Saturday, November 10, 2012

OTHER STRUCTURAL HEMOGLOBIN VARIANTS


OTHER  STRUCTURAL HEMOGLOBIN VARIANTS

Carboxyhemoglobin: 

It is formed by preferential attachment of CO over oxygen to Hb. Carboxyhemoglobin saturation levels of 15-25% are assocaited with dizziness, headaches and >50% is life threatening.

Methemoglobin: 

Under alkaline conditions, the ferrous iron is oxidized to ferric state by toxic agents like nitrates, aniline dyes, drugs like quinones, sulfonamides, etc. This oxidation convertes heme to hematin and Hb to methemoglobin. MetHb is unable to reversibly bind oxygen thus produces cyanosis. MetHb in cell is reduced to ferrous state by NADH-cytochrome reductase system. MetHbenemia is treated by administration of ascorbic acid or methylene blue.

Sulfhemoglobin: 

It is produced by reaction of sulfur containing compounds with heme to form an irreversible oxidation of Hb by introducing sulfur in porphyring rings. It also cannot carry oxygen.

All the hemogloginopathies results in unstable hemoglobins. The unstable hemoglobin variants results from neutral substitutions affecting residues that contact the haem group and generally present as a congenital Heinz body haemolytic anaemia. Amino acid susbtitution in both chains in vicinity of haem group can alter oxygen affinity or propensity to methaemoglobin formation. The diagnosis is made by heat denaturation or isopropanol precipitation test and identification of the globin mutation by protein or DNA analysis. 

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