Achlorhydria and hypochlorhydria refer to states where the production of

hydrochloric acid Hydrochloric acid, also known as muriatic acid, is an aqueous solution of hydrogen chloride. It is a colorless solution with a distinctive pungent smell. It is classified as a strong acid Acid strength is the tendency of an acid, symbol ...

in gastric secretions of the

stomach The stomach is a muscular, hollow organ in the gastrointestinal tract of humans and many other animals, including several invertebrates. The stomach has a dilated structure and functions as a vital organ in the digestive system. The stomach i ...

and other digestive organs is absent or low, respectively. It is associated with various other medical problems.

Signs and symptoms

Irrespective of the cause, achlorhydria can result as known complications of

bacterial overgrowth Small intestinal bacterial overgrowth (SIBO), also termed bacterial overgrowth, or small bowel bacterial overgrowth syndrome (SBBOS), is a disorder of excessive bacterial growth in the small intestine. Unlike the colon (or large bowel), which is r ...

and

intestinal metaplasia Intestinal metaplasia is the transformation (metaplasia) of epithelium (usually of the stomach or the esophagus) into a type of epithelium resembling that found in the intestine. In the esophagus, this is called Barrett's esophagus. Chronic inflam ...

and symptoms are often consistent with those diseases: *

gastroesophageal reflux disease Gastroesophageal reflux disease (GERD) or gastro-oesophageal reflux disease (GORD) is one of the upper gastrointestinal chronic diseases where stomach content persistently and regularly flows up into the esophagus, resulting in symptoms and/ ...

*abdominal discomfort *early satiety *weight loss *

diarrhea Diarrhea, also spelled diarrhoea, is the condition of having at least three loose, liquid, or watery bowel movements each day. It often lasts for a few days and can result in dehydration due to fluid loss. Signs of dehydration often begin w ...

constipation Constipation is a bowel dysfunction that makes bowel movements infrequent or hard to pass. The stool is often hard and dry. Other symptoms may include abdominal pain, bloating, and feeling as if one has not completely passed the bowel movement ...

*abdominal bloating *anemia *stomach infection *malabsorption of food * carcinoma of stomach Since acidic pH facilitates the absorption of iron, achlorhydric patients often develop

iron deficiency anemia Iron-deficiency anemia is anemia caused by a lack of iron. Anemia is defined as a decrease in the number of red blood cells or the amount of hemoglobin in the blood. When onset is slow, symptoms are often vague such as feeling tired, weak, s ...

. Acidic environment of stomach helps conversion of pepsinogen into pepsin, which is highly important in digesting the protein into smaller components, such as a complex protein into simple peptides and amino acids inside the stomach, which are later absorbed by the gastrointestinal tract. Bacterial overgrowth and

B12 deficiency Vitamin B12 deficiency, also known as cobalamin deficiency, is the medical condition in which the blood and tissue have a lower than normal level of vitamin B12. Symptoms can vary from none to severe. Mild deficiency may have few or absent symp ...

(

pernicious anemia Pernicious anemia is a type of vitamin B12 deficiency anemia, a disease in which not enough red blood cells are produced due to the malabsorption of vitamin B12. Malabsorption in pernicious anemia results from the lack or loss of intrinsic fa ...

) can cause micronutrient deficiencies that result in various clinical neurological manifestations, including visual changes,

paresthesias Paresthesia is an abnormal sensation of the skin (tingling, pricking, chilling, burning, numbness) with no apparent physical cause. Paresthesia may be transient or chronic, and may have any of dozens of possible underlying causes. Paresthesias ar ...

ataxia Ataxia is a neurological sign consisting of lack of voluntary coordination of muscle movements that can include gait abnormality, speech changes, and abnormalities in eye movements. Ataxia is a clinical manifestation indicating dysfunction of ...

, limb weakness, gait disturbance, memory defects, hallucinations and personality and mood changes. Risk of particular infections, such as ''

Vibrio vulnificus ''Vibrio vulnificus'' is a species of Gram-negative, motile, curved rod-shaped (bacillus), pathogenic bacteria of the genus ''Vibrio''. Present in marine environments such as estuaries, brackish ponds, or coastal areas, ''V. vulnificus'' is relat ...

'' (commonly from seafood) is increased. Even without bacterial overgrowth, low stomach acid (high pH) can lead to nutritional deficiencies through decreased absorption of basic electrolytes (

magnesium Magnesium is a chemical element with the symbol Mg and atomic number 12. It is a shiny gray metal having a low density, low melting point and high chemical reactivity. Like the other alkaline earth metals (group 2 of the periodic ta ...

zinc Zinc is a chemical element with the symbol Zn and atomic number 30. Zinc is a slightly brittle metal at room temperature and has a shiny-greyish appearance when oxidation is removed. It is the first element in group 12 (IIB) of the periodi ...

