Sandbox cerebral palsy

Pathophysiology

Mucosal barrier

• The gastric mucosa is protected from the acidic environment by mucus, bicarbonate, prostaglandins, and blood flow.
• This mucosal barrier consists of three protective components which include:
  • Layer of epithelial cells lining.
  • Layer of mucus, secreted by surface epithelial cells and Foveolar cells.
  • Bicarbonate ions, secreted by the surface epithelial cells.

Mechanism of Action

• The insoluble mucus forms a protective gel-like coating over the entire surface of the gastric mucosa.
• The mucus protects the gastric mucosa from autodigestion by e.g. pepsin and from erosion by acids and other caustic materials that are ingested.
• The bicarbonate ions act to neutralize harsh acids.
• If the balance of gastric acid secretion and mucosal defenses is disrupted, acid interacts with the epithelium to cause damage

Pathogenesis

• Regardless of etiology, if the balance of gastric acid secretion and mucosal defenses is disrupted, acid interacts with the epithelium to cause damage.
  • Helicobacter pylori disrupts the mucosal barrier and causes inflammation of the mucosa of the stomach and duodenum.
  • As the ulcer progresses beyond the mucosa to the submucosa the inflammation causes weakening and necrosis of arterial walls, leading to pseudoaneurysm formation followed by rupture and hemorrhage.
  • NSAIDs inhibit cyclooxygenase, leading to impaired mucosal defenses by decreasing mucosal prostaglandin synthesis.
  • During stress, there is acid hypersecretion; therefore, the breakdown of mucosal defenses leads to injury of the mucosa and subsequent bleeding.
  • Mucosal defects along with dilated and tortuous vessels in dieulafoy lesion put them at risk for rupture because of necrosis of the arterial wall from exposure to gastric acid.

NSAIDS

Inhibits cycloxygenase pathway

COX-1

COX-2

Reduced mucosal blood flow

Reduced mucosal and bicarbonate secreation

Impaired platelet aggregation

Reduced angiogenesis

Increased leucocyte adherence

Impaired defence Impaired healing

Mucosal Injury

A01

A02

A02

B01

B02

C01

C02

D01

E01

B01

B02

B03

C01

C02

C03

Pathogenesis of Crohns disease

• Genetic component
• Stress and environmental component
• Microbial component
• Inflammatory component

Genetic factors

Genes involved

• NOD2/CARD15 gene
• OCTN1 gene
• DLG5 gene
• TLR4 gene