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 or hypochlorhydria refer to conditions in which production of hydrochloric acid in the stomach is respectively absent or reduced. It is usually secondary to an underlying medical condition.
A study conducted in healthy people and patients with gastrointestinal (GI) diseases showed an increased incidence of achlorhydria and hypochlorhydria in women, but the results were not significant. In patients younger than 60 years of age, the incidence of achlorhydria and hypochlorhydria were 2.3% and 2% respectively; whereas, in older patients, it increased to 5%. That is an increase of almost 3-fold. Another study on autoimmune causes showed an age-related incidence of parietal cell autoantibodies. Their prevalence increases with age, for example, from 2.5% in the third decade to 12% in the eighth decade. Autoimmune gastritis is frequently found in association with other autoimmune conditions. It is also a component of autoimmune polyglandular syndrome type 3. No association has been found between pernicious anemia and HLA types.
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.
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:
Depending on the primary cause, the symptoms of achlorhydria can vary. Generally, patients develop following symptoms which are listed in order of their prevalence:
When suspecting achlorhydria, multiple tests are conducted to confirm the diagnosis and to find its primary cause:
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. 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.
Despite having a small risk of developing into gastric adenocarcinoma and gastric carcinoid tumor, achlorhydria has a good prognosis.
Majority of the complications found in achlorhydria are due to nutrient deficiency. They are also more common as compared to the other complications.
Patients are educated that due to increased gastric pH some drugs will not be absorbed effectively thus such drugs are given in higher doses.
Achlorhydria is not a very common disorder in clinical practice. Even when it presents, the signs and symptoms are vague. However, in order to avoid the high morbidity, healthcare workers including the primary care provider and nurse practitioner must consider it in the differential diagnosis when evaluating patients with epigastric discomfort. The pharmacist should assist with pain control The diagnosis of achlorhydria testing is always required. Once the diagnosis is made, the treatment depends on the cause. Even though there are no current guidelines on screening or monitoring of these patients, the clinician should always be aware that many cases of gastric cancer have been reported in these patients. (Level V)