Methemoglobin

Methemoglobin (English: methaemoglobin) (pronounced "met-hemoglobin") is a form of metalloprotein hemoglobin, in which the iron in the heme group is in the Fe³⁺ (ferric) state, not the Fe²⁺ (ferrous) of normal hemoglobin. Methemoglobin cannot bind oxygen, which means it cannot carry oxygen to tissues. It is bluish chocolate-brown in color. In human blood a trace amount of methemoglobin is normally produced spontaneously, but when present in excess the blood becomes abnormally dark bluish brown. The NADH-dependent enzyme methemoglobin reductase (a type of diaphorase) is responsible for converting methemoglobin back to hemoglobin.

Normally one to two percent of a person's hemoglobin is methemoglobin; a higher percentage than this can be genetic or caused by exposure to various chemicals and depending on the level can cause health problems known as methemoglobinemia. A higher level of methemoglobin will tend to cause a pulse oximeter to read closer to 85% regardless of the true level of oxygen saturation. An abnormal increase of methemoglobin will increase the oxygen binding affinity of normal hemoglobin, resulting in a decreased unloading of oxygen to the tissues. ^[2]

Common causes of elevated methemoglobin

Reduced cellular defense mechanisms
- Children younger than 4 months exposed to various environmental agents
- Pregnant women are considered vulnerable to exposure of high levels of nitrates in drinking water^[3]
- Cytochrome b5 reductase deficiency
- G6PD deficiency
- Hemoglobin M disease
- Pyruvate kinase deficiency
Various pharmaceutical compounds
- Local anesthetic agents, especially prilocaine and benzocaine.^[4]
- Amyl nitrite, chloroquine, dapsone, nitrates, nitrites, nitroglycerin, nitroprusside, phenacetin, phenazopyridine, primaquine, quinones and sulfonamides
Environmental agents
- Aromatic amines (e.g. p-nitroaniline, patient case)
- Arsine
- Chlorobenzene
- Chromates
- Nitrates/nitrites^[5]
Inherited disorders
- Some family members of the Fughate family in Kentucky, due to a recessive gene, had blue skin from an excess of methemoglobin.^[6]
In cats
- Ingestion of Paracetamol (i.e. acetaminophen, tylenol)^{[citation needed]}

Therapeutic uses

Amyl nitrite is administered to treat cyanide poisoning. It works by converting hemoglobin to methemoglobin, which allows for the binding of cyanide and the formation of cyanomethemoglobin. The immediate goal of forming this cyanide adduct is to prevent the binding of free cyanide to the cytochrome a₃ group in cytochrome c oxidase.^[7]

Methemoglobin saturation

Methemoglobin saturation is expressed as the percentage of hemoglobin in the methemoglobin state; That is MetHb as a proportion of Hb.

1-2% Normal
Less than 10% metHb - No symptoms
10-20% metHb - Skin discoloration only (most notably on mucous membranes)
20-30% metHb - Anxiety, headache, dyspnea on exertion
30-50% metHb - Fatigue, confusion, dizziness, tachypnea, palpitations
50-70% metHb - Coma, seizures, arrhythmias, acidosis
Greater than 70% metHb - High risk of death^[5]

Blood stains

Increased levels of methemoglobin are found in blood stains. Upon exiting the body, bloodstains transit from bright red to dark brown, which is attributed to oxidation of oxy-hemoglobin (HbO₂) to methemoglobin (met-Hb) and hemichrome (HC).^[8]

References

^ Bando, S.; Takano, T.; Yubisui, T.; Shirabe, K.; Takeshita, M.; Nakagawa, A. (2004). "Structure of human erythrocyte NADH-cytochromeb5reductase". Acta Crystallographica Section D. 60 (11): 1929–1934. doi:10.1107/S0907444904020645. PMID 15502298.
^ Denshaw-Burke, Mary (2006-11-07). "Methemoglobinema". Retrieved 2008-03-31.
^ Manassaram, D. M.; Backer, L. C.; Messing, R.; Fleming, L. E.; Luke, B.; Monteilh, C. P. (2010). "Nitrates in drinking water and methemoglobin levels in pregnancy: A longitudinal study". Environmental Health. 9: 60. doi:10.1186/1476-069X-9-60. PMC 2967503. PMID 20946657.{{cite journal}}: CS1 maint: unflagged free DOI (link)
^ http://www.fda.gov/Drugs/DrugSafety/ucm250024.htm
^ ^a ^b "Survival after severe methemoglobinemia secondary to sodium nitrate ingestion". Toxicology Communications. 11 May 2018. {{cite web}}: Cite has empty unknown parameter: |dead-url= (help)
^ http://abcnews.go.com/Health/blue-skinned-people-kentucky-reveal-todays-genetic-lesson/story?id=15759819#.T2oS0HqV2So
^ Vale, J. A. (2001). "Cyanide Antidotes: from Amyl Nitrite to Hydroxocobalamin - Which Antidote is Best?". Toxicology. 168 (1): 37–38.
^ Bremmer et al PLoS ONE 2011 http://www.plosone.org/article/info:doi/10.1371/journal.pone.0021845

External links

Methemoglobin at the U.S. National Library of Medicine Medical Subject Headings (MeSH)
MetHb Formation
The Blue people of Troublesome Creek

[1] Bando, S.; Takano, T.; Yubisui, T.; Shirabe, K.; Takeshita, M.; Nakagawa, A. (2004). "Structure of human erythrocyte NADH-cytochromeb5reductase". Acta Crystallographica Section D. 60 (11): 1929–1934. doi:10.1107/S0907444904020645. PMID 15502298.

[2] Denshaw-Burke, Mary (2006-11-07). "Methemoglobinema". Retrieved 2008-03-31.

[3] Manassaram, D. M.; Backer, L. C.; Messing, R.; Fleming, L. E.; Luke, B.; Monteilh, C. P. (2010). "Nitrates in drinking water and methemoglobin levels in pregnancy: A longitudinal study". Environmental Health. 9: 60. doi:10.1186/1476-069X-9-60. PMC 2967503. PMID 20946657.{{cite journal}}: CS1 maint: unflagged free DOI (link)

[4] ttp://www.fda.gov/Drugs/DrugSafety/ucm250024.htm

[:0-5] "Survival after severe methemoglobinemia secondary to sodium nitrate ingestion". Toxicology Communications. 11 May 2018. {{cite web}}: Cite has empty unknown parameter: |dead-url= (help)

[6] ttp://abcnews.go.com/Health/blue-skinned-people-kentucky-reveal-todays-genetic-lesson/story?id=15759819#.T2oS0HqV2So

[7] Vale, J. A. (2001). "Cyanide Antidotes: from Amyl Nitrite to Hydroxocobalamin - Which Antidote is Best?". Toxicology. 168 (1): 37–38.

[8] Bremmer et al PLoS ONE 2011 http://www.plosone.org/article/info:doi/10.1371/journal.pone.0021845

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