Achlorhydria

Overview 
Theory 
Diagnosis 
Management 
Follow up 
Resources 

Last reviewed: 10 Apr 2025

Last updated: 29 Dec 2022

Achlorhydria indicates the inability to produce gastric acid. This is most commonly caused by gastric atrophy. Gastric atrophy, with or without autoimmune gastritis, is present in about 15% of older people and is thought to be initiated by infection with Helicobacter pylori.

Patients are usually asymptomatic but may present with signs and/or symptoms of iron, cobalamin (vitamin B12), or calcium deficiency and may predispose to enteric infection with organisms such as Clostridium difficile, Salmonella, and Campylobacter.

Achlorhydria may interfere with the absorption of certain drugs including thyroxine, ketoconazole, itraconazole, and dipyridamole.

The physiologic response to achlorhydria/gastric atrophy is hypergastrinemia. This is the most common cause of hypergastrinemia.

Although the prognosis is excellent, it carries a small increased risk for the development of gastric adenocarcinoma and gastric carcinoid tumor.

Definition

Achlorhydria indicates the inability to produce gastric acid (i.e., hydrochloric acid), even after stimulation with secretagogues (e.g., pentagastrin [gastrin analog], histamine, betazole [histamine analog], or a meal). Serum gastrin is a marker for gastric acid output. A decrease in gastric acid interrupts a negative feedback pathway controlling gastrin secretion and leads to elevated serum gastrin levels (hypergastrinemia).[1][2][3][4]

The most common cause of achlorhydria is chronic atrophic gastritis of the fundus and corpus (body) of the stomach (also termed gastric corpus atrophy, oxyntic gastric atrophy, chronic atrophic gastritis, and gastric atrophy), which is characterized histopathologically as loss of oxyntic glands.[5][6][7] It is the oxyntic (oxys: Greek for acid) glands that contain the acid-producing parietal cells.

History and exam

Other diagnostic factors

age >60 years
female sex
autoimmune disorders
weakness
lethargy
decreased exercise tolerance
skin and conjunctival pallor
paresthesias and difficulty ambulating
nutritional deficiency (cobalamin, iron, calcium, vitamin D)
enteric infection
memory loss, irritability, depression, and dementia
ataxia, shuffling gait, decreased position sense, decreased vibration sense
pale, smooth, and glossy tongue
koilonychia

Full details

Risk factors

autoimmune disorders
age >60 years
Helicobacter pylori infection
prior gastric surgery
hypergastrinemia
gastric carcinoid

Full details

Diagnostic tests

1st tests to order

hemoglobin
biopsy of corpus and/or fundus of stomach
intragastric pH

Full details

Tests to consider

serum gastrin
gastric acid secretory test (gastric analysis)
parietal cell antibodies
intrinsic factor antibodies
diagnostic tests for Helicobacter pylori infection

Full details

Emerging tests

serum pepsinogen I and II (PGI and PGII)

Treatment algorithm

ACUTE

all patients

Contributors

Authors

Mitchell L. Schubert, MD

Professor of Medicine and Physiology

Virginia Commonwealth University Health System

Chief of Gastroenterology

McGuire VAMC

Richmond

Disclosures

MLS is an author of several studies referenced in this topic.

Joseph Spataro, MD

Academic Fellow

Division of Gastroenterology, Hepatology, and Nutrition

Virginia Commonwealth University Health System

Richmond

Disclosures

JS declares that he has no competing interests.

Hamzeh Saraireh, MD

Academic Fellow

Division of Gastroenterology, Hepatology, and Nutrition

Virginia Commonwealth University Health System

Richmond

Disclosures

HS declares that he is the author of one study referenced in this topic.

Acknowledgements

Dr Mitchell L. Schubert, Dr Joseph Spataro, and Dr Hamzeh Saraireh would like to gratefully acknowledge Dr Juan Diego Baltodano, a previous contributor to this topic.

Disclosures

JDB declares that he has no competing interests.

Peer reviewers

Joseph Pisegna, MD

Professor of Medicine

David Geffen School of Medicine at UCLA

Los Angeles

Disclosures

JP declares that he has no competing interests.

Heinz F. Hammer, MD

Associate Professor of Gastroenterology and Internal Medicine

Medical University of Graz

Attending Gastroenterologist

University Hospitals Graz

Austria

Disclosures

HFH has been reimbursed by AstraZeneca, Nycomed, and Janssen, the manufacturers of proton-pump inhibitors, for attending several conferences and speaking, and has been paid by AstraZeneca for running educational programs.

References

Our in-house evidence and editorial teams collaborate with international expert contributors and peer reviewers to ensure that we provide access to the most clinically relevant information possible.

Key articles

Schubert ML, Peura DA. Control of gastric acid secretion in health and disease. Gastroenterology. 2008 Jun;134(7):1842-60. Abstract

Busuttil RA, Boussioutas A. Intestinal metaplasia: a premalignant lesion involved in gastric carcinogenesis. J Gastroenterol Hepatol. 2009 Feb;24(2):193-201. Abstract

Gupta S, Li D, El Serag HB, et al. AGA clinical practice guidelines on management of gastric intestinal metaplasia. Gastroenterology. 2020 Feb;158(3):693-702.Full text Abstract

Graham DY, Rugge M, Genta RM. Diagnosis: gastric intestinal metaplasia - what to do next? Curr Opin Gastroenterol. 2019 Nov;35(6):535-43.Full text Abstract

Malfertheiner P, Megraud F, O'Morain CA, et al; European Helicobacter and Microbiota Study Group and Consensus panel. Management of Helicobacter pylori infection - the Maastricht V/Florence Consensus Report. Gut. 2017 Jan;66(1):6-30.Full text Abstract

Chey WD, Leontiadis GI, Howden CW, Moss SF. ACG clinical guideline: treatment of Helicobacter pylori infection. Am J Gastroenterol. 2017 Feb;112(2):212-39.Full text Abstract

Fallone CA, Moss SF, Malfertheiner P. Reconciliation of recent Helicobacter pylori treatment guidelines in a time of increasing resistance to antibiotics. Gastroenterology. 2019 Jul;157(1):44-53. Abstract

Howden CW. Emerging regimens for H. pylori infection should enhance efficacy and circumvent resistance. Dig Dis Sci. 2019 Oct;64(10):2691-2.Full text Abstract

Reference articles

A full list of sources referenced in this topic is available to users with access to all of BMJ Best Practice.

Differentials
- Antisecretory drug-induced hypochlorhydria and hypergastrinemia
More Differentials
Guidelines
- Adverse events associated with EGD and EGD-related techniques
- American Society for Gastrointestinal Endoscopy guideline on informed consent for GI endoscopic procedures
More Guidelines
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Achlorhydria

Summary

Definition

History and exam

Other diagnostic factors

Risk factors

Diagnostic tests

1st tests to order

Tests to consider

Emerging tests

Treatment algorithm

all patients

Contributors

Authors

Mitchell L. Schubert, MD

Disclosures

Joseph Spataro, MD

Disclosures

Hamzeh Saraireh, MD

Disclosures

Acknowledgements

Disclosures

Peer reviewers

Joseph Pisegna, MD

Disclosures

Heinz F. Hammer, MD

Disclosures

References

Key articles

Reference articles

A full list of sources referenced in this topic is available to users with access to all of BMJ Best Practice.

Differentials

Guidelines

Log in or subscribe to access all of BMJ Best Practice

Log in or subscribe to access all of BMJ Best Practice

Log in to access all of BMJ Best Practice