, etc.) and vitamins (including

vitamin C Vitamin C (also known as ascorbic acid and ascorbate) is a water-soluble vitamin found in citrus and other fruits and vegetables, also sold as a dietary supplement and as a topical 'serum' ingredient to treat melasma (dark pigment spots) ...

vitamin K Vitamin K refers to structurally similar, fat-soluble vitamers found in foods and marketed as dietary supplements. The human body requires vitamin K for post-synthesis modification of certain proteins that are required for blood coagulation ...

, and the

B complex B vitamins are a class of water-soluble vitamins that play important roles in cell metabolism and synthesis of red blood cells. Though these vitamins share similar names (B1, B2, B3, etc.), they are chemically distinct compounds that often coexist ...

of vitamins). Such deficiencies may be involved in the development of a wide range of pathologies, from fairly benign neuromuscular issues to life-threatening diseases.

Causes

* The slowing of the body's basal metabolic rate associated with hypothyroidism *

Pernicious anemia Pernicious anemia is a type of vitamin B12 deficiency anemia, a disease in which not enough red blood cells are produced due to the malabsorption of vitamin B12. Malabsorption in pernicious anemia results from the lack or loss of intrinsic fa ...

where there is

antibody An antibody (Ab), also known as an immunoglobulin (Ig), is a large, Y-shaped protein used by the immune system to identify and neutralize foreign objects such as pathogenic bacteria and viruses. The antibody recognizes a unique molecule of the ...

production against

parietal cell Parietal cells (also known as oxyntic cells) are epithelial cells in the stomach that secrete hydrochloric acid (HCl) and intrinsic factor. These cells are located in the gastric glands found in the lining of the fundus and body regions of the s ...

s which normally produce gastric acid. * The use of

antacids An antacid is a substance which neutralizes stomach acidity and is used to relieve heartburn, indigestion or an upset stomach. Some antacids have been used in the treatment of constipation and diarrhea. Marketed antacids contain salts of alu ...

or drugs that decrease gastric acid production (such as

H2-receptor antagonist H2 antagonists, sometimes referred to as H2RAs and also called H2 blockers, are a class of medications that block the action of histamine at the histamine H2 receptors of the parietal cells in the stomach. This decreases the production of st ...

s) or transport (such as

proton pump inhibitor Proton-pump inhibitors (PPIs) are a class of medications that cause a profound and prolonged reduction of stomach acid production. They do so by irreversibly inhibiting the stomach's H+/K+ ATPase proton pump. They are the most potent inhibitor ...

s). * A symptom of

rare disease A rare disease is any disease that affects a small percentage of the population. In some parts of the world, an orphan disease is a rare disease whose rarity means there is a lack of a market large enough to gain support and resources for discov ...

s such as

mucolipidosis Mucolipidosis is a group of inherited metabolic disorders that affect the body's ability to carry out the normal turnover of various materials within cells. When originally named, the mucolipidoses derived their name from the similarity in pre ...

(type IV). * A symptom of ''

Helicobacter pylori ''Helicobacter pylori'', previously known as ''Campylobacter pylori'', is a gram-negative, microaerophilic, spiral (helical) bacterium usually found in the stomach. Its helical shape (from which the genus name, helicobacter, derives) is thoug ...

'' infection which neutralizes and decreases secretion of gastric acid to aid its survival in the stomach. * A symptom of

atrophic gastritis Atrophic gastritis is a process of chronic inflammation of the gastric mucosa of the stomach, leading to a loss of gastric glandular cells and their eventual replacement by intestinal and fibrous tissues. As a result, the stomach's secretion o ...

or of stomach cancer. *

Radiation therapy Radiation therapy or radiotherapy, often abbreviated RT, RTx, or XRT, is a therapy using ionizing radiation, generally provided as part of cancer treatment to control or kill malignant cells and normally delivered by a linear accelerator. Radi ...

involving the stomach. *

Gastric bypass Gastric bypass surgery refers to a technique in which the stomach is divided into a small upper pouch and a much larger lower "remnant" pouch and then the small intestine is rearranged to connect to both. Surgeons have developed several differ ...

procedures such as a duodenal switch and RNY, where the largest acid producing parts of the stomach are either removed, or blinded. *

VIPoma A VIPoma or vipoma () is a rare endocrine tumor that overproduces vasoactive intestinal peptide (thus ''VIP'' + '' -oma''). The incidence is about 1 per 10,000,000 per year. VIPomas usually (about 90%) originate from the non-β islet cells of ...

s (vasoactive intestinal peptides) and

somatostatinoma Somatostatinomas are a tumor of the delta cells of the endocrine pancreas that produces somatostatin. Increased levels of somatostatin inhibit pancreatic hormones and gastrointestinal hormones. Thus, somatostatinomas are associated with mild diabet ...

s are both islet cell tumors of the pancreas. *

Pellagra Pellagra is a disease caused by a lack of the vitamin niacin (vitamin B3). Symptoms include inflamed skin, diarrhea, dementia, and sores in the mouth. Areas of the skin exposed to either sunlight or friction are typically affected first. Over t ...

