Regulation and Disorders of Gastric Secretion Flashcards
What are the contents of gastric juice?
Cations: Na⁺, K⁺, Mg²⁺, H⁺ Anions: Cl⁻, HPO₄²⁺, SO₄²⁻ Pepsins: secreted by chief cells Lipase: converts TG → FA and glycerol Mucus Intrinsic factor: secreted by parietal cells
How much gastric acid is in the body?
Gastric juice adds ~2.5 L/day to intestinal contents
What is the pH of gastric secretions?
pH ~3.0
Describe the structure and secretions at the top of the stomach
Thin-walled upper portion of the stomach (fundus and body) secretes mucus, HCl and pepsinogen
Describe the structure and secretions of the lower stomach
Thick-walled lower portion (antrum): ↓HCl secretion, but ↑ gastrin secretion which mediates acid secretion ∴ ↑ HCl secretion esp. In body of stomach
What is the top of the stomach called?
Fundus
Describe the structure of the stomach body
Body has numerous epithelial cells with numerous tubular glands
What is the lower half of the stomach called?
antrum
What is the pylorus?
opening from stomach into duodenum
What is the role of the stomach glands ?
Wall of the glands is lined with parietal cells
→ HCl and intrinsic factor
What are the exocrine secretions of the stomach?
Exocrine secretion of the stomach: mucus, acid, pepsinogen
Describe the secretions of the enterochromaffin-like cells
(ECL) → paracrine agents, e.g. histamine
Where is gastric acid produced?
in stomach lumen
Explain how gastric acid is produced
HCO₃⁻ dissociates into blood and is exchanged for Cl⁻
=> ↓ acidity of venous blood from stomach compared to blood serving it
Excess Cl⁻ diffuses into stomach through chloride channels as H+ is pumped into stomach lumen
(K+/H+-ATPase pumps H+ out into stomach lumen
What is the net effect of gastric acid production?
Net effect = net flow of H+ Cl⁻ out of the parietal cell and into stomach lumen (-stomach secretes ~2L of HCl/day at 150mM)
What is ‘resting juice’?
Some amount of gastric juice is described as resting juice - plasma, but alkaline (pH 7.4-7.7) due to ↑HCO₃⁻
Describe the composition of mucus
alkaline, thick and sticky; ↑HCO₃⁻; forms water-insoluble gel on epithelial surface; protects against H+ secretion
What is the role of renin?
curdles milk into casein clot
What is the role of lipase?
converts triglycerides → fatty acids and glycerol
How does pancreatic insufficiency affect lipase function?
pancreatic insufficiency = inhibits lipase production; faeces is v. sticky & smelly
What is the role of intrinsic factor?
(prevents pernicious anaemia): absorption of vitamin B12
When is HCl secretion increased?
At meal times,
Which phases are involved in food digestion and absorption?
- Cephalic
- Gastric
- Intestinal phases
How is HCl secretion regulated?
HCl secretion is regulated by neuronal pathways and duodenal hormones
How is HCl secretion directly regulated?
Directly; neuronal / hormones act on parietal cells → ↑ acid secretion
How is HCl secretion regulated indirectly?
Indirectly, on ECL cells influence the secretion of gastrin and histamine → parietal cells which ↑ acid secretion
Describe HCl secretion during the cephalic phase?
smell, sight, taste, chewing: ACh release
ACh stimulates histamine release from ECL cells
ACh acts directly on parietal cells → HCl secretion
What is the role of D cells?
stimulated due to increased acid secretion, releasing somatostatin which has inhibitory effects on ECL, Parietal cells by inhibiting G cells so acid doesn’t damage GI
What occurs during the gastric phase?
(distension of stomach; ↑ [peptide] ↑acidity (↑[H+]) - important quantitatively
How does acid secretion alter due to lumen acidity?
Acid secretion decreases as the acidity of the lumen increases
Describe the stomach acidity before a meal
Acidity of stomach lumen is ↑ before a meal (no buffers)
Describe the effect of proteins on gastric secretions
More proteins = ↑ peptides in stomach (↑ gastrin secretion)
Proteins act as buffers in the gastric lumen
HCl secretion increases, increasing luminal acidity
Outline the mechanism of protein action on gastric secretions
H+ & proteins → ↓ [H +]; by acting as buffer, proteins remove the inhibitory powers of HCl on gastrin secretion and so acid secretion also decreases
This then increases gastrin-mediated acid secretion
Why are people with acid secretion problems advised not to eat high protein diets?
