The state of low gastric acid production in the stomach is defined as hypochlorhydria, whereas an absence thereof is termed as achlorhydria. Achlorhydria is directly connected to multiple conditions and is primarily a result of chronic vomiting, stomach neoplasm, niacin deficiency, hypothyroidism or helicobacter pylori infection.
The simple definition of achlorhydria involves the complete absence of HCl in gastric secretions . Pathophysiologically, it has also been defined in the following ways:
Pathologic and surgical causes of achlorhydria are all described below. In general, this condition is considered a precancerous stage, since it is linked to metaplasia of the gastric mucosa, which can then further result in a dysplastic condition.
Hydrochloric acid is produced by the gastric lining, specifically from the parietal cells and has two functions which are vital for the digestion of food. It converts pepsinogen into pepsin and together with other chemical elements (enzymes), it is responsible for digestion. The absence or very low concentration of hydrochloric acid leads to problems with normal digestion, since its function cannot be carried out by the other enzymes alone, even pepsin needs an acidic intragastric pH in order to function.
There are many conditions leading to achlorhydria:
Even though the condition is defined as achlorhydria, in reality it is very unusual and rare for a total absence of gastric acid to be the case. Generally, gastric acid concentration is severely diminished, so that its quantity does not suffice to carry out digestion.
The exact incidence and prevalence of achlorhydria are unknown. Gastric atrophy, however, which corresponds to a concentration of pepsinogen I less than 25 nanograms/mL or pepsinogen I/II ratio less than 3.0, has been calculated by studies to be present in 10-15% of the senior population . It is also a known fact that gastric atrophy is directly linked to intestinal metaplasia and increases the risk of patients for developing a gastric adenocarcinoma, by 2 or 3 times. 16% of patients suffering from dyspepsia have been diagnosed with gastric atrophy, whose incidence fluctuates between 0%-11% per year. An important observation is that patients with an H. pylori infection tend to exhibit gastric atrophy more frequently than those unaffected by the infection .
Another autoimmune disease, pernicious anemia, caused by autoimmunity against the parietal cells and/or the intrinsic factor, has been found to be present in just over 2% of the population aged over 60 years old. In a study conducted among the German population, researchers evaluated 9684 patients aged 50-74 years old and used the ELISA technique to detect parietal cell autoantibodies. Antibodies against the hydrogen-potassium-stimulated adenosine triphosphatase (H+/K+ ATPase), the proton pump of the parietal cell, were found in 20% of the participants . Pernicious anemia causes cobalamin deficiency.
As mentioned above, the existence of an H. pylori infection plays a crucial role in the secretion of gastric acid. Even though 50% of the world's population are H. pylori carriers, not everyone exhibits an active infection. In those patients who do exhibit it, the production of gastric acid is considerably diminished and usually, the gastritis caused affects the whole of the stomach (pangastritis). An H. pylori infection produces this effect on the stomach via two mechanisms, the microorganism itself produces toxins that hinder the secretion of HCl from parietal cells and the inflammatory process that accompanies an H. pylori infection further inhibits gastric acid production . For instance, toxins released by H. pylori inhibit the expression of human hydrogen-potassium-stimulated adenosine triphosphatase (H+/K+ ATPase) alpha-subunit and hinder the transport of H+/K+ ATPase-containing tubulovesicles to the apical membrane, both indicate direct damage. On the other hand, interleukin-1beta, tumour necrosis factor-alpha as well as other cytokines, all by-products of the inflammatory process, also damage parietal cells, resulting in a diminished production of gastric acid . A complication of this process is the loss of parietal cells and the oxyntic glands atrophy and from that point and on, achlorhydria is irreversible. A potential explanation for the damage caused to the stomach by a H. pylori infection suggests that this is mediated by autoantibodies against the Lewis x and y blood group antigens, which are expressed both by the microorganism's lipopolysaccharide and the proton pump. These antibodies are believed to result in autoimmune gastritis and the subsequent gastric atrophy  .
Autoimmune gastritis is also observed in patients affected by other autoimmune diseases, such as autoimmune thyroiditis, vitiligo, Graves disease, diabetes mellitus, idiopathic adrenocortical insufficiency, postpartum thyroiditis, primary biliary cirrhosis and hypoparathyroidism  . Autoantibodies against the parietal cell and intrinsic factor are exhibited in 32% and 12% respectively, of patients affected by primary biliary cirrhosis .
Surgical interventions such as antrectomy with vagotomy also play an important role in the development of achlorhydria. The process of antrectomy removes gastrin, which stimulates the production of acid and is secreted by antral G cells. It also removes the hormone which controls oxyntic mucosa growth. Vagotomy on the other hand prevents stimulants such as the sight, taste and smell of food from being transmitted to the brain and ultimately perceived. A further reflux of bile into the stomach, a complication of the surgical procedure, deteriorates the problem, contributing to the atrophy and inflammation.
With reference to gastrin, it is the hormone primarily stimulating the production of gastric acid upon the ingestion of food. Antral G cells produce gastrin, which then performs a dual function, it acts directly on the acid-secreting parietal cells and indirectly stimulates histamine production from enterochromaffin-like (ECL) cells. Histamine is released to the region of the nearby parietal cells, binding to histamine H2 receptors and further stimulating the production of gastric acid. After digestion has been completed, somatostatin (SST) gives the signal for the cessation of gastrin production. SST is produced by the antral D cells in response to luminal acid. In cases of achlorhydria, luminal acid does not cause the proper effect on SST, whose production is diminished. As a result, it fails to control the secretion of gastrin (disinhibition) and to perform its task, leading to hypergastrinemia. This mechanism also helps to comprehend the pathway leading from hypergastrinaemia to malignancy. Given that gastrin also induces the growth of the oxyntic mucosa, a failure to restrain its production leads to a continually growing mucosa. If no intervention to correct gastrin levels is performed, ECL cells become hypertrophic. If the phenomenon continues, ECL cells proceed from hyperplasia to dysplasia and, ultimately, to potential cancerous tumors.
