Histology of the Stomach

There are four distinct layers of the gastric wall in human biology: mucosa, sub­mucosa, muscularis propria, and serosa. The inner layer of the stomach is the mucosa, which is lined with columnar epithe­lial cells of various types. Beneath the basement membrane of the epithelial cells is the lamina propria, which contains connective tis­sue, blood vessels, nerve fibers, and inflammatory cells. Beneath the lamina propria is a thin muscle layer called the muscularis mucosa. The epithelium, lamina propria, and muscularis mucosa constitute the mucosa. The epithelium of the gastric mucosa is columnar glandular. A scanning electron micrograph shows a smooth mucosal carpet punctuated by the openings of the gastric glands. The gastric glands, when viewed under a microscope, are lined with different types of epithelial cells, depending upon their location in the stomach. There are also endocrine cells present in the gastric glands that can be seen under a microscope. Progenitor cells at the base of the glands differentiate and replenish sloughed cells on a regular basis. Throughout the stomach, the carpet consists primarily of mucus-secreting surface epithelial cells that extend down into the gland pits for variable distances. These cells also secrete bicarbon­ate and play an important role in protecting the stomach from injury due to acid, pepsin, and/or ingested irritants. In fact, all epithelial cells of the stomach (except the endocrine cells) contain carbonic anhydrase and are capable of producing bicarbonate.

In the cardia, the gastric glands are branched and secrete pri­marily mucus and bicarbonate, but not much acid. In the fun­dus and body, the glands are more tubular and the pits are deep. In human biology, parietal and chief cells are common in these glands. Histamine-secreting enterochromaffin-like (ECL) cells and somatostatin-secreting D cells are also found. Parietal cells se­crete acid and intrinsic factor into the gastric lumen, and bicarbon­ate into the intercellular space. They have a characteristic ultra structural appearance with secretory canaliculi (deep invaginations of the surface membrane), and cytoplasmic tubulovesicles contain­ing the acid-producing apparatus H+/K+-ATPase (proton pump). There are numerous mitochondria that can be seen under a microscope. When the parietal cell is stimulated, the cytoplasmic tubulovesicles fuse with the mem­brane of the secretory canaliculus; when acid production ceases the process is reversed. Arguably, the only truly essential substance pro­duced by the stomach is produced by the parietal cell (i.e., intrinsic factor). Parietal cells tend to occupy the midportion of the gastric glands found in the corpus of the stomach.

Chief cells also called zymogenic cells secrete pepsinogen, which is activated at a pH below 2.5. They tend to be clustered toward the base of the gastric glands and have a low columnar shape. Ultrastructurally, chief cells have the characteristics of protein-synthesizing cells: basal granular endoplasmic reticulum, supranuclear Golgi apparatus, and apical zymogen granules. When stimulated, the chief cells produce two immunologi­cally distinct proenzyme forms of pepsinogen: pepsinogen I and II. These proenzymes are activated in an acidic luminal environment. Chief cells also produce lipase in human biology.

In the antrum, the gastric glands are again more branched and shallow, parietal cells are rare, and gastrin-secreting G cells and somatostatin-secreting D cells are present. A variety of hormone­-secreting cells are present in various proportions throughout the gastric mucosa. Histologic analysis suggests that in the normal stomach, 13% of the epithelial cells are oxyntic cells, 44% are chief (zymogenic cells), 40% are mucous cells, and 3% are endocrine cells. In general terms, the antrum produces gastrin but not acid, and the proximal stomach produces acid but not gas­trin; however, it is important to recognize two facts: (1) the border between the corpus and antrum migrates proximally with age (especially on the lesser curvature side of the stomach), and (2) there are a few parietal cells in the antrum.

Deep to the mucosa is the submucosa, which is rich in branch­ing blood vessels, lymphatics, collagen, various inflammatory cells, autonomic nerve fibers, and ganglion cells of Meissner’s autonomic submucosal plexus. The collagen-rich submucosa gives strength to gastrointestinal anastomoses. The mucosa and submucosa are folded into the grossly visible gastric folds, which tend to flatten out as the stomach becomes distended.

Below the submucosa is the thick muscularis propria, which is also referred to as the muscularis externa, which consists of an incomplete Inner oblique layer, a complete middle circular layer that is continuous with the esophageal circular muscle, and the circular muscle of the pylorus, and a complete outer longitudinal layer that is continuous with the longitudinal layer of the esophagus and duodenum. Within the muscularis propria is the rich network of autonomic ganglia and nerves that make up Auerbach’s myenteric plexus.

The outer layer of the stomach is the serosa, also known as the visceral peritoneum in human biology. This layer provides significant tensile strength to gastric anastomoses. When tumors originating in the mucosa penetrate and breach the serosa, microscopic or gross peritoneal metastases are common, presumably from the shedding of tumor cells which would not have occurred if the serosa had not been penetrated. In this way, the serosa may be thought of as a sort of outer envelope of the stomach.

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