A meal (peptides, amino acids) elicits feedback inhibitory and stimulatory signals which ultimately increase acid secretion via stimulation of gastrin secretion
Describe what happens during the intestinal phase
Balances secretory activity of stomach and digestive & absorptive capacities of small intestine
High acidity of duodenal contents reflexly inhibits acid secretion
What is the effect of increased acidity?
Increased acidity will inhibit the activity of digestive enzymes, bicarbonate and bile salts
What decreases acid secretion in the stomach?
Distension of duodenum, hypertonic solution, amino acids, fatty acids, monosaccharides all inhibit acid secretion
What does inhibiting gastric acid secretion in the small intestine depend upon?
Composition and volume of chyme
Describe how acid secretion is inhibited during the intestinal phase
Short and long neuronal reflexes and hormones inhibit acid secretion by the parietal cells / gastrin secretion by the G cells
What hormones inhibit acid secretion?
enterogastrones, e.g. secretin, CCK and GLP) inhibit acid secretion by the parietal cells or gastrin secretion by the G cells
What is G cell activity inhibited by?
somatostatin
Where is somatostatin released from?
stomach, intestine, delta cells of pancreas, hypothalamus, brainstem, hippocampus
What are the long neural reflexes causing inhibition of gastric acid secretion?
increase sympathetic (inhibitory) discharge decrease parasympathetic (stimulatory) discharge decrease contractions (NO and VIP are involved)
What short neural reflexes regulate gastric acid secretion?
Via enteric neurons
What is non-parietal secretions?
Non-parietal secretions contain resting juice = plasma; but alkaline, pH7.4; ↑HCO₃⁻
Which factors increase HCl secretion?
Histamine Acetylcholine Gastrin Caffeine* Alcohol* NSAIDs* Nicotine* Helicobacter pylori Zollinger-Ellison syndrome Hyperparathyroidism Stress Bile salts Genetic?
*avoid these drugs if peptic ulcer present
Summarise what increases HCl secretion
Histamine, ACh, and gastrin binding to their receptors on parietal cells → ↑↑HCl secretion
What is the effect of PGE2 on HCl secretion?
PGE2 negatively regulates HCl secretion - Promotes mucus and bicarbonate secretion
What is a secretagogue?
a substance which promotes secretion
What are the 3 acid secretagogues?
ACh, Gastrin and histamine have direct and indirect actions
What factors increase [HCl]?
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
Explain the significance of HCl
essential for life:
Defence
Protein digestion: activates pepsinogen to pepsin
Stimulates flow of bile + pancreatic juice
Lack of HCl = failure of protein digestion (achlorhydria or hypochlorhydria = production of gastric acid in stomach is absent/low)
What causes pepsinogen secretion?
Inputs to chief cells from nerve plexus stimulates the secretion of pepsinogen
How is pepsinogen secretion regulated?
Stimulators/inhibitors of acid secretion during the cephalic and intestinal phases exert the same effect on pepsinogen secretion
What effect does H. pylori have on D and G cells?
H. pylori infection decreases the number of D- and G-cells
Explain how the proenzyme pepsinogen is activated
Secreted by chief cells in the form of pepsinogen (inactive)
When [H+] is high it’s activated; 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+)
Where is pepsinogen released and activated?
stomach lumen
What are the functions of pepsin secretion?
Initiates digestion of proteins - degrades food proteins into peptides
But pepsin is not required for food digestion
A required substance secreted by the parietal cells is intrinsic factor
What are the symptoms of HCl deficiency?
Presence of undigested food in stool
Flatulence = bloating
White spots on fingernail?
Drowsiness after meals??
Lack of intrinsic factor?? (vitamin B12 deficiency →pernicious anemia)
Increases the chances of H. pylori infection
What are the treatments available for HCl deficiency?
Bitter herbs may stimulate HCl secretion
Dandelion, devil’s claw, yarrow and wormwood teas may be useful.
Lemon juice and vinegar stimulate HCl secretion
Vitamin B12 stimulates HCl secretion by the stomach
How do NSAIDs contribute to gastric secretion disorders?
Topical irritation of gut
Impair the barrier properties of mucosa - blocks PGE2
Suppress gastric prostaglandin synthesis
↓ gastric mucosal blood flow
Interfere with the repair of superficial injury (AX2)
Inhibit platelet aggregation
Explain how stomach acidity increases risk of NSAID-mediated gastric disorder
Presence of acid in the stomach promotes NSAID-mediated gastric disorder
Impairs restitution process
Inactivates FGF which interferes with the haemostasis process - blood in faeces
What is the function of the GI tract?
storage, secretory, digestion, absorption of nutrients, salts, water, metabolism and elimination of (undigested) wastes
What is the consequence of GI tract malformation?
