15.8: The Stomach

Structure of the Stomach

​Figure 11 | Stomach | ¹⁷ The stomach has four major regions: the cardia, fundus, body, and pylorus. The esophagus connects to the stomach leading to the lesser curvature on the medial side and the greater curvature on the lateral side. Surrounding the stomach wall is the muscularis externa, composed of three layers—outer longitudinal, middle circular, and inner oblique muscles. The food is moved through the stomach to the antrum where it is further mixed and partially digested. At the junction of the stomach and the duodenum is the pylorus which regulates the passage of food into the small intestine.

The stomach consists of four primary regions: the cardia, fundus, body, and pylorus, each playing a distinctive role in the digestive process. The cardia, situated at the connection point between the esophagus and the stomach, marks the entryway to the stomach. Positioned beneath the diaphragm, the fundus is a dome-shaped region located above and to the left of the cardia. Subsequent to the fundus is the main part of the stomach, known as the body. Finally, the funnel-shaped pylorus serves as the gateway between the stomach and the duodenum (Figure 11).

Alternatively, the stomach can be functionally characterized by dividing it into proximal (orad) and distal (caudad) portions. The orad portion, which comprises the fundus and the proximal half of the gastric body, exhibits a highly compliant, relaxed state that coincides with the relaxation of the lower esophageal sphincter. This phenomenon, known as receptive relaxation, significantly lowers intraluminal gastric pressure to accommodate the incoming food bolus. This accommodation is mediated by a vagovagal reflex. The reflex is initially triggered by the act of swallowing and is subsequently reinforced as mechanoreceptors detect physical distention in the esophagus and the orad stomach. Efferent pathways of this reflex stimulate enteric inhibitory neurons, which release nitric oxide and vasoactive intestinal peptide (VIP) to induce gastric smooth muscle relaxation. Additionally, the gastrointestinal hormones gastrin and cholecystokinin assist in this process by decreasing contractile tone and further increasing the distensibility of the orad region. Because of this physiological design, the orad region experiences minimal phasic contractile activity, resulting in very limited mixing of food in the upper stomach. Instead, the orad region maintains a sustained, low-intensity tonic contraction that gently and steadily propels the gastric contents toward the caudad region (the distal body and antrum). In contrast to the quiet orad region, the caudad portion undergoes vigorous, phasic peristaltic contractions. These powerful waves of contraction serve to thoroughly grind, shear, and mix the food with acidic gastric juices, transforming the bolus into a semi-liquid mixture called chyme before it is emptied into the duodenum.

The epithelial lining comprises surface mucous cells that produce a protective layer of alkaline mucus—the mucosal folding forms numerous gastric pits, each constituting a gastric gland responsible for secreting gastric juice. The cardia and pylorus glands consist primarily of mucus-secreting cells. The pyloric antrum glands secrete mucus and hormones, notably gastrin. The larger fundus and body glands, vital for chemical digestion, contain diverse secretory cells, including parietal cells, chief cells, mucous neck cells, and enteroendocrine cells.

Parietal cells, also known as oxyntic cells, located in the middle regions of the gastric glands, are highly specialized and secrete hydrochloric acid and intrinsic factor. Hydrochloric acid imparts high acidity (pH 1.5 to 3.5) to the stomach contents, activating the protein-digesting enzyme pepsin. This acidity not only helps denature proteins but also eliminates bacteria. Intrinsic factor, a glycoprotein, is essential for vitamin B12 absorption in the small intestine. Chief cells, found predominantly in the basal regions of the gastric glands, secrete pepsinogen, the inactive precursor of pepsin, the active enzyme. hydrochloric acid is pivotal in converting pepsinogen into pepsin. Mucous neck cells in the upper gastric glands produce a thin, acidic mucus distinct from that generated by surface epithelial goblet cells. Enteroendocrine cells within the gastric glands release various hormones into the lamina propria's interstitial fluid (Figure 12). These hormones include gastrin, chiefly produced by enteroendocrine G cells. The digestive functions of critical chemical agents secreted by the stomach are summarized in Table 4.1

Figure 12 | Histology of the Stomach |¹⁸  The stomach wall is composed of four histological layers: mucosa, submucosa, muscularis externa, and serosa. The innermost layer of the stomach is lined by a surface epithelium that folds into gastric pits. Parietal and enteroendocrine cells are dispersed among the line of chief cells. Just below this lining is a layer of lamina propria and the muscularis mucosa. Additionally, innervation of the mucosal layer can be observed. The submucosal layer is highly vascularized, supporting nutrient and oxygen exchange. Next, the muscularis externa consists of three distinct muscle layers: the oblique layer, circular layer, and longitudinal layer. Finally, the serosa, which also exhibits vascularization, forms the outermost layer.

Electrical and Mechanical Events within the Stomach

The control of gastric peristalsis relies mainly on myogenic mechanisms. Slow waves originate from a pacemaker area in the upper body of the stomach. The entire stomach contains ICC networks, but the pacemaker region is identified by the highest intrinsic frequency, creating slow wave propagation and subsequent contraction waves. While the fundus is relatively depolarized, the wavefronts from the fundus decelerate, fragment, and stop, indicating that it does not actively engage in peristalsis. Instead, it contributes to vagally mediated accommodation. Yet, phasic pressure waves might be communicated to the fundal cavity.

