Portal hypertensive gastropathy (PHG) is the condition in which the mucosa in the stomach undergoes some changes; the change denotes the existence of ectasia at the surface of mucosa, and widening of the mucosal and submucosal vessels resulting in the dilation in the stomach.

Portal hypertension that may or may not be caused due to cirrhosis is the root cause of PHG. According to the endoscopic evaluation, the structure of the mucosa in patients with PHG has a mosaic or snake-skin like appearance. The main symptom of the PHG is bleeding from the stomach; in rare cases, the presence of blood in stool might also occur.

The pathogenesis of this condition is still not clear; however, recent research in the field points out some hemodynamic and molecular changes.

Hemodynamic Changes

PHG occurs only along with portal hypertension, but it is not been proved that portal hypertension is the primary factor for PHG. The individual with portal hypertension has accompanied hemodynamic changes and resulted in hyperdynamic congestion which affects blood flow in gastric mucosa by cytokines, hormones, and growth factors that sustenance hyperdynamic gastric circulation.

Hemodynamic disorder is one of the main factors for PHG. The irregularities in portal circulation in the PHG patient is due to the lower flow of hepatic blood and, on the other side, higher pressure in portal venous.

Researchers have also found that the patient with cirrhosis has low velocity of portal venous, and as a result, the congestive index is higher in portal vein thereby contributing to the development of PHG.

Molecular Mechanisms Related to PHG Pathogenesis

There are a number of cellular and molecular mechanisms that are thought to contribute to the pathogenesis of PHG. Some of them are listed below:

Apoptosis: Few experiments done on rat model indicate the presence of augmented gastric mucosal apoptosis as well as reduced mucosal proliferation. An experiment in which a protein – p53-upregulated modulator of apoptosis (PUMA) – induced in gastric mucosa of PHG patients as well as rats suggested mucosal epithelial apoptosis that is stress-induced, and occurred due to the modulation by endoplasmic reticulum. This thought may cause mucosal injury in patients with PHG.

Free radicals and antioxidants: Rat model experiments in portal hypertensions have also shown a lower level of protective antioxidant enzymes and, on the other hand, raising the level of lysosomal enzymes and of harm-free radicals in gastric mucosal homogenates.

It has also been found that oxidative stress followed activation of weak endoplasmic reticulum serine/threonine kinase-2 (ERK2) in the gastric mucosa of rats. Gastric mucosa can undergo cell proliferation by protecting against stress in the cell via ERK2. PHG is signaled due to the damaged MAPK (ERK) caused due to the increase in ERK nitration by peroxynitrite.

Mucin: Rats with portal hypertension, due to ligation in the portal vein, are also reported with considerable reduction in the mucin mRNA expression. The gastric mucosal protection is damaged due to this low production of mucin. Exposure to compounds that are gastrotoxic is found to cause greater gastric mucosa damage to rats with portal hypertension.

Tumor necrosis factor alpha (TNF-r): The hyperdynamic circulation of the patient with PHG may be caused by TNF-α. The level of TNF-α is higher for the patients with portal hypertension, which raise the release of prostacyclin and nitric oxide (NO) in addition to other substances essential for hyperdynamic circulation.

Glucagon: The portal hypertension patients have a raised level of glucagon. The main function of glucagon is to control the vascular resistance in the systemic ways. The splanchnic vasodilation is caused due to portal pressure by glucagon; it is found the portal pressure is correlated with glucagon level.

Angiogenesis: The patient with PHG after mucosa damage has fewer angiogenic buds. The capacity of repairing PHG mucosa will be decreased in this situation; however, humans who have PHG had more VEGF (vascular endothelial growth factor). And in the PHG rat cases, the level of SaO2 and PaO2 present in arterial blood gas is lower and higher levels VEGF, respectively, and increases in expression of PCNA (proliferating cell nuclear antigen). Also, there is an increase in the blood flow within gastric mucosa. The increase in the level of PCNA and VEGF and hypoxia of gastric mucosa in portal hypertension may result in increased mucosal angiogenesis as well as blood flow.

Other cytokines and growth factors: There are many research studies carried out about the functions of vascular endothelial growth factor (VEGF), other cytokines, and endothelin-1 in PHG, which require further research. The comparison between growth factor of epidermal gastric concentration of PHG patient and those without PHG remains doubtful. The increase in the level of autotaxin serum in liver fibrosis is associated with PHG, cirrhosis in the advanced stages as well as esophageal varices.

Few other factors that are thought to contribute to the pathogenesis of PHG are nitric oxide, lipid compound like prostacyclin or prostaglandin, as well as Helicobacter pylori (a gram-negative bacteria usually present in the stomach).