Question

Put into words the process by which we make hydrochloric acid (HCl) in the stomach. Include any changes that occur to the pH of vessels near the stomach. Provide as many relevant details as you can. If an equation plays a role here, convince me you know what's going on in terms of that equation.

Answer 1

HCl is produced by the parietal cells of the stomach. To begin with, water (H₂O) and carbon dioxide (CO₂) combine within the parietal cell cytoplasm to produce carbonic acid (H₂CO₃). An enzyme called carbonic anhydrase converts carbonic acid into its component ions a hydrogen ion (H⁺) and a bicarbonate ion (HCO₃^–).

The bicarbonate ion is transported out of the cell into the blood via a transporter protein called anion exchanger which transports the bicarbonate ion out the cell in exchange for a chloride ion (Cl^–). This chloride ion is then transported into the stomach lumen via a chloride channel.

Prior to this, the hydrogen ion that was formed via the splitting of carbonic acid is transported into the stomach lumen via the H⁺– K⁺ ATPase. This channel uses ATP energy to exchange potassium ions in the stomach with hydrogen ions in the parietal cell.

This results in both hydrogen and chloride ions being present within the stomach lumen. Their opposing charges leads to them associating with each other to form hydrochloric acid (HCl).

Luminal acidity is a physiologic challenge in the foregut, and acidosis can occur throughout the gastrointestinal tract as a result of inflammation or ischemia. These conditions are surveyed by an elaborate network of acid-governed mechanisms to maintain homeostasis. Deviations from physiologic values of extracellular pH are monitored by multiple acid sensors expressed by epithelial cells and sensory neurons. Acid-sensing ion channels are activated by moderate acidification, whereas transient receptor potential ion channels of the vanilloid subtype are gated by severe acidosis. Some ionotropic purinoceptor ion channels and two-pore domain background K+ channels are also sensitive to alterations of extracellular pH.

Most tissues would rapidly disintegrate if exposed to this concentration of HCl, yet gastric acid is essential for the digestive breakdown of food and elimination of ingested pathogens. The autoaggressive potential of HCl is kept in check by an elaborate network of mucosal defense mechanisms and the functional compartmentalization of the esophago-gastro-duodenal region. Both strategies require an acid surveillance system among which acid-sensitive afferent neurons play a particular role. If the pathophysiologic impact of gastric acid gets out of control, acid-related diseases including gastritis, gastroduodenal ulceration, dyspepsia and gastroesophageal reflux disease (GERD) may ensue.

It is well established that gastrointestinal blood flow increases after meals, a phenomenon referred to as postprandial or functional hyperemia.In general, ingestion of food results in a dual hemodynamic response within the gastrointestinal tract: an initial transient response during anticipation and ingestion of food and a subsequent prolonged response during digestion and absorption.

The anticipatory/ingestion phase is characterized by increases in heart rate, cardiac output, and aortic pressure with only minor changes in gastrointestinal vascular resistance. These transient hemodynamic alterations can be blunted by adrenergic blocking agents and mimicked by allowing the animals to see and smell the food, but not allowed to ingest it. Thus, this transient phase represents a sympathetic-driven cephalic phase.

The digestive/absorptive phase is characterized by a gastrointestinal hyperemia. In conscious animals, blood flow in the left gastric, celiac, and superior mesenteric arteries increases within minutes after ingestion of a meal. Left gastric and celiac artery blood flow increases earlier and is transient (10–15 min), while superior mesenteric artery blood flow increases later and is more prolonged (up to several hours). The postprandial hyperemia is detected earlier in the jejunum (within 30 min) than the ileum (by 90 min). Collectively, these observations indicate that the postprandial hyperemia progresses along the gastrointestinal tract in association with the aboral movement of ingested food. The magnitude (25–200%) and the duration (3–7 h) of the hyperemia appear to depend on the composition of the meal. In general, lipid- and protein-rich meals are more potent than carbohydrate-rich meals in eliciting a hyperemia. A cholinergic neural pathway has been proposed to be involved in the gastrointestinal postprandial hyperemia, but this neurogenic-mediated contribution to the hyperemia may be indirect, rather than direct. In general, the characteristics of the gastrointestinal postprandial hyperemia in animals mimics those observed in humans.