Peptic Ulcers Flashcards
Primary function of GIT
Break down food into nutrients allowing it to be absorbed
- Digests food – Break down of large food into molecules
- Absorbing nutrients – From intestine to bloodstream
- Eliminating waste – Food not digested/absorbed is eliminated
The stomach
Breaks down food into chyme
Parietal cells produce HCl
Chief cells produce pepsinogen (precursor of pepsin activated at low pH)
Mucus/bicarbonate/water – Lubricates stomach and protects it from injury
Intrinsic factor of parietal cells increase cobalamin (vitamin B12 absorption)
The layers of the stomach are epithelium, mucosa (where gastric glands and cells are found), muscular layer and serosa
Gastric gland
Consists of surface epithelium
Neck cell produce mucus and bicarbonate
Parietal cell produce HCl and intrinsic factor
Enterochromaffin like cell (ECL) produce histamine
G cell produce gastrin
D cell produce stomatin
Process of gastric acid secretion
Takes place in parietal cells
Produce isotonic solution of chloridinic acid of 150 mmol/L with a pH less than 1
Concentration of H+ greater inside
Choride ions actively transported into canaliculi in the cell
Chloride secretion followed by potassium secretion
Potassium ion exchanged with H+ from inside the cell by K+H+ATPase proton pump bringing potassium back in and hydrogen out
Within the cell, carbonic anhydrase catalyses the reaction between CO2 and H2O to produce carbonic acid which dissociates into H+ and HCO3-
Bicarbonate ion then leaves the cell in exchange for Cl-
The gastrin – ECL – Parietal cell complex
- Production of gastrin from G cell
- This acts on CCK2R on ECL which stimulates release of histamine
- Histamine acts on H2 receptor of parietal cell
- This increases cAMP which activates secretion of acid by parietal cell
- Ach released by vagus nerve acts on M3R which secretes gastric acid from parietal cell
- Somatostatin acts on SST2R on all three cells to inhibit their action
- Prostaglandins act on EP2/3R on ECL cell to exhibit inhibitory effects
Protective mechanism of stomach
Prevents pepsin, H+ and HCl from digesting the cell wall via:
Mucus
Bicarbonate increases the pH to 7.0 to neutralise the wall
Prostaglandins keep blood vessels dilated for good blood flow into stomach allowing regeneration of the epithelium. It also stimulates mucus and bicarbonate production
GORD (Gastroesophageal reflux disorder)
Backflow of acid which occurs due to low pressure at lower oesophageal sphincter causing its opening or if it doesn’t close properly
Clinical presentations of GORD
Difficulty/pain when swallowing, pain in upper abdomen/chest, nausea, vomiting, acid taste in mouth, bloated, indigestion, burning pain when swallowing, chronic cough, sore throat, voice change, gum problems, bad breath
Factors causing GORD
Spicy and hot foods, tight clothing, smoking, alcohol, being overweight, pregnancy due to pressure of womb into abdomen pushing stomach up, hiatal hernia
Treatment options
- Drugs that inhibit/neutralise gastric acid secretion i.e. Antacids, H2R antagonists, muscarinic antagonists, proton pump inhibitors
- Drugs that promote protection i.e. Prostaglandin analogs, mucosal barrier fortifiers
Antacids
Weak bases that act with gastric HCl forming salt and water i.e. Sodium bicarbonate and sodium citrate which form carbon dioxide and sodium chloride
- CO2 leads to gastric distention
- Unreacted alkali is absorbed and can cause metabolic alkalosis
- NaCl absorption may exacerbate fluid retention in some patients
The most preferred antacids are magnesium hydroxide, magnesium trisilicate, aluminium hydroxide and calcium carbonate
- They form water instead of CO2
- Unabsorbed Mg = Osmotic diarrhoea
- Unabsorbed Al = constipation
- Both given together helps minimise effect
Useful for relieving symptoms after a heavy meal but not recommended for long-term or chronic conditions
H2 Receptor antagonists
Cimetidine, Ranitidine, Famotidine
Competitively block H2 Receptor on parietal cell
Most effective in supressing nocturnal gastric secretion
Less potent than PPI’s
Side effect: diarrhoea, headache, myalgia (muscle aches), constipation, fatigue, confusion, hallucination
Anticholinergic agents
Piperizine, Telenzepine
Block Ach stimulated gastric acid secretion
Competitively and selectively block M1 receptors on parietal cells
Inhibit acid secretion and delay gastric emptying
Not commonly used as it has low efficacy and anticholinergic side effects (dry mouth, dry eyes, blurred vision, constipation, dizziness, urinary retention)
Proton pump inhibitors
Omeprazole, esameprazole, lansoprazole
Irreversibly inhibits H+K+ATPase supressing gastric acid secretion
Administer before meal as absorption is greater
Supressed for 24 hours as it takes 18 hours to synthesise new H+K+ATPase
Highly bound to plasma proteins
Metabolised in liver and secreted in urine
Enteric coated or powder containing sodium bicarbonate to prevent degradation
SE: headache, diarrhoea, abdominal pain, skin rashes, arthralgia (joint pain), may decrease vitamin B12 absorption, increase rate of infections, increase rate of fracture of bones, inhibit metabolism of phenytoin/warfarin/diazepam and decrease bioavailability of itraconazole/iron salts
Mucosal barrier fortifiers
Sucralfate, bismuth salicylates and colloidal bismuth subcitrate
Form a complex gel with the mucus creating a protective coat
1. Sucralfate – complex of AlOH and sulphated sucrose to which is polymerises in acidic pH to form a sticky gel which adheres to ulcer base and protects for 6 hours.
2. Bismuth salicylate and colloidal bismuth subcitrate – React with proteins in base of ulcer and protect it from peptic digestion. It also stimulates secretion of PGE2, Mucus and bicarbonate. It is anti-microbial against H.Pylori. Binds to enterotoxins in traveler’s diarrhoea
