Physiology, Stomach

Article Author:
Mark Hsu
Article Author:
Autumn Bass
Article Editor:
Forshing Lui
4/28/2020 12:31:34 PM
PubMed Link:
Physiology, Stomach


The stomach is a digestive system organ located in the upper left part of the abdominal cavity. It receives contents from the esophagus through the gastroesophageal sphincter and empties its content into the duodenum through the pyloric sphincter. The stomach can be divided into 4 sections: the cardia, fundus, body, and pylorus. Functions of the stomach include digestion, gastrointestinal motility, and microbial defense.


Similar to other intraperitoneal gastrointestinal (GI) organs, the walls of the stomach consist of 4 layers: the mucosa, submucosa, muscularis externa, and serosa. Compared to other organs of the GI tract, the stomach is unique in that its muscularis externa features an inner oblique layer in addition to a circular and longitudinal layer. Exterior to the submucosa is the submucosal Meissner’s plexus, which controls secretions and blood flow. In between the circular and longitudinal layer of the muscularis externa is the myenteric Auerbach’s plexus, which controls GI motility.

Simple columnar epithelium lines the gastric mucosa, featuring mucosal invaginations known as gastric pits and ducts, are known as gastric glands. Four major cell types line these gastric glands: parietal cells, chief cells, foveolar cells, and enteroendocrine cells.

The right and left gastric arteries, left and right gastro-omental arteries, and short gastric arteries are responsible for blood supply to the stomach. Celiac ganglia and the vagus nerve innervate the stomach. The vagus nerve serves as an important link between the brain and the gut with respect to appetite control, acid secretion, and gastric motility.


Food bolus, which consists of chewed up food from the mouth and esophagus, is processed by the stomach into chyme, which is partially digested food that is more readily absorbable as nutrients in the small intestine. The stomach accomplishes this food processing through forceful back-and-forth churning by the inner oblique layer of the muscularis externa. The circular and longitudinal layers facilitate gastric emptying of chyme through the pyloric sphincter which allows only liquids and small enough food particles to pass through. Gastric emptying may be slowed by the presence of fats and acids in the duodenum, stress, exercise, and various hormones. Chyme that is not emptied will continue to churn in the stomach until it can pass through the pyloric sphincter. Contractions of gastric smooth muscles are generated by slow waves generated by myenteric interstitial cells of Cajal, which serve as GI pacemakers.[1]

The stomach itself does not significantly contribute directly to the body’s absorption of nutrients, although it absorbs some substances such as alcohol and aspirin.[2] Parietal cells secrete intrinsic factor, which is essential in the absorption of vitamin B12 distally in the digestive tract by enterocytes of the ileum.

Hydrochloric acid (HCl), the main constituent of gastric acid, is also secreted by parietal cells. The hydrogen (H) and chloride (Cl) components of HCl are secreted separately by hydrogen/potassium ATPase pumps and chloride channels in the stomach. Pepsinogen, a proenzyme for pepsin, is secreted by chief cells. Collectively, gastric acid creates an acidic environment that denatures proteins and activates the conversion of pepsinogen to pepsin.[3] Pepsin breaks down proteins into smaller peptides which may be further processed and later absorbed in the small intestine. The secretion of acid is regulated by both hormonal and neural components, including gastrin, histamine, prostaglandins, somatostatin, gastric inhibitory polypeptide, secretin, and the vagus nerve.[4] Interventional inhibition of acid secretion to avoid various complications of excess acid is commonly done by administering proton pump inhibitors.

The acidic environment of the stomach is not only useful for protein denaturing but also for protection against potentially infectious agents. All material consumed by the body must pass through the stomach, making it an important defense against microbes. Many bacteria are killed or inhibited by the stomach’s acidity.

Additional secretory cells of the gastric glands include foveolar cells and enteroendocrine cells. Foveolar cells protect the stomach from the corrosive nature of its acidic environment by producing mucus and bicarbonate (HCO3). Enteroendocrine cells secrete various digestive hormones such as gastrin, somatostatin, and ghrelin. Gastrin is released in response to increased gastric distension, increased gastric pH, and the presence of amino acids in the stomach.[5]


Dyspepsia describes symptoms of indigestion, including nausea, vomiting, fullness, heartburn, belching, and abdominal pain. Functional dyspepsia refers to patients experiencing these symptoms in the absence of any clear cause.[6] However, most cases of dyspepsia are caused by pathologies, a number of which involve the stomach.

