Gastric Secretion: An Overview

• The topic is gastric secretion.

Structural Bases

• The stomach is a J-shaped sac situated between the esophagus and the duodenum.
• It is closed at its ends by two sphincters: the cardia (upper) and the pylorus (lower).

Gastric Juice

• Consists of: Study methods, Description, and Composition.

Secretion Control

• Includes: Hormonal regulation, Nervous regulation, and Implementation of control.

Role of Gastric Juice

• Explores function and includes: Actions in the blood, and Actions in the gastric juice.

Physiopathology

• Concerns insufficiencies and hypersecretions.

Structural Bases of Gastric Secretion

• The stomach serves as an expandable reservoir between the cardia and pylorus sphincters.
• The proximal region consists of the fundus and body for receiving and storing via muscle relaxation.
• This aids the emptying of liquids.
• The distal region includes the antrum and pylorus.
• It facilitates muscle contractions, churning of gastric chyme, and emptying of solids.

Regions of the Fundus

• Contains: main cells (pepsin), parietal cells (HCl and FI), and mucous cells (mucus).

Region of the Antrum

• Consists of: endocrine G cells (gastrin), mucous cells (mucus), and enterochromaffin cells (histamine).

Gastric Juice Study Methods

• Gastric juice is hard to study, except in animals.
• Gastric pouches allow communication between the stomach and the exterior.
• Tubing can be used in humans, however are subject to salivary contamination.

Gastric Juice - Description

• It is a colorless, odorless, acidic liquid with a pH less than 3.
• It is slightly viscous due to mucus, with a volume of 1.5 to 2 liters per day, varying with meals.

Gastric Juice - Composition

• Mineral elements are present: H+ (0 to 150 mEq/L), Cl- (120 to 170 mEq/L), and Na+ (10 to 100 mEq/L).
• Also contains HCO3-, K+, Mg2+, and P.
• Electrolyte concentrations vary with the rate of secretion.

Organic Substances - Proteins

• Pepsin is the only gastric enzyme in humans.
• It is secreted by the chief cells of the fundus and acts only at an acidic pH of around 2.
• It hydrolyzes proteins into peptones and functions as an endopeptidase.
• Pepsin is produced by pepsinogen reacting with HCl resulting in pepsin and an inactive peptide.
• The formed pepsin acts on pepsinogen to activate it.

The Mucus

• It comprises polypeptide chains and glucidic chains.
• It includes glycoproteins, mucopolysaccharides = mucins
• There are neutral mucins, sialomucins, and sulfomucins.

The Intrinsic Factor (IF)

• A glycoprotein secreted exclusively in humans by parietal cells.
• It's stored in the liver and aids in the intestinal absorption of Vitamin B12.
• It plays a crucial role in hematopoiesis (red blood cell formation).

Gastric Secretion Control - Hormonal Regulation

• Agents of control are stimulating and inhibiting.

Stimulating Agents

• Gastrin is a protein hormone secreted by endocrine G cells, located in the antrum, duodenum, jejunum, and endocrine pancreas.
• Molecular forms include:
• G 17 is abundant in the antrum.
• G 34 is abundant in the duodenum.
• G 14 exists
• The tetrapeptide C terminal supports biological activity.
• Pentagastrin being a synthetic hormone used in functional exploration.

Other Stimulating Agents

• Histamine is a cytokine in the immune system, skin, stomach, and vertebrate brain.
• It induces acidic gastric secretion via H2 receptors on parietal cells.
• Insulin-induced hypoglycemia stimulates secretion
• It has an indirect effect via the vagus nerve.

Inhibitory Agents

• Antral acidification gives negative feedback dependent on pH decrease.
• Intestinal agents are inhibitory.
• Secretin, a protein hormone, is released by endocrine S cells due to duodenal acidification.
• GIP (Gastric Inhibitory Peptide) inhibits.
• VIP (Vasoactive Intestinal Peptide) inhibits.

Factors for Gastrin Release

• These include mechanical distension of the antrum.
• Secretagogue foods (proteins, peptones).
• Alkalinization of the antrum (pH neutral or alkaline).
• The vagus nerve.

Inhibition Factors

• Acidification of the gastric contents gives negative pH-dependent feedback.
• Intestinal hormones such as secretin, somatostatin, and glucagon are inhibitory.

Biological Effects of Gastrin

• Gastrin stimulates parietal cells, causing rapid secretion of H₂O, HCl, and IF.
• It stimulates principal cells less powerfully than the vagus nerve.
• Has a trophic action on the gastric mucosa.
• Increases tone of the lower esophageal sphincter (LES)

Nervous Regulation of Secretion

• The vagus nerve is a key component of nervous regulation.
• Stimulation of this nerve leads to gastric secretion rich in pepsin and HCl.
• Occurs via direct action on fundus cells and action on endocrine G cells that secrete gastrin.
• It increases parietal cell sensitivity to gastrin.
• Vagotomy reduces Parietal cell response to Gastrin and Antrectomy reduces Parietal cell response ot the Vagus nerve.
• Together they have Vago-gastric synergy

Control Mechanisms

• Basal gastric secretion occurs in low quantities outside of meals.
• It varies by gender and age.
• Significant gastric secretion occurs during meals, reaching a maximum.
• and then gradually declines over 4 to 5 hours.
• There are 3 main phases.

