Endothelial cells (ECs) line the lumen of the entire vascular system and actively regulate blood flow; maintain blood fluidity; control water, solute, and macromolecular transfer between blood and tissue; and modulate circulating immune cell recruitment and activation. These vital functions, combined with the broad anatomic distribution of ECs, implicate them in all forms of critical illness. The present article discusses how ECs adapt and break down during the course of critical illness. We first review the biology of ECs, highlighting the vascular segmental differences and their specific roles in the maintenance of homeostasis. We then discuss how ECs acquire new functions to restore local and systemic homeostasis (activation) as well as how breakdowns in EC functions (dysfunction) contribute to local and systemic pathologic responses, with clinical correlations. Lastly, how these processes have been studied in critically ill children is discussed.

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