In humans, intrinsic factor is secreted by the parietal cells (chief cells do so in some other species). Its secretion is stimulated by the same receptors that stimulate gastric acid secretion. Intrinsic factor is a 44-kilodalton glycoprotein that complexes with vitamin B12 in the stomach and duodenum, a step necessary for subsequent absorption of the vitamin in the ileum. Autoantibodies directed against intrinsic factor or parietal cells themselves lead to an intrinsic factor deficiency, resulting in malabsorption of vitamin B12 and pernicious anemia (see Folder 17.1).
 FOLDER 17.2
Clinical Correlation: Zollinger-Ellison Syndrome
Excessive secretion of gastrin usually has its origin in a tumor of the gastrin-producing enteroendocrine cells located in the duodenum or in the pancreatic islet. This condition, known as the Zollinger-Ellison syndrome or gastrinomas, is characterized by excessive secretion of hydrochloric acid by continuously stimulated parietal cells. The excess acid cannot be adequately neutralized in the duodenum, thereby leading to gastric and duodenal ulcers. Gastric ulcers are present in 95% of patients with this syndrome and are six times more prevalent than the duodenal ulcers. Patients with Zollinger-Ellison syndrome may experience intermittent abdominal pain, diarrhea, and steatorrhea (excretion of stool containing a large amount of fat). Patients without symptoms who have severe ulceration of the stomach and small intestine, especially if they fail to respond to conventional treatment, should be also suspected of having a tumor that is producing excess gastrin. Treatment of Zollinger-Ellison syndrome in the past involved blockage of the parietal cell membrane receptors that stimulate HCl production. Recently, proton pump inhibitors have become the treatment of choice in managing HCl hypersecretion. In addition, surgical excision of the tumor, when possible, removes the source of gastrin production and alleviates symptoms.
FIGURE 17.11 • Diagram of parietal cell HCl synthesis. After parietal cell stimulation, several steps occur leading to the production of HCl. Carbon dioxide (CO2) from the blood diffuses across the basement membrane into the cell to form H2CO3. The H2CO3 dissociates into H and HCO3 . The reaction is catalyzed by carbonic anhydrase, which leads to the production of H ions in the cytoplasm, which are then transported across the membrane to the lumen of the intracellular canaliculus by a H/K-ATPase proton pump. Simultaneously, K within the canaliculus is transported into the cell in exchange for the H ions. Cl ions are also transported from the cytoplasm of the parietal cell into the lumen of the canaliculus by Cl channels in the membrane. HCl is then formed from H and Cl. The HCO3 / Cl anion channels maintain the normal concentration of both ions in the cell, as well as Na/K-ATPase on the basolateral cell membrane.
Enteroendocrine cells secrete their products into either Most of them represent small cells that rest on the basal lamina the lamina propria or underlying blood vessels. and do not always reach the lumen; they are known as enteroendocrine “closed” cells (Fig. 17.12ab and Plate 57,
Enteroendocrine cells are found at every level of the fundic page 612). Some, however, have a thin cytoplasmic extension gland, although they tend to be somewhat more prevalent in the bearing microvilli that are exposed to the gland lumen base (Folder 17.3). In general, two types of enteroendocrine (Fig 17.12c); these are referred as enteroendocrine cells can be distinguished throughout the gastrointestinal tract.
 FOLDER 17.3
Functional Considerations: The Gastrointestinal Endocrine System