regulation and disorders of gastric acid secretion Flashcards
what is the contents of gastric juice ?
Contents of gastric juice (fasting state):
* Cations: Na+, K+, Mg2+, H+
* Anions: Cl-, HPO42+, SO42-
* Pepsinogen
* Lipase
* Mucus
* Intrinsic factor
pH ~1-3.0
describe the anatomy of the stomach
- Thin-walled upper portion of the stomach (fundus and body): mucus, HCl and pepsinogen
- Thick-walled lower portion (antrum): ↑ gastrin secretion; gastrin mediates acid secretion (HCl secretion)
- Fundus - pepsinogen
- Body has numerous epithelial cells with
numerous tubular glands - Wall of the glands is lined with parietal
cells→ HCl and intrinsic factor - Pylorus- mucus, gastrin
how is gastric acid made in the stomach lumen ?
- HCO3- is exchanged for Cl- (chloride shift) 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)
What is resting juice?
Gastric juice described as resting juice, similar to plasma, secreted by non-parietal cells with ↑HCO3- and ~pH 7.4.
Resting juice refers to the baseline gastric secretion that occurs when the stomach is not actively digesting food.
What is the function of mucus in gastric juice?
Forms an alkaline, thick, and sticky gel on the epithelial surface; ↑HCO3– protects against H+ secretion.
Mucus helps to protect the stomach lining from the acidic environment and digestive enzymes.
What is the role of rennin (chymosin) in the digestive process?
Produced at birth; curdles milk into casein clot; production replaced by pepsinogen.
Rennin is crucial for infants as it helps in digesting milk.
What does lipase do?
Converts triglycerides into fatty acids and glycerol.
Lipase is essential for fat digestion in the stomach and small intestine.
What condition may arise from the absence of lipase?
Steatorrhoea.
Steatorrhoea is characterized by the presence of excess fat in the stool, often due to malabsorption.
What is the function of intrinsic factor in the stomach?
Prevents pernicious anaemia; essential for absorption of vitamin B12.
Intrinsic factor is crucial for vitamin B12 absorption in the small intestine.
What is the main component of gastric acid?
Hydrochloric acid (HCl).
Gastric acid has a crucial role in digestion and maintaining a sterile environment in the stomach.
What are the effects of gastric acid?
Kills bacteria; acid denaturation of digested food; activates pepsinogen to pepsin for protein digestion; promotes gastric lipase action; and secretion of pancreatic HCO3-.
Gastric acid is vital for digestion and protecting against pathogens.
what are the 3 stages of the secretion of gastric juice ?
- At meal times, ↑ HCl secretion
The 3 phases involved: - Cephalic phase
- Gastric phase
- Intestinal phase
how do neuronal pathways and duodenal hormones regulate secretion of gastric juice ?
- Direct pathway, by acting on parietal cells → ↑ acid secretion
- Indirect pathway, by influencing the secretion of gastrin and histamine → ↑ acid secretion
describe the cephalic phase
- Cephalic phase (meal times- smell, sight, taste, chewing)
- ACh stimulates histamine release from ECL cells
- ACh acts directly on parietal cells → HCl secretion
- Gastrin stimulates histamine release from ECL cells
- Gastrin acts directly on parietal cells → HCl secretion
describe the gastric phase
distension of stomach; ↑ peptide concentration): ↑ acidity (↑[H+])
- Acidity of lumen of stomach is ↑ before a meal (no buffers)
- Food mass containing proteins → ↑ peptides in stomach (↑ gastrin secretion)
What do proteins do to luminal acidity?
- Proteins act as buffers in the gastric lumen
And so what? HCl secretion increases
Mechanism explained:
H+ + proteins → ↓ [H +]; protein acts as a buffer; proteins remove the inhibitory powers of HCl on gastrin secretion
This then increases gastrin-mediated acid secretion
Why does acid secretion decrease as the acidity of the lumen increases?
Somatostatin inhibits gastrin-secreting cells (G cells)
describe the intestinal phase
- 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
- Thus, inhibition of acid secretion in the small
intestine depends 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) 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 Direct and indirect actions of the three acid secretagogues: ACh, gastrin, and histamine
what factors cause HCL secretion ?
- Histamine, acetylcholine, gastrin,
- Caffeine, alcohol, NSAIDs, nicotine
- Helicobacter pylori
- Zollinger-Ellison syndrome
- Hyperparathyroidism (8-30%)
*Avoid these drugs if you have peptic ulcer - Note that the [HCl] can reach 150mM, depending on:
- Rate of gastric secretion, motility & rate of gastric emptying
- Amount of diffusion back into mucosa
- Amount of buffering provided by the non-parietal cells
- Composition of ingested food
what is the function of HCL ?
- Defence – kills germs
- Protein digestion: activates pepsinogen to pepsin which initiates protein digestion
- 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
what stimulates the secretion of pepsinogen ?
- 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+)
How does NSAIDs (e.g. aspirin) play a role in gastric acid secretion disorders ?
Neural Stimulation (Gastric Vagus Nerve):
The vagus nerve releases acetylcholine (ACh), which stimulates:
Histamine-secreting cells, leading to the release of histamine.
