Chapter 49 Stomach
Anatomy
Gross Anatomy
Divisions

FIGURE 49-1 Divisions of the stomach.
(From Yeo C: Shackelford’s surgery of the alimentary tract, ed 6, Philadelphia, 2007, WB Saunders.)
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
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 |
Physiology
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 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
Table 49-2 Causes of Hypergastrinemia
ULCEROGENIC CAUSES | NONULCEROGENIC CAUSES |
---|---|
Antral G-cell hyperplasia or hyperfunction | Antisecretory agents (PPIs) |
Retained excluded antrum | Atrophic gastritis |
Zollinger-Ellison syndrome | Pernicious anemia |
Gastric outlet obstruction | Acid-reducing procedure (vagotomy) |
Short-gut syndrome | Helicobacter pylori infection |
Chronic renal failure |
Somatostatin
Somatostatin is produced by D cells and exists endogenously as the 14– or 28–amino acid peptide. The predominant molecular form in the stomach is somatostatin-14. It is produced by diffuse neuroendocrine cells located in the fundus and antrum. In these locations, D cell cytoplasmic extensions have direct contact with the parietal cells and G cells, where it presumably exerts its actions through paracrine effects on acid secretion and gastrin release.3 Somatostatin is able to inhibit parietal cell acid secretion directly but can also indirectly inhibit acid secretion through inhibition of gastrin release and downregulation of histamine release from ECL cells. The principal stimulus for somatostatin release is antral acidification, whereas acetylcholine from vagal fibers inhibits its release.
Gastric Acid Secretion
Activation and Secretion by the Parietal Cell
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.
Pharmacologic Regulation
One notable side effect of all antisecretory agents is the elevation of serum gastrin levels. Serum gastrin levels are higher after treatment with PPIs than with H2 receptor antagonists. This effect is accompanied by hyperplasia of G cells and ECL cells when these agents are administered chronically. Chronic administration of omeprazole has been found to cause ECL hyperplasia that could progress to carcinoid tumors in rats.3 This effect, however, was not specific for omeprazole and was reproduced by other agents that caused prolonged inhibition of acid secretion and resultant hypergastrinemia.
Gastric Motility
Abnormal Gastric Motility
Symptoms of abnormal gastric motility are nausea, fullness, early satiety, abdominal pain, and discomfort. Although mechanical obstruction can and should be ruled out with upper endoscopy or radiographic contrast studies, objective evaluation of a patient with a suspected motility disorder can be accomplished with gamma scintigraphy, real-time ultrasound, and magnetic resonance imaging (MRI). Gastric motility disorders usually encountered in clinical practice are gastric dysmotility following vagotomy, delayed gastric emptying associated with diabetes mellitus, and gastric motility dysfunction related to H. pylori infection. Vagotomy results in loss of receptive relaxation and gastric accommodation in response to meal ingestion, with resultant early satiety, postprandial bloating, accelerated emptying of liquids, and delay in emptying of solids. Clinical manifestations of diabetic gastropathy, which can occur in insulin-dependent or insulin-independent patients, closely resemble the clinical picture of postvagotomy gastroparesis. Furthermore, structural changes have been identified in the vagus nerve of patients with diabetes, suggesting that a diabetic autonomic neuropathy may be responsible. However, the metabolic effects of diabetes have also been implicated. Specifically, hyperglycemia has been shown to cause a decrease in contractility of the gastric antrum, increase in pyloric contractility, and suppression of the migrating motor complex (MMC). Suppression of MMC activity is thought to be responsible for the accumulation of gastric bezoars seen in some diabetic patients. In contrast, hyperinsulinemia, which is often associated with non–insulin-dependent diabetes, may play a role in the gastroparesis seen in non–insulin-dependent diabetes because it also leads to suppression of MMC activity.4
H. pylori–infected patients with nonulcer dyspepsia have also been demonstrated to have impaired gastric emptying accompanied by a reduction in gastric compliance.5 In rats, lipopolysaccharide derived from H. pylori causes a reduction in gastric emptying of a liquid meal for up to 12 hours by an unknown mechanism. Regardless of the cause of gastroparesis, treatment consists of prokinetic agents, such as metoclopramide and erythromycin, which have been shown to have some benefit, although the evidence is more compelling in diabetics.
Peptic Ulcer Disease
Epidemiology
The estimated prevalence of PUD ranges from 5% to 15% in Western populations, with a lifetime incidence of almost 10%.6 Although the incidence and hospitalization rate for PUD have been decreasing since the 1980s, it remains one of the most prevalent and costly GI diseases. Medical costs associated with PUD are an estimated $5.65 billion annually. An estimated 15,000 operations are performed each year on patients hospitalized with PUD. Significant progress has been made over the past 2 decades, with total admissions for PUD decreasing by almost 30%. Admissions for complications of ulcer disease have also been decreasing, which has led to a significant decrease in ulcer-related mortality, from 3.9% in 1993 to 2.7% in 2006.7 Although overall mortality remains low, this still represents over 4000 deaths caused by PUD each year.
The role of surgery in the treatment of ulcer disease has also decreased, primarily caused by a marked decline in elective surgical therapy for chronic disease because the percentage of patients who require emergent surgery for complicated disease has remained constant, at 7% of hospitalized patients.7 This represents over 11,000 surgical procedures annually.
