The stomach is a hollow organ that is part of the gastrointestinal system, and it is responsible for functions including the formation of chyme, synthesis of proteins necessary for vitamin absorption, microbial defenses, and propagates the peristaltic reflex. Contrary to popular thought, the stomach does not contribute to the absorption of any nutrients. This organ can is in the peritoneal cavity, located in the left upper abdominal quadrant or in the epigastric abdominal region that acts to relay ingested food between the nervous system and the endocrine system. Gastric acid secretion, peristaltic propulsion, and other physiologic functions of the stomach are finely controlled by the integration of the enteric nervous system, parasympathetic nervous system, and the secretion of various neurohormonal molecules (i.e., gastrin, HCl acid, intrinsic factor, bicarbonate, mucus, etc.)
As a component of the alimentary canal (i.e., the tubal passageway for ingested food to be digested, absorbed, then excreted as waste), the stomach's physiological function is structured around creating an environment where the food ingested can be safely acted on by proteolytic enzymes and acidic solutions. There are pathologic consequences that can develop with the failure of the gastric mucosa to isolate the lumenal contents from the surrounding peritoneal cavity.
As with most physiologic processes, the structure of an organ largely defines the function it contributes to the body. The gastric wall is specifically designed to aid in the formation of a transient acidic environment that allows for the digestion of food into a semisolid mixture called chyme. The stomach organ has four regions; fundus, cardia, body, and pylorus. The inner surface of the stomach is rugated to increase the surface area of the gastric mucosa allowing for gastric expansion with food ingestion. The wall of the stomach consists of four different tissue layers; mucosal layer, submucosa, muscularis externa, and adventitia/serosa. The gastric mucosal layer further subdivides into three layers; the surface epithelium, a connective tissue layer called the lamina propria, and the muscularis mucosa. The gastric epithelial layer invaginates into the lamina propria forming the gastric pits and glands. These gastric glands are lined with four specialized cells; surface mucous cells (foveolar cells), parietal cells, chief cells, and neuroendocrine cells (G-cells or ECL-like cells) that all contribute independent functions.
The surface mucus cells (foveolar cells) are mucus-producing cells that primarily line the gastric mucosa. The secreted mucus acts as a barrier to the corrosive nature of the gastric acid. The rest of the specialized cells are found deep within the gastric glands (i.e., gastric pits).
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 layers of the muscularis externa is the myenteric Auerbach's plexus, which controls GI motility.
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 essential link between the brain and the gut respective to appetite control, acid secretion, and gastric motility.
In addition to the stomach's secretory function, the stomach also has a muscular component, as do all structures within the alimentary canal. The muscularis externa is composed of smooth muscle cells that orient in three directions: oblique layer (unique to only the stomach), a circular muscle layer, and the longitudinal layer. Together these three muscle layers are responsible for the gastric movements needed to break the food bolus into smaller components. A food bolus, which consists of partially digested food from the mouth and the esophagus, is processed by the stomach into chyme, which is a more readily absorbable substance by the small intestine. The stomach accomplishes this food processing through forceful back-and-forth churning motions 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, too, can pass through the pyloric sphincter. Slow-wave contractions of the gastric smooth muscles are generated by myenteric interstitial cells of Cajal, which serve as GI pacemakers.
All mechanical movements are the result of coordinated muscle contractions. The muscle layer is regulated primarily by the enteric nervous system (ENS), which is the intrinsic nervous system of the alimentary canal. The ENS can become activated by various inputs from the CNS like olfaction, sight, mechanical reception of the food bolus, or chemical mediators (PSNS/SNS). The mesh-work of neurons that makes up the ENS is found between the longitudinal and circular muscle layers. Commonly, it is referred to as the Auerbach's plexus or the myenteric plexus. The degree and rate of peristalsis are established by the myenteric interstitial cells of Cajal (ICC), as previously mentioned.
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. Parietal cells secrete intrinsic factor, which is essential in the absorption of vitamin B12 distally in the digestive tract by enterocytes of the terminal ileum.
Brief Cellular Review (refer to the "cellular" section for more information)
Hydrochloric acid (HCl), the main constituent of gastric acid, is 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. Pepsin breaks down proteins into smaller peptides, which may be further processed and later absorbed in the small intestine. The secretion of acid is under the regulation of both hormonal and neural components, including gastrin, histamine, prostaglandins, somatostatin, gastric inhibitory polypeptide, secretin, and the vagus nerve. 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.
Additionally, 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 release occurs in response to increased gastric distension, increased gastric pH, and the presence of amino acids in the stomach.
Blood Supply and Lymphatics
The stomach is susceptible to several primary pathologies that all manifest with similar symptomatology of epigastric pain, burning, gnawing discomfort, nausea/vomiting (+/- blood), satiety, and distention. Pathologies can subdivide into the following categories:
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. 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. 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 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, the widespread use of the most efficacious acid-reducing therapies, the proton pump inhibitors (PPI). PPIs are most effective in reducing 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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