Biochemical sequence:
(1) chemical oxidation of iron in hemoglobin from the ferrous to ferric state
(2) reduced conversion of methemoglobin back to hemoglobin associated with an inherited defect in hemoglobin reductase
(3) reduced oxygen carrying capacity by the methemoglobin results in symptoms
Oxidizing chemicals that have caused methemoglobinemia:
(1) nitrates – silver nitrate (nitrate needs to be converted to nitrite by the gut flora to get methemoglobinemia)
(2) nitrites – in well water, processed meats, vegetables, amyl nitrite, nitroglycerin, nitroprusside, isobutyl nitrite, nitric oxide, industrial salts
(3) aniline
(4) dapsone
(5) local anesthetics (benzocaine, prilocaine, lidocaine, others)
(6) metoclopramide
(7) pyridium
(8) primaquine or chloroquine
(9) sulfamethoxazole
(10) chlorates
(11) resorcinol
(12) copper sulfate
(13) naphthalene
(14) nitrobenzene
Reduced activity of hemoglobin reductase may be caused by either:
(1) dominant form (hemoglobin mutations with hemoglobin M) – methemoglobinemia may occur frequently
(2) recessive form (mutation in NADH-cytochrome b5 reductase) - methemoglobinemia follows a significant chemical exposure
Clinical findings:
(1) cyanosis, not explained by cardiac or pulmonary disease
(2) headache
(3) dizziness
(4) dyspnea
(5) weakness
(6) coma and death at very high levels
Laboratory findings:
(1) freshly drawn blood samples are a chocolate brown
(2) shaking tube or bubbling oxygen through the sample does not cause the blood color to change to red
(3) increased methemoglobin (normal levels are <= 1%)
(4) may contain sulfhemoglobin
(5) PaO2 and PaCO2 may be normal
