Why hEDS, POTS, and MCAS Almost Always Come Together: The Mechanistic Triad and the Upstream Lesion Standard Medicine Doesn't Treat — The Mechanistic Convergence: Connective Tissue, Mast Cells, and Autonomic Function as One Integrated System

The integration of the three subsystems is anatomical, cellular, and bioenergetic. Each level reinforces the others. The Anatomical Integration Connective tissue, mast cells, and autonomic nerve terminals share the same tissue compartments. The submucosa of the gut wall contains the densest mast cell population in the body, the vagal afferent terminals that signal to the brainstem, and the connective tissue framework that supports the mucosa and the smooth muscle layer. The blood vessel wall contains mast cells in the adventitia, autonomic nerve fibers that regulate vascular tone, and the collagen and elastin that determine vessel mechanical properties. The skin contains mast cells in the dermis, autonomic fibers that regulate sweat glands and pilomotor function, and the connective tissue matrix that gives skin its elasticity. When connective tissue is structurally and bioenergetically abnormal, the mast cells embedded in that tissue are in an abnormal environment. When the autonomic fibers running through that tissue are firing differently because of the local biochemical environment, mast cells receive different signals. The three systems are not three independent layers stacked on top of one another. They are three components of one tissue, and their behavior is integrated by the local environment of that tissue. The Cellular Integration The cells involved in all three subsy