Chapter 49 – Stomach

1182 CHAPTER 49 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 a disproportionate elongation of the greater curvature into its normal anatomic shape and position. Following birth, it is the most proximal abdominal organ of the alimentary tract. The most proximal region of the stomach is called the cardia, which attaches to the esophagus. Immediately proximal to the cardia is a physiologi- cally competent lower esophageal sphincter. Distally, the pylorus connects the distal stomach (antrum) to the proximal duode- num. Although the stomach is fixed at the gastroesophageal (GE) junction and pylorus, its large midportion is mobile. The fundus represents the superiormost part of the stomach and is floppy and distensible. The stomach is bounded superiorly by the diaphragm and laterally by the spleen. The body of the stomach represents the largest portion and is also referred to as the corpus. The body also contains most of the parietal cells and is bounded on the right by the relatively straight lesser curvature and on the left by the longer greater curvature. At the angularis incisura, the lesser curvature abruptly angles to the right. It is here that the body of the stomach ends and the antrum begins. Another important anatomic angle (angle of His) is that formed by the fundus with the left margin of the esophagus (Fig. 49-1). Most of the stomach resides within the upper abdomen. The left lateral segment of the liver covers a large portion of the stomach anteriorly. The diaphragm, chest, and abdominal wall bound the remainder of the stomach. Inferiorly, the stomach is attached to the transverse colon, spleen, caudate lobe of the liver, diaphragmatic crura, and retroperitoneal nerves and vessels. Superiorly, the GE junction is found about 2 to 3 cm below the diaphragmatic esophageal hiatus in the horizontal plane of the seventh chondrosternal articulation, a plane only slightly cepha- lad to that containing the pylorus. The gastrosplenic ligament attaches the proximal greater curvature to the spleen. 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 addi- tion, 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 gastro- duodenal artery). The left gastroepiploic artery originates from the splenic artery and the right gastroepiploic originates from the gastroduodenal artery. The extensive anastomotic connec- tion 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 gastroepi- ploic 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 cur- vature into the left gastric and paracardial nodes. The suprapy- loric 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 exten- sive submucosal plexus of lymphatics accounts for the fact that anatomy physiology ppeptic ulcer disease stress gastritis postgastrectomy syndromes gastric cancer other gastric lesions STOMACH David M. Mahvi and Seth B. Krantz Stomach  Chapter 49  1183 SECTIO N X aB D o m EN in the floor of the fourth ventricle and traverses the neck in the carotid sheath to enter the mediastinum, where it divides into several branches around the esophagus. These branches coalesce above the esophageal hiatus to form the left and right vagus nerves. It is not uncommon to find more than two vagal trunks at the distal esophagus. At the GE junction, the left vagus is anterior, and the right vagus is posterior (LARP). The left vagus gives off the hepatic branch to the liver and then continues along the lesser curvature as the anterior nerve of Latarjet. Although not shown, the so-called criminal nerve of Grassi is the first branch of the right or posterior vagus nerve; it is recognized as a potential cause of recurrent ulcers when left undivided. The right nerve gives a branch off to the celiac plexus and then continues posteriorly along the lesser curvature. A truncal vagotomy is performed above the celiac and hepatic branches of the vagi, whereas a selective vagotomy is performed below. A highly selective vagotomy is performed by dividing the crow’s feet to the proximal stomach while preserving the inner- vation of the antral and pyloric parts of the stomach. Most (90%) of the vagal fibers are afferent, carrying stimuli from the gut to the brain. Efferent vagal fibers originate in the dorsal nucleus of the medulla and synapse with neurons in the myen- teric and submucosal plexuses. These neurons use acetylcholine as their neurotransmitter and influence gastric motor function and gastric secretion. In contrast, the sympathetic nerve supply comes from T5 to T10, traveling in the splanchnic nerve to the there is frequently microscopic evidence of malignant cells several centimeters from gross disease. Innervation As shown in Figure 49-4, the extrinsic innervation of the stomach is parasympathetic (via the vagus) and sympathetic (via the celiac plexus). The vagus nerve originates in the vagal nucleus FIGURE 49-1  Divisions of  the  stomach.  (From Yeo c: Shackelford’s  surgery  of  the  alimentary  tract,  ed  6,  Philadelphia,  2007,  WB  Saunders.) Esophagus Cardia Pylorus Duodenum Lesser curvature Greater curvature Fundus Body Pyloric antrum FIGURE 49-2  Blood supply to the stomach and duodenum showing anatomic relationships to the spleen and pancreas. the stomach is reflected  cephalad. (From Yeo c: Shackelford’s surgery of the alimentary tract, ed 6, Philadelphia, 2007, WB Saunders.) Stomach Branches to greater omentum Left gastric artery Splenic artery and vein Left gastroepiploic artery Right gastroepiploic artery Right gastric artery Portal vein Pylorus Gastroduodenal artery and vein Pancreas Pancreatic duct Duodenum Superior pancreaticoduodenal artery Inferior pancreaticoduodenal artery Ileocolic artery Abdominal aorta Hepatic artery Short gastric arteries (vasa brevia) Spleen Jejunum Superior mesenteric artery and vein Inferior mesenteric artery Celiac artery Transverse colon Descending colon 1184  SeCtION X  aBDomEN Moreover, the parasympathetic nervous system contains adren- ergic neurons and the sympathetic system also contains cholin- ergic neurons. Gastric Morphology The stomach is covered by peritoneum, which forms the outer serosa of the stomach. Below it is the thicker muscularis propria, or muscularis externa, which is made up of three layers of smooth muscles. The middle layer of smooth muscle is circular and is the only complete muscle layer of the stomach wall. At the pylorus, this middle circular muscle layer becomes progres- sively thicker and functions as a true anatomic sphincter. The outer muscle layer is longitudinal and continuous with the outer layer of longitudinal esophageal smooth muscle. Within the layers of the muscularis externa is a rich plexus of autonomic nerves and ganglia, called Auerbach’s myenteric plexus. The sub- mucosa lies between the muscularis externa and mucosa and is a collagen-rich layer of connective tissue that is the strongest layer of the gastric wall. In addition, it contains the rich anas- tomotic network of blood vessels and lymphatics and Meissner’s plexus of autonomic nerves. The mucosa consists of surface epithelium, lamina propria, and muscularis mucosae. The latter is on the luminal side of the submucosa and is probably respon- sible for the rugae that greatly increase epithelial surface area. It also marks the microscopic boundary for invasive and noninva- sive gastric carcinoma. The lamina propria represents a small connective tissue layer and contains capillaries, vessels, lymphat- ics, and nerves necessary to support the surface epithelium. 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 celiac ganglion. Postganglionic fibers then travel with the arterial system to innervate the stomach. The intrinsic or enteric nervous system of the stomach consists of neurons in Auerbach’s and Meissner’s autonomic plexuses. In these locations, cholinergic, serotoninergic, and peptidergic neurons are present. However, the function of these neurons remains poorly understood. Nevertheless, a number of neuropeptides have been localized to these neurons; these include acetylcholine, serotonin, substance P, calcitonin gene– related peptide (CGRP), bombesin, cholecystokinin (CCK), and somatostatin. Consequently, it is an oversimplification to think of the stomach as only containing parasympathetic (cholinergic input) and sympathetic (adrenergic input) supply. FIGURE 49-3  Lymphatic drainage of the stomach.  Pancreaticolienal group of nodes Inferior gastric subpyloric group Superior gastric group of nodes Suprapyloric group of nodes FIGURE 49-4  Vagal  innervation of the stomach. the line of division  for  truncal  vagotomy  is  shown;  it  is  above  the  hepatic  and  celiac  branches of the left and right vagus nerves, respectively. the line of  division  for  selective  vagotomy  is  shown;  this  is  below  the hepatic  and celiac branches. (From mercer D, Liu t: open truncal vagotomy.  oper tech Gen Surg 5:8–85, 2003.) Right vagus nerve Line of division for truncal vagotomy Line of division for selective vagotomy Left vagus nerve Hepatic branch of left vagus Pyloric branch of left vagus Celiac branch of right vagus Anterior nerve of Latarjet table 49-1  Gastric Cell types, Location, and Function CeLL tYpe LOCatION FUNCtION Parietal Body Secretion of acid and  intrinsic factor mucus Body, antrum mucus chief Body Pepsin Surface epithelial Diffuse mucus, bicarbonate,  prostaglandins (?) Enterochromaffin-like Body histamine G antrum Gastrin D Body, antrum Somatostatin Gastric mucosal  interneurons Body, antrum Gastrin-releasing  peptide Enteric neurons Diffuse calcitonin gene–related  peptide, others Endocrine Body Ghrelin Stomach  Chapter 49  1185 SECTIO N X aB D o m EN In addition to storing food, the stomach begins digestion of a meal. Starches undergo enzymatic breakdown through the activity of salivary amylase. Peptic digestion metabolizes a meal into fats, proteins, and carbohydrates by breaking down cell walls. Although the duodenum and proximal small intestine are primarily