GIT & NUT - L1 Physio: Secretory Functions of the Stomach

Secretory Functions of the Stomach

Gastric Glands and Secretions

• The gastric mucosa contains gastric glands responsible for gastric secretion.

• Cardiac and Pyloric Regions:

  • Glands secrete mucus.

• Fundus and Body:

  • Parietal (Oxyntic) Cells: Secrete $HCl$ (hydrochloric acid) and intrinsic factor.

  • Chief (Peptic) Cells: Secrete pepsinogen.

  • Mucus Neck Cells: Secrete mucus.

  • Enterochromaffin-like (ECL) Cells: Secrete histamine.

• Antrum:

  • G Cells: Secrete gastrin hormone.

  • D Cells: Secrete somatostatin hormone.

  • Mucus Cells: Secrete mucus.

Gastric Secretion

• Volume: Approximately 2 liters per day.

• pH: Highly acidic (around 2).

• Contents:

  1. Water (most of the volume).

  2. Inorganic constituents: $Na^+$, $K^+$, $Ca^{2+}$, $Mg^{2+}$.

  3. Hydrochloric acid (HCl).

  4. Organic constituents: Enzymes (pepsinogen, gelatinase, gastric lipase), intrinsic factor, and mucus.

Hydrochloric Acid (HCl) Secretion

Mechanism of HCl Secretion

• Oxyntic cells produce HCl through an active process.

• These cells contain many mitochondria (40% of cell volume) and canaliculi communicating with the gastric gland lumen.

• HCl forms at the membrane of these canaliculi to protect the cytoplasm from the acid.

• $H^+$ and $Cl^-$ are actively secreted by the oxyntic cells.

  • $H^+$ is secreted into the lumen via primary active transport, exchanging for $K^+$ through the $H^+-K^+$ ATPase pump (proton pump) at the luminal membrane.

  • $K^+$ passively leaks back into the lumen through $K^+$ channels, recycling $K^+$ between the cell and the lumen.

  • The secreted $H^+$ comes from the breakdown of $H_2O$ into $H^+$ and $OH^-$.

  • $OH^-$ is neutralized by another $H^+$ derived from $H<em>2CO</em>3$.

  • $H<em>2CO</em>3$ is generated from $CO<em>2$ and water by carbonic anhydrase enzyme (CAE). $CO</em>2$ comes from cell metabolism or plasma diffusion.

  • $Cl^-$ is secreted via secondary active transport, exchanging with $HCO<em>3^-$ through a $Cl^-$,$HCO</em>3^-$ exchanger in the basolateral membrane, driven by the $HCO_3^-$ concentration gradient.

  • $Cl^-$ diffuses out of the cell through a luminal $Cl^-$ channel into the lumen.

  • Water diffuses out of the cell into the lumen by osmosis.

Postprandial Alkaline Tide

• After a meal, increased gastric secretion leads to excess $HCO_3^-$ entering the blood, raising blood pH.

Control of HCl Secretion

Stimulating Factors:

1. Acetylcholine:

   • Secreted by cholinergic neurons.

   • Acts on $M_3$ receptors.

   • Increases intracellular $Ca^{2+}$.

2. Histamine:

   • Secreted by ECL cells.

   • Acts in a paracrine manner on $H_2$ receptors.

   • Increases intracellular cAMP.

3. Gastrin Hormone:

   • Secreted by G cells.

   • Reaches the stomach via blood.

   • Direct Action: Increases intracellular $Ca^{2+}$.

   • Indirect Action: Stimulates histamine release (main mechanism).

• These stimuli bind to receptors on parietal cells, releasing second messengers ($Ca^{2+}$ & cAMP), which transfer the $H^+,K^+$ ATPase from intracellular vesicles to the luminal membrane, increasing their number.

Inhibiting Factors:

1. Prostaglandin $E_2$: Decreases cAMP.

2. Somatostatin:

   • Acts in a paracrine manner.

   • Directly decreases cAMP in oxyntic cells.

   • Indirectly inhibits gastrin and histamine release.

3. Excess HCl:

   • Decreases pH below 2.

   • Stimulates somatostatin release.

   • HCl inhibits its own secretion (autoregulation).

Functions of HCl

1. Kills most ingested bacteria (sterilization of the stomach).

2. Dissolves food particles, converting them into chyme.

3. Activates pepsinogen into pepsin.

4. Provides an optimal pH (2-3.5) for pepsin action.

5. Aids iron absorption by converting $Fe^{3+}$ to $Fe^{2+}$ and calcium absorption by preventing precipitation of calcium salts.

6. Stimulates bile flow and pancreatic secretions.

Gastric Enzymes

Pepsinogen

• Secreted by peptic (chief) cells.

• Release is stimulated by substances that stimulate HCl secretion.

