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Encyclopedia > Methemoglobinemia
Classification & external resources
ICD-10 D74.
ICD-9 289.7
DiseasesDB 8100
eMedicine med/1466  emerg/313
MeSH D008708

Methemoglobinemia, also known as "met-Hb", is a disorder characterized by the presence of a higher than normal level of methemoglobin in the blood. Methemoglobin is a form of hemoglobin that does not bind oxygen. When its concentration is elevated in red blood cells a functional anemia and tissue hypoxia may occur. Normally methemoglobin levels are <1%, as measured by the co-oximetry test. Elevated levels of methemoglobin in the blood are caused when the mechanisms that defend against oxidative stress within the red blood cell are overwhelmed and the oxygen carrying ferrous ion (Fe2+) of the heme group of the hemoglobin molecule is oxidized to the ferric state (Fe3+). This converts hemoglobin to methemoglobin, a non-oxygen binding form of hemoglobin that binds a water molecule instead of oxygen. Spontaneous formation of methemoglobin is normally counteracted by protective enzyme systems: NADH methemoglobin reductase (cytochrome-b5 reductase) (major pathway), NADPH methemoglobin reductase (minor pathway) and to a lesser extent the ascorbic acid and glutathione enzyme systems. The International Statistical Classification of Diseases and Related Health Problems (most commonly known by the abbreviation ICD) provides codes to classify diseases and a wide variety of signs, symptoms, abnormal findings, complaints, social circumstances and external causes of injury or disease. ... The International Statistical Classification of Diseases and Related Health Problems 10th Revision (ICD-10) is a coding of diseases and signs, symptoms, abnormal findings, complaints, social circumstances and external causes of injury or diseases, as classified by the World Health Organization (WHO). ... // C00-D48 - Neoplasms (C00-C14) Malignant neoplasms, lip, oral cavity and pharynx (C00) Malignant neoplasm of lip (C01) Malignant neoplasm of base of tongue (C02) Malignant neoplasm of other and unspecified parts of tongue (C03) Malignant neoplasm of gum (C04) Malignant neoplasm of floor of mouth (C05) Malignant neoplasm of... The International Statistical Classification of Diseases and Related Health Problems (most commonly known by the abbreviation ICD) provides codes to classify diseases and a wide variety of signs, symptoms, abnormal findings, complaints, social circumstances and external causes of injury or disease. ... The following is a list of codes for International Statistical Classification of Diseases and Related Health Problems. ... The Disease Bold textDatabase is a free website that provides information about the relationships between medical conditions, symptoms, and medications. ... eMedicine is an online clinical medical knowledge base that was founded in 1996. ... Medical Subject Headings (MeSH) is a huge controlled vocabulary (or metadata system) for the purpose of indexing journal articles and books in the life sciences. ... Methemoglobin (also hemiglobin) is a type of hemoglobin that is produced by the oxidation of the ferrous iron contained in hemoglobin to ferric iron which doesnt have the capacity for carrying oxygen. ... Human blood smear: a - erythrocytes; b - neutrophil; c - eosinophil; d - lymphocyte. ... Structure of hemoglobin. ... General Name, symbol, number oxygen, O, 8 Chemical series nonmetals, chalcogens Group, period, block 16, 2, p Appearance colorless (gas) very pale blue (liquid) Standard atomic weight 15. ... Human red blood cells Red blood cells are the most common type of blood cell and are the vertebrate bodys principal means of delivering oxygen to body tissues via the blood. ... This article discusses the medical condition. ... Oxidative stress is a medical term for damage to animal or plant cells (and thereby the organs and tissues composed of those cells) caused by reactive oxygen species, which include (but are not limited to) superoxide, singlet oxygen, peroxynitrite or hydrogen peroxide. ... Ferrous in chemistry is a term used for the iron with an oxidation number +2. ... Structure of Heme b A heme or haem is a prosthetic group that consists of an iron atom contained in the center of a large heterocyclic organic ring called a porphyrin. ... Ferric is a term used for the iron with the oxidation number +3. ... Methemoglobin reductase is an enzyme which converts methemoglobin to hemoglobin. ...



Congenital methemoglobinemia

Due to a deficiency of the enzyme diaphorase I (NADH methemoglobin reductase), methemoglobin levels rise and the blood of met-Hb sufferers has reduced oxygen-carrying capacity. Instead of being red in colour, the arterial blood of met-Hb sufferers is brown. This results in skin of white sufferers gaining a bluish cast (thus making them "blue people"). Hereditary met-Hb is caused by a recessive gene. If only one parent has this gene, offspring will have normal-hued skin, but, if both parents carry the gene there is a chance the offspring will have blue-hued skin. Ribbon diagram of the enzyme TIM, surrounded by the space-filling model of the protein. ... This article does not cite its references or sources. ... It has been suggested that this article or section be merged into Dominance relationship. ...

