Achlorhydria Clinical Presentation

  • Author: Jennifer (Zone-En) Lee, MD; Chief Editor: Julian Katz, MD   more...
 
Updated: Aug 18, 2011
 

History

An appropriate history should be taken in patients suspected of having achlorhydria. Risk factors for achlorhydria, including prior gastric bypass surgery, history of chronic H pylori infection, chronic PPI use, and autoimmune conditions (eg, diabetes, autoimmune thyroid disease), should be elicited.

Irrespective of the cause, achlorhydria can result as known complications of bacterial overgrowth, intestinal metaplasia, and hip fracture. Therefore, a history of abdominal discomfort, early satiety, weight loss, bowel movement frequency, reflux symptoms, and abdominal bloating should be taken.

Bacterial overgrowth can cause micronutrient deficiencies that result in various clinical neurological manifestations. A complete neurological history, including history of visual changes, paresthesias, ataxia, limb weakness, gait disturbance, memory defects, hallucinations, and personality and mood changes, should also be obtained.

Next

Physical

Achlorhydria is not associated with any characteristic physical findings.

Previous
Next

Causes

Achlorhydria may develop as a result of the following conditions:

  • Antiparietal cell antibodies
    • Antibodies directed against gastric intrinsic factor results in cobalamin deficiency; this is called pernicious anemia.
    • The 2 types of anti-intrinsic factor antibodies are as follows: (1) antibodies that block attachment of cobalamin to intrinsic factor, and (2) antibodies that block attachment of the intrinsic factor-cobalamin complex to ileal receptors.
    • Clinically, highly specific anti-intrinsic factor antibodies are found in about 70% of patients with pernicious anemia. A second component of pernicious anemia is chronic atrophic gastritis that leads to a decline in intrinsic factor production. The chronic atrophic gastritis in pernicious anemia is also associated with an increased risk of intestinal gastric cancer and gastric carcinoid tumors.
    • Pernicious anemia occurs in association with other autoimmune disorders.[8] In one study, autoimmune thyroid disorders were observed in 24% of 162 patients with pernicious anemia. In this condition, fundic histology is characterized by severe gland atrophy. Ninety percent of patients have antibodies directed against the H+/K+ -ATPase pump. In these patients, achlorhydria leads to pronounced hypergastrinemia (>1000 pg/mL) with subsequent hyperplasia of gastric ECL cells. Gastric carcinoid tumors develop in 3-5% of patients.
    • Parietal cell antibodies are found in 20% of patients with type 1 diabetes, denoting autoimmune gastritis, achlorhydria, and pernicious anemia. This condition may predispose to ECL cell proliferation and gastric carcinoid tumors.
  • Chronic gastric H pylori infection
    • ECL cells in the gastric mucosa control acid secretion by releasing histamine from gastrin stimulation. During chronic H pylori infection, proinflammatory cytokines, such as interferon (IFN)-alpha and tumor necrosis factor (TNF)-alpha, are released. This cytokine release can affect ECL cells by impairing their secretory function and lead to achlorhydria and subsequently gastric cancer via ECL hyperplasia by increased gastrin stimulation.[9, 10] Chronic gastric H pylori infection produces gastritis, most prominently in the body of the stomach, and leads to profound suppression of gastric acid secretion.
  • Proton pump inhibitor therapy
    • The use of PPIs alters the role of gastrin in maintaining gastric homeostasis and the control of acid secretion. Profound suppression of gastric acid has been associated with bacterial overgrowth, enteric infections, and hypergastrinemia.
    • Gastric knockout mouse models with inactivated parietal cells subsequently have achlorhydria. Achlorhydria stimulates antral G cells to release gastrin. Gastrin, in turn, stimulates the oxyntic mucosa, which may ultimately lead to hyperplasia of ECL cells. In these models, bacterial overgrowth and intestinal metaplasia leading to gastric tumors have been observed. Further, perturbation of gastrin (and gastrin precursor) homeostasis leading to colorectal carcinogenesis has been examined in these models.
    • PPIs should be used in disorders that clearly benefit from this therapy and in patients in whom the benefits outweigh the risks associated with PPI therapy.
Previous
Proceed to Differential Diagnoses
 
 
Contributor Information and Disclosures
Author

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, and American Society of Gastrointestinal Endoscopy

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, and American Physiological Society

Disclosure: Nothing to disclose.

