The mast cell integrates the splanchnic and systemic inflammatory response in portal hypertension

Abstract

Portal hypertension is a clinical syndrome that is difficult to study in an isolated manner since it is always associated with a greater or lesser degree of liver functional impairment. The aim of this review is to integrate the complications related to chronic liver disease by using both, the array of mast cell functions and mediators, since they possibly are involved in the pathophysiological mechanisms of these complications. The portal vein ligated rat is the experimental model most widely used to study this syndrome and it has been considered that a systemic inflammatory response is produced. This response is mediated among other inflammatory cells by mast cells and it evolves in three linked pathological functional systems. The nervous functional system presents ischemia-reperfusion and edema (oxidative stress) and would be responsible for hyperdynamic circulation; the immune functional system causes tissue infiltration by inflammatory cells, particularly mast cells and bacteria (enzymatic stress) and the endocrine functional system presents endothelial proliferation (antioxidative and antienzymatic stress) and angiogenesis. Mast cells could develop a key role in the expression of these three phenotypes because their mediators have the ability to produce all the aforementioned alterations, both at the splanchnic level (portal hypertensive enteropathy, mesenteric adenitis, liver steatosis) and the systemic level (portal hypertensive encephalopathy).This hypothetical splanchnic and systemic inflammatory response would be aggravated during the progression of the chronic liver disease, since the antioxidant ability of the body decreases. Thus, a critical state is produced, in which the appearance of noxious factors would favor the development of a dedifferentiation process protagonized by the nervous functional system. This system rapidly induces an ischemia-reperfusion phenotype with hydration and salinization of the body (hepatorenal syndrome, ascites) which, in turn would reduce the metabolic needs of the body and facilitate its temporary survival.

Portal hypertension-related inflammatory phenotypes: From a vitelline and amniotic point of view

“…Prehepatic portal hypertension by partial portal vein ligation in the rat induces a splanchnic and systemic chronic low-degree inflammatory response that could be developed through the expression of three successive and overlapping phenotypes: ischemia-reperfusion phenotype, immune phenotype and angiogenic phenotype [2,3]. Thus, it has been already proposed that these phenotypes could represent the expression of trophic functional systems with increasing metabolic complexity [2,10].…”

“…In this way, the gastrointestinal tract often represents the source for the development of systemic inflammation with multiple organ dysfunction [20,21]. The association of mucosal hypoxia, splanchnic hyperemia and development of portal systemic collaterals bypassing the liver in portal hypertension also suggests that the gastrointestinal tract could play a key role in the induction and maintenance of a low-grade inflammatory response [2,3].…”

“…Therefore, the splanchnic and systemic impairments that are produced during the evolution of the syndrome associated with portal hypertension could be considered of an inflammatory nature. If so, and similar to other type of inflammatory response, it would begin in the interstitial space [2,3,29] ( Table 2). Table 2.…”

“…Compensation of the acute phase response includes the production of positive acute phase proteins that bind proteolytic enzymes and inhibitors of leukocyte and liposomal proteolytic enzymes [33,34]. Likewise, the natural inhibitors of matrix metalloproteinases (TIMPs) could promote anti-enzymatic stress [3]. Portal hypertension is one factor determining bacterial intestinal translocation to mesenteric lymph nodes [30,32].…”

“…This splanchnic and systemic hemodynamic response would be aggravated during the progression of the chronic liver disease [2,3]. Thus, a critical state is produced in which the appearance of noxious factors during the progressive evolution of chronic liver disease would favor the development of a high-grade splanchnic and systemic inflammatory response [2,4,5].…”