microcytic anaemia Flashcards
what are microcytic anaemias classified by visually
erythrocytes smaller than normal
paler than normal ( hypochromic)
what are the two causes of microcytic anaemia
- reduced haem synthesis
- reduced globin chain synthesis
what are the four causes of reduced haem synthesis
- iron deficiency
- lead poisoning
- anaemia of chronic disease
- sideroblastic anaemia
what is sideroblastic anaemia
inherited defect in haem synthesis
what are the two causes of reduced globin chain synthesis
- a thalassemia
- b thalassemia
what does TAILS stand for
T- thalassemia
A- anaemia of chronic
I- iron deficiency
L- lead poisoning
S- sideroblastic anaemia
what is iron require for
- oxygen carriers in Hb and myoglobin
- co-factors in enzymes:
cytochromes
krebs
cytochrome P450
catalase
why is free iron dangerous
free iron is toxic to cells but body has no mechanism for excreting iron
what is ferrous iron
Fe2+
what is ferric iron
Fe3+
what is the difference between ferric and ferrous iron
Fe2+ is reduced form while Fe3+ is oxidised form
what does dietary iron consist of
haem iron Fe2+
non-haem (mix of 2+ and 3+)
how much iron do we need a day in our diet
10-15 mg/day
where is iron absorbed
duodenum
jejunum
what is chyme
food passing through intestine
what form of iron is only absorbed
only ferrous iron (Fe2+) can be absorbed so ferric iron must be reduced to ferrous iron to be absorbed
what are the ways iron is absorbed from the diet into enterocytes
- haem readily absorbed converted to Fe2+ by haem oxygenase
- Fe2+ is transported through DMT1 (divalent metal transporter) into cells
- Fe3+ converted to Fe2+ by reductase using vitamin C
where is iron stored
ferritin protein
what transport ferrous iron into blood
ferroportin
what is hephaestin
converts Fe2+ to Fe3+ in blood to be transported around the body
what is hepcidin and where is it made
inhibits ferrroportin so less iron absorbed into blood
liver
what is transferrin
transports Fe3+ around the body
what factors negatively influence iron absorption
- tannins in tea
- phytates (pulses, chapattis)
- fibre
- antacids (gavison)
what factors positively influence iron absorption
vitamin C and citrate
how do the negative factors reduce absorption of iron
bind to non - haem iron in the intestine
how do positive factors increase iron absorption
- prevent formation of insoluble iron compounds
- vit C helps reduce ferric to ferrous iron
in what form is iron transported around the body
Fe3+
where is functional iron found in the body
- haemoglobin
- myoglobin
- enzymes
- transported iron
what is the soluble form of stored iron
ferritin
what is the insoluble store of iron
haemosiderin
where is haemosiderein accumulated.
macrophages, liver, spleen and marrow
what is haemosiderin
aggregates of clumped ferritin particles, denatured proteins and lipid
how is iron uptaken by cells
- transferrin with Fe3+ binds to transferrin receptor and enters cytosol by receptor mediated endocytosis
- Fe3+ in endosome released by acidic microenvironment and reduced to Fe2+
- Fe2+ transported to cytosol by DMT1
- Fe2+ stored in ferritin, exported by ferroportin or taken up by mitochondria for use in cytochrome enzymes
where is most of the total daily iron requirement from
more than 80% of iron requirement met from recycling damaged or old RBC
how is iron recycled
old RBC engulfed by macrophages bby splenic cells and kupffer ells
macrophages catabolise haem released from RBC
iron exported to blood (transferrin) or returned to storage pool as ferritin in macrophage
how is iron absorption regulated
- depend on dietary factors, body iron stores and erythropoiesis
- sensed by enterocytes
- regulation or transporters, receptors, hepcidin and cytokines
what regulates hepcidin synthesis
- increased by iron overload
- decreased by high erythropoietic activity
how does hepcidin regulate iron absorption
induces internalisation and degradation of ferroportin
how does anaemia of chronic disease cause anaemia
- inflammatory condition releases cytokines
- increases production of hepcidin
- ## inhibits ferroportin
