What controls the acid in your stomach?

The stomach is a gastrointestinal organ that is responsible for preliminary digestion and destroying any potential pathogenic microorganisms that may have been ingested. It is an acidic environment with a pH that can vary between 1.5-3.5.

This article will outline the production of gastric acid, the regulation of this and some clinical conditions that result from this process going wrong.

Hydrochloric Acid Production

HCl is produced by the parietal cells of the stomach. To begin with, water (H2O) and carbon dioxide (CO2) combine within the parietal cell cytoplasm to produce carbonic acid (H2CO3), which is catalysed by carbonic anhydrase. Carbonic acid then spontaneously dissociates into a hydrogen ion (H+) and a bicarbonate ion (HCO3-).

The hydrogen ion that is formed is transported into the stomach lumen via the H+- K+ ATPase ion pump. This pump uses ATP as an energy source to exchange potassium ions into the parietal cells of the stomach with H+ ions.

The bicarbonate ion is transported out of the cell into the blood via a transporter protein called anion exchanger which transports the bicarbonate ion out the cell in exchange for a chloride ion (Cl-). This chloride ion is then transported into the stomach lumen via a chloride channel.

This results in both hydrogen and chloride ions being present within the stomach lumen. Their opposing charges leads to them associating with each other to form hydrochloric acid (HCl).

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Control of gastric acid production

At rest, the number of H+- K+ ATPases present within the parietal cell membrane is minimal. The rest are sequestered within tubulovesicles in the parietal cell. Upon stimulation the vesicles fuse with the cell membrane which leads to the increased insertion of H+- K+ ATPase into the membrane, hence allowing for the increased movement of hydrogen ions into the stomach thus increasing acid production.

Increasing gastric acid production

There are three ways in which acid production is increased. The first of these is via ACh, which is released from the vagus nerve. This is released firstly during the cephalic phase of digestion, which is activated upon seeing or chewing food, leading to direct stimulation of parietal cells via the vagus nerve. It is also produced during the gastric phase of digestion when intrinsic nerves detect distension of the stomach, stimulating the production of ACh by the vagus nerve.

The main regulation pathway involves the hormone gastrin which is secreted from G cells in the stomach. G cells are activated by the vagus nerve, gastrin related peptide and by peptides in the stomach lumen produced via protein digestion. Activation of the G cells leads to the production of gastrin which is released into the blood and travels through the blood until it reaches the parietal cells. Gastrin binds to CCK receptors on the parietal cells which also elevates calcium levels causing increased vesicular fusion.

Finally, enterochromaffin like cells in the stomach secrete histamine which binds to H2 receptors on the parietal cells. These cells release histamine in response to the presence of gastrin and ACh. This leads to increased fusion however it is via the secondary messenger cAMP as opposed to calcium in the other methods.

Decreasing gastric acid production

There are a number of ways in which acid production can be decreased.

The first of these is via accumulation of acid in the empty stomach between meals. This increase in acid leads to a lower pH within the stomach, which inhibits the secretion of gastrin, via the production of somatostatin from D cells. Once food has been broken down into chyme, it passes into the duodenum, triggering the enterogastric reflex. This reflex can be stimulated by distention of the small bowel, if there is excess acid in the upper intestine, the presence of protein breakdown products as well as excess irritation to the mucosa. Inhibitory signals are sent to the stomach via the enteric nervous system, as well as signals to medulla - reducing vagal stimulation of the stomach. The enterogastric reflex, is important is slowing down gastric emptying when the intestines are already filled.

The presence of chyme within the duodenum also stimulates entero-endocrine cells to release cholecystokinin and secretin, both of which play a variety of important roles in completing digestion, but also inhibit gastric acid secretion. Secretin is released by the S cells of the duodenum when there is excessive acid production in the stomach.

Other hormones including glucose dependent insulinotropic peptide (GIP) and vasoactive intestinal polypeptide also work to decrease acid production in the stomach.

