Red cell physiology and signaling relevant to the critical care setting

Purpose of review Oxygen (O₂) delivery, the maintenance of which is fundamental to supporting those with critical illness, is a function of blood O₂ content and flow. Here, we review red blood cell (RBC) physiology relevant to disordered O₂ delivery in the critically ill. Recent findings Flow (rather than content) is the focus of O₂ delivery regulation. O₂ content is relatively fixed, whereas flow fluctuates by several orders of magnitude. Thus, blood flow volume and distribution vary to maintain coupling between O₂ delivery and demand. The trapping, processing and delivery of nitric oxide (NO) by RBCs has emerged as a conserved mechanism through which regional blood flow is linked to biochemical cues of perfusion sufficiency. We will review conventional RBC physiology that influences O₂ delivery (O₂ affinity & rheology) and introduce a new paradigm for O₂ delivery homeostasis based on coordinated gas transport and vascular signaling by RBCs. Summary By coordinating vascular signaling in a fashion that links O₂ and NO flux, RBCs couple vessel caliber (and thus blood flow) to O₂ need in tissue. Malfunction of this signaling system is implicated in a wide array of pathophysiologies and may be explanatory for the dysoxia frequently encountered in the critical care setting.