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Achlorhydria – Causes, Symptoms, Diagnosis, Treatment

Achlorhydria or hypochlorhydria refers to conditions in which the production of hydrochloric acid in the stomach is respectively absent or reduced. It is usually secondary to an underlying medical condition.[rx][rx]

Gastric acid is the fluid secreted by the stomach. It is composed of hydrochloric acid, potassium chloride, and sodium chloride. Hydrochloric acid plays an integral part in the digestion of food and protects our body against pathogens ingested with food or water. The parietal cells lining the stomach are mainly involved in its production.

Achlorhydria and pernicious anemia occurring as part of the APSs are associated with the presence of circulating autoantibodies against gastric parietal cells (PCAs) and, less frequently, against blocking vitamin B12 binding to intrinsic factor (IFBA). Approximately 10% of patients with type 1 diabetes mellitus have co-existing-circulating PCAs, of whom many develop achlorhydria. The pathogenic importance of these immunoglobulins is suggested by their toxic effects on the gastric mucosas of frogs and rats. The parietal cell proton pump (H, K+-ATPase) represents at least one target of PCA.

Pathophysiology

Parietal cells lining the stomach wall are vital in maintaining the acidic pH of the stomach. They do this with the help of hydrogen potassium ATPase pump (HKA pump) which pushes potassium out and hydrogen back into the stomach. To keep the pump working, potassium ions must enter back into the stomach through the apical membrane. The apical membrane is lined with potassium-selective channels that are responsible for potassium ion efflux. These are called inward rectifier channels (Kir). A study conducted on knock out mice showed genetic evidence of one such channel: KCNE2-KCNQ1. KCNQ1 a transmembrane voltage-gated, homotetrameric potassium-selective channel. KCNE2 alters the voltage dependence of KCNQ1, converting it to a voltage-independent gate that has increased current conduction at low pH. KCNE2 and KCNQ1 are often found at the apical membrane of parietal cells. Targetted gene deletion of either of these subunits was found to result in achlorhydria. This study showed that these play an essential role in gastric acid secretion by maintaining the supply of luminal potassium to keep the HK-ATPase pump functional. In the same study, dysfunction of KCNQ1 also caused the development of gastric neoplasia independent of H. Pylori infection (secondary to achlorhydria).

Thus any insult to parietal cells by any means (antibodies, surgery, drugs) can lead to achlorhydria which further activates multiple cascades of events that can lead to bacterial proliferation, GI symptoms, and even gastric cancer.

Causes of Achlorhydria

Multiple disorders can cause achlorhydria. [rx][rx][rx]

