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Introduction

Methemoglobinemia is a condition characterized by elevated methemoglobin, a form of hemoglobin that contains iron in the ferric state (Fe³⁺), instead of the normal ferrous state (Fe2+).  Ferric iron cannot bind oxygen effectively, resulting in impaired oxygen delivery and tissue hypoxia.  Methemoglobinemia can be congenital or acquired.

Pathogenesis

Hemoglobin is a tetramer composed of 4 subunits ( Figure 1).  Each subunit consists of an iron-containing heme molecule attached to a globin chain.  A normal red blood cell (RBC) contains approximately 270 million hemoglobin molecules that transport oxygen to peripheral tissues.  Approximately 98% of the oxygen in blood is attached to iron in hemoglobin.  The remaining 2% is dissolved in plasma, represented by the partial pressure of oxygen in arterial blood (PaO2).

The iron in hemoglobin is normally in the ferrous (Fe²⁺) state, which is required to bind, transport, and release oxygen.  Under physiologic conditions, a fraction of the iron in RBCs transitions between the ferrous (Fe²⁺) and the ferric (Fe³⁺) states through a series of oxidation-reduction reactions (

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