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.

Specialty Editor Board

David Greenwald, MD  Associate 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, American College of Gastroenterology, American College of Physicians, American Gastroenterological Association, American Society for Gastrointestinal Endoscopy, and New York Society for Gastrointestinal Endoscopy

Disclosure: Nothing to disclose.

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

Disclosure: Medscape Salary Employment

James L Achord, MD  Professor Emeritus, Department of Medicine, Division of Digestive Diseases, University of Mississippi School of Medicine

James L Achord, MD is a member of the following medical societies: American Association for the Study of Liver Diseases, American College of Gastroenterology, American College of Physicians, American Gastroenterological Association, American Medical Association, American Society for Gastrointestinal Endoscopy, Mississippi State Medical Association, New York Academy of Sciences, Sigma Xi, and Southern Medical Association

Disclosure: Nothing to disclose.

Alex J Mechaber, MD, FACP  Senior Associate Dean for Undergraduate Medical Education, Associate Professor of Medicine, University of Miami Miller School of Medicine

Alex J Mechaber, MD, FACP is a member of the following medical societies: Alpha Omega Alpha, American College of Physicians-American Society of Internal Medicine, and Society of General Internal Medicine

Disclosure: Nothing to disclose.

Chief Editor

Julian Katz, MD  Clinical Professor of Medicine, Drexel University College of Medicine

Julian Katz, MD is a member of the following medical societies: American College of Gastroenterology, American College of Physicians, American Gastroenterological Association, American Geriatrics Society, American Medical Association, American Society for Gastrointestinal Endoscopy, American Society of Law, Medicine & Ethics, American Trauma Society, Association of American Medical Colleges, and Physicians for Social Responsibility

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. Jul 6 2010;5(7):e11451. [Medline]. [Full Text].

  2. 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].

  3. 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. Jan 2011;140(1):210-20. [Medline].

  4. 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. Feb 2010;138(2):550-61, 561.e1-8. [Medline].

  5. 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. Dec 2010;139(6):2061-2071.e2. [Medline]. [Full Text].

  6. 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. Mar 2011;140(3):857-67. [Medline].

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

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

  9. 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. Sep 26 2008;283(39):26714-25. [Medline].

  10. 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. Apr 1 2008;14(7):2227-35. [Medline].

  11. 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. Nov 2009;16(11):3154-60. [Medline].

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

  13. 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. Feb 1994;39(2):362-5. [Medline].

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

  15. 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].

  16. 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. Mar 2005;50(3):509-13. [Medline].

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

  18. 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. Aug 9-23 1999;159(15):1726-30. [Medline].

  19. 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. Jun 2004;27 (6):1387-93. [Medline].

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

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

  22. 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. Jul 1997;113(1):15-24. [Medline].

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

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

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

  26. 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.

  27. 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].

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

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

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

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

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

  33. 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. Oct 27 2004;292(16):1955-60. [Medline].

  34. 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].

  35. 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. Mar 15 2000;48(6):327-38. [Medline].

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

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

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

  39. 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].

  40. 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. Aug 18 2006;281(33):23740-7. [Medline].

  41. 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. Feb 3 1998;95(3):1207-12. [Medline].

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

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

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

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

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

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

 
Previous
Next
 
 
 
 
All material on this website is protected by copyright, Copyright © 1994-2012 by WebMD LLC.
This website also contains material copyrighted by 3rd parties.

DISCLAIMER: The content of this Website is not influenced by sponsors. The site is designed primarily for use by qualified physicians and other medical professionals. The information contained herein should NOT be used as a substitute for the advice of an appropriately qualified and licensed physician or other health care provider. The information provided here is for educational and informational purposes only. In no way should it be considered as offering medical advice. Please check with a physician if you suspect you are ill.