading to surgically induced achlorhydria, has been associated with severe postoperative infections. It has been observed in humans that the lack of an acidic environment may favor bacterial overgrowth. This, in turn, can lead to various nutrient deficiencies with significant clinical manifestation.

According to a study from the Netherlands by Janssen et al, patients with achlorhydria who take nonsteroidal anti-inflammatory drugs (NSAIDs) develop upper gastrointestinal ulcers during NSAID use in a similar fashion as patients who produce acid normally.[17]

Drug-induced achlorhydria is a particularly important condition in elderly patients, in whom it may be associated with secondary bacterial overgrowth.

Patients with pernicious anemia and achlorhydria may demonstrate impaired absorption of iron and may be screened for iron deficiency.

Differential Diagnoses

 
 
Contributor Information and Disclosures
Author

Divyanshoo Rai Kohli, MD Fellow, Department of Gastroenterology, Hepatology and Nutrition, Virginia Commonwealth University School of Medicine

Divyanshoo Rai Kohli, MD is a member of the following medical societies: American College of Physicians

Disclosure: Nothing to disclose.

Coauthor(s)

Timothy R Koch, MD Professor of Medicine (Gastroenterology), Georgetown University School of Medicine

Timothy R Koch, MD is a member of the following medical societies: American College of Gastroenterology, American Gastroenterological Association, American Physiological Society

Disclosure: Nothing to disclose.

Jennifer (Zone-En) Lee, MD Fellow, Section of Gastroenterology, Georgetown University School of Medicine, Washington Hospital Center

Jennifer (Zone-En) Lee, MD is a member of the following medical societies: American College of Gastroenterology, American Gastroenterological Association, American Society for Gastrointestinal Endoscopy

Disclosure: Nothing to disclose.

Specialty Editor Board

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Received salary from Medscape for employment. for: Medscape.

Chief Editor

BS Anand, MD Professor, Department of Internal Medicine, Division of Gastroenterology, Baylor College of Medicine

BS Anand, MD is a member of the following medical societies: American Association for the Study of Liver Diseases, American College of Gastroenterology, American Gastroenterological Association, American Society for Gastrointestinal Endoscopy

Disclosure: Nothing to disclose.

Additional Contributors

David Greenwald, MD Professor of Clinical Medicine, Fellowship Program Director, Department of Medicine, Division of Gastroenterology, Montefiore Medical Center, Albert Einstein College of Medicine

David Greenwald, MD is a member of the following medical societies: Alpha Omega Alpha, New York Society for Gastrointestinal Endoscopy, American College of Gastroenterology, American College of Physicians, American Gastroenterological Association, American Society for Gastrointestinal Endoscopy

Disclosure: Nothing to disclose.

Acknowledgements

Hiral Shah, MD Chief Resident, Department of Internal Medicine, Georgetown University Hospital at Washington Hospital Center

Hiral Shah, MD is a member of the following medical societies: American College of Gastroenterology, American College of Physicians, American Gastroenterological Association, and American Medical Association

Disclosure: Nothing to disclose.

References
  1. Roepke TK, Purtell K, King EC, La Perle KM, Lerner DJ, Abbott GW. Targeted deletion of Kcne2 causes gastritis cystica profunda and gastric neoplasia. PLoS One. 2010 Jul 6. 5(7):e11451. [Medline]. [Full Text].

  2. Lee SM, Nguyen D, Anand M, et al. Kcne2 deletion causes early-onset nonalcoholic fatty liver disease via iron deficiency anemia. Sci Rep. 2016 Mar 17. 6:23118. [Medline].

  3. Miller ML, Andringa A, Schultheis PJ, Shull GE. Loss of the NHE2 Na+/H+ exchanger in mice results in dilation of folliculo-stellate cell canaliculi. J Biomed Biotechnol. 2011. 2011:510827. [Medline].

  4. Lofgren JL, Whary MT, Ge Z, Muthupalani S, Taylor NS, Mobley M. Lack of commensal flora in Helicobacter pylori-infected INS-GAS mice reduces gastritis and delays intraepithelial neoplasia. Gastroenterology. 2011 Jan. 140(1):210-20. [Medline].

