Normally accounts for less than 2% of total hemoglobin.
It is formed at a low rate via oxygen transport, and the rate of formation is balanced by its reduction back to the ferrous state by cytochrome-b5 reductase.
Does not release oxygen from hemoglobin in tissues because of increased oxygen affinity.
Can be congenital or acquired.
Acquired process is more frequent in result from increased methemoglobin formation.
Acquired type can be caused when toxins cause oxidation of heme molecule.
Most common toxins to cause acquired disease are nitrates and nitrite containing molecules which include dapsone, sulfonamides, chloroquine, primaquine and topical bezocaine spray.
Dapsone is one of the most common causes of acquired disease accounting for nearly half the cases.
Dapsone undergoes N-hydroxylation by P-450 enzymes in the liver to form N-hydroxy dapsone the metabolite that causes methemoglobinemia.
N-hydroxy dapsone product of dapsone mediated the oxidation of the iron molecule of heme to produce methemoglobinemia in a dose dependent fashion.
Patients with acute illness present with shortness of breath, tachypnea, and findings of cerebral ischemia and cyanosis.
Methemoglobin develops after oxidation of the iron moiety of hemoglobin from the ferrous state to the ferric state, resulting in increased oxygen affinity and less ability of the red blood cells to release oxygen to tissues.
Normal hemoglobin contains iron in the ferrous state in the heme molecule.
Oxidation of iron to the ferric state gives rise to aberrant form of hemoglobin, methemoglobin.
Ferric iron is unable to bind oxygen, and it causes allosteric changes in the hemoglobin molecule to increase the affinity of the remaining ferrous iron for oxygen, this leading to a left shift of the oxygen, hemoglobin, dissociation curve.
The dual effects of reduced oxygen release and decreased oxygen binding capacity result in tissue hypoxia.
Erythrocytes are under continuous exposure to oxidative stress that convert hemoglobin to methemoglobin: a normal methemoglobin level is typically maintained through enzymatic, reduction pathways, most importantly, cytochrome b5 reductase pathway.
Elevated methemoglobin levels, occurr with congenital, enzyme deficiency, hemoglobin, variants, or exposure to exogenous oxidizing agents.
PaO2 and oxygen saturation are normal or elevated despite the appearance of cyanosis.
As methhemoglobin levels approach 30%, the oxygen saturation on pulse oximetry approaches 85% and is unaffected by supplemental oxygen, a process that mimics a physiological shunt.
Blood appears muddy chocolate and methemoglobin levels are increased.
Symptoms in a non-anemic patients are usually correlated with methemoglobin blood levels.
Cyanosis maybe present even when methemoglobin levels are less than 15% are present.
Methemoglobin levels of 20-50% can cause anxiety, fatigue, headache, confusion, tachypnea, whereas life-threatening arrhythmias, acidosis, seizures and coma can arise if levels exceed 50%.
Treatment for acquired disease includes removing the responsible toxic agent.
Symptomatic individuals and those with methemoglobin levels greater than 50% require methylene blue intravenously at 1-2 mg/kg.
In patients with glucose-6-phosphate dehydrogenase deficiency methylene blue is not helpful and may worsen the process.
Results in a functional anemia due to the inability of methemoglobin to bind oxygen.
Methemoglobin has an allosteric effect on neighboring oxyhemoglobin molecules and can shift the oxyhemoglobin dissociation curve to the left, increasing the risk of tissue hypoxemia and worsening the clinical effect of anemia.