Cephalic Phase

• Smelling or tasting a pleasant meal stimulates gastric secretion through a purely nervous action (vagus nerve).
• This phase involves stimulation via the nervous system.
• Centers in the hypothalamus and cerebral cortex.
• The efferent pathway is actioned by the vagus nerve.

Gastric Phase

• It is a neuro-hormonal phase due to direct contact of food with the gastric mucosa.
• Food in the stomach causes secretion of Gastrin and HCl
• There is a Feed-back loop.

Intestinal Phase

• It involves the slowing down of the gastric acid secretion.
• This is caused by the release of intestinal hormones like secretin, VIP, and GIP.
• That counteract acid secretion by exerting negative feedback on parietal cells.
• HCl in the duodenum promotes Secretin-GIP-VIP secretion, decreasing gastric juice.

Role of Gastric Juice

• Concerns role of HCl, Pepsin, Intrinsic Factor, ad Mucus.

Role of HCl

• It ensures an optimal pH for pepsinogen activation into pepsin.
• Has a bacteriostatic role by stopping the development of bacteria and sterilizing the gastric content.
• It stimulates duodenal secretin release.
• Promotes absorption of Calcium and iron.
• Iron exists in two forms: ferrous (Fe2+) or ferric.
• Iron is absorbed in the intestinal level as Fe2+.
• Dietary iron reduces Fe3+ to Fe2+

Pepsin

• Hydrolyzes proteins initiating proteolysis into peptones.

Intrinsic Factor (IF)

• It plays a key role in intestinal absorption of vitamin B12 in the ileum.
• Malabsorption of Vitamin B12 leads to Biermer's anemia.

Mucus

• Protects against auto-digestion from acid and pepsin.

Functional Exploration

• Includes actions done in the blood.
• Gastrin, VIP, and GIP dosage analysis.
• Tubing is used for gastric acid secretion measurement.
• Basal secretion spontaneously with subject fasting.
• Stimulated secretion is aided by Pentagastrin mimicking Gastrin effects.
• And insulin injection that aid the vagus nerve

Physiopathology

• Studies secretory insufficiencies in relation to acid hypersecretion.

Secretory Insufficiencies

• These are Atrophy of Parietal and Principal Cells due to Chronic atrophic gastritis.
• Involves, Atrophy of fundic glandular tissue, and decreased number of Parietal Cells.
  • Decreased HCl with a Lack of IF, causing Vitamin B12 deficiency and Biermer's anemia.

Acid Hypersecretions

• They lead to ulcerative diseases, resulting in loss of substance in the gastric mucosa.
• Involves aggressive factors and defense factors.

Aggressive Factors

• Include: Acid hypersecretion (Zollinger-Ellison syndrome).
• Non-Steroidal Anti-Inflammatory Drugs (NSAIDs), and Helicobacter Pylori (HP).

Defensive Factors

• Include: Mucus, HCO3-, Prostaglandins, Cellular barrier, Angiogenesis, and Mucosal blood flow.
• They protect the gastric mucosal barrier from acid aggression.

Zollinger-Ellison Syndrome

• Involves a gastrin-secreting tumor causing hypergastrinemia, leading to excessive gastric acid secretion
• Results in aggressive and refractory gastroduodenal ulcers

AINS

• NSAIDs decrease prostaglandin secretion, reducing mucus secretion.
• It causes acid-peptic autodigestion and gastric ulcers.

Helicobacter Pylori (HP)

• Is a bacteria colonizing the gastrointestinal system of mammals.
• Active in very acidic environments.
• Increases Gastric acidity, creating erosion of gastric and duodenal mucosa.
• Presence of HP in the Fundus leads to gastritis and antrum ulcers.
• HP in the Antrum promotes duodenal ulcers.

Treatment

• Treatment is medical or surgical.
• For medical conditions Anti-secretories are used.
• Anti-Cholinergics: Inhibit vagus nerve action (Atropine).
• Proton Pump Inhibitors (PPI) inhibit the H+/K+-ATPase pump.
• H2 Receptor Antagonists (Cimetidine, Ranitidine, etc.).
• Antihistamines that act on histamine

Medical

• The primary goal of antisecretory is to reduce acid secretions.
• Gastric Bandages:
• Forms protective barriers between the mucosa.
• Eradication of Hp, given in combination with Amoxicillin, Metronidazole and Claritromycin.

Surgical Treatment

• Includes Vagotomy to limit the vagus nerve
• And Antrectomy to remove the antra.