ICC, dependent on stem cell factor signaling through the Kit receptor tyrosine kinase, generates and propagates slow waves. Slow waves trigger the ICC membrane potential oscillations, further transmitting rhythmically to adjacent smooth muscle cells through gap junctions. This transmission modulates the smooth muscle cell membrane potential in a cyclic pattern that influences excitation-contraction coupling. Neural activity plays a crucial role in maintaining typical gastric motility. Slow waves, stemming from the pacemaker region, develop into ring wavefronts that travel aborally. Once established, the circumferential propagation halts, and the rings propagate longitudinally. Near the terminal antrum, the conduction speed significantly accelerates, particularly contributing to powerful terminal antral contractions. Effective solid gastric emptying results primarily from antral peristalsis, impacted by wave strength, pyloric tone, and duodenal coordination.¹

Regulation of Gastric Emptying

The regulation of gastric juice secretion involves a complex interplay of neural, hormonal, and reflex mechanisms. It occurs in three distinct phases: the cephalic, gastric, and intestinal phases. Each phase is activated or inhibited in response to specific stimuli, and they can occur simultaneously once gastric secretion begins.

Cephalic Phase: This initial phase, also known as the reflex phase, is relatively brief and occurs before food enters the stomach. It is triggered by sensory cues such as the smell, taste, sight, or even the mere thought of food. Receptors in the taste buds send signals to the brain upon food contact with the tongue, prompting increased gastric secretion. This phase primes the stomach for digestion.

Gastric Phase: The gastric phase spans 3 to 4 hours and begins when food enters the stomach, activating local neural and hormonal mechanisms. Distention caused by the arrival of food stimulates stretch receptors, triggering parasympathetic neurons to release ACh, which prompts increased gastric juice secretion. Additionally, partially digested proteins, caffeine, and rising pH levels induce the release of gastrin from enteroendocrine G cells. Gastrin then signals parietal cells to boost the production of hydrochloric acid, crucial for creating an acidic environment essential for protein digestion. Notably, the stomach regulates excessive acid secretion and potential heartburn. When pH levels drop too low, stomach cells halt production of hydrochloric acid and increase mucous secretion, acting as a protective mechanism.

Intestinal Phase: This phase comprises both excitatory and inhibitory components. The duodenum plays a significant role in modulating stomach activity. When the partially digested food fills the duodenum, intestinal mucosal cells release a hormone called intestinal gastrin, further stimulating gastric juice secretion. However, as the intestine distends with chyme, the enterogastric reflex kicks in, inhibiting further gastric juice secretion. This reflex not only checks gastric secretions but also closes the pyloric sphincter, preventing additional chyme from entering the duodenum.

The successful transit of chyme into the duodenum at an appropriate pace is crucial. This ensures optimal pH levels for effective enzyme action and adequate time for nutrient absorption. Gastric emptying must strike a balance, allowing nutrient absorption in the small intestine without overwhelming its capacity. Several factors influence this process, including increased orad stomach tone, forceful peristaltic contractions aiding chyme movement, reduced pyloric tone regulating stomach emptying, and the absence of segmental contractions in the intestine.

CCK release in response to fats and proteins slows gastric emptying. CCK increases stomach distensibility, allowing more time for fat and protein digestion and absorption in the small intestine. ¹

​Figure 15 | The Three Phases of Gastric Secretion |²⁰ In the cephalic phase, the sight or thought of food activates the cerebral cortex and initiates a conditional reflex which sends a signal to the hypothalamus and medulla oblongata. This stimulates the vagus nerve promoting stomach secretory activity. Similarly, the stimulation of taste and smell receptors directly signals the hypothalamus and medulla further stimulating the vagus nerve. Reciprocally, the loss of appetite or depression reduces stimulation of the cerebral cortex. The lack of signaling to the parasympathetic center inhibits gastric activity. In the next phase, the stretch receptors of the stomach are activated which induce the local and vagovagal reflexes. This signals the medulla and stimulates the vagus nerve to increase gastric activity. The rising pH in the stomach activates chemoreceptors which promote G cells to secrete the hormone gastrin into the bloodstream further increasing secretion. In contrast, excess acidity in the stomach decreases gastric secretion. Additionally, emotional distress overrides the parasympathetic system by activating the sympathetic nervous system instead further inhibiting secretory activity. In the intestinal phase, the presence of the partially digested food and low pH in the duodenum stimulates the release of gastrin into the blood which increases stomach secretory activity. However as the duodenum extends and detects the presence of fatty, acidic chyme and irritants, it stimulates local reflexes, enterogastric reflexes, and vagal nuclei which decrease gastric motility and secretion. Additionally, the release of intestinal hormones contributes to the inhibition of gastric activity, helping to regulate the pace of digestion.

