C H A P T E R  56 
Stomach
STRUCTURE AND FUNCTION
Kenneth W. Simpson
Functional Anatomy
The stomach acts as a reservoir to control the size and rate of passage
of ingesta into the small intestine, to initiate the digestion of protein
and fat, and to facilitate the absorption of vitamins and minerals
(see Chapter 1)
The stomach is composed of five anatomic regions: cardia,
fundus, corpus, antrum, and pylorus (Figure 56-1). The fundus and
body expand greatly to accommodate ingesta and to regulate the
emptying of liquids. The antrum grinds food into smaller particles
(<2 mm) that are sieved into the duodenum. The gastroesophageal
sphincter prevents reflux of gastric fluid into the esophagus, and the
pyloric sphincter controls emptying into the small intestine.
The gastric wall contains a mucosa, submucosa, muscularis
externa, and serosa (see Figures 56-2 and 1-3, B). The mucosa has
a superficial epithelium, gastric glands, and an innermost layer of
smooth muscle (the muscularis mucosa), with fine structure and
function varying depending on the gastric region. The mucosa in
the cardia and pylorus is thinner and less glandular than in the
fundus and body. The mucosa of the body contains mucous neck
cells (producing mucous, pepsinogen A, and gastric lipase), parietal
cells (producing H+, pepsinogen A, and intrinsic factor), and chief
cells (producing pepsinogen A) (Figure 56-2).1-4 A variety of neu-
roendocrine cells are involved in the regulation of acid secretion
and are interspersed between the glands. The predominant cells are
enterochromaffin-like and somatostatin-producing cells in the
fundus, and gastrin and somatostatin-producing cells in the antrum
(see Figure 56-2). Localized small aggregates of lymphoid tissues are
frequently observed at the base of the gastric glands. A rich network
of blood vessels, lymphatics, and nerves weaves between the gastric
glands. Beneath the submucosa are two layers of smooth muscle
(circular and longitudinal) that run perpendicular to one another.
The serosa is the outermost layer.
Regulation of Acid Secretion
Physiologically, luminal peptides and gastric distention are the
primary stimuli for H+ secretion from parietal cells. Pharmacologi-
cally, parietal cell acid secretion is regulated by endocrine (gastrin),
neurocrine (acetylcholine), and paracrine (histamine) mecha-
nisms.4,5 Somatostatin released in response to gastric pH levels
below 3 provides negative feedback and decreases gastrin, histamine,
and acid secretion.
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Luminal peptides and gastric distention stimulate gastrin secre-
tion from G cells and effect histamine release from enterochromaffin-
like cells. Gastrin-releasing peptide and acetylcholine are the
primary enteric neurotransmitters regulating gastrin release from
antral G cells (Figure 56-3).
Unstimulated acid secretion in dogs and cats is minimal6-8 (e.g.,
dogs <0.04 mmol/kg0.75/h) and the unstimulated H+/K+-adenosine
triphosphatase (ATPase), “the proton pump,” is localized within
tubulovesicles in the cytoplasm of parietal cells.4,9 The stimulated
H+/K+-ATPase and KCl transporters are incorporated into the pari-
etal cell canalicular membrane and hydrogen ions (derived from the
ionization of water within the parietal cells) are transported into the
gastric lumen in exchange for K+ by H+/K+-ATPase. Potassium and
chloride transporters in the canalicular membrane enable luminal
transfer of potassium (for recycling via H+/K+-ATPase) and chloride.
Hydroxide combines with CO2, catalyzed by carbonic anhydrase, to
form HCO3−, which diffuses into the blood giving rise to the “alka-
line tide” phenomenon. Recent studies have expanded our knowl-
edge of ion transport in the parietal cell by identifying KCNQ1 as
the primary channel responsible for K+ recycling and establishing
the contribution of CFTR (cystic fibrosis transmembrane regulator)
and SLC26A9 to the process of chloride secretion.5 Figure 56-4
shows a schematic of ion transport in the parietal cell incorporating
these findings. Stimulation results in a rapid increase in fluid and
hydrogen ion secretion, with pH rapidly declining to around pH 1.
The concentrations of K+ (10 to 20 mmol/L) and Cl− (approxi-
mately 120 to 160 mmol/L) in gastric juice are higher than in
plasma.
The stomach is protected from gastric acid injury by a functional
unit known as the gastric mucosal barrier.10,11 The gastric mucosal
barrier comprises tightly opposed epithelial cells coated with a layer
of bicarbonate-rich mucus and an abundant mucosal blood supply
that delivers bicarbonate, oxygen, and nutrients. Local production
of prostaglandin (PGE2) is important in modulating blood flow,
bicarbonate secretion, and epithelial cell renewal. When damage
occurs, epithelial cells rapidly migrate over superficial mucosal
defects aided by the local production of growth factors such as epi-
dermal growth factor.
Evaluating Gastric Secretory Function
Gastric secretory testing is primarily performed in patients with
esophagitis, gastrointestinal (GI) ulceration, mucosal hypertrophy,
and in patients suspected of having acid hypersecretion.
As a starting point, fasting gastric pH and serum gastrin can be
measured to determine if acid hypersecretion is likely. Ideally, anti-
secretory therapy should be discontinued for 7 days prior to testing,12
and renal and hepatic function should be monitored as these may