• Inactive and activated into pepsin by HCl; pepsin further activates pepsinogen (autoactivation).

• Pepsins are proteolytic enzymes that start protein digestion, resulting in polypeptides and peptones (incomplete digestion).

• Requires a highly acidic medium for action (optimum pH 2-3.5).

Gelatinase

• Liquefies gelatin.

Gastric Lipase

• Acts on triglycerides, producing fatty acids and monoglycerides (minor role in fat digestion).

Intrinsic Factor

• Glycoprotein secreted by oxyntic cells.

• Essential for vitamin $B_{12}$ absorption in the terminal ileum.

• Its absence leads to pernicious anemia.

Mucus

• Soluble (Thin) Mucus:

  • Produced by cardiac, pyloric, antral, and mucus neck cells in the gastric glands of the body and fundus.

  • Lubricates chyme and protects the mucosa.

• Insoluble (Thick) Mucus:

  • Thick, alkaline mucus secreted by surface epithelial cells.

  • Forms a flexible gel layer (1.5 mm thick) that coats the gastric mucosa.

  • Surface epithelial cells secrete $HCO_3^-$, trapped in the mucus gel, protecting against HCl and pepsin and contributing to food lubrication.

Phases of Gastric Secretion

1. Cephalic Phase:

   • Occurs before food reaches the stomach (cephalic = head).

   • Accounts for 1/3 of gastric secretion.

   • Mediated through conditioned and unconditioned reflexes (neural mechanism).

   • Stimulates vagal nucleus and vagal stimulation.

   • Vagal fibers terminate at the neurons of the enteric nervous system.

     • a) Stimulates oxyntic, peptic, and ECL cells by releasing acetylcholine.

     • b) G cells releases gastrin releasing peptide (GRP) which releases gastrin hormone.

2. Gastric Phase:

   • Occurs when food reaches the stomach.

   • Accounts for 2/3 of gastric secretion.

   • Stimuli:

     • Distention of the stomach with food.

     • Protein (most potent stimulus).

     • Caffeine and alcohol.

   • Mediated by nervous and hormonal mechanisms:

     • Nervous Mechanism:

       • Mechanical and chemical stimulation initiates impulses.

       • Afferent vagal fibers → vagal nucleus → efferent vagal fibers (long vago-vagal reflex).

       • Short local enteric reflex.

     • Hormonal Mechanism:

       • Gastrin secretion mainly due to the local enteric reflex and the vago-vagal reflex.

• Caffeine and alcohol stimulate highly acidic gastric juice secretion, even without food.

  • Avoided by individuals with peptic ulcers and hyperacidity.

1. Intestinal Phase:

   • Occurs in response to chyme in the duodenum.

   • Excitatory (weak) and inhibitory (powerful) components.

     • Excitatory Component:

       • Products of protein digestion stimulate intestinal gastrin secretion, increasing acid and pepsin secretion (minor role).

     • Inhibitory Component:

       • Acidity, fat, osmolarity changes (hypo- or hyperosmolarity), and distention of the duodenum inhibit gastric secretion.

         • Nervous Mechanism:

           • Enterogastric reflex (inhibitory reflex) inhibits oxyntic and peptic cells.

         • Hormonal Mechanisms (Enterogastrones):

           • Several hormones (secreted by special cells in the mucosa of the duodenum and jejunum) inhibit gastric secretion.

           • Include cholecystokinin (CCK, most important), secretin, and glucose-dependent insulinotropic polypeptide (GIP).

Gastric Mucosal Barrier

• Protects the gastric mucosa from damage by HCl and autodigestion by pepsin:

  1. Surface epithelium secretes insoluble mucus, forming a flexible gel layer.

     • pH ranges from 2 at the luminal side to 6-7 at the surface of epithelial cells due to trapped $HCO_3^-$.

  2. Tight junctions between mucosal cells prevent HCl penetration.

  3. The luminal membrane of mucosal cells is impermeable to $H^+$.

  4. Active transport mechanism of $H^+$ from the mucosal surface to the gastric lumen.

  5. Prostaglandins (secreted by surface mucus cells) strengthen the gastric mucosa membrane by stimulating mucus and $HCO_3^-$ secretion.

  6. Continuous regeneration of the gastric mucosa.

Peptic Ulcer

• Lost (eroded) area of gastric mucosa caused by autodigestion by gastric juice.

Causes

• Breakdown of Gastric Mucosal Barrier:

  • By alcohol, aspirin, and bacterial infection (Helicobacter pylori).

  • Leads to diffusion of $H^+$ from the lumen, increasing intracellularly and destroying cell metabolic function, resulting in mucosal ulcer.

• Excess HCl Secretion:

  • In cases of Zollinger-Ellison syndrome, caused by gastrinomas (tumors that secrete gastrin) developing in the stomach, duodenum, and more commonly in the pancreas.