responsible for digestion of a meal, the stomach facili- tates this process. Regulation of Gastric Function Gastric function is under neural (sympathetic and parasympa- thetic) and hormonal control (peptides or amines that interact with target cells in the stomach). An understanding of the roles of endocrine and neural regulation of digestion is critical to understanding gastric physiology. Abnormal secretion of gastrin and pepsin was thought to be the major causative factor in peptic ulcer disease (PUD). The discovery of Helicobacter pylori (H. pylori) and the effect of this organism on ulcer disease has rendered moot many of the theoretical rationales for acid hyper- secretion. A general understanding of gastric physiology and the specific impact of peptides on acid secretion, however, is still critical to understanding the physiologic effects of gastric surgi- cal procedures on digestion. We will initially focus here on peptide regulation of gastric function and then describe the interactions of these peptides with neural inputs in regard to acid secretion and gastric function. Gastric Peptides 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 func- tionally 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. Pro- longed hypergastrinemia from any cause leads to mucosal hyper- plasia 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 patho- logic 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 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. PHYSIOLOGY The principal function of the stomach is to prepare ingested food for digestion and absorption as it is propulsed into the small intestine. The initial period of digestion requires that solid com- ponents of a meal be stored for several hours while they undergo a reduction in size and break down into their basic metabolic constituents. Receptive relaxation of the proximal stomach enables the stomach to function as a storage organ. Receptive relaxation refers to the process whereby the proximal portion of the stomach relaxes in anticipation of food intake. This relaxation enables liquids to pass easily from the stomach along the lesser curvature, whereas the solid food settles along the greater cur- vature of the fundus. In contrast to liquids, emptying of solid food is facilitated by the antrum, which pumps solid food com- ponents into and through the pylorus. The antrum and pylorus function in a coordinated fashion, allowing entry of food com- ponents into the duodenum and also returning material to the proximal stomach until it is suitable for delivery into the duodenum. FIGURE 49-5  cells  residing  within  a  gastric  gland.  (From  Yeo  c:  Shackelford’s surgery of the alimentary tract, ed 6, Philadelphia, 2007,  WB Saunders.) Surface mucous cells Mucous neck cells Argentaffin cells Chief cells Gastric pit Isthmus Neck Base Gastric gland Parietal cells 1186  SeCtION X  aBDomEN through the inhibition of adenylate cyclase, with a resultant reduction in cyclic AMP levels. Gastrin-Releasing Peptide Bombesin was discovered in 1970 in an extract prepared from skin of the amphibian Bombina bombina (European fire-bellied toad). Its mammalian counterpart is gastrin-releasing peptide (GRP). GRP is particularly prominent in nerves ending in the acid-secreting and gastrin-secreting portions of the stomach and is found in the circular muscular layer. In the antral mucosa, GRP stimulates gastrin and somatostatin release by binding to receptors located on the G and D cells, respectively. It is rapidly cleared from the circulation by a neutral endopeptidase and has a half-life of approximately 1.4 minutes. Peripheral administra- tion of exogenous GRP stimulates gastric acid secretion, whereas central administration in the ventricles inhibits acid secretion. The inhibitory pathway activated is not mediated by a humoral factor, is unaffected by vagotomy, and appears to involve the sympathetic nervous system. Histamine Histamine plays a prominent role in parietal cell stimulation. Administration of histamine 2 (H2) receptor antagonists almost completely abolishes gastric acid secretion in response to gastrin and acetylcholine. This suggests that histamine may be a neces- sary intermediary of gastrin- and acetylcholine-stimulated acid secretion. Histamine is stored in the acidic granules of ECL cells and in resident mast cells. Its release is stimulated by gastrin, acetylcholine, and epinephrine following receptor-ligand inter- actions on ECL cells. In contrast, somatostatin inhibits gas trin- stimulated histamine release through interactions with somatostatin receptors located on the ECL cell. Thus, the ECL cell plays an essential role in parietal cell activation that possesses stimulatory and inhibitory feedback pathways that modulate the release of histamine and therefore acid secretion. Ghrelin Ghrelin is a 28–amino acid peptide predominantly produced by endocrine cells of the oxyntic mucosa of the stomach, with substantially lower amounts