Mucus-secreting cells, which produce mucus for gastric protection.
Parietal cells via muscarinic receptors, increasing acid secretion.
Hormonal Stimulation (Gastrin):
Gastrin stimulates histamine-secreting cells, which then release histamine.
Histamine binds to H₂ receptors on parietal cells, promoting acid (H⁺) secretion.
Protective Mechanisms (Prostaglandins):
Prostaglandin E₂ (PGE₂) induces vasodilation and promotes mucus secretion, which helps protect the stomach lining.
Effect of Aspirin:
Aspirin blocks the synthesis of PGE₂ and thromboxane A₂ (TXA₂).
This reduces mucus production and vasodilation, making the stomach lining more vulnerable to acid damage, which can lead to ulcers.
what are the Protective factors that prevent autodigestion of the stomach by HCl and pepsin ?
- Mucus layer protects the gastric mucosa from the low pH
- Secretion of alkaline mucus and HCO3-
- Somatostatin inhibits gastrin release (negative feedback control)
- Protein buffers- protein content of food is important
- Epithelial cells remove excess H+ via membrane transport systems; tight junctions of epithelial cells prevent back diffusion of H+ ions
- Prostaglandins (E and I): inhibit acid secretion and enhance blood flow
- Mucosal blood flow removes excess acid that has diffused across the epithelial layer
- Maintenance of mucosal integrity and repair: growth factors (e.g., epidermal growth factor, insulin-like growth factor I)
- Replacement of damaged cells within the gastric pits (crypt cells)
what are some Predisposing factors to peptic ulcer formation ?
- Gastric and duodenal infection with H. pylori is a major risk factor
- H. pylori - acquired in childhood (present in 10-15% of UK population)
- Environmental and host factors can determine the distribution and colonisation of H. pylori in the stomach
- If you have duodenal ulcer, there is 80% chance that you have H. pylori infection
How do NSAIDs (e.g. aspirin) play a role in gastric acid secretion disorders ?
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
how do gastric acid secretion problems lead to disorders ?
GIT function: storage, secretory, digestion, absorption of nutrients, salts, water, metabolism and elimination of (undigested) wastes
Malformation of GIT: ↓ nutrient status of the individual
Peptic ulcer and mechanism of peptic ulcer formation
10% of population affected by ulcers
Sites affected: Oesophagus, stomach and duodenum
Breakage of mucosal barrier]
…imbalance between protective and damaging factors of GIT
…exposure of tissues to the erosive effects of gastric acids (HCl, bile acids) and pepsin
what are some areas of the alimentary tract where ulcers are common ?
Distal oesophagus, especially in Barrett’s oesophagus
The stomach – junction of antrum and body
Duodenal cap/ampulla: first part of the duodenum; smooth walled; dilated; mesenteric
Meckel’s diverticulum – outpouching or bulge in the small intestine (congenital)
Weight loss surgery (gastroenterostomy) weight loss
what are the causes of peptic ulcers ?
Causes of peptic ulcer:
Hyperacidity; reflux of duodenal contents (oesophagus, stomach and duodenum)
Presence of H. pylori is a risk factor for gastric cancer – eradication → ↓ risk
NSAIDs; genetic factors; sex – being male?
Outcome:
Complete healing and replacement of tissue and some scarring
what is a chronic peptic ulcer ?
Chronic peptic ulcer is common
Occurs in upper GIT (pepsin and HCl)
Asymptomatic in >80% of people
common in over 50s; low incidence in young
90% incidence in developing countries
Inflammation plays a key role in the disease process
what is an acute peptic ulcer ?
Acute peptic ulcer: less frequent
Develops from areas of corrosive gastritis (oesophagus, stomach, proximal duodenum), severe stress or shock (burns, trauma)
Acute hypoxia of surface epithelium (i.e., ischaemia of gastric mucosa)
Outcomes:
Severe bleeding
Heal with no scarring
Chronic peptic ulcer
what are the virulence factors of H pylori ?
Motility: flagella; helps move it closer to the epithelium (pH 7)
Produces urease (converts urea to ammonia, which buffers gastric acid and produces CO2)
Cytotoxin-associated antigen (CagA) – inserts pathogenicity islands and confers ulcer-forming potential
Vacuolating toxin A (VacA) – alters the trafficking of intracellular protein in gastric cells
A large number of outer membrane proteins: Adhesins (BabA), phospholipases, porins, iron transporters, and flagellum-associated proteins
H. Pylori is the commonest cause of peptic ulcer – ↑peptic ulcer risk by 10-20%
how are ulcers investigated ?
Diagnostic tests
Endoscopy (oesophagogastroduodenoscopy, EGD)
Histological examination and staining of an EGD biopsy
Test for the presence of H. pylori
Stool antigen test
Evaluate urease activity
Urea breath test
what are the complications of a peptic ulcer ?
Haemorrhage (GI bleeding)
Perforation (peritonitis) and penetration (liver and pancreas may be affected); leakage of luminal contents
Narrowing of pyloric canal (stricture causing acquired pyloric stenosis in the stomach) or oesophageal stricture
Malignant change becomes 3-6 times likely with H. pylori infection
