Interstitium is a key player in septic shock pathophysiology

Abstract

During septic shock, hypovolemia caused by capillary leak is compensated by fluid therapy. Despite the beneficial effects of fluid resuscitation, it is responsible for the development of diffuse edema, associated with poor prognosis. Capillary leak is classically described as the result of sepsis-associated damages of the microvascular endothelium and glycocalyx. However, intersititum seems to play a major role in edema formation during inflammation and its role is described in a growing number of preclinical and clinical studies. Indeed, interstitial hydrostatic pressure is regulated by interstitial extracellular matrix (ECM) thanks to fibroblasts’ interaction with collagens of the ECM. This tension applied by fibroblasts can be released by inflammatory mediators, leading to a sudden interstitial pressure decrease, increasing oedema formation. The role of interstitium during sepsis has been overlooked but a growing body of evidence suggesting its pivotal role in capillary filtration regulation. Thereby, interstitium is probably a major determinant of fluid balance regulation, which is a major aspect of sepsis management. Thus, interstitium analysis could serve as a new diagnostic and therapeutic approach for the future of septic shock management.