, caused by niacin deficiency. * Chloride, sodium, potassium, zinc and/or iodine deficiency, as these elements are needed to produce adequate levels of

stomach acid Gastric acid, gastric juice, or stomach acid is a digestive fluid formed within the stomach lining. With a pH between 1 and 3, gastric acid plays a key role in digestion of proteins by activating digestive enzymes, which together break down the ...

(HCl). * Sjögren's syndrome, an

autoimmune disorder An autoimmune disease is a condition arising from an abnormal immune response to a functioning body part. At least 80 types of autoimmune diseases have been identified, with some evidence suggesting that there may be more than 100 types. Nearly ...

that destroys many of the body's moisture-producing enzymes *

Ménétrier's disease Ménétrier disease is a rare, acquired, premalignant disease of the stomach characterized by massive gastric folds, excessive mucous production with resultant protein loss, and little or no acid production. The disorder is associated with excess ...

, characterized by hyperplasia of mucous cells in the stomach also causing excess protein loss, leading to hypoalbuminemia. Presents with abdominal pain and edema

Risk Factors

Age It was found that the incidence of achlorhydria in patients under the age of 60 was around 2.3%, whereas it was 5% in patients over the age of 60. In a person's 30s, the prevalence is about 2.5%, and increases to 12% in a person's 80s. An absence of

increases with advancing age. A lack of hydrochloric acid produced by the stomach is one of the most common age-related causes of a harmed digestive system. Among men and women, 27% experience a varying degree of achlorhydria. US researchers found that over 30% of women and men over the age of 60 have little to no acid secretion in the stomach. Additionally, 40% of postmenopausal women have shown to have no basal gastric acid secretion in the stomach, with 39.8% occurring in females 80 to 89 years old Autoimmune Disorders

Autoimmune disorders An autoimmune disease is a condition arising from an abnormal immune response to a functioning body part. At least 80 types of autoimmune diseases have been identified, with some evidence suggesting that there may be more than 100 types. Nearly a ...

are also linked to advancing age, specifically autoimmune gastritis, which is when the body produces unwelcomed antibodies and causes inflammation of the stomach. Autoimmune disorders are also a cause for small bacterial growth in the bowel and a deficiency of Vitamin B-12. These have also proved to be factors of acid secretion in the stomach. '' Hypothyroidism:'' Thyroid hormones are a factor in the decreasing of hydrochloric acid in the stomach, thus hypothyroidism is associated with a greater risk of developing achlorhydria. Autoimmune conditions are often managed using various treatments; however, these treatments have no known effect on achlorhydria.

Other

Other risk factors include, over the counter acid-blocking medications and antibiotics that may be used to block stomach acid. These medications are often taken by individuals for a longer than recommended period, even for years, despite causing adverse effects on stomach acid secretion. Stress has also been proven to be linked to symptoms associated with achlorhydria including constant belching, constipation, and abdominal pain.

Diagnosis

For practical purposes, gastric pH and

endoscopy An endoscopy is a procedure used in medicine to look inside the body. The endoscopy procedure uses an endoscope to examine the interior of a hollow organ or cavity of the body. Unlike many other medical imaging techniques, endoscopes are inse ...

should be done in someone with suspected achlorhydria. Older testing methods using fluid aspiration through a nasogastric tube can be done, but these procedures can cause significant discomfort and are less efficient ways to obtain a diagnosis. A complete 24-hour profile of gastric acid secretion is best obtained during an

esophageal pH monitoring Esophageal pH monitoring is the current gold standard for diagnosis of gastroesophageal reflux disease (GERD). It provides direct physiologic measurement of acid in the esophagus and is the most objective method to document reflux disease, assess t ...

study. Achlorhydria may also be documented by measurements of extremely low levels of pepsinogen A (PgA) () in blood serum. The diagnosis may be supported by high serum gastrin levels (). The " Heidelberg test" is an alternative way to measure stomach acid and diagnose hypochlorhydria/achlorhydria. A check can exclude deficiencies in iron, calcium,

prothrombin time The prothrombin time (PT) – along with its derived measures of prothrombin ratio (PR) and international normalized ratio (INR) – is an assay for evaluating the ''extrinsic'' pathway and common pathway of coagulation. This blood test is als ...

vitamin B-12 Vitamin B12, also known as cobalamin, is a water-soluble vitamin involved in metabolism. It is one of eight B vitamins. It is required by animals, which use it as a cofactor in DNA synthesis, in both fatty acid and amino acid metabolism. It ...

vitamin D Vitamin D is a group of fat-soluble secosteroids responsible for increasing intestinal absorption of calcium, magnesium, and phosphate, and many other biological effects. In humans, the most important compounds in this group are vitamin D3 (c ...

