In addition to mucus-secreting cells that line the entire surface of the stomach, the stomach mucosa has two important types of tubular glands: oxyntic glands (also called gastric glands) and pyloric glands. The oxyntic (acid-forming) glands secrete hydrochloric acid, pepsinogen, intrinsic factor, and mucus. The pyloric glands secrete mainly mucus for protection of the pyloric mucosa from the stomach acid. They also secrete the hormone gastrin.
The oxyntic glands are located on the inside surfaces of the body and fundus of the stomach—the proximal 80 percent of the stomach. The pyloric glands are located in the antral portion of the stomach—the distal 20 percent of the stomach.
Secretions from the Oxyntic (Gastric) Glands
A typical stomach oxyntic gland is shown in Figure 1. It is composed of three types of cells: (1) mucous neck cells, which secrete mainly mucus; (2) peptic (or chief) cells, which secrete large quantities of pepsinogen; and (3) parietal (or oxyntic) cells, which secrete hydrochloric acid and intrinsic factor. Secretion of hydrochloric acid by the parietal cells involves special mechanisms, as follows.
Fig1. Oxyntic gland from the body of the stomach.
Basic Mechanism of Hydrochloric Acid Secretion. When stimulated, the parietal cells secrete an acid solution that contains about 160 mmol/L of hydrochloric acid, which is nearly isotonic with the body fluids. The pH of this acid is about 0.8, demonstrating its extreme acidity. At this pH, the hydrogen ion concentration is about 3 million times that of the arterial blood. To concentrate the hydrogen ions this tremendous amount requires more than 1500 calories of energy per liter of gastric juice. At the same time that hydrogen ions are secreted, bicarbonate ions diffuse into the blood so that gastric venous blood has a higher pH than arterial blood when the stomach is secreting acid.
Figure 2 shows schematically the functional structure of a parietal cell (also called an oxyntic cell), demonstrating that it contains large branching intracellular canaliculi. The hydrochloric acid is formed at the villus-like projections inside these canaliculi and is then conducted through the canaliculi to the secretory end of the cell.
Fig2. Schematic anatomy of the canaliculi in a parietal (oxyntic) cell.
The main driving force for hydrochloric acid secretion by the parietal cells is a hydrogen-potassium pump (H+-K+ adenosine triphosphatase [ATPase]). The chemical mechanism of hydrochloric acid formation is shown in Figure 3 and consists of the following steps:
1. Water inside the parietal cell becomes dissociated into H+ and hydroxide (OH−) in the cell cytoplasm. The H+ is then actively secreted into the canaliculus in exchange for K+, an active exchange process that is catalyzed by H+-K+ ATPase. Potassium ions trans ported into the cell by the sodium Na+-K+ ATPase pump on the basolateral (extracellular) side of the membrane tend to leak into the lumen but are recycled back into the cell by the H+-K+ ATPase. The basolateral Na+-K+ ATPase creates low intracellular Na+, which contributes to Na+ reabsorption from the lumen of the canaliculus. Thus, most of the K+ and Na+ in the canaliculus is reabsorbed into the cell cytoplasm, and hydrogen ions take their place in the canaliculus.
2. The pumping of H+ out of the cell by the H+-K+ ATPase permits OH− to accumulate and form bicarbonate (HCO3−) from CO2, either formed during metabolism in the cell or while entering the cell from the blood. This reaction is catalyzed by carbonic anhydrase. The HCO3− is then transported across the basolateral membrane into the extracellular fluid in exchange for chloride ions, which enter the cell and are secreted through chloride channels into the canaliculus, giving a strong solution of hydrochloric acid in the canaliculus. The hydrochloric acid is then secreted outward through the open end of the canaliculus into the lumen of the gland.
3. Water passes into the canaliculus by osmosis because of extra ions secreted into the canaliculus. Thus, the final secretion from the canaliculus contains water, hydrochloric acid at a concentration of about 150 to 160 mEq/L, potassium chloride at a concentration of 15 mEq/L, and a small amount of sodium chloride.
To produce a concentration of hydrogen ions as great as that found in gastric juice requires minimal backleak into the mucosa of the secreted acid. A major part of the stomach’s ability to prevent backleak of acid can be attributed to the gastric barrier due to the formation of alkaline mucus and to tight junctions between epithelia cells, as described later. If this barrier is damaged by toxic sub stances, such as occurs with excessive use of aspirin or alcohol, the secreted acid does leak down an electro chemical gradient into the mucosa, causing stomach mucosal damage.
The Basic Factors That Stimulate Gastric Secretion Are Acetylcholine, Gastrin, and Histamine. Acetyl choline released by parasympathetic stimulation excites secretion of pepsinogen by peptic cells, hydrochloric acid by parietal cells, and mucus by mucous cells. In comparison, both gastrin and histamine strongly stimulate secretion of acid by parietal cells but have little effect on the other cells.
Secretion and Activation of Pepsinogen. Several slightly different types of pepsinogen are secreted by the peptic and mucous cells of the gastric glands, but all the pepsinogens perform the same basic functions.
When pepsinogen is first secreted, it has no digestive activity. However, as soon as it comes in contact with hydrochloric acid, it is activated to form active pepsin. In this process, the pepsinogen molecule, having a molecular weight of about 42,500, is split to form a pepsin molecule, having a molecular weight of about 35,000.
Pepsin functions as an active proteolytic enzyme in a highly acidic medium (optimum pH 1.8 to 3.5), but above a pH of about 5 it has almost no proteolytic activity and becomes completely inactivated in a short time. Hydrochloric acid is as necessary as pepsin for protein digestion in the stomach, as discussed in Chapter 66.
Secretion of Intrinsic Factor by Parietal Cells. The substance intrinsic factor, which is essential for absorption of vitamin B12 in the ileum, is secreted by the parietal cells along with the secretion of hydrochloric acid. When the acid-producing parietal cells of the stomach are destroyed, which frequently occurs in persons with chronic gastritis, not only does achlorhydria (lack of stomach acid secretion) develop, but pernicious anemia also often develops because of failure of maturation of the red blood cells in the absence of vitamin B12 stimulation of the bone marrow. This condition is discussed in detail in Chapter 33.
