O B J E C T I V E S
• Identify the secretory products of the stomach, their cells of origin, and their functions.
• Understand the mechanisms making it possible for the stomach to secrete 150 mN hydrochloric acid.
• Describe the electrolyte composition of gastric secre- tion and how it varies with the rate of secretion.
• Identify the major stimulants of the parietal cell and explain their interactions.
• Discuss the phases involved in the stimulation of gas- tric acid secretion and the processes acting in each.
• Identify factors that both stimulate and inhibit the release of the hormone gastrin.
• Explain the processes that result in the inhibition of gastric acid secretion following the ingestion of a meal and its emptying from the stomach.
• Describe the processes resulting in gastric and duode- nal ulcer diseases.
Gastric Secretion
8
Five constituents of gastric juice—intrinsic factor, hydro- gen ion (H+), pepsin, mucus, and water—have physi- ologic functions. They are secreted by the various cells present within the gastric mucosa. The only indispensable ingredient in gastric juice is intrinsic factor, required for the absorption of vitamin B12 by the ileal mucosa. Acid is necessary for the conversion of inactive pepsinogen to the enzyme pepsin. Acid and pepsin begin the digestion of pro- tein, but in their absence pancreatic enzymes hydrolyze all ingested protein, so no nitrogen is wasted in the stools. Acid also kills a large number of bacteria that enter the stomach, thereby reducing the number of organisms reaching the intestine. In cases of severely reduced or absent acid secre- tion, the incidence of intestinal infections is greater. Mucus lines the wall of the stomach and protects it from damage.
Mucus acts primarily as a lubricant, protecting the mucosa from physical injury. Together with bicarbonate (HCO3−), mucus neutralizes acid and maintains the surface of the mucosa at a pH near neutrality. This is part of the gastric mucosal barrier that protects the stomach from acid and pepsin digestion. Water acts as the medium for the action of acid and enzymes and solubilizes many of the constitu- ents of a meal.
Gastric juice and many of its functions originally were described by a young army surgeon, William Beaumont, stationed at a fort on Mackinac Island in northern Michigan. Beaumont was called to treat a
French Canadian, Alexis St. Martin, who had been acci- dentally shot in the side at close range with a shotgun.
St. Martin unexpectedly survived but was left with a per- manent opening into his stomach from the outside (gas- tric fistula). The accident occurred in 1822, and during the ensuing 3 years Beaumont nursed St. Martin back to health. Beaumont retained St. Martin “for the purpose of making physiological experiments,” which were begun in 1825. Beaumont’s observations and conclusions, many of which remain unchanged today, include the description of the juice itself and its digestive and bacteriostatic func- tions, the identification of the acid as hydrochloric, the realization that mucus was a separate secretion, the reali- zation that mental disturbances affected gastric function, a direct study of gastric motility, and a thorough study of the ability of gastric juices to digest various foodstuffs.
63 CHAPTER 8 Gastric Secretion
The gastric mucosa is composed of pits and glands (Fig. 8.2). The pits and surface itself are lined with mucous or surface epithelial cells. At the base of the pits are the openings of the glands, which project into the mucosa toward the outside or serosa. The oxyntic glands contain the acid-producing parietal cells and the peptic or chief cells, which secrete the enzyme precursor pepsinogen.
Pyloric glands contain the gastrin-producing G cells and mucous cells, which also produce pepsinogen. Mucous neck cells are present where the glands open into the pits.
Each gland contains a stem cell in this region. These cells divide; one daughter cell remains anchored as the stem cell, and the other divides several times. The resulting new cells migrate both to the surface, where they differentiate into mucous cells, and down into the glands, where they become parietal cells in the oxyntic gland area. Endocrine cells such as the G cells also differentiate from stem cells.
Peptic cells are capable of mitosis, but evidence indicates that they also can arise from stem cells during the repair of damage to the mucosa. Cells of the surface and pits are replaced much more rapidly than are those of the glands.
The parietal cells secrete hydrochloric acid (HCl) and, in humans, intrinsic factor. In some species the chief cells also secrete intrinsic factor. The normal human stomach con- tains approximately 1 billion parietal cells, which produce acid at a concentration of 150 to 160 mEq/L. The number of parietal cells determines the maximal secretory rate and accounts for interindividual variability. The human stom- ach secretes 1 to 2 L of gastric juice per day. Because the pH of the final juice at high rates of secretion may be less than 1 and that of the blood is 7.4, the parietal cells must expend a large amount of energy to concentrate H+. The energy for the production of this more than a million-fold concentra- tion gradient comes from adenosine triphosphate (ATP), which is produced by the numerous mitochondria located within the cell (Fig. 8.3).
During the resting state, the cytoplasm of the parietal cells is dominated by numerous tubulovesicles. There is
also an intracellular canaliculus that is continuous with the lumen of the oxyntic gland. The tubulovesicles contain the enzymes carbonic anhydrase (CA) and H+, potassium (K+)-ATPase (H+,K+-ATPase), necessary for the production and secretion of acid, on their apical membranes. Thus in the resting parietal cell, any basal secretion is directed into the lumen of the tubulovesicles and not into the cytoplasm of the cell. Stimulation of acid secretion causes the migra- tion of the tubulovesicles and their incorporation into the membrane of the canaliculus as microvilli. As a result, the surface area of the canaliculus is greatly expanded to occupy much of the cell. The activities of the enzymes, which are now in the canalicular membrane, increase significantly during acid secretion. Acid secretion begins within 10 min- utes of administering a stimulant. This lag time probably Lower esophageal
sphincter Fundus
Body Antrum
Pylorus
Pyloric gland mucosa
Oxyntic gland mucosa
Fig. 8.1 Areas of the stomach.
Gastric lumen Mucus
Superficial epithelial cells
Mucous neck cells
Parietal cells
Peptic cells
Muscularis mucosae Fig. 8.2 Oxyntic gland and surface pit. Note the positions of the various cell types.
64 CHAPTER 8 Gastric Secretion
A
Tubulovesicles
Mitochondria
Secretory canaliculus
Microvilli
Nucleus
B
Fig. 8.3 Parietal cell. (A) Electron photomicrograph. (B) Schematic. ([A] Courtesy Dr. Bruce MacKay.)
65 CHAPTER 8 Gastric Secretion
is expended in the morphologic conversion and enzyme activations described previously. Following the removal of stimulation, the tubulovesicles reform and the canaliculus regains its resting configuration.
The surface epithelial mucous cells are recognized pri- marily by the large number of mucous granules at their apical surfaces. During secretion, the membranes of the granules fuse with the cell membrane and expel mucus.
Peptic cells contain a highly developed endoplasmic reticulum for the synthesis of pepsinogen. The proenzyme is packaged into zymogen granules by the numerous Golgi structures within the cytoplasm. The zymogen granules migrate to the apical surface, where, during secretion, they empty their contents into the lumen by exocytosis.
This entire procedure of enzyme synthesis, packaging, and secretion is discussed in greater detail in Chapter 9.
Endocrine cells of the gut also contain numerous gran- ules. Unlike in the peptic and mucous cells, however, these hormone-containing granules are located at the base of the cell. The hormones are secreted into the intercellular space, from which they diffuse into the capillaries. The endocrine cells have numerous microvilli extending from their apical surface into the lumen. Presumably the microvilli contain receptors that sample the luminal contents and trigger hor- mone secretion in response to the appropriate stimuli.