Regulation of gastric acid secretion Flashcards
Describe the anatomy of the stomach
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Describe the contents of the gastric juice
- Cations: Na+, K+, Mg2+, H+
- Anions: Cl-, HPO42+, SO42-
- Pepsinogen
- Lipase
- Mucus
- Intrinsic factor
- pH ~3.0
How much gastric juice is added to intestinal contents every day?
2.5L/day
What is the upper portion of the stomach called and what does it secrete?
Thin-walled upper portion of the stomach (fundus and body): mucus, HCl and pepsinogen
What is the thick lower portion of the stomach called? and what does it secrete?
Thick-walled lower portion (antrum): ↑ gastrin secretion; gastrin mediates acid secretion (HCl secretion)
Describe the structure of the fundus
- Body has numerous epithelial cells with numerous tubular glands
- Wall of the glands is lined with parietal cells→ HCl and intrinsic factor
How is gastric acid (HCl) made in the stomach lumen?
- HCO3- is exchanged for Cl- in the blood → ↓ acidity of venous blood from stomach compared to blood serving it
- Excess Cl- diffuses out into the stomach through chloride channels; K+/H+-ATPase pumps H+ out into stomach lumen
- Net effect = net flow of H+ and Cl – (forming HCl) out of the parietal cell and into stomach lumen (-stomach secretes ~2L of HCl/day at 150mM)
Describe the mucus, rennin, lipase and intrinsic factor gastric secretions and what they do
• Technically, some amount of gastric juice is described as resting juice (= plasma, but alkaline, pH 7.4 - 7.7; ↑HCO3-)
• Mucus: alkaline, thick and sticky, forms water-insoluble gel on epithelial surface; ↑HCO3– protect against H+ secretion
• Rennin (chymosin): curdles milk into casein clot
• Lipase: triglycerides → fatty acids and glycerol
What will happen if you do not release lipase?
• Intrinsic factor (prevents pernicious anaemia): absorption of vitamin B12
What is the function of HCl?
- Kills bacteria; acid denaturation of digested food; creates the optimum pH for the activation of pepsinogen to pepsin for protein digestion
- Promotes the action of gastric lipase; and the secretion of pancreatic HCO3-
What is the difference between parietal secretions and non-parietal secretions?
non-parietal cells = non-parietal juice, similar to plasma pH 7.4
Parietal cells = parietal cell juice ( 170mM HCl, 10 mM K+ and low Na+)
Give a summary of the inputs regulating parietal cell acid secretion that occurs during the cephalic and gastric phases for digestion
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Describe the intestinal phase
What inhibits acid secretion?
Intestinal phase: balances the secretory activity of the stomach and the digestive and absorptive capacities of small intestine
• High acidity of duodenal contents reflexly inhibits acid secretion
Increased acidity inhibits the activity of digestive enzymes, bicarbonate and bile salts
• Distension of duodenum, hypertonic solution, amino acids, fatty acids, monosaccharides all inhibit acid secretion
What does inhibition of acid secretion in the small intestine depend on?
- Composition of chyme
- Volume of chyme
- Distension of duodenum
How is acid secretion inhibited during the intestinal phase?
• Short and long neuronal reflexes and hormones (enterogastrones, e.g. secretin, CCK and GIP) inhibit acid secretion by the parietal cells or gastrin secretion by the G cells, which is inhibited by somatostatin (stomach, intestine, delta cells of pancreas, hypothalamus, brainstem, hippocampus)
Describe the role of histamine, acetylcholine and gastrin in gastric acid secretion
What is the role of PEG2?
- Histamine, ACh, and gastrin binding to their receptors on parietal cells → ↑↑HCl secretion
- PEG2 promotes bicarbonate secretion, blood flow, mucus secretion. These are all gastroprotective
Describe the direct and indirect actions of ACh, gastrin, and histamine
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What chemicals cause HCl secretion to increase
• Histamine • Acetylcholine • Gastrin • Caffeine* • Alcohol* • NSAIDs* • Nicotine* • Helicobacter pylori • Zollinger-Ellison syndrome • Hyperparathyroidism (8-30%) • Bile salts • Genetic? *Avoid these drugs if you have peptic ulcer
Why is HCl essential for life?
- Defence – kills germs
- Protein digestion: activates pepsinogen to pepsin
- Lack of HCl causes failure of protein digestion (achlorhydria or hypochlorhydria = production of gastric acid in the stomach is absent or low)
- Stimulates flow of bile and pancreatic juice (HCO3–rich watery secretions)
- Promotes the action of gastric lipase
When can HCl reach 150mM?
- Rate of secretion
- Amount of buffering provided by the resting juice
- Composition of ingested food
- Gastric motility
- Rate of gastric emptying
- Amount of diffusion back into mucosa
What stimulates the secretion of pepsinogen?
Describe the mechanism of action of pepsinogen secretion
- Inputs to chief cells from nerve plexus
- There are parallels between gastric acid secretion and pepsinogen secretion
- Stimulators/inhibitors of acid secretion during the cephalic and intestinal phases exert same effect on pepsinogen secretion
- Secreted by chief cells in the form of pepsinogen (inactive, a zymogen)
- Activated if [H+] is high; shape altered by high acidity which exposes its active site
- Autocatalytic feedback process
- Inactivated upon entry of food in the small intestine (HCO3- and peptides neutralise the H+)
What is the point of pepsin secretion?
- Initiates digestion of proteins - degrades food proteins into peptides
- But pepsin is not required for food digestion
Which other enzymes could digest proteins?
A required substance secreted by the parietal cells is intrinsic factor
How do NSAIDs (e.g. aspirin) play a role in gastric acid secretion disorders?
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- NSAIDs = acidic, cause topical irritation of gut
- …impair the barrier properties of mucosa
- …suppress gastric prostaglandin (PG) synthesis
- …↓ gastric mucosal blood flow
- …interfere with the repair of superficial injury
- …inhibit platelet aggregation
- Presence of acid in the stomach promotes NSAID-mediated gastric disorder
how?
- Impairs restitution process
- Inactivates FGF which interferes with the haemostasis process
- Way forward = discover and develop stomach-sparing NSAIDs
