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The stomach has a number of critical functions in the processes of digestion: storage, digestion, and defense. The volume of the stomach is quite small at rest, but the gastric musculature can undergo receptive relaxation to accommodate a meal volume of 1 to 2 L. Food is broken down in the presence of acid by the grinding actions of the thick muscular coats of the stomach, and the contents then pass in a regulated manner into the duodenum. Gastric acid not only serves to facilitate digestion, but it also provides an effective antimicrobial milieu that facilitates defense against pathogens.

Gastric acid and pepsin in the stomach normally do not produce damage or symptoms of acid-peptic diseases because of intrinsic defense mechanisms. The stomach is protected by a number of factors, collectively referred to as “mucosal defense,” many of which are stimulated by the local generation of prostaglandins (PGs) and nitric oxide (NO). If these defenses are disrupted, a gastric or duodenal ulcer may form. The treatment and prevention of acid-related disorders are accomplished by decreasing gastric acidity and enhancing mucosal defense. The appreciation that an infectious agent, Helicobacter pylori, plays a key role in the pathogenesis of acid-peptic diseases revolutionized approaches to prevention and therapy of these common disorders.

Barriers to the reflux of gastric contents into the esophagus comprise the primary esophageal defense. If these protective barriers fail and reflux occurs, dyspepsia or erosive esophagitis may result. Therapies are directed at decreasing gastric acidity, enhancing the tone of the lower esophageal sphincter, and stimulating esophageal motility (see Chapter 54).



ACh: acetylcholine

cAMP: cyclic adenosine monophosphate (cyclic AMP)

CCK: cholecystokinin

CNS: central nervous system

CYP: cytochrome P450

DU: duodenal ulcer

ECL: enterochromaffin-like cell

ENS: enteric nervous system

GERD: gastroesophageal reflux disease

GI: gastrointestinal

GPCR: G protein-coupled receptor

GRP: gastrin-releasing peptide

GU: gastric ulcer

HIST: histamine

IP3: inositol 1,4,5-trisphosphate

NO: nitric oxide

NSAID: nonsteroidal anti-inflammatory drug

OTC: over the counter

PG: prostaglandin

PK: protein kinase

PLC: phospholipase C

PPI: proton pump inhibitor

SARS-CoV-2 (COVID-19): severe acute respiratory syndrome coronavirus 2 (coronavirus disease 2019)

SST: somatostatin


Gastric acid secretion is a complex and continuous process: Neuronal (acetylcholine [ACh], gastrin-releasing peptide [GRP]); paracrine (histamine); and endocrine (gastrin) factors regulate the secretion of H+ by parietal cells (acid-secreting cells) (Figure 53–1). Their specific receptors (M3, BB2, H2, and CCK2, respectively) are on the basolateral membrane of parietal cells in the body and fundus of the stomach. Some of these receptors are also present on ECL cells, where they regulate the release of histamine. The H2 receptor is a G protein-coupled receptor (GPCR) that activates the Gs–adenylyl cyclase–cyclic AMP–PKA pathway (see Chapters 3 and 43). ACh and gastrin signal ...

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