**2.1 Tissue hypoxia**

CO competes with oxygen in binding with hemoglobin to form carboxyhemoglobin. The affinity between CO and hemoglobin is 200 times higher than that of oxygen (Ernst and Zibrak 1998; Piantadosi 2002; Weaver 2009). The production of carboxyhemoglobin shifts the oxygen-hemoglobin curve to the left and dissociates oxygen from hemoglobin (Ernst and Zibrak 1998). These reactions consequently reduce oxygen delivery to tissues and result in a hypoxic microenvironment.
