Medical Physiology, 3rd Edition

Functional Anatomy of the Stomach

The mucosa is composed of surface epithelial cells and glands

The basic structure of the stomach wall is similar to that of other regions of the gastrointestinal (GI) tract (see Fig. 41-2); therefore, the wall of the stomach consists of both mucosal and muscle layers. The stomach can be divided, based on its gross anatomy, into three major segments (Fig. 42-1): (1) A specialized portion of the stomach called the cardia is located just distal to the gastroesophageal junction and is devoid of the acid-secreting parietal cells. (2) The body or corpus is the largest portion of the stomach; its most proximal region is called the fundus. (3) The distal portion of the stomach is called the antrum. The surface area of the gastric mucosa is substantially increased by the presence of gastric glands, which consist of a pit, a neck, and a base. These glands contain several cell types, including mucous, parietal, chief, and endocrine cells; endocrine cells also are present in both corpus and antrum. The surface epithelial cells, which have their own distinct structure and function, secrete image and mucus.

image

FIGURE 42-1 Anatomy of the stomach. Shown are the macroscopic divisions of the stomach as well as two progressively magnified views of a section through the wall of the body of the stomach.

Marked cellular heterogeneity exists not only within segments (e.g., glands versus surface epithelial cells) but also between segments of the stomach. For instance, as discussed below, the structure and function of the mucosal epithelial cells in the antrum and body are quite distinct. Likewise, although the smooth muscle in the proximal and distal portions of the stomach appear structurally similar, their functions and pharmacological properties differ substantially.

With increasing rates of secretion of gastric juice, the H+ concentration rises and the Na+ concentration falls

The glands of the stomach typically secrete ~2 L/day of a fluid that is approximately isotonic with blood plasma. As a consequence of the heterogeneity of gastric mucosal function, early investigators recognized that gastric secretion consists of two distinct components: parietal-cell and nonparietal-cell secretion. Accordingly, gastric secretion consists of (1) an Na+-rich basal secretion that originates from nonparietal cells, and (2) a stimulated component that represents a pure parietal-cell secretion that is rich in H+. This model helps to explain the inverse relationship between the luminal concentrations of H+ and Na+ as a function of the rate of gastric secretion (Fig. 42-2). Thus, at high rates of gastric secretion—for example, when gastrin or histamine stimulates parietal cells—intraluminal [H+] is high whereas intraluminal [Na+] is relatively low. At low rates of secretion or in clinical situations in which maximal acid secretion is reduced (e.g., pernicious anemia imageN42-1), intraluminal [H+] is low but intraluminal [Na+] is high.

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FIGURE 42-2 Effect of the gastric secretion rate on the composition of the gastric juice.

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Pernicious Anemia

Contributed by Henry Binder

The close relationship between acid and gastrin release is clearly manifested in individuals with impaired acid secretion. In pernicious anemia, atrophy of the gastric mucosa in the corpus and an absence of parietal cells result in a lack in the secretion of both gastric acid and intrinsic factor (IF). Many patients with pernicious anemia exhibit antibody-mediated immunity against their parietal cells, and many of these patients also produce anti-IF autoantibodies.

Because IF is required for cobalamin absorption in the ileum, the result is impaired cobalamin absorption. In contrast, the antrum is normal. Moreover, plasma gastrin levels are markedly elevated as a result of the absence of intraluminal acid, which normally triggers gastric D cells to release somatostatin (see pp. 868–870); this, in turn, inhibits antral gastrin release (see Box 42-1). Because parietal cells are absent, the elevated plasma gastrin levels are not associated with enhanced gastric acid secretion.

The clinical complications of cobalamin deficiency evolve over a period of years. Patients develop megaloblastic anemia (in which the circulating red blood cells are enlarged), a distinctive form of glossitis, and a neuropathy. The earliest neurological findings are those of peripheral neuropathy, as manifested by paresthesias and slow reflexes, as well as impaired senses of touch, vibration, and temperature. If untreated, the disease will ultimately involve the spinal cord, particularly the dorsal columns, thus producing weakness and ataxia. Memory impairment, depression, and dementia can also result. Parenteral administration of cobalamin reverses and prevents the manifestations of pernicious anemia, but it does not influence parietal cells or restore gastric secretion of either IF or intraluminal acid.

The proximal portion of the stomach secretes acid, pepsinogens, intrinsic factor, bicarbonate, and mucus, whereas the distal part releases gastrin and somatostatin

Corpus

The primary secretory products of the proximal part of the stomach—acid (protons), pepsinogens, and intrinsic factor—are made by distinct cells in glands of the corpus. The two primary cell types in the gastric glands of the body of the stomach are parietal cells and chief cells.

