6. Gastric Secretion

Gastric Secretion (Simple Stomach)

• Gastric juice is composed of:
  • HCl: Isotonic (150mM H+, 150 mM Cr) + Abomasum
  • Water
  • Pepsin (secreted as pepsinogen)
  • Intrinsic factor
  • Mucus
  • Proteolytic enzymes (secreted as pepsinogen) from pancreatic acini in dogs and cats. Primates and pigs secrete these from pancreatic acini.

Functional Anatomy of Gastric Mucosa

• The gastric mucosa is lined with simple columnar epithelium dotted with numerous gastric pits (up to 3 million).
• Each pit leads to 1-3 gastric glands.
• Gastric glands are composed of several cell types, and those regions differ across species (see Figure 1 of Section 1).

Regions of Stomach by Species (Figure 1)

• Various species show different regional stomach anatomical structures. (e.g., stratified squamous, nonglandular, cardiac glands, proper gastric/fundic, pyloric/antrum in different animals).

Gastric Gland Cell Types and Products (Figure 2)

• Oxyntic Gland (Proper Gastric):
• Parietal Cells: Secrete HCl and intrinsic factor.
• Chief Cells: Secrete pepsinogen.
• Mucous Cells: Secrete mucus and pepsinogen.
• Enteroendocrine Cells: Release histamine, somatostatin, ghrelin, and gastrin. ECL cells (Enterochromaffin-like cells) specifically secrete histamine.
• Pyloric Gland (Antral):
• Mucous Cells: Secrete mucus and pepsinogen.
• Enteroendocrine Cells: Secrete gastrin, somatostatin, and ghrelin

Ghrelin (Hunger Hormone)

• Found mainly in oxyntic glands of stomach.
• Released during fasting or negative energy balance.
• Agonists of ghrelin are used to stimulate appetite in dogs and cats.

Functions of Gastric HCl

• Activates pepsinogen to pepsin.
• Creates optimal pH (2-4) for pepsin function.
• Denatures proteins.

Mechanism of Gastric Acid Secretion

• HCl secretion occurs via H+-K+ ATPase (proton pump) in parietal cells.
• Requires energy (ATP).
• Secretion against a concentration gradient.
• Processes CO2 and H2O in the parietal cell.

Mediators Affecting Parietal Cell HCl Secretion

• Histamine: A paracrine mediator that stimulates HCl secretion by binding to H2 receptors, increasing cAMP, directly stimulating H-K ATPase, and potentiating the effect of other stimuli on H-K ATPase. ECL cells are the main source, and stimuli include gastrin and acetylcholine. Somatostatin inhibits ECL cell function and histamine release.
• Acetylcholine: A neurotransmitter from parasympathetic nerves that stimulates HCl secretion via muscarinic receptors. Indirect stimulation can result in gastrin and histamine release which further stimulate parietal cell activity.
• Gastrin: A hormone that stimulates HCl secretion, mainly by increasing histamine release. Gastrin binds to gastrin (CCKB) receptors and increases intracellular Ca2+, further stimulating the H-K ATPase activity.

Inhibitor: Somatostatin

• Paracrine inhibitor produced by D cells in oxyntic and antral stomach.
  • Acts on parietal cells, ECL cells, and G cells to inhibit HCl secretion, histamine release, and gastrin release, respectively.
  • Stimuli for release include increased luminal H+ (low pH).

Three Phases of Gastric Secretion

• Cephalic Phase: (15% of total gastric secretion) - Triggered by anticipation or smell of food; mediated by long-chain reflexes. Relays via central nervous system (CNS) to vagus nerve. Releases gastrin, histamine, and stimulates parietal cells.

• Gastric Phase: (70-80% of total gastric secretion) - Triggered by presence of food in the stomach. Stimuli include mechanical stretching, chemical stimulation (amino acids and peptides). Includes both neural mechanisms (mechanical and/or chemical stimuli) and direct hormonal stimulation.

• Intestinal Phase: (5% of total gastric secretion) - Triggered by presence of chyme in the small intestine, mediated by feedback mechanisms from the intestines.

Physiological Inhibitors of Acid Secretion

• Local feedback control: As gastric acidity rises, it inhibits gastrin release and stimulates somatostatin in the stomach.
• Feedback control: Duodenum mechanisms like enterogastric reflexes use CCK and GLP-1 to regulate gastric function and output.

Other Gastric Juice Constituents

• Pepsin: A protease secreted as pepsinogen. Pepsinogen becomes pepsin via HCl activation. It has optimal activity at pH 2-4.

• Intrinsic factor: A glycoprotein secreted by parietal cells. Essential for vitamin B12 absorption in the small intestine.

• Rennin: A milk-clotting enzyme found in neonatal ruminants (and some other species).

Clinical Relevance

• Gastroduodenal ulcers linked to Helicobacter pylori. Treatments involve antibacterial agents, proton pump inhibitors, and H2 receptor antagonists to address the acid production issue.