PARIETAL CELLS: CHARACTERISTICS, HISTOLOGY, FUNCTIONS, DISEASES - BIOLOGY - 2025

The parietal cells, oxyntic cells or delomorfas cells are cells belonging to or gastric fundic gland, found in the fundus, a region of the mammalian stomach. These are especially important, as they are responsible for the secretion of hydrochloric acid and intrinsic factor.

To better understand the functions of cells, it should be noted that the stomach of mammals is divided into four parts or anatomical regions known as the cardia, fundus, body and pyloric antrum.

Electron micrograph of prominent parietal cells of the stomach (Source: Nephron via Wikimedia Commons)

The cardia and the pyloric antrum can be seen as the entry and exit points of the stomach, which connect the stomach with the esophagus and duodenum (first portion of the small intestine) while the fundus and the body represent the largest portion of the stomach.

However, according to the type of gland present in each anatomical region of the stomach, some authors assure that it is only subdivided into three histological regions: the cardial region, the fundic region and the pyloric region.

The cardial region is characterized by the presence of the cardial glands, meanwhile, the fundic and pyloric regions contain the fundic and antral glands, respectively. The fundic glands are the most abundant type of gland in the stomach (more than 75%).

These glands are made up of five different cell types, namely: mucosal cells, main cells, enteroendocrine cells, undifferentiated cells, and parietal cells.

The latter were described for the first time in 1870 and since then they have been the focus of numerous investigations of various kinds. It is thought that for each fundic gland there are about 70 or 90 parietal cells.

Representative diagram of a gastric gland (fundic or oxyntic) and the cells that compose it (Source: Boumphreyfr via Wikimedia Commons, modified by Raquel Parada)

Many diseases are related to the parietal cells, especially with their defects that are related to deficiencies in the production and release of intrinsic factor, which causes important deficiencies of vitamin B12.

Characteristics and histology

Parietal cells are cells with a rounded appearance, although in histological sections they appear rather pyramidal or triangular, which would represent the "vertex" of the triangle directed towards the lumen of the gland and its "base" supported by the basal lamina, closer to the mucous epithelium.

They are large in size and have one or two prominent nuclei in the central region of the cytosol.

Stomach parietal cells microscopy (Source: Jpogi at en.wikipedia via Wikimedia Commons)

They are not evenly distributed, as they are mostly concentrated in the upper and middle region of the gastric glands, where they mix with the neck cells and the main cells, two other types of cells.

If observed under the light microscope, the parietal cells present an elaborate system of invaginations in their apical portion and these invaginations are known as intracellular canaliculi.

The function of these canaliculi is to mediate the communication of the cells, and ultimately the glands to which they belong, with the gastric lumen (the internal space of the stomach).

Another important characteristic is that these cells have a large number of mitochondria closely associated with microvilli that intertwine or "interdigitate" with the intracellular canaliculi described and with the abundant smooth endoplasmic reticulum that characterizes them.

The cytosol also contains what has been called a complex tube-vesicular membranous system, which diminishes or disappears when the cells are in a state of active secretion and which serves as a reserve for the plasma membrane, rich in proton pumps.

ID

Thanks to the exuberant number of mitochondria present in their cytosol, parietal cells can be identified with relative ease in histological sections, as they stain densely with acidic dyes such as eosin, Congo red, and fast benzyl red.

The typical appearance of their cytosol and this staining characteristic make them distinguishable from the rest of the secretory cells belonging to the fundic glands.

Hydrochloric acid and intrinsic factor secretion

The hydrochloric acid (HCl) secreted by the parietal cells fulfills the hydrolytic function necessary to begin the digestion of proteins and other molecules contained in food that are ingested during the day.

It is very important for the activation of proteolytic enzyme zymogens (proteases) such as pepsin, which is responsible for the digestion of proteins.

Its secretion is stimulated in these cells thanks to the presence of three types of membrane receptors, which stimulate the production of HCl responding to the presence of acetylcholine, histamine and, especially, gastrin. The hydrochloric acid secretion process is nothing trivial and begins with:

- The production of protons (H +) in the cytosol of parietal cells thanks to the enzymatic action of carbonic anhydrase, which hydrolyzes carbonic acid to protons and bicarbonate ions (HCO3-).

- Protons are subsequently transported from the cytosol of the parietal cell to the lumen of the canaliculi. A sodium (Na +) and potassium (K +) ATPase participates in this transport, which transports K + to the cytosol and expels protons towards the canaliculi.

