Stomach
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Chapter 49 Stomach David M. Mahvi, Seth B. Krantz ANATOMY PHYSIOLOGY PPEPTIC ULCER DISEASE STRESS GASTRITIS POSTGASTRECTOMY SYNDROMES GASTRIC CANCER OTHER GASTRIC LESIONS Anatomy Gross Anatomy Divisions The stomach begins as a dilation in the tubular embryonic foregut during the fifth week of gestation. By the seventh week, it descends, rotates, and further dilates with…
Thoracic Key
Blood Supply

The celiac artery provides most of the blood supply to the stomach (Fig. 49-2). There are four main arteries—the left and right gastric arteries along the lesser curvature and the left and right gastroepiploic arteries along the greater curvature. In addition, a substantial quantity of blood may be supplied to the proximal stomach by the inferior phrenic arteries and by the short gastric arteries from the spleen. The largest artery to the stomach is the left gastric artery, and it is not uncommon (15% to 20%) for an aberrant left hepatic artery to originate from it. Consequently, proximal ligation of the left gastric artery occasionally results in acute left-sided hepatic ischemia. The right gastric artery arises from the hepatic artery (or the gastroduodenal artery). The left gastroepiploic artery originates from the splenic artery and the right gastroepiploic originates from the gastroduodenal artery. The extensive anastomotic connection between these major vessels ensures that in most cases, the stomach will survive if three out of four arteries are ligated, provided that the arcades along the greater and lesser curvatures are not disturbed. In general, the veins of the stomach parallel the arteries. The left gastric (coronary) and right gastric veins usually drain into the portal vein. The right gastroepiploic vein drains into the superior mesenteric vein and the left gastroepiploic vein drains into the splenic vein.

Lymphatic Drainage

The lymphatic drainage of the stomach parallels the vasculature and drains into four zones of lymph nodes (Fig. 49-3). The superior gastric group drains lymph from the upper lesser curvature into the left gastric and paracardial nodes. The suprapyloric group of nodes drains the antral segment on the lesser curvature of the stomach into the right suprapancreatic nodes. The pancreaticolienal group of nodes drains lymph high on the greater curvature into the left gastroepiploic and splenic nodes. The inferior gastric and subpyloric group of nodes drains lymph along the right gastroepiploic vascular pedicle. All four zones of lymph nodes drain into the celiac group and into the thoracic duct. Although these lymph nodes drain different areas of the stomach, gastric cancers may metastasize to any of the four nodal groups, regardless of the cancer location. In addition, the extensive submucosal plexus of lymphatics accounts for the fact that there is frequently microscopic evidence of malignant cells several centimeters from gross disease.

Gastric Microscopic Anatomy

Gastric mucosa consists of columnar glandular epithelia. The cellular populations (and functions) of the cells forming this glandular epithelium vary based on their location in the stomach (Table 49-1). The glandular epithelium is divided into cells that secrete products into the gastric lumen for digestion (parietal cells, chief cells, mucus-secreting cells) and cells that control function (gastrin-secreting G cells, somatostatin-secreting D cells) cells. In the cardia, the mucosa is arranged in branched glands and the pits are short. In the fundus and body, the glands are more tubular and the pits are longer. In the antrum, the glands are more branched. The luminal ends of the gastric glands and pits are lined with mucus-secreting surface epithelial cells, which extend down into the necks of the glands for variable distances. In the cardia, the glands are predominantly mucus-secreting. In the body, the glands are mostly lined from the neck to the base with parietal and chief cells (Fig. 49-5). There are a few parietal cells in the fundus and proximal antrum, but none in the cardia or prepyloric antrum. The endocrine G cells are present in greatest quantity in the antral glands.

Table 49-1 Gastric Cell Types, Location, and Function

Gastrin

Gastrin is produced by G cells located in the gastric antrum (see Table 49-1). It is synthesized as a prepropeptide and undergoes post-translational processing to produce biologically reactive gastrin peptides. Several molecular forms of gastrin exist. G-34 (big gastrin), G-17 (little gastrin), and G-14 (minigastrin) have been identified. However, 90% of antral gastrin is released as the 17–amino acid peptide, although G-34 predominates in the circulation because its metabolic half-life is longer than that of G-17. The pentapeptide sequence contained at the carboxyl terminus of gastrin is the biologically active component and is identical to that found on another gut peptide, CCK. CCK and gastrin differ by tyrosine sulfation sites. The release of gastrin is stimulated by food components in a meal, especially protein digestion products. Luminal acid inhibits the release of gastrin. In the antral location, somatostatin and gastrin release are functionally linked, and an inverse reciprocal relationship exists between these two peptides.1

