Ageing and maintenance of the interstitial fluid traffic: possible roles of initial lymphatics and circadian hormones.

It is here proposed that the interstitial fluid traffic depends on the widespread system of initial lymphatics without valves. The filtered fluid forced by the interstitial hydrostatic pressure enters initial lymphatics through loose junctions in segments that are near arterial ends of blood capillaries. Loose junctions might also allow fluid to leave initial lymphatics in segments that are near the venous ends of blood capillaries. Thus, initial lymphatics help daily transfer of 24 L of interstitial fluid from points of filtration to the points of resorption. Muscle contractions compress initial lymphatics and force the intraluminal content to enter collecting lymphatics. Contractions are needed to re-establish initial lymphatics as interstitial fluid shortcuts. Even small differences in interstitial flow can become important and lead to uneven flow distribution that might damage tissue and accelerate ageing. The proposed model of interstitial traffic maintenance requires three separate effects: (a) Thyroid hormones and control of tissue metabolism. It directly affects the cell shape and size, synthesis or degradation of interstitial material. Thyroid hormones control metabolic rates and prevent accumulation of interstitial material, as can be seen in severe hypothyroidism. (b) Somatotropin anabolic effects. Somatotropin increases number and volumes of cells, synthesis of interstitial material. These actions increase interstitial flow resistance. (c) Cortisol catabolic action. A cortisol induced tissue catabolism reduces the interstitial flow resistance toward normal. The presented idea is that known rhythms of GH and cortisol (GH during night sleep and cortisol in the morning) separate anabolic and catabolic actions in time, or otherwise they would diminish each other. The model predicts that the maintenance would be best during growth, when GH surges are higher. GH and cortisol are secreted together in cases of trauma, stress or starvation. Since this would probably block the proposed mechanism, a possible speculation is that frequent repetitions of stressful conditions accelerate ageing. The same prediction can be made for the long term glucocorticoid administration.