Gastroesophageal reflux disease (GERD) is a common medical problem due to reflux of gastric acid and contents into the esophagus causing symptoms or esophageal mucosal injury. The symptoms may include heartburn, regurgitation, dyspepsia, hoarseness and chronic cough. Treatment will include weight loss and lifestyle changes to decrease the reflux or use of acid-reducing medications such as proton pump inhibitors.

Gastritis refers to gastric mucosa inflammation. Acute cases of gastritis are due to an imbalance between the stomach’s acidic environment and its mucosal defense to the acid. This can arise with alcohol, chronic use of nonsteroidal anti-inflammatory drugs (NSAIDs), chemotherapy, decreased mucosal perfusion, or increased acid production. Chronic cases of gastritis involve atrophy of the gastric mucosa and intestinal metaplasia and are primarily divided into 2 subtypes: autoimmune gastritis and bacterial gastritis. Autoimmune gastritis involves the autoimmune destruction of parietal cells while bacterial gastritis refers to a gastric infection by Helicobacter pylori.

Gastric ulcers occur when the mucosa and submucosa of the stomach lining breaks down, and are commonly due to H. pylori or NSAID use. Less common causes include stress, diet, infection, and rarely, tumors.

Gastric cancer is composed of two types: intestinal and diffuse. The intestinal type results from metaplasia and atrophy due to chronic gastritis, and is associated with smoking, alcohol, nitrosamines, and type A blood. The diffuse type is less common and features a diffusely thickened stomach wall. Gastric cancers are associated with a number of extra-systemic clinical findings, including acanthosis nigricans, Leser-Trelat sign, Virchow’s node, Sister Mary Joseph’s nodule, and Krukenberg tumors. Most gastric cancers are adenocarcinomas, and they most commonly metastasize to the liver.

Gastroparesis is a condition where stomach contractions are impaired, and thus stagnating the movement of food within the stomach. This condition can be idiopathic or caused by connective tissue disease, neurologic dysfunction, diabetes, infection, cancer, or obstruction.

Crohn disease is a granulomatous inflammatory bowel disease that can affect any portion of the GI tract, including the stomach.  

Menetrier’s disease is a hyperplasia of foveolar cells. The excessive mucus results in achlorhydria and protein loss.

Clinical Significance

Since everything the human body consumes by mouth passes through the stomach, it is exposed to a variety of foreign agents and is prone to homeostatic disruption. The prevalence of dyspepsia in the Western world is approximately 25%. Worldwide, gastric carcinoma is the fourth most common malignancy and the second deadliest.[7] H. pylori, which causes multiple gastric disorders, remains a challenging infection to treat, and approximately 20% of H. pylori-infected people will continue to experience dyspepsia and may even develop extra-systemic diseases over their lifetime.[8] Furthermore, with increasing rates of obesity worldwide, surgical manipulations of the stomach such as bariatric surgery are becoming more prevalent. Because of these factors, it is essential to continue increasing awareness and advancing the understanding of gastric function and disorders of the stomach.

Acid-reducing therapies had been used as the mainstay in the treatment of stomach related pathologies and symptoms varying from dyspepsia, GERD, gastritis to peptic ulcer diseases. Due to the high acidity or low pH (1.0) of gastric content, the simple antacids are commonly used and available over the counter. They are not effective except for transient relief of some symptoms. The antihistamine (H2 blockers) are more efficacious than acid-reducing therapies, and recently, there is greater, widespread use of the most efficacious acid reducing therapies, the proton pump inhibitors (PPI). PPIs are most effective in reducing the acid production and help many symptoms related to gastric pathology. As a consequence, long-term use without clear indications is not uncommon. It is generally safe, yet the reduced acid-pepsin digestion of B12 containing food may lead to vitamin B12 deficiency especially in the elderly and vegans.


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