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A vascular mechanistic approach to understanding Raynaud phenomenon

Key Points

  • During cold exposure, human bodies attempt to maintain core temperature by reducing heat loss via cutaneous vasoconstriction and by increasing heat production via shivering and nonshivering thermogenesis

  • In selected skin areas, nutritional capillaries are bypassed by arteriovenous anastomoses; these thermoregulatory structures are predominantly closed during heat conservation and fully dilated during heat elimination

  • Cold exposure activates and amplifies sympathetic nervous system signalling, triggering cutaneous vasoconstriction and thermogenesis: sympathetic vasoconstriction selectively restricts blood flow through arteriovenous anastomoses while protecting nutritional capillary blood flow

  • In Raynaud phenomenon, the already heightened sympathetic vasoconstriction in areas rich in arteriovenous anastomoses is further amplified in intensity and scope, with expansion into the adjoining nutritional system

  • Cold-induced vasospasm and interruption of capillary blood flow is mediated by sympathetic vasoconstriction, and modulation by endothelial vasodilatation perhaps contributes to differences between primary and secondary forms of Raynaud phenomenon

  • Despite the exuberant increase in cold-induced vasoconstriction in Raynaud phenomenon, reflecting upregulation of heat-conservation mechanisms, surprisingly little is known about thermogenesis in this disorder

Abstract

During exposure to cold, our bodies attempt to maintain normal core temperature by restricting heat loss through cutaneous vasoconstriction, and by increasing heat production through shivering and nonshivering thermogenesis. In selected areas of human skin (including on the fingers and toes), the vascular system has specialized structural and functional features that enable it to contribute to thermoregulation. These features include arteriovenous anastomoses, which directly connect the arterial and venous systems and bypass the nutritional capillaries supplying blood to the skin tissue. Of note, Raynaud phenomenon predominantly affects the arterial territories supplying these specialized areas of skin. Indeed, Raynaud phenomenon can be considered a disorder of vascular thermoregulatory control. This Review presents an understanding of Raynaud phenomenon in the context of vascular and thermoregulatory control mechanisms, including the role of unique thermosensitive vascular structural and functional specialization, and describes the potential role of thermogenesis in this disorder. This new approach provides remarkable insight into the disease process and builds a framework to critically appraise the existing knowledge base. This paradigm also explains the deficiencies in some current therapeutic approaches, and highlights new areas of potential relevance to the pathogenesis and treatment of Raynaud phenomenon that should be expanded and explored.

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Figure 1: Structure of the human cutaneous microvascular system.
Figure 2: Arteriovenous anastomoses in the cutaneous circulation.
Figure 3: Simultaneous measurements of blood flow velocity in the third fingers of the left (blue circles) and right (red circles) hands of an individual unaffected by Raynaud phenomenon.
Figure 4: Cold-induced digital vasoconstriction in Raynaud phenomenon.

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Flavahan, N. A vascular mechanistic approach to understanding Raynaud phenomenon. Nat Rev Rheumatol 11, 146–158 (2015). https://doi.org/10.1038/nrrheum.2014.195

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