Figure 1612

Diagram of an enteroendocrine cell. This cell is drawn to show that it does not reach the epithelial surface. The secretory granules are regularly lost during routine preparation. Because of the absence of other distinctive organelles, the nucleus appears to be surrounded by a small amount of clear cytoplasm in H & E-stained sections. (Based on Ito S, Winchester RJ. The fine structure of the gastric mucosa of the bat. J Cell Biol 1963;16:574.)

Achlorhydria is a condition characterized by the absence of parietal cells. Consequently, intrinsic factor is not secreted, thereby leading to pernicious anemia. Lack of intrinsic factor is the most common cause of vitamin Bl2 deficiency. However, other factors such as Gram-negative anaerobic bacterial overgrowth in the small intestine are associated with B12 deficiency. These bacteria bind to the vitamin B,2—intrinsic factor complex, preventing Its absorption. Parasitic tapeworm infections also produce clinical symptoms of pernicious anemia. Because the liver has extensive reserve stores of vitamin Bl2, the disease is often not recognized until long after significant changes in the gastric mucosa have taken place.

Another cause of reduced secretion of intrinsic factor and subsequent pernicious anemia is the loss of gastric epithelium because of chronic or recurrent peptic ulcer disease. Often, even healed ulcerated regions produce insufficient intrinsic factor. Repeated loss of epithelium and consequent scarring of the gastric mucosa can significantly reduce the amount of functional mucosa.

Histamine H2 receptor antagonist drugs (e.g., Zantac and Tagamet), which block attachment of histamine to its receptors in the gastric mucosa, suppress both acid and intrinsic factor production and have been used extensively in the treatment of peptic ulcers. They prevent further mucosal erosion and promote healing of the previously eroded surface. However, long-term use can cause vitamin B|2 deficiency. Recently, new proton pump inhibitors (e.g., Omeprazole and Lansoprazole) have been designed that inhibit the H 7K+-ATPase. They suppress acid production in the parietal cells and do not affect intrinsic factor secretion.

Although it was generally thought that the parietal cells are the direct target of the H, receptor antagonist drugs, recent evidence from a combination of in situ hybridization histochemistry and antibody staining has unexpectedly revealed that the immunoglobulin A (IgA)-secretlng plasma cells and some of the macrophages in the lamina propria display a positive reaction for gastrin receptor mRNA, not the parietal cells. These findings Indicate that the agents used to treat peptic ulcers may act directly on plasma cells and/or macrophages and that these cells then transmit their effects to the parietal cells to inhibit HCI secretion. The factor that mediates the interaction between the connective tissue cells and the epithelial cells has not been elucidated.

Recent evidence, however, suggests that most common peptic ulcers (95%) are actually caused by a chronic infection of the gastric mucosa by the bacterium Helicobacterium pylori. Lipopolysac-charide antigens are expressed on its surface that mimic those on human gastric epithelial cells. The mimicry appears to cause an initial immunologic tolerance to the pathogen by the host immune system, thus helping to enhance the infection and ultimately causing the production of antibodies. These antibodies against H. pylori bind to the gastric mucosa and cause damage to the mucosal cells. Treatment includes antibiotic eradication of the bacteria. These treatments for ulcerative disease have made the common surgical interventions of the past infrequent.


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