Another cause of congenital methemoglobinemia is seen in patients with abnormal hemoglobin variants such as hemoglobin M (HbM), or hemoglobin H (HbH), which are not amenable to reduction despite intact enzyme systems. Thalassemia (American English) or thalassaemia (British English) is a recessive trait inherited disease of the red blood cells. ... In ring theory, a ring R is said to be reduced if it has no non-zero nilpotent elements. ...

Methemoglobinemia can also arise in patients with pyruvate kinase deficiency due to impaired production of NADH - the essential cofactor for diaphorase I. Similarly, patients with Glucose-6-phosphate dehydrogenase (G6PD) deficiency may have impaired production of another co-factor, NADPH. Pyruvate Kinase Deficiency is an inherited autosomal recessive disorder which affects the survival of red blood cells, causing them to break down easily. ... Nicotinamide adenine dinucleotide (NAD+) Nicotinamide adenine dinucleotide (NAD) and nicotinamide adenine dinucleotide phosphate (NADP) are two important coenzymes found in cells. ... Glucose-6-phosphate dehydrogenase (G6PD) deficiency is an X-linked recessive hereditary disease featuring nonimmune hemolytic anemia in response to a number of causes. ... Nicotinamide adenine dinucleotide (NAD+) Nicotinamide adenine dinucleotide (NAD) and nicotinamide adenine dinucleotide phosphate (NADP) are two important coenzymes found in cells. ...

Acquired/Toxic methemoglobinemia

The protective enzyme systems normally present in red blood cells maintain methemoglobin levels at less than one percent of the total hemoglobin in healthy people. Exposure to exogenous oxidizing drugs and their metabolites (such as benzocaine, dapsone and nitrates) may accelerate the rate of formation of methemoglobin up to one-thousandfold, overwhelming the protective enzyme systems and acutely increasing methemoglobin levels. Other classical drug causes of methaemoglobinaemia include antibiotics (trimethoprim, sulphonamides and dapsone), local anaesthetics (especially lignocaine and prilocaine), and others such as aniline dyes, metoclopramide, chlorates and bromates. Benzocaine is a local anesthetic commonly used as a topical pain reliever. ... Dapsone is an antibiotic medication most commonly used for the treatment of Mycobacterium leprae infections (leprosy). ... Trinitrate redirects here. ...

Infants under 6 months of age are particularly susceptible to methemoglobinemia caused by nitrates ingested in drinking water, dehydration usually caused by gastroenteritis with diarrhea, sepsis and topical anesthetics containing benzocaine or prilocaine. Nitrates that are used in agricultural fertilizers leaked into the ground and may contaminate well water. The current EPA standard of 10 ppm nitrate-nitrogen for drinking water is specifically designed to protect infants.

It has been reported (Heard & Ashworth 1968 apud Basrani et al. 2007) that, when placed in an aqueous solution, Chlorhexidine Gluconate (antiseptic) slowly hydrolyzes and forms para-chloroaniline (4-Chloroaniline, p-Chloroaniline or PCA) (24). Para-chloroaniline (PCA) has been shown to be toxic (28, 29). As an aromatic amine, the primary toxic effect is methemogloblin formation (28). Toxicological studies in rats and mice have shown that the hemopoietc system is the major target for PCA (28). In 1990, Chhabra et al (28) conducted a 90-day study (with p-chloroaniline) and found that methaemoglobin formation and accompanying haemolytic anaemia, extra-medullary haematopoiesis, and splenomegaly were indicative of erythrocyte toxicity and regenerative anemia. Chlorhexidine Gluconate is a chemical antiseptic, to combat both gram positive and gram negative microbes. ...


Methemoglobinemia is treated with supplemental oxygen and methylene blue 1% solution (10mg/ml) 1-2mg/kg administered intravenously slowly over five minutes followed by IV flush with normal saline. Methylene blue restores the iron in hemoglobin to its normal (reduced) oxygen-carrying state. This is achieved through the enzyme inducing effect of methylene blue on levels of diaphorase II (NADPH methemoglobin reductase). Diaphorase II normally contributes only a small percentage of the red blood cells reducing capacity but is pharmacologically activated by exogenous cofactors, such as methylene blue, to 5 times its normal level of activity. Genetically induced chronic low-level methemoglobinemia may be treated with oral methylene blue daily. Methylene blue is a heterocyclic aromatic chemical compound with molecular formula: C16H18ClN3S. It has many uses in a range of different fields, such as biology or chemistry. ... In ring theory, a ring R is said to be reduced if it has no non-zero nilpotent elements. ... Enzyme induction is a process in which a molecule ( a drug) induces ( initiates or enhances) the expression of an enzyme. ...


Signs and symptoms of methemoglobinemia (methemoglobin >1%) include shortness of breath, cyanosis, mental status changes, headache, fatigue, exercise intolerance, dizziness and loss of consciousness. Arterial blood with elevated methemoglobin levels has a characteristic chocolate-brown color as compared to normal bright red oxygen containing arterial blood.

