peptic ulcer

• Peptic ulcer disease


  Disorders of the upper GI tract caused by the action of hydrochloric acid and pepsin
• Peptic ulcers


  • Can be acute and chronic, and superficial or deep
  • Superficial defects of the GIT lining that involve mucosa, but do not affect the submucosal layer are called erosions
  • Deeper defects of the GIT lining are called ulcers
  • Penetrating ulcers may damage the blood vessels, causing hemorrhage, or may perforate the wall of the stomach
• Localization of peptic ulcers in GIT

  • Most frequent site is in the duodenum, within a few centimeters of the pylorus
  • Ulcers may also occur along the lesser curvature of the antral part of the stomach
  • More rarely, ulcers may be found in the lower end of the esophagus
  • Marginal ulcers of the stomach can be found in patients that had a surgical operation of the gastrojejunostomy

  
• Pathogenesis of peptic ulcer

  Peptic ulcer develops due to imbalance between the factors that protect gastric mucosa and factors that produce an injury

  
• Damaging factors


  • Hydrochloric acid
  • Pepsin
• Protective factors


  • Mucosal diffusion barrier
  • Growth factors
• Mucosal diffusion barrier


  Consists of mucus, bicarbonates, and the mucosal lining itself

  
• Mucus and bicarbonate secretion

  1. Mucous cells in the gastric gland secrete mucus and bicarbonates

  2. Mucus forms a physical barrier that slows diffusion of acid and pepsin

  3. Bicarbonates form a chemical barrier that neutralizes acid and inactivates pepsin

  
• The entire mucosal lining is replaced every three days
• When the mucosal protective barrier is damaged

  H+ penetrates to deeper layers of the stomach wall, stimulating conversion of pepsinogen to pepsin and release of histamine

  
• Histamine release


  Promotes gastric acid secretion, inflammation, and increased capillary permeability
• Causes of peptic ulcer disease

  • Increased secretion of gastric acid and pepsin
  • Reduced secretion of mucus and bicarbonates
  • Impaired integrity of the mucosal lining
  • Reduced ability of mucosal cells to regenerate

  
• Precipitating factors


  • Helicobacter pylori (causes 80% of all peptic ulcers)
  • Non-steroid anti-inflammatory drugs, e.g. aspirin (cause 20% of all peptic ulcers)
• Facilitating factors


  • Stressful lifestyle
  • Irritating diet (spicy foods, alcohol, caffeine)
  • Smoking
  • Genetics
• How Helicobacter pylori survives in acidic environment


  1. Has flagella to escape gastric lumen and reside under alkaline mucus

  2. Preferentially settles in the antrum which contains no parietal cells

  3. Produces urease to split urea into ammonia and CO2, neutralizing acid locally

  4. Produces catalase to protect from phagocytosis

  5. Ammonia damages protective mucous layer

  6. Produces adhesion proteins to attach to mucosal cells

  
• Helicobacter pylori infection


  Causes persistent inflammation of gastric mucosa, impairing structural integrity and making it permeable to acid

  
• How NSAIDs cause peptic ulcers


  Chronic use suppresses prostaglandin synthesis, reducing inhibition of acid secretion and increasing acid secretion, while reducing secretion of bicarbonates and mucin that protect mucosa

  
• Helicobacter pylori


  Bacteria that secrete toxins causing persistent inflammation of the gastric mucosa (chronic gastritis)

  
• Helicobacter pylori secretes toxins

  Causes persistent inflammation of the gastric mucosa (chronic gastritis)

  
• Chronic gastritis caused by H. pylori

  Impairs structural integrity of the mucosal cells, making them permeable for gastric acid

  
• Mucosal lining becomes extremely leaky


  Loses its protective properties
• NSAIDs


  Chronic use suppresses prostaglandin synthesis in GIT mucosa
• Prostaglandin E2


  Normally inhibits secretion of gastric acid, and increases secretion of bicarbonates and mucin

  
• Inhibition of prostaglandin secretion by NSAIDs

  Causes increased secretion of gastric acid, and reduced secretion of bicarbonates and mucin

  
• Changes caused by NSAIDs

  Promote the development of peptic ulcer