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. 28-1). 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 (called 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.

Figure 28-1 The three functional regions of the stomach. The regions have different luminal secretions and patterns of smooth muscle activity indicative of their unique functions in response to food.

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. 28-2). 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).

Figure 28-2 Representation of the structure of the gastric mucosa showing a section through the wall of the stomach (A) and detail of the structure of gastric glands and cell types in the mucosa (B).

The structure of a gastric gland from the oxyntic glandular region is illustrated in Figure 28-2. 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 B₁₂), and chief or peptic cells, which secrete pepsinogens, are located deeper in the gland. Oxyntic glands also contain enterochromaffin-like (ECL) cells, which secrete histamine, and D cells, which 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, which secrete the hormone gastrin. The parietal glands can also be 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

The fluid secreted into the stomach is called gastric juice. Gastric juice is a mixture of the secretions of the surface epithelial cells and the secretions of gastric glands. One of the most important components of gastric juice is H⁺, a secretion that occurs in the face of 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, 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 HCO₃⁻ and mucus, important for protection of the gastric mucosa against the acidic and peptic luminal environment. However, in a healthy human the only gastric secretion required is intrinsic factor, which is necessary for the absorption of vitamin B₁₂ (cobalamin). The functions of other components of gastric juice are redundant with secretions provided more distally in the GI tract.

Cellular Mechanisms of Gastric Acid Secretion

Parietal cells have a distinctive ultrastructure (Fig. 28-3). Branching secretory canaliculi course through the cytoplasm and are connected by a common outlet to the cell’s luminal surface. Microvilli line the surfaces of the secretory canaliculi. The cytoplasm of unstimulated parietal cells contains numerous tubules and vesicles, which is called the tubulovesicular system. The membranes of tubulovesicles contain the transport proteins responsible for secretion of H⁺ and Cl⁻ into the lumen of the gland. When parietal cells are stimulated to secrete HCl (Fig. 28-3), tubulovesicular membranes fuse with the plasma membrane of the secretory canaliculi. This extensive membrane fusion greatly increases the number of H⁺-K⁺ antiporters in the plasma membrane of the secretory canaliculi. When parietal cells secrete gastric acid at the maximal rate, H⁺ is pumped against a concentration gradient that is about 1 million—fold. Thus, the pH is 7 in the parietal cell cytosol and 1 in the lumen of the gastric gland.

Figure 28-3 Parietal cell ultrastructure. A, A resting parietal cell showing the tubulovesicular apparatus in the cytoplasm and the intracellular canaliculus. B, An activated parietal cell that is secreting acid. The tubulovesicles have fused with the membranes of the intracellular canaliculus, which is now open to the lumen of the gland and lined with abundant long microvilli.

The cellular mechanism of H⁺ secretion by the parietal cell is depicted in Figure 28-4. Cl⁻ enters the cell across the basolateral membrane in exchange for HCO₃⁻ generated in the cell by the action of carbonic anhydrase, which produces HCO₃⁻ and H⁺. H⁺ is secreted across the luminal membrane by H⁺,K⁺-ATPase in exchange for K⁺. Cl⁻ enters the lumen via an ion channel (a ClC Cl⁻ channel) located in the luminal membrane. Increased intracellular Ca⁺⁺ and cAMP stimulate luminal membrane conduction of Cl⁻ and K⁺. Increased K⁺ conductance hyperpolarizes the luminal membrane potential, which increases the driving force for efflux of Cl⁻ across the luminal membrane. The K⁺ channel in the basolateral membrane also mediates the efflux of K⁺ that accumulates in the parietal cell via the activity of H⁺,K⁺-ATPase. In addition, cAMP and Ca⁺⁺ promote the trafficking of Cl⁻ channels into the luminal membrane and the fusion of cytosolic tubulovesicles containing H⁺,K⁺-ATPase with the membrane of the secretory canaliculi (Figs. 28-3 and 28-4). Parietal cell secretion of H⁺is also accompanied by transport of HCO₃⁻ into the bloodstream to maintain intracellular pH.

Figure 28-4 Mechanism of H⁺ and Cl⁻ secretion by an activated parietal cell in the gastric mucosa.

< div class='tao-gold-member'>

Only gold members can continue reading. Log In or Register to continue

Stay updated, free articles. Join our Telegram channel

Join