Peptic Ulcers Flashcards
Define peptic ulcer
An area of damage to the:
• inner lining of the stomach (gastric ulcer)
OR
• the upper part of the duodenum (duodenal ulcer)
How can the 2 different ulcers be distinguished?
Based on TIMING of symptoms:
Gastric ulcer
• pain at mealtimes when acid is secreted
Duodenal ulcer
• pain relieved by a meal as the pyloric sphincter closes (pain starts after 2-3hours)
Explain the protective factors of the GI barrier
Lubricate the food and protect the mucosal surface:
- mucus from gastric mucosa creates a gastrointestinal mucosal barrier
- HCO3- ions are trapped in the mucous and generate a protective pH of 6-7 at the mucosal surface
- locally produced prostaglandins stimulate mucus and bicarbonate production (paracrine action), inhibit gastric acid secretion and facilitate a good blood supply to the stomach.
Some factors that convert the food into chyme can damage the mucosal barrier - explain
Parietal cells
– acid secretion from parietal cells of the oxyntic glands in the gastric mucosa
Chief cells
– pepsinogens which erode the mucous layer
Factors that contribute to mucosal damage?
o Increased acid or decreased HCO3-
o Decreased thickness of mucosal layer
o Increase in pepsin type 1
o Decreased mucosal blood flow
o Infections with H. pylori
o Risk factors – genetics, stress, diet (alcohol, smoking)
5 types of drugs for anti-ulcers?
- Antibiotics
• eradicate H.pylori - Inhibitors of gastric acid secretion
• prevent gastric acid production - Cytoprotectice drugs
• promote healing - Antacids
• neutralise gastric acid - Triple therapy
Why are antibiotics used as a drug against peptic ulcers?
Eliminates H.pylori
• cause of ~100% dudodenal & ~80-90% gastric ulcers
How does H.pylori contribute to ulcer formation?
- Increased gastric acid formation
• increase gastrin OR decrease somatostain - Gastric metaplasia
• due to excessive acid exposure - Downregulation of defence factors
• decrease epidermal GF
• decrease HCO3- production
What contributes to the virulence of H.pylori?
Urease
- Catalyses urea –> ammonium chloride + monochloramine
• damages epithelial cells - Antigenic
• evokes I.R - Certain strains produce CagA (antigenic) & VacA (cytotoxic)
• more intense tissue inflammation
Example antibiotics used?
Amoxicillin
Clarithromycin/Metronidazole
(antibiotics used agaisnt H.pylori)
What is included in gastric acid inhibitors?
- Proton pump inhibitors
- H2 receptor antagonists
- Anti-muscarinics
Drugs associated with the inhibitors of gastric acid secretion
- Proton pump inhibitors
• Omeprazole - H2 receptor antagonists
• Cimetidine, Ranitidine
Explain how gastric acid is produced in the body
- Presence/smell of food can trigger acid production
- In the fundus, there are acid-secreting parietal cells
• PNS can act on H-cells to stimulate histamine production - In the antrum, aa can trigger the g-cells to secrete gastrin
• gastrin triggers MORE histamine release OR can simply trigger MORE acid production directly (CCKB receptors)
Acid is produced by the H+/K+ exchanger
Histamine then acts on H2 receptors on parietal cells to trigger activation of these exchangers via a cAMP-pathway
Superficial epithelial cells provide the protective HCO3- secretion which mixes with the mucus to protect.
MoA of PPIs e.g. Omeprazole
Inhibits basal and stimulated gastric acid secretion by >90%
MoA
• irreversible inhibitor of the H+/K+ ATPase exchanger
Becomes inactive at neutral pH – limits the action on other PPs around the body
Accumulates at the canaliculi as it is a weak base – concentrates action at the canaliculi
How do PP work and contribute to ulcer formation?
Expressed on secretory vesicles within parietal cells
• increase [Ca2+] = increase cAMP = secretory vesicles translocate to parietal cell apical surface = H+ secretion
Ulcer formation:
• increased activity of PP = increased H+ secretion = reduction in gastric pH
MoA of H2-receptor antagonists?
Inhibit gastric acid secretion by parietal cells
• LESS effective than PPIs
• MoA = competitive H2-receptor antagonists
What is an issue with H2-receptor antagonists however?
Relapse are LIKELY after withdrawal from treatment
• HENCE is part of triple therapy
What helps regulate gastric acid?
- ACh
• released from neurones
• acts on muscrainic receptors (M3)
• INCREASE [Ca2+] = increase H+ - Prostaglandins
• released from local cells
• act on EP3 receptors
• DECREASED cAMP = increase H+ - Histamine
• released from enterchromaffin-like cells
• acts oh H2-receptors
• INCREASE cAMP = increase H+ - Gastrin
• released from G-cell
• acts on cholecystokinin B receptors
• INCREASE [Ca2+] = increase H+
Explain what molecules have an effect on gastric acid secretion
o INCREASED [Ca2+] & cAMP
• translocation of secretory vesicles to PARIETAL CELL apical surface
• INCREASE H+ SECRETION
o Somatostatin
• peptide that inhibits G-cells, ECL cells & parietal cells