Severe methemoglobinemia (methemoglobin >50%) patients have dysrhythmias, seizures, coma and death. Healthy people may not have many symptoms with methemoglobin levels < 15%, however patients with co-morbidities such as anemia, cardiovascular disease, lung disease, sepsis, or presence of other abnormal hemoglobin species (e.g. carboxyhemoglobin, sulfehemoglobin or sickle hemoglobin) may experience moderate to severe symptoms at much lower levels (as low as 5-8%).


The Fugates, a family that lived in the hills of Kentucky, are the most famous example of this hereditary chromosomal error. Known as the Blue Fugates, Martin Fugate, settled near Hazard, Kentucky, circa 1800. His wife was a carrier of the recessive methemoglobinemia (met-H) gene, as was a nearby clan with whom the Fugates intermarried. As a result, many descendants of the Fugates were born with met-H. The Blue Fugates are an extended family from the Appalachian Mountains famous for having a high occurrence of the rare disorder methemoglobinemia. ... Motto: Queen City of the Mountains. ... It has been suggested that this article or section be merged into Dominance relationship. ... For other uses, see Gene (disambiguation). ...

The 'blue men of Lurgan' were a pair of Lurgan men suffering from what was described as 'familial idiopathic methaemoglobinaemia' who were treated by Dr. James Deeny in 1942. Deeny, who would later become the Chief Medical Officer of the Republic of Ireland, prescribed a course of ascorbic acid and sodium bicarbonate. In case one, by the eighth day of treatment there was a marked change in appearance and by the twelfth day of treatment the patient's complexion was normal. In case two, the patient's complexion reached normality over a month-long duration of treatment. Reference to these cases is found in the British Medical Journal, June 12, Vol. 1 ,pg. 721, written by J. Deeny, E.T. Murdock and J.J. Rogan and appears also in the book of essays, The End of an Epidemic, by James Deeny ISBN I 899047 06 9. , Lurgan (from the Irish: An Lorgain meaning the long low ridge of land), is a town in County Armagh, Northern Ireland with a population of approximately 38,000. ... Idiopathic means arising spontaneously or from an obscure or unknown cause. ... Year 1942 (MCMXLII) was a common year starting on Thursday (the link will display the full 1942 calendar) of the Gregorian calendar. ... This article deals with the molecular aspects of ascorbic acid. ... Flash point Non-flammable. ...


Basrani BR, Manek S, Sodhi RNS, Fillery E, Manzur A. Interaction between sodium hypochlorite and chlorhexidine gluconate. J Endod, 33(8): 966 –969, August, 2007. "doi:10.1016/j.joen.2007.04.001"

24. Heard DD, Ashworth RW. The colloidal properties of chlorhexidine and its integration with some macromolecules. J Pharm Pharmac 1968;20;505–12.

28. Chhabra RS, Huff JE, Haseman JK, Elwell MR, Peters AC. Carcinogenicity of p-chloroaniline in rats and mice. Food Chem Toxicol 1991;29:119 –24.

29. Burkhardt-Holm P, Oulmi Y, Schroeder A, Storch V, Braunbeck T. Toxicity of 4-chloraniline in early life stages of Zebrafish (Danio rerio): II. Cytopathology and regeneration of liver and gills after prolonged exposure to waterborne 4 chloraniline. Arch Environ Contam Toxicol 1999;37:85–102.

30. Hazardous Substances Data Bank (HSDB). A database of the National Library of Medicines TOXNET System, http://toxnet. nlm.nih.gov; last accessed Feb 2007.

External links

  Results from FactBites:
Methemoglobinemia, beta-globin type - Genetics Home Reference (603 words)
Beta-globin type methemoglobinemia is an inherited blood disorder that disrupts the function of hemoglobin, the molecule in red blood cells that delivers oxygen to cells in the body.
Methemoglobinemia is characterized by increased levels of an abnormal form of hemoglobin that is unable to deliver oxygen effectively.
In most individuals with beta-globin type methemoglobinemia, the only symptom is cyanosis, a bluish tint of the skin, mucous membranes, or area underneath the fingernails due to a lack of oxygen in the blood.
nbc6.net - Health Encyclopedia - Methemoglobinemia (709 words)
Methemoglobinemia is a condition in which the iron in the hemoglobin molecule (the red blood pigment) is defective, making it unable to carry oxygen effectively to the tissues.
In patients with acquired methemoglobinemia from chemical or drug exposure: headache, fatigue, shortness of breath, lack of energy, and potentially shock, seizures, and death.
Cyanosis caused by exposure to an offending chemical is treated by avoiding that chemical, blood or exchange transfusion for a patient in shock, and repeated doses of IV methylene blue.
  More results at FactBites »



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