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Clinical relevance - Hypersecretion

Excessive secretion of stomach acid can lead to the formation of peptic ulcers. Potential complications of peptic ulcers include excessive bleeding due to erosion through a blood vessel. There are two main drugs used to prevent excessive acid formation. H2 antagonists such as ranitidinebind to the H2 receptors preventing the binding of histamine and thus reduce acid secretion.

It is important to note that the other two pathways for stomach acid secretion still operate, thus acid secretion is only reduced and not completely inhibited. Proton pump inhibitors (PPIs) such as omeprazolebind to the H+- K+ ATPase (proton pump), hence preventing the transportation of hydrogen ions into the stomach lumen. PPIs completely prevent stomach acid formation due to hydrogen ions not being able to react with chloride ions in the stomach.

Clinical Relevance - Achlorhydria

This is a state where there is a decrease in the volume of stomach acid produced. Achlorhydria can result in an increased risk of salmonella and cholera. There are a variety of causes and further tests must be undertaken to ascertain the cause to allow for a targeted treatment regime.

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Created: December 31, 2009; Last Update: August 21, 2016; Next update: 2020.

The stomach is a muscular hollow organ. It takes in food from the esophagus (gullet or food pipe), mixes it, breaks it down, and then passes it on to the small intestine in small portions.

The entire digestive system is made up of one muscular tube extending from the mouth to the anus. The stomach is an enlarged pouch-like section of this digestive tube. It is located on the left side of the upper abdomen and shaped somewhat like an oversized comma, with its bulge pointing out to the left. The stomach’s shape and size vary from person to person, depending on things like people’s sex and build, but also on how much they eat.

At the point where the esophagus leads into the stomach, the digestive tube is usually kept shut by muscles of the esophagus and diaphragm. When you swallow, these muscles relax and the lower end of the esophagus opens, allowing food to enter the stomach. If this mechanism does not work properly, acidic gastric juice might get into the esophagus, leading to heartburn or an inflammation.

The upper-left part of the stomach near the opening curves upward towards the diaphragm. This part is called fundus. It is usually filled with air that enters the stomach when you swallow. In the largest part of the stomach, called the body, food is churned and broken into smaller pieces, mixed with acidic gastric juice and enzymes, and pre-digested. At the exit of the stomach, the body of the stomach narrows to form the pyloric canal, where the partially digested food is passed on to the small intestine in portions.

The stomach wall is made up of several layers of mucous membrane, connective tissue with blood vessels and nerves, and muscle fibers. The muscle layer alone has three different sub-layers. The muscles move the contents of the stomach around so vigorously that solid parts of the food are crushed and ground, and mixed into a smooth food pulp.

The inner mucous membrane (lining) has large folds that are visible to the naked eye. These folds run toward the exit of the stomach, providing “pathways” along which liquids can quickly flow through the stomach. If you look at the mucous membrane under a microscope, you can see lots of tiny glands. There are three different types of glands. These glands make digestive enzymes, hydrochloric acid, mucus and bicarbonate.

Gastric juice is made up of digestive enzymes, hydrochloric acid and other substances that are important for absorbing nutrients – about 3 to 4 liters of gastric juice are produced per day. The hydrochloric acid in the gastric juice breaks down the food and the digestive enzymes split up the proteins. The acidic gastric juice also kills bacteria. The mucus covers the stomach wall with a protective coating. Together with the bicarbonate, this ensures that the stomach wall itself is not damaged by the hydrochloric acid.

Sources

• Menche N. (ed.) Biologie Anatomie Physiologie. Munich: Urban & Fischer/ Elsevier; 2012.

• Pschyrembel W. Klinisches Wörterbuch. Berlin: De Gruyter; 2014.

• Schmidt R, Lang F, Heckmann M. Physiologie des Menschen: mit Pathophysiologie. Heidelberg: Springer; 2011.

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