**4. Pathophysiology**

The pathogenesis of PHG is still poorly understood. Portal hypertension is essential in the presence of PHG, due to the mechanical effect of the increased pressure in the portal vein which leads to hyper‐dynamic congestion with a net increase in the gastric blood flow, this increase occurs in the submucosal, muscle, and serosal layers, while decreasing in the muco‐ sal layer due to congestion and stasis. These hemodynamic changes impair gastric muco‐ sal defense mechanisms, which lead to release of pro‐inflammatory mediators, and alter the growth factors which render gastric mucosa more susceptible to injury, and impair mucosal healing. This defenseless mucosa may explain the increase in the rate of bleeding from PHG, additionally this abnormal gastric microcirculation, may render gastric mucosa more vulnera‐ ble to hypoxia, and more susceptible to noxious gastric factors, such as aspirin and ethanol [4].

Many other factors have also been implicated in the pathogenesis of PHG such as increased pro‐ duction of nitric oxide (NO), oxygen free radicals, endothelin‐1, tumor necrosis factor‐α, and prostaglandins. The most important factor, NO, is a potent vasodilator secreted by endothelial cells which may underlie the gastric vascular dilation and hyper‐dynamic circulation in PHG. Furthermore, the expression of transforming growth factor α (TGF‐α) and the epidermal growth factor (EGF) receptors in the gastric mucosa were reported to be highly elevated in areas of spon‐ taneous gastric injury. Recently, studies found other factors, like p53‐upregulated modulator of apoptosis (PUMA), to be markedly induced in the gastric mucosa of PHG patients [11]. Increased gastric mucosal apoptosis and decreased mucosal proliferation, were also noted in rats with PGH.
