A) TOXICOLOGY: Oxidization of iron in the hemoglobin ring
to the ferric form leads to the inability of hemoglobin
to bind or transport oxygen. Heme in the ferric (Fe3+)
state also induces a hemoglobin conformational change
increasing oxygen affinity of the remaining binding
sites and decreasing the oxygen dissociation. Cyanosis
occurs when more than 1.5 g/dL of hemoglobin is in the
methemoglobin form, compared to 5 g/dL of
deoxyhemoglobin to yield similar cyanosis.
Methemoglobinemia may result from acquired or
congenital causes (hemoglobin M or cytochrome b5
reductase deficiency). Acquired methemoglobinemia is
caused by strong oxidizing agents, most commonly local
anesthetics and dapsone, though many drugs have been
implicated. In addition, recreational drugs, industrial
chemicals, as well as medical conditions such as
pediatric gastrointestinal infections, sepsis, surgery,
or sickle cell crisis are rarely capable of inducing
acquired methemoglobinemia.