Gastrin is the major hormonal regulator of the gastric phase of acid secretion following a meal. Histamine, released from enterochromaffin-like (ECL) cells, is also a potent stimulant of acid release from the parietal cell. Gastrin also has considerable trophic effects on the parietal cells and gastric ECL cells. Prolonged hypergastrinemia from any cause leads to mucosal hyperplasia and an increase in the number of ECL cells and, under some circumstances, is associated with the development of gastric carcinoid tumors.2

The detection of hypergastrinemia may suggest a pathologic state of acid hypersecretion but generally is the result of treatment with agents to lower acid secretion, such as proton pump inhibitors. Table 49-2 lists common causes of chronic hypergastrinemia. Hypergastrinemia that results from the administration of acid-lowering drugs is an appropriate response caused by loss of feedback inhibition of gastrin release by luminal acid. Lack of acid causes a reduction in somatostatin release, which in turn causes increased release of gastrin from antral G cells. Hypergastrinemia can also occur in the setting of pernicious anemia or uremia, or following surgical procedures such as vagotomy or retained gastric antrum after gastrectomy. In contrast, gastrin levels increase inappropriately in patients with gastrinoma (Zollinger-Ellison syndrome [ZES]). These gastrin-secreting tumors are not located in the antrum and secrete gastrin autonomously.

Table 49-2 Causes of Hypergastrinemia

Activation and Secretion by the Parietal Cell

The two second messengers principally involved in stimulation of acid secretion by parietal cells are intracellular cyclic AMP (cAMP) and calcium. Synthesis of these two messengers in turn activates protein kinases and phosphorylation cascades. The intracellular events following ligand binding to receptors on the parietal cell are shown in Figure 49-7. Histamine causes an increase in intracellular cAMP, which activates protein kinases to initiate a cascade of phosphorylation events that culminate in activation of H+, K+-ATPase. In contrast, acetylcholine and gastrin stimulate phospholipase C, which converts membrane-bound phospholipids into inositol triphosphate (IP3) to mobilize calcium from intracellular stores. Increased intracellular calcium activates other protein kinases that ultimately activate H+, K+-ATPase in a similar fashion to initiate the secretion of hydrochloric acid.

H+, K+-ATPase is the final common pathway for gastric acid secretion by the parietal cell. It is composed of two subunits, a catalytic α-subunit (100 kDa) and a glycoprotein β-subunit (60 kDa). During the resting, or nonsecreting, state, gastric parietal cells store H+, K+-ATPase within intracellular tubulovesicular elements. Cellular relocation of the proton pump subunits through cytoskeletal rearrangements must occur in order for acid secretion to increase in response to stimulatory factors. The subsequent insertion and heterodimer assembly of the H+, K+-ATPase subunits into the microvilli of the secretory canaliculus causes an increase in gastric acid secretion. A KCl efflux pathway must exist to supply potassium to the extracytoplasmic side of the pump. Cytosolic hydrogen is secreted by H+, K+-ATPase in exchange for extracytoplasmic potassium (see Fig. 49-7), which is an electroneutral exchange and therefore does not contribute to the transmembrane potential difference across the parietal cell. Secretion of chloride is accomplished through a chloride channel moving chloride from the parietal cell cytoplasm to the gastric lumen. The secretion or exchange of hydrogen for potassium, however, does require energy in the form of adenosine triphosphate (ATP) because hydrogen is being secreted against a gradient of more than a million-fold. Because of this large energy requirement, the parietal cell also has the largest mitochondrial content of any mammalian cell, with a mitochondrial compartment representing 34% of its cell volume. In response to a secretagogue, the parietal cell undergoes a conformational change, and a several-fold increase in the canalicular surface area occurs (Fig. 49-8). In contrast to stimulated acid secretion, cessation of acid secretion requires endocytosis of H+, K+-ATPase, with regeneration of cytoplasmic tubulovesicles containing the subunits, and this occurs through a tyrosine-based signal. The tyrosine-containing sequence is located on the cytoplasmic tail of the β-subunit and is highly homologous to the motif responsible for internalization of the transferrin receptor.

More than 1 billion parietal cells are found in the normal human stomach and are responsible for secreting about 20 mmol/hr of hydrochloric acid in response to a protein meal. Each individual parietal cell secretes 3.3 billion hydrogen ions/second, and there is a linear relationship between maximal acid output and parietal cell number. However, gastric acid secretory rates may be altered in patients with upper gastrointestinal (GI) disease. For example, gastric acid is often increased in patients with duodenal ulcer or gastrinoma, whereas it is decreased in patients with pernicious anemia, gastric atrophy, gastric ulcer, or gastric cancer. The lower secretory rates observed in gastric ulcer patients are typically for proximal gastric ulcers, whereas distal, antral, or prepyloric ulcers are associated with acid secretory rates similar to those in duodenal ulcer patients.

Gastric acid thus plays a critical role in the digestion of a meal. It is required to convert pepsinogen into pepsin, elicits the release of secretin from the duodenum, and limits colonization of the upper GI tract with bacteria.