  5. Xiao C, Ogle SA, Schumacher MA, Orr-Asman MA, Miller ML, Lertkowit N. Loss of parietal cell expression of Sonic hedgehog induces hypergastrinemia and hyperproliferation of surface mucous cells. Gastroenterology. 2010 Feb. 138(2):550-61, 561.e1-8. [Medline].

  6. El-Zaatari M, Zavros Y, Tessier A, Waghray M, Lentz S, Gumucio D, et al. Intracellular calcium release and protein kinase C activation stimulate sonic hedgehog gene expression during gastric acid secretion. Gastroenterology. 2010 Dec. 139(6):2061-2071.e2. [Medline]. [Full Text].

  7. Chandra M, Zhou H, Li Q, Muallem S, Hofmann SL, Soyombo AA. A role for the Ca2+ channel TRPML1 in gastric acid secretion, based on analysis of knockout mice. Gastroenterology. 2011 Mar. 140(3):857-67. [Medline].

  8. Miceli E, Lenti MV, Padula D, et al. Common features of patients with autoimmune atrophic gastritis. Clin Gastroenterol Hepatol. 2012 Jul. 10(7):812-4. [Medline].

  9. Lahner E, Annibale B. Pernicious anemia: new insights from a gastroenterological point of view. World J Gastroenterol. 2009 Nov 7. 15(41):5121-8. [Medline]. [Full Text].

  10. Wang F, Xia P, Wu F, Wang D, Wang W, Ward T, et al. Helicobacter pylori VacA disrupts apical membrane-cytoskeletal interactions in gastric parietal cells. J Biol Chem. 2008 Sep 26. 283(39):26714-25. [Medline]. [Full Text].

  11. Argent RH, Thomas RJ, Aviles-Jimenez F, Letley DP, Limb MC, El-Omar EM, et al. Toxigenic Helicobacter pylori infection precedes gastric hypochlorhydria in cancer relatives, and H. pylori virulence evolves in these families. Clin Cancer Res. 2008 Apr 1. 14(7):2227-35. [Medline].

  12. Harris PR, Serrano CA, Villagran A, et al. Helicobacter pylori-associated hypochlorhydria in children, and development of iron deficiency. J Clin Pathol. 2013 Apr. 66(4):343-7. [Medline].

  13. Christiansen PM. The incidence of achlorhydria and hypochlorhydria in healthy subjects and patients with gastrointestinal diseases. Scand J Gastroenterol. 1968. 3(5):497-508. [Medline].

  14. Bins M, Burgers PI, Selbach SG, van Wettum TB, Lamers CB, van Tongeren JH. Prevalence of achlorhydria in a normal population and its relation to serum gastrin. Hepatogastroenterology. 1984 Feb. 31(1):41-3. [Medline].

  15. Segal HL, Samloff IM. Gastric cancer--increased frequency in patients with achlorhydria. Am J Dig Dis. 1973 Apr. 18(4):295-9. [Medline].

  16. Betesh AL, Santa Ana CA, Cole JA, Fordtran JS. Is achlorhydria a cause of iron deficiency anemia?. Am J Clin Nutr. 2015 Jul. 102 (1):9-19. [Medline].

  17. Janssen M, Dijkmans BA, Vandenbroucke JP, Biemond I, Lamers CB. Achlorhydria does not protect against benign upper gastrointestinal ulcers during NSAID use. Dig Dis Sci. 1994 Feb. 39(2):362-5. [Medline].

  18. Yago MR, Frymoyer AR, Smelick GS, et al. Gastric reacidification with betaine HCl in healthy volunteers with rabeprazole-induced hypochlorhydria. Mol Pharm. 2013 Nov 4. 10 (11):4032-7. [Medline].

  19. Gladdy RA, Strong VE, Coit D, Allen PJ, Gerdes H, Shia J, et al. Defining surgical indications for type I gastric carcinoid tumor. Ann Surg Oncol. 2009 Nov. 16(11):3154-60. [Medline].

