Hydrodynamic regulation of lymphatic transport and the impact of aging

Abstract

To accomplish its normal roles in body fluid regulation/macromolecular homeostasis, immune function, and lipid absorption; the lymphatic system must transport lymph from the interstitial spaces, into and through the lymphatics, through the lymphatic compartment of the nodes, back into the nodal efferent lymphatics and eventually empty into the great veins. The usual net pressure gradients along this path do not normally favor the passive movement of lymph. Thus, lymph transport requires the input of energy to the lymph to propel it along this path. To do this, the lymphatic system uses a series of pumps to generate lymph flow. Thus to regulate lymph transport, both lymphatic pumping and resistance must be controlled. This review focuses on the regulation of the intrinsic lymph pump by hydrodynamic factors and how these regulatory processes are altered with age. Intrinsic lymph pumping is generated via the rapid/phasic contractions of lymphatic muscle, which are modulated by local physical factors (pressure/stretch and flow/shear). Increased lymph pressure/stretch will generally activate the intrinsic lymph pump up to a point, beyond which the lymph pump will begin to fail. The effect of increased lymph flow/shear is somewhat more complex, in that it can either activate or inhibit the intrinsic lymph pump, depending on the pattern and magnitude of the flow. The pattern and strength of the hydrodynamic regulation of the lymph transport is different in various parts of the lymphatic tree under normal conditions, depending upon the local hydrodynamic conditions. In addition, various pathophysiological processes can affect lymph transport. We have begun to evaluate the influence of the aging process on lymphatic transport characteristics in the rat thoracic duct. The pressure/stretch-dependent activation of intrinsic pumping is significantly impaired in aged rat thoracic duct (TD) and the flow/shear-dependent regulatory mechanisms are essentially completely lacking. The loss of shear-dependent modulation of lymphatic transport appears to be related to a loss of normal eNOS expression and a large rise in iNOS expression in these vessels. Therefore, aging of the lymph transport system significantly impairs its ability to transport lymph. We believe this will alter normal fluid balance as well as negatively impact immune function in the aged animals. Further studies are needed to detail the mechanisms that control and alter lymphatic transport during normal and aged conditions.