Morphological, Mechanical and Hydrodynamic Aspects of Diaphragmatic Lymphatics

SIMPLE SUMMARY: The diaphragm is both the main respiratory muscle and the septum separating the thoracic from the abdominal cavity. As most tissues, it is supplied by a vascular lymphatic system whose function is to absorb fluid, solutes and cells from the interstitial tissue surrounding the cells and to propel the so formed lymph back into the venous blood stream. However, the diaphragmatic lymphatic network plays an additional role, being directly involved in draining fluid from the pleural and peritoneal cavities. The aim of this review is to present a comprehensive description of the structure and function of the diaphragmatic lymphatic network, including its unique morphology, the mechanisms supporting diaphragmatic lymph formation and progression and the importance of the mechanical events developing in the diaphragm during tidal breathing on lymph formation and propulsion. This information may prove to be useful in understanding some abnormal fluid accumulation in the pleural or peritoneal cavities observed in clinical settings. ABSTRACT: The diaphragmatic lymphatic vascular network has unique anatomical characteristics. Studying the morphology and distribution of the lymphatic network in the mouse diaphragm by fluorescence-immunohistochemistry using LYVE-1 (a lymphatic endothelial marker) revealed LYVE1(+) structures on both sides of the diaphragm—both in its the muscular and tendinous portion, but with different vessel density and configurations. On the pleural side, most LYVE1(+) configurations are vessel-like with scanty stomata, while the peritoneal side is characterized by abundant LYVE1(+) flattened lacy-ladder shaped structures with several stomata-like pores, particularly in the muscular portion. Such a complex, three-dimensional organization is enriched, at the peripheral rim of the muscular diaphragm, with spontaneously contracting lymphatic vessel segments able to prompt contractile waves to adjacent collecting lymphatics. This review aims at describing how the external tissue forces developing in the diaphragm, along with cyclic cardiogenic and respiratory swings, interplay with the spontaneous contraction of lymphatic vessel segments at the peripheral diaphragmatic rim to simultaneously set and modulate lymph flow from the pleural and peritoneal cavities. These details may provide useful in understanding the role of diaphragmatic lymphatics not only in physiological but, more so, in pathophysiological circumstances such as in dialysis, metastasis or infection.