Pathogenesis
Peptic ulcers are caused by increased aggressive factors, decreased defensive factors, or both.8 This in turn leads to mucosal damage and subsequent ulceration. Protective (or defensive) factors include mucosal bicarbonate secretion, mucus production, blood flow, growth factors, cell renewal, and endogenous prostaglandins. Damaging (or aggressive) factors include hydrochloric acid secretion, pepsins, ethanol ingestion, smoking, duodenal reflux of bile, ischemia, NSAIDs, hypoxia and, most notably, H. pylori infection.
Helicobacter pylori Infection
Duodenal Ulcer
Diagnosis
Treatment
Medical Management
Treatment of Helicobacter pylori Infection
Current therapy is twofold in its approach, combining antibiotics against H. pylori with antacid medications. The primary goal of the antacids is to promote short-term healing by reducing pathologic acid levels and improve symptoms. H. pylori eradication helps with initial healing, but its primary efficacy is in preventing recurrence. There have been numerous trials comparing eradication therapy with ulcer-healing drugs alone or no treatment. Eradication of H. pylori has shown recurrence rates as low as 2%, with initial healing as high as 90%. This compares with recurrence rates of up to 25% with ulcer-healing medications alone. One review has analyzed the results of these trials and further validated the role of antibiotics in the treatment of H. pylori–positive duodenal ulcers.10 Both eradication therapy and ulcer-healing drugs alone have shown initial healing rates higher than 80%. Eradication therapy has resulted in long-term recurrence of less than 15%, in contrast to 64% recurrence in patients treated with only a short initial course of ulcer-healing drugs. Patients could achieve low recurrence rates similar to those of eradication therapy, but only if they were maintained on their antacid regiment long term, as opposed to a 1- or 2-week course of eradication therapy.
Complicated Ulcer Disease
Box 49-2 Surgical Treatment Recommendations for Complications Related to Peptic Duodenal Ulcer Disease
Intractable: Parietal cell vagotomy ± antrectomy
Bleeding: Oversewing of bleeding vessel with treatment of H. pylori
Perforation: Patch closure with treatment of H. pylori
Obstruction: Rule out malignancy and gastrojejunostomy with treatment of H. pylori
Hemorrhage
Upper GI bleeding remains a relatively common problem, with an annual incidence of approximately 1/1000.11 Most nonvariceal bleeding (70%) is attributable to peptic ulcers. Most bleeding will stop spontaneously and requires no intervention; persistent bleeding, however, is associated with a 6% to 8% mortality.
The primary clinical criteria that predict persistent bleeding or rebleeding after initial cessation of bleeding, and thus increased mortality, are increased age, decreased hemoglobin (<10 g/dL) at presentation, shock, melena, and need for blood transfusion. Patients who meet any of these criteria should be considered as high risk.11
Patients who are noted to have active bleeding, via an arterial jet or oozing, an adherent clot, or a visible vessel within the ulcer, are at high risk and intervention is required. Patients without active bleeding, no visible vessel, and a clean ulcer base are low risk and do not require further intervention. All patients undergoing endoscopic examination should be tested for their H. pylori status. For the high-risk patient requiring intervention, the best initial approach is endoscopic control, which results in primary hemostasis in approximately 90% of patients. The most common method of control is injection of a vasoconstrictor at the site of bleeding. However, with this method alone, primary hemostasis rates are high but up to 30% of patients have rebleeding. This has led to the development of new techniques, including use of a second vasoconstrictor or sclerosing agent, thermal coagulation, and placement of clips at the site of bleeding. A 2007 meta-analysis has compared the use of epinephrine alone to epinephrine plus any second technique.12 A dual approach, when compared with epinephrine alone, showed better primary hemostasis, reduction in rebleeding rate, lower rate of surgery, and decreased mortality.
Importantly, both thermal coagulation and mechanical clips, in single-method comparisons with epinephrine, have shown significant superiority with respect to primary hemostasis and rebleeding. A meta-analysis comparing either of these two techniques alone to the use of dual methods has shown no significant difference, except in cases of active arterial bleeding, in which case use of a second method was superior. Although the cost and complications from epinephrine remain small, the use of dual methods does have slightly higher, although still less than 1%, complication rates (e.g., necrosis, perforation), than any single technique. Current 2003 guidelines for endoscopic control of bleeding advocate the use of epinephrine plus an additional method.11 As more data become available, it may be demonstrated that thermal or mechanical treatment alone can be used for most patients. For patients who have rebleeding, repeat endoscopy does not increase their mortality and should be attempted prior to surgical intervention.
All high-risk patients should be placed in a monitored setting, preferably an intensive care unit, until all bleeding has stopped for 24 hours. As part of the 2003 consensus guidelines, all high-risk patients should be placed on an IV PPI, with an initial bolus followed by continuous infusion or intermittent dosing for up to 72 hours. When compared with a histamine blocker and placebo, the IV PPI showed lower rebleeding rates, lower rate of emergency surgery, and decreased mortality.13 Patients deemed high risk based on clinical factors who are awaiting endoscopy should probably begin therapy, even prior to endoscopy.

FIGURE 49-10 A-E, Heineke-Mikulicz pyloroplasty.
(From Soreide JA, Soreide A: Pyloroplasty. Oper Tech Gen Surg 5:65–72, 2003.)
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