A peptic ulcer is defined as disruption of the mucosal integrity of the stomach and/or duodenum leading to a local defect or excavation due to active inflammation. Although burning epigastric pain exacerbated by fasting and improved with meals is a symptom complex associated with peptic ulcer disease (PUD), it is now clear that >90% patients with this symptom complex (dyspepsia) do not have ulcers and that the majority of patients with peptic ulcers may be asymptomatic. Ulcers occur within the stomach and/or duodenum and are often chronic in nature. Acid peptic disorders are very common in the United States, with 4 million individuals (new cases and recurrences) affected per year. Lifetime prevalence of PUD in the United States is ~12% in men and 10% in women. PUD significantly affects quality of life by impairing overall patient well-being and contributing substantially to work absenteeism. Moreover, an estimated 15,000 deaths per year occur as a consequence of complicated PUD. The financial impact of these common disorders has been substantial, with an estimated burden on direct and indirect health care costs of ~$6 billion per year in the United States, with $3 billion spent on hospitalizations, $2 billion on physician office visits, and $1 billion in decreased productivity and days lost from work.
The gastric epithelial lining consists of rugae that contain microscopic gastric pits, each branching into four or five gastric glands made up of highly specialized epithelial cells. The makeup of gastric glands varies with their anatomic location. Glands within the gastric cardia comprise <5% of the gastric gland area and contain mucous and endocrine cells. The 75% of gastric glands are found within the oxyntic mucosa and contain mucous neck, parietal, chief, endocrine, enterochromaffin, and enterochromaffin-like (ECL) cells (Fig. 317-1). Pyloric glands contain mucous and endocrine cells (including gastrin cells) and are found in the antrum.
Diagrammatic representation of the oxyntic gastric gland. (Adapted from S Ito, RJ Winchester: J Cell Biol 16:541, 1963. © 1963 Ito and Winchester.)
The parietal cell, also known as the oxyntic cell, is usually found in the neck, or isthmus, or in the oxyntic gland. The resting, or unstimulated, parietal cell has prominent cytoplasmic tubulovesicles and intracellular canaliculi containing short microvilli along its apical surface (Fig. 317-2). H+,K+-adenosine triphosphatase (ATPase) is expressed in the tubulovesicle membrane; upon cell stimulation, this membrane, along with apical membranes, transforms into a dense network of apical intracellular canaliculi containing long microvilli. Acid secretion, a process requiring high energy, occurs at the apical canalicular surface. Numerous mitochondria (30–40% of total cell volume) generate the energy required for secretion.
Gastric parietal cell undergoing transformation after secretagogue-mediated stimulation. cAMP, cyclic adenosine monophosphate. (Adapted from SJ Hersey, G Sachs: Physiol Rev 75:155, 1995.)
Gastroduodenal Mucosal Defense
The gastric epithelium is under constant ...