This narrative review portrays the lymphatic system, a poorly understood but important physiological system. While several reviews have been published that are related to the biology of the lymphatic system and lymphedema, the physiological alternations, which arise due to disturbances of this system, and during lymphedema therapy, are poorly understood and, consequently, not widely reported. We present an inclusive collection of evidence from the scientific literature reflecting important developments in lymphedema research over the last few decades. This review aims at advancing the knowledge on the area of lymphatic system function as well as how system dysfunction, as seen in lymphedema, affects physiological systems and how lymphedema therapy modulates these mechanisms. We propose that future studies should aim at investigating, in-detail, aspects that are related to fluid regulation, hemodynamic responses, and endothelial and/or vascular changes due to lymphedema and lymphedema therapy.

Faculty of Science Masaryk University Kotlářská 2 61137 Brno Czech Republic

Gravitational Physiology and Medicine Research Unit Division of Physiology Otto Loewi Research Center Medical University of Graz 3810 Graz Austria

Linfamed 33100 Udine Italy

Wolfsberg Clinical Center for Lymphatic Disorders Wolfsberg State Hospital KABEG 9400 Wolfsberg Austria

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