<P> Methemoglobinaemia is a form of abnormal hemoglobin where the iron centre has been oxidised from the + 2 oxidation state (the normal form) to the + 3 state . This causes a leftward shift in the oxygen hemoglobin dissociation curve, as any residual heme with oxygenated ferrous iron (+ 2 state) is unable to unload its bound oxygen into tissues (because 3 + iron impairs hemoglobin's cooperativity), thereby increasing its affinity with oxygen . However, methemoglobin has increased rbc affinity for cyanide, and is therefore useful in the treatment of cyanide poisoning . In cases of accidental ingestion, administration of a nitrite (such as amyl nitrite) can be used to deliberately oxidise hemoglobin and raise methemoglobin levels, restoring the functioning of cytochrome oxidase . The nitrite also acts as a vasodilator, promoting the cellular supply of oxygen, and the addition of an iron salt provides for competitive binding of the free cyanide as the biochemically inert hexacyanoferrate (III) ion, (Fe (CN)). An alternative approach involves administering thiosulfate, thereby converting cyanide to thiocyanate, SCN, which is excreted via the kidneys . Methemoglobin is also formed in small quantities when the dissociation of oxyhemoglobin results in the formation of methemoglobin and superoxide, O, instead of the usual products . Superoxide is a free radical and causes biochemical damage, but is neutralised by the action of the enzyme superoxide dismutase . </P> <P> Myo - inositol trispyrophosphate (ITPP), also known as OXY111A, is an inositol phosphate that causes a rightward shift in the oxygen hemoglobin dissociation curve through allosteric modulation of hemoglobin within red blood cells . It is an experimental drug intended to reduce tissue hypoxia . The effects appear to last roughly as long as the affected red blood cells remain in circulation . </P> <P> Fetal hemoglobin (HbF) is structurally different from normal adult hemoglobin (HbA), giving HbF a higher affinity for oxygen than HbA . HbF is composed of two alpha and two gamma chains whereas HbA is composed of two alpha and two beta chains . The fetal dissociation curve is shifted to the left relative to the curve for the normal adult because of these structural differences . </P> <P> Typically, fetal arterial oxygen pressures are lower than adult arterial oxygen pressures . Hence higher affinity to bind oxygen is required at lower levels of partial pressure in the fetus to allow diffusion of oxygen across the placenta . At the placenta, there is a higher concentration of 2, 3 - BPG formed, and 2, 3 - BPG binds readily to beta chains rather than to alpha chains . As a result, 2, 3 - BPG binds more strongly to adult hemoglobin, causing HbA to release more oxygen for uptake by the fetus, whose HbF is unaffected by the 2, 3 - BPG . HbF then delivers that bound oxygen to tissues that have even lower partial pressures where it can be released . </P>

Explain the oxyhaemoglobin dissociation curve and the factors that may alter it