title: Red cell physiology and signaling relevant to the critical care setting.
abstract: OBJECTIVE
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: aDepartment of Pediatrics, Division of Critical Care Medicine bDepartment of Biochemistry and Molecular Biophysics, School of Medicine, Washington University in Saint Louis, St. Louis, Missouri, USA.
authors.forename: Ahmed
authors.initials: A
authors.lastname: Said
authors.forename: Stephen
authors.initials: S
authors.lastname: Rogers
authors.forename: Allan
authors.initials: A
authors.lastname: Doctor
mesh_terms: D000222:Adaptation, Physiological; D001692:Biological Transport; D002648:Child; D003422:Critical Care; D016638:Critical Illness / Q000628:therapy*; D004730:Endothelium, Vascular / Q000503:physiopathology*; D004912:Erythrocytes / Q000502:physiology*; D006706:Homeostasis; D006801:Humans; D008833:Microcirculation / Q000502:physiology*; D009569:Nitric Oxide / Q000378:metabolism*; D010100:Oxygen / Q000378:metabolism*; D010477:Perfusion / Q000379:methods*; D015398:Signal Transduction
chemical_list: D009569:Nitric Oxide; D010100:Oxygen