Lymphatic Vessels and Their Surroundings: How Local Physical Factors Affect Lymph Flow

Abstract

Lymphatic vessels drain and propel lymph by exploiting external forces that surrounding tissues exert upon vessel walls (extrinsic mechanism) and by using active, rhythmic contractions of lymphatic muscle cells embedded in the vessel wall of collecting lymphatics (intrinsic mechanism). The latter mechanism is the major source of the hydraulic pressure gradient where scant extrinsic forces are generated in the microenvironment surrounding lymphatic vessels. It is mainly involved in generating pressure gradients between the interstitial spaces and the vessel lumen and between adjacent lymphatic vessels segments. Intrinsic pumping can very rapidly adapt to ambient physical stimuli such as hydraulic pressure, lymph flow-derived shear stress, fluid osmolarity, and temperature. This adaptation induces a variable lymph flow, which can precisely follow the local tissue state in terms of fluid and solutes removal. Several cellular systems are known to be sensitive to osmolarity, temperature, stretch, and shear stress, and some of them have been found either in lymphatic endothelial cells or lymphatic muscle. In this review, we will focus on how known physical stimuli affect intrinsic contractility and thus lymph flow and describe the most likely cellular mechanisms that mediate this phenomenon.

Keywords: extrinsic mechanism; hydraulic pressure; intrinsic contractility; lymph flow; lymphatic vessels; osmolarity; shear stress; tissue temperature.

Figure 1

Functional scheme of how lymph is drained and propelled. Extrinsic forces and/or intrinsic rhythmic contractions generate transmural pressure gradients (ΔP_TM) across the wall of initial lymphatic capillaries and intraluminal pressure gradients (ΔP_Lymph) between adjacent lymphangions. Intraluminal valve leaflets are devoid of LM. (P_in) interstitial hydraulic pressure; (P_L) intraluminal hydraulic pressure; (EC) lymphatic endothelial cells; (LM) lymphatic muscle cells.

Figure 2

Modulation of lymphatic function: difference in oscillatory lymph flow induced by intrinsic contractions and one extrinsic contraction (experimentally induced at the time point indicated by the vertical dotted line).

Figure 3

Temperature-dependent modulation of diaphragmatic lymphatics contractility, affecting both CF and contraction amplitude (Δd). Upper panel: positive chronotropic effect on CF (solid line) and negative inotropic effect on Δd (dashed line). Gray area highlights the range of steepest variation of both parameters. Lower panel shows representative traces of vessel diameter over time recorded in the range of 36–38 °C. Data taken from [94].