Potential outcomes and complications of the disease have not yet been fully investigated. Nevertheless, achlorhydria is considered to be a precancerous stage, as the risk of malignancy is high.
An interesting fact is that a gastric environment of normal pH value only renders it possible for bacteria of the helicobacter species to grow, a stomach with a pH >4 also allows for the development of other, non-helicobacter species. There have been experiments proving that non-helicobacter bacteria can also cause atrophic gastritis and subsequent gastric carcinoma .
In order to assess a patient suspected of suffering from achlorhydria, a detailed medical history should be obtained. A physician should evaluate the corresponding risk factors: Gastric bypass surgery, chronic PPI use, persisting H. pylori infection and autoimmune diseases (eg, diabetes, autoimmune thyroid disease).
In order to determine the existence of possible complications arising from achlorhydria (bacterial overgrowth, intestinal metaplasia, hip fracture) additional questions are of vital importance. A doctor will investigate the presence of weight loss, feeling of fullness too early in the course of a meal, bowel movement frequency, abdominal discomfort and bloating, as well as potential reflux symptoms. Patients should also undergo tests to determine a possible anemia, since an acidic pH mediates the absorption of iron and achlorhydric patients often develop iron deficiency and subsequent anemia .
A lack of various nutrients resulting from a possible bacterial overgrowth can also lead to neurological symptoms. For this reason, a corresponding medical history, including the existence of visual changes, hallucinations, paresthesias, ataxia, numbness, gait imbalance, memory impairment, personality and mood alterations, should not be omitted.
The first step towards the diagnosis of a suspected achlorhydria is the evaluation of gastric pH. Gastric fluid is collected via naso- or orogastric tubes following the patient's fasting. pH values >3.5 constitute a definite sign of achlorhydria . Further tests may be used to determine the concentration of gastrin in blood, which is usually high in achlorhydric patients. Levels of pepsinogen A (PgA) in the blood are also used to determine the existence of achlorhydria, with levels <17 mcg/L being a strong indication of the condition. Pepsinogen is also an enzyme mediating the digestion of food .
Another useful test towards the diagnosis of achlorhydria involves the evaluation of gastric bacterial overgrowth, since it is a state that is many times responsible for hypo- or achlorhydria. This can be performed with a gastric or upper intestinal aspirate culture, with a breath test that assesses the release of hydrogen after a patients ingests plain sugar or a breath test involving the ingestion of specific, radioactive sugar. In the latter method, radioactive sugar is actually digested by gastric bacteria; should an overgrown population exist intragastrically, the patient is expected to exhale large amounts of radioactivity, a product of bacterial digestion.
Intervention in cases of achlorhydric patients is individualized depending on the cause of the condition:
There are no specific guidelines as to how an individual can prevent the occurrence of achlorhydria. Following basic hygienic measures does, however, prevent an H. pylori infection in many cases, and following a therapeutic scheme upon such a diagnosis, helps to eradicate the bacterium from the intragastric region. In this way, the danger of atrophic or autoimmune gastritis is diminished. Since achlorhydria is also caused by gastric surgery, its incidence can also be reduced by surgeons avoiding a great number of surgical processes on the stomach, in cases where conservative treatment can be applied.
Achlorhydria is a clinical condition featuring diminished or absent production of acidic fluid in the stomach. It is linked with multiple medical conditions.
Achlorhydria is caused by many types of conditions, some of which include:
The clinical manifestation of achlorhydria includes:
Achlorhydria causes symptoms that closely resemble those of gastroesophagel reflux disease, even though the mechanisms involved in the two conditions are completely distinct. A crucial complication of achlorhydria involves the potential overgrowth of bacteria in the stomach, such as the vibrio vulnificus, which is found in seafood. Prolific amounts of bacteria in the stomach may lead to diarrhoic phenomena or vitamin/nutient deficiency, including zinc, magnesium, B,C and K complex vitamins; these conditions may further lead to multiple pathologies, ranging from neuromuscular disorders to fatal diseases. In cases of achlorhydria, food is not digested successfully by the responsible enzymes, a state which causes pain, bloating and a great amount of discomfort after consuming food.
Achlorhydria is diagnosed after the evaluation of stomach pH value, levels that are greater than 4.0 even after stimulation with pentagastrin are typical of achlorhydria. Gastrin levels in the blood are also a common finding. Lastly, almost 90% of patients with achlorhydria are found to have antibodies against the H+/K+ ATP-ase proton pump.
The most successful way of treating achlorhydria is by eradicating its initial cause, as described before. Apart from the different types of intervention depending on its causes, many doctors also prescribe Betaine HCL/Betaine hydrochloride, in order to increase the gastric acids and facilitate proper digestion. Betaine HCL contains chloride, which releases hydrochloric acid in the stomach, partially compensating for the reduced amount of acidic fluids that the stomach itself can naturally produce. It is sold as a preparation containing pepsin, an enzyme partaking in the digestion process.