The Interstitium and Lymphatics have an Important Role in Edema Generation during Sepsis

Abstract

Increased fluid filtration is one of the hallmarks of inflammation. During systemic inflammatory response syndrome (SIRS) and sepsis, excessive fluid extravasation takes place. Restoring and maintaining an adequate intravascular fluid volume is, therefore, one of the most important goals in the clinical situation. There are two reasons for this: First, the increased fluid filtration results in edema, which may lead to organ dysfunction or failure. Importantly, the increased tissue water and edema may impede normal lung function. Furthermore, the increased amount of tissue fluid will lead to increased diffusion distance for nutrients and waste products. Second, the increased fluid filtration is a central element of septic pathophysiology, and may, combined with increased vasodilatation, lead to hypovolemic shock. Based on the prominent role of fluid filtration, it is no surprise that much of the discussion on sepsis pathophysiology is focused on the capillary wall. Here we will review recent data showing that the interstitium or the extracellular matrix outside the blood vessels has a central pathogenetic role in fluid extravasation and edema generation in sepsis. We will also discuss data on the potential role of the lymphatics in this context since they are crucial for maintaining a normal fluid balance in the tissues, and even more so for returning extravasated plasma proteins to the circulation. In doing so, we will briefly address normal transcapillary exchange and edema prevention while maintaining our focus on the extravascular compartment.