Methemoglobinemia

W. Michael Kutayli Creighton University Medical Center, Omaha, USA

Peter Silberstein Creighton University School of Medicine, Omaha, USA
ã 2007 Elsevier Inc. All rights reserved.

Introduction

Oxygen is transported through the blood by hemoglobin (Hgb), a tetrameric molecule

with four heme subunits that consist of two alpha and two beta chains. Iron is enclosed
within each porphyrin heme structure in the form of ferrous iron (Fe++). When iron is in
the ferrous form, hemoglobin has a high affinity for oxygen, making it more effective in
transporting oxygen throughout the body. Methemoglobinemia is a condition caused by
iron bound to hemoglobin being in the Fe+++, reducing the binding, and therefore the
transport, of oxygen in blood.

Definition

Methemoglobinemia refers to a condition where the iron in hemoglobin is oxidized from

the ferrous state (Fe++) to the ferric state (Fe+++), forming methemoglobin. When iron is
in this ferric state, hemoglobin is less capable of binding and transporting oxygen or
carbon dioxide.

Classification

Methemoglobinemia is classified as acquired or as congenital/genetic/hereditary types.

Acquired Methemoglobinemia
The majority of cases of methemoglobinemia are acquired, resulting from exposure to
agents that may act by directly oxidizing iron, or indirectly by reducing oxygen to its free
radical form, O-2, which in turn acts on iron. Substances that can cause oxidation include
benzocaine and other topical anesthetics, nitrates, nitrites, dapsone, antimalarials,
pyridium, and naphthalene. The second most common cause of methemoglobinemia is
systemic acidosis, such as that encountered in infants <6 months of age, which is usually
secondary to diarrhea and dehydration. Typically, such children have a higher level of
gram negative bacteria in the intestine, which can be ingested in the diet or through
contaminated water that can convert nitrates to nitrites, which in turn, cause oxidation to
form methemoglobin. It is postulated that fetal hemoglobin is more readily oxidized than
adult hemoglobin making infants particularly susceptible to methemoglobinemia.

Congenital/Genetic/Hereditary Methemoglobinemia
Hereditary methemoglobinemia is caused either by an altered form of hemoglobin
(Hemoglobin M), or by the absence of an enzyme needed, such as with cytochrome-b5
/b5 reductase deficiency.
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