  20. Hirschowitz BI, Griffith J, Pellegrin D, Cummings OW. Rapid regression of enterochromaffinlike cell gastric carcinoids in pernicious anemia after antrectomy. Gastroenterology. 1992 Apr. 102(4 Pt 1):1409-18. [Medline].

  21. Andersen J, Strom M. A technique for screening of achlorhydria and hypochlorhydria during upper gastrointestinal endoscopy. Scand J Gastroenterol. 1990 Oct. 25(10):1084-8. [Medline].

  22. Andersen J, Strom M. Pentagastrin given during upper gastrointestinal endoscopy: a simple screening method for hypo- and achlorhydria. Gastrointest Endosc. Jan-Feb 1992. 38(1):47-8. [Medline].

  23. Attila T, Santharam R, Blom D, Komorowski R, Koch TR. Multifocal gastric carcinoid tumor in a patient with pernicious anemia receiving lansoprazole. Dig Dis Sci. 2005 Mar. 50(3):509-13. [Medline].

  24. Banerjee S, Ardill JE, Beattie AD, McColl KE. Effect of omeprazole and feeding on plasma gastrin in patients with achlorhydria. Aliment Pharmacol Ther. 1995 Oct. 9(5):507-12. [Medline].

  25. Centanni M, Marignani M, Gargano L, Corleto VD, Casini A, Delle Fave G, et al. Atrophic body gastritis in patients with autoimmune thyroid disease: an underdiagnosed association. Arch Intern Med. 1999 Aug 9-23. 159(15):1726-30. [Medline].

  26. De Block CE, Colpin G, Thielemans K, Coopmans W, Bogers JJ, Pelckmans PA, et al. Neuroendocrine tumor markers and enterochromaffin-like cell hyper/dysplasia in type 1 diabetes. Diabetes care. 2004 Jun. 27 (6):1387-93. [Medline].

  27. Demiroglu H, Dundar S. Pernicious anaemia patients should be screened for iron deficiency during follow up. N Z Med J. 1997 Apr 25. 110(1042):147-8. [Medline].

  28. Drake WM, Innes DF. Primary gastric lymphoma presenting with vitamin B12 deficiency and achlorhydria. Am J Gastroenterol. 1996 Dec. 91(12):2605-6. [Medline].

  29. El-Omar EM, Oien K, El-Nujumi A, Gillen D, Wirz A, Dahill S, et al. Helicobacter pylori infection and chronic gastric acid hyposecretion. Gastroenterology. 1997 Jul. 113(1):15-24. [Medline].

  30. Elphick HL, Elphick DA, Sanders DS. Small bowel bacterial overgrowth. An underrecognized cause of malnutrition in older adults. Geriatrics. 2006 Sep. 61(9):21-6. [Medline].

  31. Feldman M, Barnett C. Fasting gastric pH and its relationship to true hypochlorhydria in humans. Dig Dis Sci. 1991 Jul. 36(7):866-9. [Medline].

  32. Freston JW. Long-term acid control and proton pump inhibitors: interactions and safety issues in perspective. Am J Gastroenterol. 1997 Apr. 92(4 Suppl):51S-55S; discussion 55S-57S. [Medline].

  33. Friss-Hansen L. Achlorhydria is associated with gastric microbial overgrowth and development of cancer: lessons learned from the gastrin knockout mouse. Scandanavian Journal of Clinical Lab Investigation. 2006. 66(7):607-621.

  34. Griffith JL, Cummings OW, Hirschowitz BI. Development of sustained achlorhydria in a patient with the Zollinger- Ellison syndrome treated with omeprazole [published erratum appears in Gastroenterology 1992 Mar;102(3):1096]. Gastroenterology. Jul 1991. 101(1):242-6. [Medline].

  35. Haboubi NY, Montgomery RD. Small-bowel bacterial overgrowth in elderly people: clinical significance and response to treatment. Age Ageing. 1992 Jan. 21(1):13-9. [Medline].

  36. Howden CW. Vitamin B12 levels during prolonged treatment with proton pump inhibitors. J Clin Gastroenterol. 2000 Jan. 30(1):29-33. [Medline].