Digestive Functions of the Stomach

The stomach serves as a temporary storage site for ingested food, where it is held briefly and mixed with gastric secretions to begin digestion. Specialized cells in the stomach lining release intrinsic factor, a glycoprotein essential for vitamin B12 absorption in the small intestine. Vitamin B12 is necessary for forming mature red blood cells. Through mechanical and enzymatic processes, the stomach converts food into a semi-fluid mixture called chyme. This churning and mixing action, combined with protein breakdown by gastric juices containing hydrochloric acid and pepsin, simplifies food particles, preparing them for further digestion.

The stomach plays a central role in protein digestion by breaking down complex protein molecules into simpler forms. Gradually, it releases chyme into the small intestine, controlling the flow to prevent overwhelming the intestine and allowing efficient digestion and absorption. Although most nutrient absorption occurs in the small intestine, the stomach can absorb certain nonpolar substances, such as alcohol and aspirin. Thus, the stomach is crucial in mechanical and chemical digestion, while ingestion and defecation occur outside its primary functions.

Mechanical Digestion: Upon food entry into the stomach, mixing waves initiate at intervals of approximately 20 seconds, softening and combining the food with gastric juices to form chyme. These mixing waves, a specialized form of peristalsis, start gently and gradually intensify, traveling from the stomach's body toward the pylorus.

The pylorus acts as a filter, holding approximately 30 mL of chyme and permitting only liquids and small food particles to pass through the mostly closed pyloric sphincter. Gastric emptying occurs through rhythmic mixing waves, which release about 3 mL of chyme at a time into the duodenum. This controlled release prevents the small intestine from being overloaded with too much chyme at once. Feedback signals from both the stomach and the duodenum regulate gastric emptying. Receptors in the duodenum, activated by chyme, inhibit further gastric secretion, ensuring that the duodenum is ready to process the incoming chyme before the stomach releases more. Anesthesia affects the tone of the lower esophageal sphincter and pyloric sphincter. Relaxation of the lower esophageal sphincter under anesthesia can increase the chance of acid reflux, making positioning (such as elevating the head) critical to reduce aspiration risk.

Chemical Digestion: The fundus, a storage area in the stomach, houses undigested food, allowing food to begin mixing with chyme. During this time, the salivary amylase continues digesting carbohydrates until the food encounters the acidic gastric juice. The acidity deactivates salivary amylase as the mixing waves integrate the food with chyme. Gastric lipase is an enzyme produced by the chief cells in the stomach that plays a role in the digestion of dietary fats. It specifically targets triglycerides, breaking them down into free fatty acids and monoglycerides. Gastric lipase functions best in the acidic environment of the stomach but has limited capacity compared to pancreatic lipase, which does the majority of fat digestion in the small intestine. However, gastric lipase is particularly important in early fat digestion, especially for infants, who rely heavily on milk fats in their diet. Protein digestion begins with the actions of hydrochloric acid and the enzyme pepsin, and in infancy, gastric glands produce rennin, an enzyme aiding in milk protein digestion.

Pepsinogen is the precursor or inactive form of the enzyme pepsin. It is secreted by the chief cells in the stomach lining as an inactive zymogen or precursor. It is not functional in its original state and requires a specific conversion to become active pepsin. Upon secretion into the stomach, pepsinogen comes into contact with hydrochloric acid. The acidic environment of the stomach triggers the activation of pepsinogen into its active form, pepsin. Once a small amount of pepsin is formed, pepsin can catalyze the conversion of more pepsinogen into active pepsin. This self-catalyzing process amplifies the amount of active pepsin available for protein digestion. Pepsin is a proteolytic enzyme which breaks down proteins into smaller peptides. It primarily targets peptide bonds in proteins, leading to their hydrolysis and digestion into smaller fragments. Pepsin functions optimally in an acidic environment with a pH ranging from 1.8 to 3.5. Pepsin activity is sensitive to changes in pH. It is reversibly inactivated when exposed to a pH higher than 5.0 and is irreversibly inactivated at pH levels between 7 and 8. 

The stomach content is emptied into the duodenum within 2 to 4 hours post-meal. The processing times for different food types vary, with carbohydrates emptying quickest, followed by high-protein foods, and high-fat meals remaining in the stomach longest. Typically, full digestion takes 24 to 72 hours, but the stomach's role in this process is a duration of 2 to 4 hours.

Vomiting, or emesis, is the forceful expulsion of stomach contents through the mouth. This reflex is controlled by the vomiting center in the medulla oblongata and can be triggered by a range of stimuli, including stomach irritants, inner ear disturbances (such as motion sickness), certain medications, infections, and psychological factors. The process begins with the relaxation of the lower esophageal sphincter and the contraction of the pyloric sphincter, preventing stomach contents from moving into the intestines. Next, the diaphragm and abdominal muscles contract sharply, increasing abdominal pressure. This pressure forces the stomach contents upward and out through the mouth. Vomiting serves as a protective mechanism to expel harmful substances from the body, but frequent vomiting can lead to dehydration, electrolyte imbalances, and irritation of the esophagus. Many anesthetics increase the risk of postoperative nausea and vomiting (PONV). Prophylactic antiemetics are often administered to help reduce these effects, as PONV can disrupt digestion and is uncomfortable for the patient.¹