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The Gastric Phase of the Integrated Response to a Meal
Learning Objectives
Upon completion of this chapter, you should be able to answer the following questions:
- 1
What are the major functions of the stomach?
- 2
What are the gross functional regions of the stomach?
- 3
What is the role of the gastric epithelium in digestion and absorption?
- 4
What is the role of the proton pump in parietal cell function?
- 5
What are some examples of how gastric acid secretion is regulated during the postprandial period?
- 6
What are the differences between gastric mucosal protection and defense?
- 7
What is the functional anatomy of GI smooth muscle?
- 8
What is the significance of gap junctions, interstitial cells of Cajal, and pacemaker cells in the functioning of GI smooth muscle?
- 9
How is the basic electrical rhythm (slow wave) generated, how is it regulated by chemical messengers (hormones, paracrine, neurotransmitters), and what causes contractions associated with the slow wave to occur?
- 10
What physiological events in gastric motility occur in the gastric phase?
In this chapter, gastrointestinal (GI) tract physiology when food is in the stomach (i.e., the gastric phase of digestion) will be discussed. This includes gastric function and its regulation, in addition to changes in function that occur in more distal regions of the GI tract. The main functions of the stomach are to act as a temporary reservoir for the meal and to initiate protein digestion through secretion of acid and the enzyme precursor pepsinogen. Other functions are listed in Box 29.1 .
BOX 29.1
Functions of the Stomach
-
Storage—acts as temporary reservoir for the meal
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Secretion of H + to kill microorganisms and convert pepsinogen to its active form
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Secretion of intrinsic factor to absorb vitamin B 12 (cobalamin)
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Secretion of mucus and HCO 3 − to protect the gastric mucosa
-
Secretion of water for lubrication and to provide aqueous suspension of nutrients
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Motor activity for mixing secretions (H + and pepsin) with ingested food
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Coordinated motor activity to regulate the emptying of contents into the duodenum
Food entering the stomach from the esophagus causes mechanical stimulation of the gastric wall via distention and stretching of smooth muscle. Food, predominantly oligopeptides and amino acids, also provides chemical stimulation when present in the gastric lumen. Regulation of gastric function during the gastric phase is dependent on endocrine, paracrine, and neural pathways. These pathways are activated by mechanical and chemical stimuli, which result in intrinsic and extrinsic neural reflex pathways that are important for regulation of gastric function. Afferent neurons that pass from the GI tract to the central nervous system via the vagus nerve (and to a lesser extent to the spinal cord) respond to these mechanical and chemical stimuli and activate parasympathetic outflow.
The endocrine pathways include the release of gastrin, which stimulates gastric acid secretion, and the release of somatostatin, which inhibits gastric secretion. Important paracrine pathways include histamine release, which stimulates gastric acid secretion. The responses elicited by activation of these pathways include both secretory and motor responses; secretory responses include secretion of acid, pepsinogen, mucus, intrinsic factor, gastrin, lipase, and HCO 3 − . Overall, these secretions initiate protein digestion and protect the gastric mucosa. Motor responses (changes in activity of smooth muscle) include inhibition of motility of the proximal part of the stomach (receptive relaxation) and stimulation of motility of the distal part of the stomach, which causes antral peristalsis. These changes in motility play important roles in storage and mixing of the meal with secretions and are also involved in regulating the flow of contents out of the stomach.
Functional Anatomy of the Stomach
The stomach is divided into three regions: the cardia, the corpus (also referred to as the fundus or body ), and the antrum ( Fig. 29.1 ). However, when discussing the physiology of the stomach, it is helpful to think of it as subdivided into two functional regions: the proximal and distal parts of the stomach. The proximal portion of the stomach ( proximal because it is the most cranial) and the distal portion of the stomach (furthest away from the mouth) have quite different functions in the postprandial response to a meal, which will be discussed later.
The lining of the stomach is covered with a columnar epithelium folded into gastric pits; each pit is the opening of a duct into which one or more gastric glands empty ( Fig. 29.2 ). The gastric pits account for a significant fraction of the total surface area of the gastric mucosa. The gastric mucosa is divided into three distinct regions based on the structure of the glands. The small cardiac glandular region, located just below the lower esophageal sphincter (LES), primarily contains mucus-secreting gland cells. The remainder of the gastric mucosa is divided into the oxyntic or parietal (acid-secreting) gland region, located above the gastric notch (equivalent to the proximal part of the stomach), and the pyloric gland region, located below the notch (equivalent to the distal part of the stomach).
