Micro- and Meso-Scale Analyses for Quantifying Hypoxemia in Methemoglobinemia

Methemoglobinemia is a disease that results from abnormally high levels of methemoglobin (MetHb) in the red blood cell (RBC) caused by simultaneous uptake of oxygen (O-2) and nitric oxide (NO) in the human lungs. MetHb is produced in the RBC by irreversible NO-induced oxidation of the oxygen carrying ferrous ion (Fe2+) in the heme group of the hemoglobin (Hb) molecule to its non-oxygen binding ferric state (Fe3+). In this paper, we study the role of NO in the pathophysiology of methemoglobinemia by performing a multiscale quantitative analysis of the relation between levels of NO inhaled by the patient and the hypoxemia resulting from the disease. Reactions of NO occurring in the RBC with both Hb and oxyhemoglobin are considered in conjunction with the usual reaction between oxygen and Jib to form oxyhemoglobin. Our dynamic simulations of NO and O-2 uptake in the RBC and in the plasma in pulmonary capillaries under continuous, simultaneous exposure to both gases reveal that at the end of the pulmonary transit time of 1 s, the oxygen saturation in the RBC equilibrates at 97% in absence of NO but it shows a steady decline to 95% as the concentration of NO increases to 50 ppm. We further show that NO levels of 150 ppm or higher while breathing in room air may be considered to be fatal for methemoglobinemia patients since it causes severe hypoxemia by decreasing the oxygen saturation to below its critical value of 90%. Our analysis shows that the diagnosis of hypoxemia in methemoglobinemia cannot be done by measuring oxygen partial pressures in the patient's pulmonary artery, but by estimating the oxygen saturation in the patient's erythrocyte using a standard procedure such as pulse oximetry.