  37. Hurwitz A, Brady DA, Schaal SE, Samloff IM, Dedon J, Ruhl CE. Gastric acidity in older adults. JAMA. 1997 Aug 27. 278(8):659-62. [Medline].

  38. Husebye E. The pathogenesis of gastrointestinal bacterial overgrowth. Chemotherapy. 2005. 51 Suppl 1:1-22. [Medline].

  39. Jensen RT. Consequences of long-term proton pump blockade: insights from studies of patients with gastrinomas. Basic Clinical Pharmacology and Toxicology. 2006 Jan. 98(1):4-19. [Medline].

  40. Laheij RJ, Sturkenboom MC, Hassing RJ, Dieleman J, Stricker BH, Jansen JB. Risk of community-acquired pneumonia and use of gastric acid-suppressive drugs. JAMA. 2004 Oct 27. 292(16):1955-60. [Medline].

  41. Lanfranchi J, Sachs RN, Beaudet B, Deblock C, Tellier P. [Study of dilated cardiomyopathies using gallium 67 myocardial scintigraphy]. Ann Med Interne (Paris). 1989. 140(6):486-8. [Medline].

  42. Lehy T, Roucayrol AM, Mignon M. Histomorphological characteristics of gastric mucosa in patients with Zollinger-Ellison syndrome or autoimmune gastric atrophy: role of gastrin and atrophying gastritis. Microsc Res Tech. 2000 Mar 15. 48(6):327-38. [Medline].

  43. Moncur PH, Heatley RV. Safety of proton-pump inhibitors: the acid test. Eur J Gastroenterol Hepatol. 2000 Feb. 12(2):145-7. [Medline].

  44. Pereira SP, Gainsborough N, Dowling RH. Drug-induced hypochlorhydria causes high duodenal bacterial counts in the elderly. Aliment Pharmacol Ther. 1998 Jan. 12(1):99-104. [Medline].

  45. Prinz C, Zanner R, Gratzl M. Physiology of gastric enterochromaffin-like cells. Annu Rev Physiol. 2003. 65:371-82. [Medline].

  46. Rantala A, Ovaska J. Association between medically induced achlorhydria of the stomach and a severe postoperative infection? A report of two cases. Ann Chir Gynaecol. 1994. 83(3):268-70. [Medline].

  47. Roepke TK, Anantharam A, Kirchhoff P, Busque SM, Young JB, Geibel JP, et al. The KCNE2 potassium channel ancillary subunit is essential for gastric acid secretion. J Biol Chem. 2006 Aug 18. 281(33):23740-7. [Medline].

  48. Schiffmann R, Dwyer NK, Lubensky IA, Tsokos M, Sutliff VE, Latimer JS, et al. Constitutive achlorhydria in mucolipidosis type IV. Proc Natl Acad Sci U S A. 1998 Feb 3. 95(3):1207-12. [Medline].

  49. Schubert ML. Gastric secretion. Curr Opin Gastroenterol. Nov 2002. 18(6):639-49.

  50. Seery JP. Achlorhydria and gastric carcinogenesis. Lancet. 1991 Dec 14. 338(8781):1508-9. [Medline].

  51. Singh VV, Toskes PP. Small bowel bacterial overgrowth: presentation, diagnosis, and treatment. Curr Gastroenterol Rep. 2003 Oct. 5(5):365-72. [Medline].

  52. Williams C, McColl KE. Review article: proton pump inhibitors and bacterial overgrowth. Aliment Pharmacol Ther. 2006 Jan 1. 23(1):3-10. [Medline].

  53. Wormsley KG. Therapeutic achlorhydria and risk of gastric cancer. Gastroenterol Jpn. Oct 1989. 24(5):585-96. [Medline].

  54. Yang YX, Lewis JD, Epstein S, Metz DC. long-term proton pump inhibitor therapy and risk of hip fracture. JAMA. 2006 Dec 27. 296:2947-2953. [Medline].

 
Previous
Next
 
 
 
 
All material on this website is protected by copyright, Copyright © 1994-2016 by WebMD LLC. This website also contains material copyrighted by 3rd parties.