Increased susceptibility of the portal hypertensive gastric mucosa to damage.

Portal hypertensive gastropathy has recently been recognized as a unique entity distinct from other gastropathies involving the normotensive gastric mucosa. To delineate the pathophysiology of this disorder, we developed a rat model of portal hypertension using two-staged portal vein ligation. In this model, features of the portal hypertensive mucosa include increased luminal hydrogen ion loss, reduced electronegativity of potential difference, and increased submucosal edema. Ultrastructurally, the portal hypertensive gastric mucosa has marked endothelial hypertrophy of capillaries resulting in prominent compromise of microvascular lumina. Combined with the submucosal edema, the microvasculopathy results in reduced oxygenation of the surface gastric mucosa. This is associated with diminished prostaglandin production, which impairs gastric mucosal protection in portal hypertension. These observations are strengthened by experiments that demonstrated significantly increased gastric mucosal damage by alcohol, bile acids, aspirin, and shock/reperfusion in portal hypertensive rats compared to normotensive sham-operated controls. Many of our experimental findings have been confirmed clinically; however, much more research in this area is clearly needed.