- Other K + and chlorine (Cl-) transport channels (uniport) in the plasma membrane are responsible for the transport of these ions from the cytosol of the parietal cells to the canaliculi and it is from protons and chloride ions that finally hydrochloric acid (HCl) is formed.

Regulation

The secretion of hydrochloric acid is a highly regulated process and some authors consider that this regulation occurs in different “stages” or “phases” known as the cephalic phase, the gastric phase and the intestinal phase.

The cephalic phase depends on the vagus nerve and is mainly mediated by sensory stimuli such as smell, sight and taste. The vagus nerve exerts its effects on HCl secretion by either direct (acetylcholine-mediated) or indirect (gastrin-related) stimulation.

The gastric phase accounts for more than half of the secretory response during food intake. At this point, many factors stimulate HCl synthesis, including some external factors like caffeine, alcohol, and calcium.

The intestinal phase is the one that involves the regulatory action of hormones such as secretin, somatostatin and neurotensin downstream of the stomach.

As has also been mentioned, intrinsic factor is a secretion product of parietal cells in mammals. This factor is a 45 kDa glycoprotein whose secretion is stimulated by the same elements that stimulate the secretion of hydrochloric acid.

Features

Parietal cells perform a fundamental function, not only for the glandular structure to which they belong, but also for the digestive functions of the stomach, since they are responsible for the secretion of large amounts of concentrated hydrochloric acid.

In addition, they also secrete bicarbonate (HCO3-) into the bloodstream and the so-called intrinsic factor, essential for the absorption of vitamin B12 and the only truly essential element of stomach secretion, since human beings cannot live without it.

The hydrochloric acid secreted by the parietal cells not only activates pepsinogen, but also imposes the necessary conditions for protein hydrolysis and generates a “bacteriostatic” microenvironment that prevents the growth of potentially pathogenic bacteria that can enter with food.

Related diseases

Pernicious anemia

Pernicious anemia is a clinical condition caused by a lack of vitamin B12, which is absorbed in the ileum in the presence of intrinsic factor secreted by parietal cells.

Other digestive problems related to the parietal cells have to do with the delicate nature of the hydrochloric acid secretion process, since any interruption or defect in the components necessary for this purpose practically "inactivates" the cells and prevents them from fulfilling their digestive functions.

Gastritis

Gastritis or gastric ulcers caused by Helicobacter pylori infections often involve exacerbated production of hydrochloric acid. However, some patients with similar infections have rather a degree of hypochlorhydria, which means that the secretion of acid in these cells is inhibited.

Atrophy

Parietal cell atrophy is a relatively common event in patients and this leads to ongoing gastric inflammation, in addition to preneoplastic lesions.

Likewise, there are autoimmune diseases that can cause apoptotic "destruction" of these cells, which can end up as pernicious anemia or gastritis, as is the case with some H. pylori infections.

This induction of apoptosis in parietal cells may be due to the action of different pro-inflammatory cytokines, whose signaling cascades are activated in the presence of different conditions.

Stress-related illnesses

In favor of what many people consider to be true, being permanently subjected to stressful conditions or events can have serious health implications, especially from a gastrointestinal point of view.

Many people today suffer from gastric ulcers caused by gastric acid hypersecretion, which are directly related to the stimulation of the parietal cells in the fundic glands.

Although the mechanisms of action of this type of pathology are not fully resolved, it is true that it affects different types of people and not always in the same way, since patients respond in physiologically different ways to stress, anxiety, depression, guilt, resentment and other irritating emotions.

References

1. Feher, J. (2017). The Stomach. In Quantitative Human Physiology: An Introduction (pp. 785–795). Elsevier Inc.
2. Ito, S. (1961). The Endoplasmic Reticulum of Gastric Parietal Cells. Journal of Cell Biology, 333–347.
3. Kopic, S., Murek, M., & Geibel, JP (2010). Revisiting the parietal cell. American Journal of Physiology - Cell Physiology, 298 (1), 1–10.
4. Merchant, JL (2018). Parietal Cell Death by Cytokines. Cellular and molecular gastroenterology and hepatology, 5 (4), 636.
5. Murayama, Y., Miyagawa, J., Shinomura, Y., Kanayama, S., Yasunaga, Y., Nishibayashi, H.,… Matsuzawa, Y. (1999). Morphological and functional restoration of parietal cells in Helicobacter pylori associated enlarged fold gastritis after eradication. Gut, 45 (5), 653–661.
6. Peters, MN, & Richardson, CT (1983). Stressful Life Events, Acid Hypersecretion, and Ulcer Disease. Gastroenterology, 84 (1), 114–119.