ETIOPATHOGENESIS OF PEPTIC ULCER

ETIOPATHOGENESIS OF PEPTIC ULCER

• PUD refers to chronic mucosal ulceration affecting mostly the duodenum or stomach

• Can occur in any part of GIT like esophagus (GERD) or in meckels diverticulum

• Most commonly associated with H.pylori

MECHANISMS WHICH PROTECT NORMAL MUCOSA

• Mucin secreted by surface foveolar cells
• Bicarbonate ion secretion into mucous by epithelial cells
• Gastric epithelial cells form physical barrier
• Regeneration of epithelial cells every 3 to 7 days
• Rich vascularity which delivers bicarbonates , oxygen and nutrients and washes the acid which has back diffused into the lumen

ETIO PATHOGENESIS 

Peptic ulcers develop because of – 

• Fall in mucosal defenses

• Decreased mucosal blood flow

• Delayed gastric emptying

• Impaired epithelial restitution

• Impaired prostaglandin synthesis

ETIOLOGICAL FACTORS

• H.PYLORI INFECTION –Host factors as well as variation among H.pylori strains determine the clinical outcomes.

  • Helicobacter Pylori is Gram negative, nonsporing curvilinear bacilli, measuring 5 x 0.5 µm

  • H.pylori genome encodes 1500 proteins

  • H.pylori causes gastritis by 2 ways :

    •  Direct injury of epithelial cells

    • Stimulating production of pro-inflammatory cytokines  (IL – 1β and TNF)

• • Pathogenesis of H.pylori

    • H.pylori moves in the viscous mucin layer via flagella 

    • It has Urease which produces ammonia from endogenous urea  and buffers  gastric acid in the immediate vicinity of organism

    • Expresses of Bacterial adhesins that enhances the bacterial adherence to foveolar cells

    • Expression of Bacterial toxins

      • Cag  A (Cytotoxin associated gene  A protein) – Cytotoxin which alters signaling pathway, alters the cytoskeletal rearrangement and alters the tight junctions between the cells

      • Vac  A (Vacuolating cytotoxin gene A protein) – It causes formation of vacoules in the cells, induces apoptosis, causes disruption of epithelial junctions and blocks the T cells response

• • H.pylori infection often presents as antral gastritis with normal or increased acid production

  • In severe cases presents as pan gastritis

  • H.pylori infection along with host factors like increased expression of proinflammatory cytokines like TNF, IL-1β or decreased expression of antiinflammatory cytokines like IL-10 leads to pangastritis, atrophy, and gastric cancer

• ZOLLINGER ELLISON SYNDROME – uncontrolled release of gastrin by a tumor and the resulting massive acid production

• CHRONIC NSAID USE-

  • suppress prostaglandin synthesis necessary for mucosal protection

  • Toxic injury to the epithelium and endothelium

• DRUGS LIKE COCAINE – reduces mucosal blood flow

• CIGARETTE SMOKING, which impairs mucosal blood flow and healing

• PSYCHOLOGICAL STRESS may increase gastric acid production.

• GENETIC FACTORS – people with blood group O are more prone for the development of peptic ulcer

• VIRAL INFECTIONS like CMV and herpes simplex virus

PATHOGENESIS 

Different pathogenetic mechanism involved in gastric and duodenal ulcers

• Duodenal ulcers- Mechanism for the development of duodenal ulcers
  • Mucosal digestion from hyperacidity and damage to mucosal barrier. This is due to  
    • Hypersecretion of gastric acid into the stomach at night under the influence of vagal stimulation
    • Rapid emptying of stomach so that food which normally neutralizes the gastric acid passes into the small intestine so that aggressive acid acts on duodenal mucosa

• • H.pylori gastritis –
    • Gastric mucosal defense is broken down by bacterial urease, protease, catalase and phospholipase.
    • Host factors – H.pylori infected mucosal epithelium releases proinflammatory cytokines such as IL-1, IL-6, Il-8 and tumor necrosis factor –alpha
    • Bacterial factors –  epithelial injury induced by Cag A protein and Vac A which induces secretion of cytokines

• Gastric ulcer

  • Mainly due to impaired gastric mucosal defenses against acid –pepsin secretions

  • Mucosal defense mechanism is 

    • Mucous layer with bicarbonate 

    • Surface epithelium

  • Mucin has acid resistant property and this is enhanced by secretion of sodium and bicarbonate by the epithelial cells into mucin which neutralizes the HCl.

  • Surface epithelium  forms second line of defense. An adequate blood supply to the mucosa is important for these functions

  • An ulcer results due to failure of this defense mechanism. 

    • H.Pylori colonization in gastric mucosa

    • Trauma due to spicy food or alcohol

    • Smoking impairs mucosal blood flow and impairs healing

    • Hyperacidity – due to increased serum gastrin levels in response to ingested food in atonic stomach

    • Incompetence of pyloric sphincter leads to  bile reflux whic damages the mucosal barrier. Cigarette smoking reduces the resting tone of the sphincter

References

1. Vinay kumar, Abul K.Abbas, Nelson Fausto, Jon C. Aster. Robbins and Cotran Pathologic basis of disease. 8th edition.

2. Harsh mohan. Text book of Pathology.8th edition.2019

3. Dr.A.K Mandal, Dr. Sharmana Choudhary. Diseases of Gastrointestinal tract. In: Text Book for Pathology for MBBS Second series, volume II:2018.