title: Multiscale analysis of hypoxemia in methemoglobin anemia.
abstract: Methemoglobinemia is a disease that results from abnormally high levels of methemoglobin (MetHb) in the red blood cell (RBC), which is 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 (Fe(2+)) present in the heme group of the hemoglobin (Hb) molecule to its non-oxygen binding ferric state (Fe(3+)). This paper studies the role of NO in the pathophysiology of methemoglobinemia and presents a multiscale quantitative analysis of the relation between the 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 Hb to form oxyhemoglobin. Our dynamic simulations of NO and O(2) uptake in the RBC (micro scale), alveolar capillary (meso scale) and the entire lung (macro scale) under continuous, simultaneous exposure to both gases, reveal that NO uptake competes with the reactive uptake of O(2), thus suppressing the latter and causing hypoxemia. We also find that the mass transfer resistances increase from micro through meso to macro scales, thus decreasing O(2) saturation as one goes up the scales from the cellular to the organ (lung) level. We show that NO levels of 203 ppm or higher while breathing in room air may be considered to be fatal for methemoglobinemia patients since it causes severe hypoxemia by reducing the O(2) saturation below a critical value of 88%, at which Long Term Oxygen Therapy (LTOT) becomes necessary.
authors.affiliation: Department of Chemical Engineering, Indian Institute of Technology - Kharagpur, Kharagpur 721302, India.
authors.forename: Tanmoy
authors.initials: T
authors.lastname: Sanyal
authors.forename: Saikat
authors.initials: S
authors.lastname: Chakraborty
mesh_terms: D003198:Computer Simulation; D004912:Erythrocytes / Q000378:metabolism*; D006801:Humans; D008708:Methemoglobinemia / Q000097:blood*; D008954:Models, Biological; D009569:Nitric Oxide / Q000097:blood; D010084:Oxidation-Reduction; D010100:Oxygen / Q000097:blood*
chemical_list: D009569:Nitric Oxide; D010100:Oxygen