Pernicious anemia (anti-parietal and anti-intrinsic factor antibodies) – It is an autoimmune phenomenon in which antibodies are formed. These autoantibodies cause the autoimmune destruction of parietal cells leading to atrophic gastritis.
Use of antisecretory medications – Short-term standard-dose treatment with PPI has been shown to have low risk, but long-term use of PPI has been linked to hypochlorhydria.
Helicobacter pylori infection – Acute H. pylori infection of gastric epithelial cells represses H-K-ATPase alpha subunit gene expression leading to transient hypochlorhydria and supporting H. pylori proliferation. This growth of H. pylori may even initiate a pathological process causing gastric cancer.
Gastric bypass – Gastric bypass is a gastric exclusion operation performed in patients with massive obesity to reduce food intake. Studies show that the acid secretion unbuffered by the food in the excluded stomach results in lowered gastrin secretion hence leading to achlorhydria in such patients.
VIPomas – VIPoma is an endocrine tumor that usually arises from beta-pancreatic cells and secretes Vasoactive intestinal peptide. It may be associated with MEN1. The massive amounts of VIP secretion cause watery diarrhea, hypokalemia, achlorhydria, vasodilation, hypercalcemia, and hyperglycemia.
Hypothyroidism – Thyroid hormone plays a role in hydrochloric acid secretion hence hypothyroidism can lead to achlorhydria.
Hypothyroidism – This condition can significantly slow down your metabolism, resulting in a decrease of gastric acid production.
Medications – Antacids are a useful solution to heartburn and indigestion. Proton pump inhibitors (PPIs) can alleviate symptoms from gastroesophageal reflux disease (GERD). Both medications reduce acidity in the stomach. Overuse or complications can prevent the body from producing stomach acids at all, leading to achlorhydria.
Surgery – Weight loss surgeries, such as the gastric bypass procedure, reduce the size of your stomach and alter how your body handles food. When the function of a significant portion of the stomach is changed, stomach acid production can decrease.
Autoimmune disorders – Certain autoimmune disorders can affect stomach acid production.
Radiation to stomach – Radiation to stomach has also been reported to cause achlorhydria.
Gastric cancer – Animal studies have shown evidence of achlorhydria in gastric cancer.
The slowing of the body’s basal metabolic rate associated with hypothyroidism
Pernicious anemia where there is antibody production against parietal cells which normally produce gastric acid.
The use of antacids or drugs that decrease gastric acid production (such as H2-receptor antagonists) or transport (such as proton pump inhibitors).
A symptom of rare diseases such as mucolipidosis (type IV).
A symptom of Helicobacter pylori infection which neutralizes and decreases secretion of gastric acid to aid its survival in the stomach.
A symptom of atrophic gastritis or stomach cancer.
Radiation therapy involving the stomach.
Gastric bypass procedures such as a duodenal switch and RNY, where the largest acid-producing parts of the stomach are either removed or blinded.
VIPomas (vasoactive intestinal peptides) and somatostatinomas are both islet cell tumors of the pancreas.
Pellagra, caused by niacin deficiency.
Chloride, sodium, potassium, zinc, and/or iodine deficiency, as these elements are needed to produce adequate levels of stomach acid (HCl).
Sjögren’s syndrome, an autoimmune disorder that destroys many of the body’s moisture-producing enzymes
Ménétrier’s disease, characterized by hyperplasia of mucous cells in the stomach also causing excess protein loss, leading to hypoalbuminemia. Presents with abdominal pain and edema

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Symptoms of

Irrespective of the cause, achlorhydria can result as known complications of bacterial overgrowth and intestinal metaplasia and symptoms are often consistent with those diseases:

gastroesophageal reflux disease^[rx]
abdominal discomfort
early satiety
weight loss
diarrhea
constipation
abdominal bloating
anemia
stomach infection
malabsorption of food
carcinoma of stomach
Achlorhydria and lack of tone in the digestive organs, particularly in the elderly.
Atonic dyspepsia and some cases of stomach acidity.
Anorexia and difficulties with food.
Bad breath.
Nausea and vomiting.
Overindulgence in food and/or alcohol.
Sluggish liver and bowel activity and associated range of conditions – skin, joints, etc.
Depression associated with atonic liver/liver congestion.
Gall bladder problems.
Colic, flatulence and bloating.
Tonic after illness to regain strength, and in constitutional arterial hypotension.
Tonic in nervous exhaustion.
External application for aching muscles and joints.
Topical wash with honey for ulcers and other skin erosions.

Diagnosis of Achlorhydria

Studies have shown evidence of changes in oxyntic mucosa in longstanding autoimmune gastritis. The oxyntic mucosa is mainly composed of parietal cell, activation of which increases acid production in the stomach. The oxyntic mucosa undergoes four distinctive yet overlapping histological changes:

In the early phase, the plasma cells and lymphocytes migrate into the lamina propria, patchy destruction of oxyntic cells may be seen.
The lymphocytes and plasma cells then form dense infiltrate in the lamina propria. A metaplastic process is observed in the oxyntic cells; the large pale staining oxyntic cells are replaced by a new phenotype of clear cells also known as pseudo-pyloric metaplasia.
Then follows intestinal metaplasia of gastric glands which can later lead to malignancy.
In advanced gastritis, atrophy of oxyntic mucosa is seen. There can also be fibrosis, polyp formation, hyperplasia of muscularis mucosae and/or enterochromaffin-like cells.

