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The dyshemoglobinemias are a constellation of disorders in which
the hemoglobin molecule is functionally altered and prevented from
carrying oxygen. The most clinically relevant dyshemoglobinemias
are carboxyhemoglobin, methemoglobin, and sulfhemoglobin.1 Carboxyhemoglobin
is created following carbon monoxide exposure and, because of its
unique importance and prevalence, is usually considered an environmental
emergency (see Chapter 217, Carbon Monoxide). The
prevalence for methemoglobinemia and sulfhemoglobinemia is unknown,
and presentation to the ED for symptoms related to one of these dyshemoglobinemias
is uncommon.
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Under normal circumstances, the iron moiety within deoxyhemoglobin exists
in the ferrous (bivalent or Fe2+) form. Iron in
this oxidation state avidly interacts with compounds seeking electrons,
such as oxygen, and in the process is oxidized to the ferric (trivalent
or Fe3+) state. On exposure to an oxidizing agent,
iron donates an electron and transforms oxidation states from ferrous
to ferric. Hemoglobin in the ferric form is unable to bind oxygen
and is termed methemoglobin.2–4 Under
normal circumstances, <1% to 2% of circulating
hemoglobin exists as methemoglobin and accumulation of higher concentrations
defines the condition of methemoglobinemia.
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Accumulation of methemoglobin is enzymatically limited by the
rapid reduction of the ferric iron back to the ferrous form.
The enzyme cytochrome b5 reductase is primarily responsible
for this reduction, in which reduced nicotinamide adenine dinucleotide (NADH)
donates its electrons to cytochrome b5 that subsequently
reduces methemoglobin to hemoglobin.5 In this process,
oxidized nicotinamide adenine dinucleotide is regenerated (Figure 201-1). This pathway is responsible
for reducing nearly 95% of methemoglobin produced under
typical circumstances. Methemoglobinemia occurs only when this enzymatic
reduction is overwhelmed by an exogenous oxidant stress, such as
a drug or chemical agent (Table 201-1).
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A second enzymatic pathway uses the reduced form of nicotinamide
adenine dinucleotide phosphate ...