, and

thiamine Thiamine, also known as thiamin and vitamin B1, is a vitamin, an essential micronutrient, that cannot be made in the body. It is found in food and commercially synthesized to be a dietary supplement or medication. Phosphorylated forms of thi ...

Complete blood count A complete blood count (CBC), also known as a full blood count (FBC), is a set of medical laboratory tests that provide information about the cells in a person's blood. The CBC indicates the counts of white blood cells, red blood cells and pl ...

with indices and peripheral smears can be examined to exclude

anemia Anemia or anaemia (British English) is a blood disorder in which the blood has a reduced ability to carry oxygen due to a lower than normal number of red blood cells, or a reduction in the amount of hemoglobin. When anemia comes on slowly, t ...

. Elevation of serum

folate Folate, also known as vitamin B9 and folacin, is one of the B vitamins. Manufactured folic acid, which is converted into folate by the body, is used as a dietary supplement and in food fortification as it is more stable during processing an ...

is suggestive of small bowel bacterial overgrowth. Bacterial folate can be absorbed into the circulation. Once achlorhydria is confirmed, a

hydrogen breath test A hydrogen breath test (or HBT) is used as a diagnostic tool for small intestine bacterial overgrowth and carbohydrate malabsorption, such as lactose, fructose, and sorbitol malabsorption. The test is simple, non-invasive, and is performed after ...

can check for bacterial overgrowth.

Treatment

Treatment focuses on addressing the underlying cause of symptoms. Treatment of gastritis that leads to

consists of parenteral vitamin B-12 injection. Associated immune-mediated conditions (e.g., insulin-dependent

diabetes Diabetes, also known as diabetes mellitus, is a group of metabolic disorders characterized by a high blood sugar level ( hyperglycemia) over a prolonged period of time. Symptoms often include frequent urination, increased thirst and increased ...

mellitus,

autoimmune thyroiditis Autoimmune thyroiditis, is a chronic disease in which the body interprets the thyroid glands and its hormone products T3, T4 and TSH as threats, therefore producing special antibodies that target the thyroid's cells, thereby destroying it. It may ...

) should also be treated. However, treatment of these disorders has no known effect in the treatment of achlorhydria. Achlorhydria associated with ''

'' infection may respond to ''H. pylori'' eradication therapy, although resumption of gastric acid secretion may only be partial and it may not always reverse the condition completely. Antimicrobial agents, including metronidazole, amoxicillin/clavulanate potassium, ciprofloxacin, and

rifaximin Rifaximin, is a non-absorbable, broad spectrum antibiotic mainly used to treat travelers' diarrhea. It is based on the rifamycin antibiotics family. Since its approval in Italy in 1987, it has been licensed in over more than 30 countries for th ...

, can be used to treat bacterial overgrowth. Achlorhydria resulting from long-term

proton-pump inhibitor Proton-pump inhibitors (PPIs) are a class of medications that cause a profound and prolonged reduction of stomach acid production. They do so by irreversibly inhibiting the stomach's H+/K+ ATPase proton pump. They are the most potent inhibitor ...

(PPI) use may be treated by dose reduction or withdrawal of the PPI.

Prognosis

Little is known on the prognosis of achlorhydria, although there have been reports of an increased risk of gastric cancer. A 2007 review article noted that non-''Helicobacter'' bacterial species can be cultured from achlorhydric (pH > 4.0) stomachs, whereas normal stomach pH only permits the growth of ''Helicobacter'' species. Bacterial overgrowth may cause false-positive ''H. pylori'' test results due to the change in pH from

urease Ureases (), functionally, belong to the superfamily of amidohydrolases and phosphotriesterases. Ureases are found in numerous bacteria, fungi, algae, plants, and some invertebrates, as well as in soils, as a soil enzyme. They are nickel-contai ...

activity. Small bowel bacterial overgrowth is a chronic condition. Retreatment may be necessary once every 1–6 months. Prudent use of antibacterials now calls for an

antimicrobial stewardship Antimicrobial stewardship is the systematic effort to educate and persuade prescribers of antimicrobials to follow evidence-based prescribing, in order to stem antimicrobial overuse, and thus antimicrobial resistance. AMS has been an organized eff ...

policy to manage antibiotic resistance.

References

External links

{{Gastroenterology Stomach disorders