Malformation of GIT leads to ↓ nutrient status of the individual
Which sites in the body are affected by peptic ulcers?
Oesophagus (due to reflux), stomach and duodenum
Outline the mechanism of peptic ulcer formation
- Breakage of mucosal barrier
- Causes imbalance between protective + damaging GIT
factors - Leads to exposure of tissues to erosive HCl effects,
bile acids and pepsin
What factors lead to Gastric acid secretion disorders?
Same factors that increase HCl secretion:
Histamine
Acetylcholine
Gastrin
Food/protein, alcohol, smoking, caffeine, NSAIDs
Zollinger-Ellison syndrome
Hyperparathyroidism
Stress - Can aggravate it once ulcer is present
Bile acids are irritants
Genetic?
Helicobacter pylor
When are peptic ulcers commonly formed?
Peptic ulcers are common in the following:
Duodenal cap: first part of the duodenal cap
The stomach – junction of antrum and body
Distal oesophagus, especially in Barrett’s oesophagus
Meckel’s diverticulum
After gastroenterostomy (weight loss, recurrent pains, ulcers)
What is meckel’s diverticulum?
a true congenital abnormal pouch in intestine
What are the causes of peptic ulcer formation?
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
What is the long term effect of a peptic ulcer?
Complete healing and replacement of tissue and some scarring
Outline the clinical features of a chronic peptic ulcer
Chronic peptic ulcer is common
Occurs in upper GIT (pepsin + HCl)
Asymptomatic in >80% of people
Low incidence in young; common in over 50s
90% incidence in developing countries
Inflammation plays key role in disease process
Outline features of an 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)
What are the long term outcomes of an acute peptic ulcer?
Severe bleeding
Heal with no scarring
Chronic peptic ulcer
What factors can predispose a peptic ulcer?
Gastric and duodenal infection with H. pylori is a major risk factor
Describe H. Pylori features
H. pylori is 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 a duodenal ulcer, there is 80% chance that you have H. pylori infection
What are the functions of HCl and pepsin?
Kill aerobic microorganisms
↓ infection of gastric mucosa
What other factors prevent gastric mucosa infections?
Mucus production Peristalsis and fluid movement Seamless epithelium with tight junctions Fast cell turnover IgA secretion at mucosal surfaces Peyer’s patches – protection
How is stomach autodigestion prevented?
Secretion of alkaline mucus and HCO3-
Protein content of food
Presence of tight junction between the epithelial cells lining the stomach and fibrin coat
Replacement of damaged cells within the gastric pits
Prostaglandins (E and I): inhibit acid secretion and enhance blood flow
How is the stomach protected from it’s own low pH?
Mucus, secreted by neck and surface mucous cells in the body and fundus and similar cells elsewhere in the stomach form a water-insoluble gel that coats the mucosa from the low pH
What is the significance of H. Pylori in the gut?
The virulence factors enable H. pylori attach and colonise the gastric epithelium
Gram negative; spiral shaped (can be coccoid too) aerobic bacterium
Penetrates gastric mucosa (able to survive under the harsh condition of the stomach)
Highly pathogenic, with many virulence factors
The flagella enable its ‘corkscrew’ motility towards the gut epithelium
What are the different bacteria shape types?
Coccus (round)
Bacillus (rod shaped)
Spirochetes (spiral)
Explain how H. pylori causes Peptic ulcer formatoin
Flagella; moves close to epithelium (pH 7) Produces urease (converts urea to ammonia, buffering gastric acid + produces CO2)
Cytotoxin-associated antigen (CagA) – inserts pathogenicity islands + confers ulcer-forming potential
Vacuolating toxin A (VacA) – alters trafficking of intracellular protein in gastric cells
Large number of outer membrane proteins: Adhesins (BabA), phospholipases, porins, iron transporters, and flagellum-associated proteins
H. Pylori is commonest cause of peptic ulcer – ↑peptic ulcer risk by 10-20%
What diagnostic tests are carried out to detect peptic ulcers?
Endoscopy (oesophagogastroduodenoscopy, EGD)
Histological examination and staining of an EGD biopsy
How is H. pylori detected?
Test for the presence of H. pylori
Stool antigen test
Evaluate urease activity
Urea breath test
what complications are associated with peptic ulcers?
Haemorrhage (GI bleeding)
Perforation (peritonitis) + penetration (liver & pancreas may be affected); leakage of luminal contents
Narrowing of pyloric canal (stricture = acquired pyloric stenosis in stomach) or oesophageal stricture
Malignant change becomes 3-6 times likely with H. pylori infection
