Portal hypertension remains a very major cause of mortality and morbidity. What is known is that it may by prehepatic, where the cause is in the vascular network which supplies the lever, it may be post-hepatic, as in Budd-Chairri syndrome, where the post-hepatic veins are obstructed, but most commonly it is hepatic (cirrhosis being the most common). Either increased inflow or increased vascular resistance in the hepatic sinusoids or both may be implicated. Thus rise in the portal venous pressure above 10-12 mm Hg constitutes Portal Hypertension
The authors have given a detailed description of various factors (humoral, endocrinological, inflammatory), which have been implicated in the pathophysiology. The role of all of these is not clear, some are purely at an investigational stage. Agents like adrenergic agonists (norepinephrine), thromboxanes (cycloxygenase), cysteinyl leukotrienes, endothelins, Angiotensin-II, endocannabinoids have been suggested in increasing vascular resistance in the hepatic vascular bed by causing vasoconstriction.
While the role of adrenergic agonists, and thromboxanes is reasonably clear, the relative importance of the role of others is not clarified by the article (yet). NO (nitric oxide) has been thought responsible in endothelial dysfunction, as its relative lack in the liver make the vessels more susceptible to vasoconstrictive action. Increased splanchnic flow is another major cause. Increased peripheral vasodilators (glucagon, endocannabinoids) and locally available vasodilators are thought to be increased.
A minor role of carbon monoxide, circulating hydrogen sulphide and cyclooxgenase has also been suggested. VEGF is a endothelial growth factor, gradually gaining importance due to its role in splanchnic circulation increase To summarize, most of these agents are investigational,and further analysis is required, the clinical benefit of the study (as of today), needs to be established.