Hypovolemia with peripheral edema: What is wrong?

Fluid normally exchanges freely between the plasma and interstitial space and is returned primarily via the lymphatic system. This balance can be disturbed by diseases and medications. In inflammatory disease states, such as sepsis, the return flow of fluid from the interstitial space to the plasma seems to be very slow, which promotes the well-known triad of hypovolemia, hypoalbuminemia, and peripheral edema. Similarly, general anesthesia, for example, even without mechanical ventilation, increases accumulation of infused crystalloid fluid in a slowly equilibrating fraction of the extravascular compartment. Herein, we have combined data from fluid kinetic trials with previously unconnected mechanisms of inflammation, interstitial fluid physiology and lymphatic pathology to synthesize a novel explanation for common and clinically relevant examples of circulatory dysregulation. Experimental studies suggest that two key mechanisms contribute to the combination of hypovolemia, hypoalbuminemia and edema; (1) acute lowering of the interstitial pressure by inflammatory mediators such as TNF alpha, IL-1 beta, and IL-6 and, (2) nitric oxide-induced inhibition of intrinsic lymphatic pumping.

Automated summary

Fluid balance plays a crucial role in maintaining normal physiology, but can be disrupted by diseases and medications. Inflammatory conditions and anesthesia can lead to impaired fluid return and accumulation in the tissues, causing a range of circulatory dysregulation. Experimental studies have identified the involvement of inflammatory mediators and nitric oxide in this process, highlighting potential targets for therapeutic interventions.