History and Physical

Depending on the primary cause, the symptoms of achlorhydria can vary. Generally, patients develop following symptoms which are listed in order of their prevalence:

Epigastric pain
Weight loss
Heartburn
Nausea
Bloating
Diarrhea
Abdominal pain
Acid regurgitation
Early satiety
Vomiting
Postprandial fullness
Constipation
Dysphagia
Glossitis
Decreased position and vibration sense

Evaluation

When suspecting achlorhydria, multiple tests are conducted to confirm the diagnosis and to find its primary cause:

Antiparietal and anti-intrinsic factor antibody
Biopsy of stomach
Gastric pH monitoring
Serum pepsinogen level (a low serum pepsinogen level indicates achlorhydria)
Serum gastrin levels (high serum gastrin levels greater than 500 to 1000 pg/mL may indicate achlorhydria)
Tests for detecting H. pylori infection (urea breath test, stool antigen test, biopsy, polymerase chain reaction-PCR or fluorescent in situ hybridization [FISH])
Hemoglobin level

Treatment of Achlorhydria

There is no specific treatment for achlorhydria. Eradication of H. pylori is recommended in patients who are found to have it. Other treatments are targeted at improving the complications of achlorhydria. [rx][rx][rx]These include replacement of calcium, vitamin D, iron, and vitamin B12. There are no specific guidelines for surveillance, although it is a preneoplastic condition. The Kyoto consensus in 2015 stated that endoscopic surveillance and follow up should be done in patients who underwent eradication therapy for H. pylori and were found to have a preneoplastic condition.

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Treatment of gastritis that leads to pernicious anemia consists of parenteral vitamin B-12 injection. Associated immune-mediated conditions (e.g., insulin-dependent diabetes mellitus, autoimmune thyroiditis) should also be treated. However, treatment of these disorders has no known effect in the treatment of achlorhydria.

Achlorhydria associated with Helicobacter pylori 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, can be used to treat bacterial overgrowth.

Achlorhydria resulting from long-term proton-pump inhibitor (PPI) use may be treated by dose reduction or withdrawal of the PPI.

Natural Remedies for Hypochlorhydria

Some alternative practitioners believe that this condition is relatively common, particularly in older people with weak or brittle hair and nails, bloating, indigestion, and tiredness.

It’s important to keep in mind that there is a lack of supporting research on the remedies that are typically recommended by alternative medicine practitioners for hypochlorhydria.

Consider taking bitter herbs. Some alternative practitioners say that bitter herbs taken before meals may stimulate the secretion of stomach acid and digestive enzymes. Examples of bitter herbs are gentian and dandelion. They’re often recommended in liquid vs. capsule form because it’s the bitterness that’s thought to trigger the release of digestive juices. Another option is to buy an herbal tea containing bitter herbs and drink one cup before eating.
Try taking betaine hydrochloride capsules. According to some alternative medicine practitioners, look for a capsule (not tablet) that contains both betaine hydrochloride and pepsin. It’s often suggested that the capsule be taken at the start of a meal. This supplement is controversial and should only be taken under the supervision of a health care practitioner because of possible side effects and drug interactions.
Chew thoroughly.
Take a multivitamin. Because hypochlorhydria may lead to deficiencies of certain vitamins and minerals, a multivitamin and mineral supplement may be recommended.
Try vitamin B complex. Some practitioners suggest an additional vitamin B complex. Though it is not a treatment for hypochlorhydria, it may be recommended to replete potential B12 and other B vitamin deficiencies. B12 is the most notable vitamin deficiency with low HCl.
Consider certain herbs. Grapefruit seed extract, garlic, oregano oil, and enteric-coated peppermint oil are some supplements thought to help if there is bacterial overgrowth.
Take probiotics.
Take digestive enzymes.
Make sure you get enough glutamine.
Drink ginger tea. Ginger is thought to aid digestion and reduce bloating. In Ayurvedic medicine and traditional Chinese medicine, ginger is considered a digestive tonic.