The structure of a gastric gland from the oxyntic glandular region is illustrated in Fig. 29.2 . Surface epithelial cells extend slightly into the duct opening. The opening of the gland is called the isthmus and is lined with surface mucous cells and a few parietal cells. Mucous neck cells are located in the narrow neck of the gland. Parietal or oxyntic cells, which secrete HCl and intrinsic factor (involved in absorption of vitamin B 12 ), and chief or peptic cells, which secrete pepsinogens, are located deeper in the gland. Oxyntic glands also contain enterochromaffin-like (ECL) cells that secrete histamine, and D cells that secrete somatostatin. Parietal cells are particularly numerous in glands in the fundus, whereas mucus-secreting cells are more numerous in glands of the pyloric (antral) glandular region. In addition, the pyloric glands contain G cells that secrete the hormone gastrin. The parietal glands are also divided into regions: the neck (mucous neck cells and parietal cells) and the base (peptic/chief and parietal cells). Endocrine cells are scattered throughout the glands.
Gastric Secretion
Gastric secretion is a mixture of secretions from the surface epithelial cells and cells in the gastric glands. One of the most important components is H + , which is secreted against a very large concentration gradient. Thus H + secretion by the parietal mucosa is an energy-intensive process. The cytoplasm of the parietal cell is densely packed with mitochondria, which have been estimated to fill 30% to 40% of the cell’s volume. One major function of H + is conversion of inactive pepsinogen (the major enzyme product of the stomach) to pepsins, which initiate protein digestion in the stomach. Additionally, H + ions are important for preventing invasion and colonization of the gut by bacteria and other pathogens that may be ingested with food. The stomach also secretes significant amounts of HCO 3 − and mucus, which are important for protection of the gastric mucosa against the acidic and peptic luminal environment. The gastric epithelium also secretes intrinsic factor, which is necessary for absorption of vitamin B 12 (cobalamin).
Composition of Gastric Secretions
Gastric secretion consists of inorganic and organic constituents together with water. Among the important components of gastric juice are HCl, salts, pepsins, intrinsic factor, mucus, and HCO 3 − . Secretion of all these components increases after a meal.
Inorganic Constituents of Gastric Secretion
The ionic composition of gastric secretions depends on the rate of secretion. The higher the secretory rate, the higher the concentration of H + ions. At lower secretory rates, [H + ] decreases and [Na + ] increases. [K + ] is always higher in gastric juice than in plasma. Consequently, prolonged vomiting may lead to hypokalemia. At all rates of secretion, Cl − is the major anion of gastric juice. Gastric HCl converts pepsinogens to active pepsins and provides the acid pH at which pepsins are active.
The rate of gastric H + secretion varies considerably among individuals. In humans, basal (unstimulated) rates of gastric H + production typically range from about 1 to 5 mEq/hr. During maximal stimulation, HCl production rises to 6 to 40 mEq/hr. The basal rate is greater at night and lowest in the early morning. The total number of parietal cells in the stomach of normal individuals varies greatly, and this variation is partly responsible for the wide range in basal and stimulated rates of HCl secretion.
Organic Constituents of Gastric Secretions
The predominant organic constituent of gastric secretions is pepsinogen, the inactive proenzyme of pepsin. Pepsins, often collectively called “pepsin,” are a group of proteases secreted by the chief cells of the gastric glands. Pepsinogens are contained in membrane-bound zymogen granules in the chief cells. Zymogen granules release their contents by exocytosis when chief cells are stimulated to secrete ( Table 29.1 ). Pepsinogens are converted to active pepsins by the cleavage of acid-labile linkages. Pepsins also act proteolytically on pepsinogens to form more pepsin. Pepsins are most proteolytically active at pH 3 and below. Pepsins may digest as much as 20% of the protein in a typical meal but are not required for digestion, because their function can be replaced by that of pancreatic proteases. When the pH of the duodenal lumen is neutralized, pepsins are inactivated by the neutral pH.
TABLE 29.1
Stimulation of Chief Cells in the Integrated Response to a Meal
| Stimulant | Source |
|---|---|
| Acetylcholine (ACh) | Enteric neurons |
| Gastrin | G cells in the gastric antrum |
| Histamine | ECL cells in the gastric corpus |
| Cholecystokinin (CCK) | I cells in the duodenum |
| Secretin | S cells in the duodenum |
Intrinsic factor, a glycoprotein secreted by parietal cells of the stomach, is required for normal absorption of vitamin B 12 . Intrinsic factor is released in response to the same stimuli that elicit secretion of HCl by parietal cells.
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