Haemoglobin Flashcards
alpha thalessemia?
- alpha globin gene deletion or less frequently gene mutations
- loss of all 4 genes is incompatible with life because alpha globin is essential in fetal and adult life.
- can lead to hydrops fetalis
- loss of 3 genes leads to moderately severe microcytic, hypochromic anaemia with splenomegaly.
- loss of 1 or 2 genes is not usually associated with anaemia
- low mcv, low mch and red cell count over 5.5 x 10^12/L
when O2 is unloaded from Hb, the beta chains pull apart, allowing entry of 2,3-DPG. This causes what?
- a lower affinity of O2 which results in the O2 curve shifting to the right.
note: High 2,3-DPG causes a shift to the right; 2,3-DPG reduces the haemoglobin’s affinity for oxygen thus allowing it to be given off to tissue cells
what is P50?
- the partial pressure of O2 at which haemoglobin is half saturated with O2
- the p50 of normal blood is 26.6 mmHg
What happens when the O2 curve shifts to the left?
- an increased affinity for O2
- decreased 2,3-DPG
note: low 2,3-DPG causes a shift to the left
Hb synthesis begins at the proerythroblast stage. T or F.
T
Whats the rate limiting stage of Hb synthesis?
the formation of δ aminolevulinic acid (ALA)
note: ALA synthase- rate limiting enzyme
steps in the formation of haemoglobin?
- begin in the mitochondria: condensation of glycine + succinyl CoA to make δ aminolevulinic acid (ALA); catalysed by ALA synthase.
- move to the cytoplasm where δ ALA undergoes many steps to become protoporphyrin IX- back in the mitochondria
- protoporphyrin IX is combined with Fe2+ to form heme; catalysed by ferrochelatase.
- heme leaves the mitochondria to combine with globin chains to make haemoglobin
whats the composition of the heme molecule?
4 pyrrole rings arranged around a molecule of iron (FE2+)
how does lead poisoning affect Hb synthesis?
it inhibits ferrocheletase and ALA dehydratase activities
whats porphyrias?
deficiencies of enzymes of heme synthesis which cause a build up of porphyrias (toxic at high concs)
note: treated with hemin
low concentrations of Hb can result in microcytic, hypochromic RBCs. T or F.
T
Beta thalessemia?
- occurs when either no β chain or small amounts are synthesized.
- Excess α chains precipitate in erythroblasts and in mature red cells causing severe ineffective erythropoiesis and haemolysis; severe anaemia
- Enlargement of the liver and spleen due to excess red cell destruction