Parietal cells (or oxyntic cells) secrete both acid and intrinsic factor, a glycoprotein that is required for cobalamin (vitamin B12) absorption in the ileum (see pp. 935-937). The parietal cell has a very distinctive morphology (see Fig. 42-1). It is a large triangular cell with a centrally located nucleus, an abundance of mitochondria, intracellular tubulovesicular membranes, and canalicular structures. We discuss H+secretion in the next subchapter and intrinsic factor on page 937.

Chief cells (or peptic cells) secrete pepsinogens, but not acid. These epithelial cells are substantially smaller than parietal cells. A close relationship exists among pH, pepsin secretion, and function. Pepsins are endopeptidases (i.e., they hydrolyze “interior” peptide bonds) and initiate protein digestion by hydrolyzing specific peptide linkages. The basal luminal pH of the stomach is 4 to 6; with stimulation, the pH of gastric secretions is usually reduced to <2. At pH values that are <3, pepsinogens are rapidly activated to pepsins. A low gastric pH also helps to prevent bacterial colonization of the small intestine. imageN42-2

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Gastric pH and Pneumonia

Contributed by Henry Binder

Many patients hospitalized in the intensive care unit (ICU) receive prophylactic anti-ulcer treatments (e.g., proton pump inhibitors, such as omeprazole) that inhibit proton secretion and thereby raise gastric pH. Patients in the ICU who are mechanically ventilated or who have coagulopathies are highly susceptible to hemorrhage from gastric stress ulcers, a complication that can contribute significantly to overall morbidity and mortality. These different anti-ulcer regimens do effectively lessen the risk of developing stress ulcers. However, by raising gastric pH, these agents also lower the barrier to gram-negative bacterial colonization of the stomach. Esophageal reflux and subsequent aspiration of these organisms are common in these very sick patients, many of whom are already immunocompromised or even mechanically compromised by the presence of a ventilator tube. If these bacteria are aspirated into the airway, pneumonia can result. The higher the gastric pH, the greater the risk of pneumonia.

In addition to parietal and chief cells, glands from the corpus of the stomach also contain mucus-secreting cells, which are confined to the neck of the gland (see Fig. 42-1), and five or six endocrine cells. Among these endocrine cells are enterochromaffin-like (ECL) cells, which release histamine.

Antrum

The glands in the antrum of the stomach do not contain parietal cells. Therefore, the antrum does not secrete either acid or intrinsic factor. Glands in the antral mucosa contain chief cells and endocrine cells; the endocrine cells include the so-called G cells and D cells, which secrete gastrin and somatostatin, respectively (see Table 41-1). These two peptide hormones function as both endocrine and paracrine regulators of acid secretion. As discussed in more detail below, gastrin stimulates gastric acid secretion by two mechanisms and is also a major trophic or growth factor for GI epithelial-cell proliferation. As discussed more fully below, somatostatin also has several important regulatory functions, but its primary role in gastric physiology is to inhibit both gastrin release and parietal-cell acid secretion.

In addition to the cells of the gastric glands, the stomach also contains superficial epithelial cells that cover the gastric pits as well as the surface in between the pits. These cells secrete image.

The stomach accommodates food, mixes it with gastric secretions, grinds it, and empties the chyme into the duodenum

In addition to its secretory properties, the stomach also has multiple motor functions. These functions are the result of gastric smooth-muscle activity, which is integrated by both neural and hormonal signals. Gastric motor functions include both propulsive and retrograde movement of food and liquid, as well as a nonpropulsive movement that increases intragastric pressure.

Similar to the heterogeneity of gastric epithelial cells, considerable diversity is seen in both the regulation and contractility of gastric smooth muscle. The stomach has at least two distinct areas of motor activity; the proximal and distal portions of the stomach behave as separate, but coordinated, entities. At least four events can be identified in the overall process of gastric filling and emptying: (1) receiving and providing temporary storage of dietary food and liquids; (2) mixing food and water with gastric secretory products, including pepsin and acid; (3) grinding food so that particle size is reduced to enhance digestion and to permit passage through the pylorus; and (4) regulating the exit of retained material from the stomach into the duodenum (i.e., gastric emptying of chyme) in response to various stimuli.

The mechanisms by which the stomach receives and empties liquids and solids are significantly different. Emptying of liquids is primarily a function of the smooth muscle of the proximal part of the stomach, whereas emptying of solids is regulated by antral smooth muscle.