7.2 - Anaemia II Flashcards
what are microcytic anaemias
- due to deficit in haemoglobin
- erythrocytes smaller than normal
- cells paler than normal (hypochromic)
due to…
reduced haem synthesis
- iron deficiency
- lead poisoning
- anaemia of chronic disease aka anaemia of inflammation
- sideroblastic anaemia
reduced globin chain synthesis
- α thalassaemia
- β thalassaemia
more about each one on other slide
causes of microcytic anaemia
- α thalassaemia where there is a deletion or loss of function of one more more of the 4 α globin genes
- β thalassaemia where there is a mutation in β globin genes, leading to reduction or absence of β protein
- anaemia of chronic disease/inflamation where hepicidin results in functional iron deficiency. Note this can also be normocytic.
- iron deficiency insufficient iron for haem synthesis
- lead poisioning aquired. Lead inhibits enzymes involved with haem synthesis
- sideroblastic anaemia inherited defect in haem synthesis
broad categories: reduced globin chain synthesis (thalassaemia) and reduced haem synthesis (all the others)
can be remembered using TAILS mneumonic
iron
- essential element in all living cells
- required as oxygen carrier (eg haemoglobin in red cells and myoglobin in myocytes)
- required as co-factor in many enzymes (cytochromes in oxidative phosphorylation, kreb’s, detoxification and catalase)
- free iron is very toxic to cells (Fenton reaction - formation of free radicals that can cause oxidative damage)
- complex regulatory to ensure safe absorbtion, transportation and utilisation
- body has no mechanism for excreting iron
- this means can get iron build up
ferrous vs ferric iron
iron can exist in range of oxidation states
ferrous
- Fe 2+
- used in kreb’s, haemoglobin etc
- ie reduced state
- Fe 2+ → Fe 3+ + e- (oxidation, occurs at high pH)
ferric
- Fe 3+
- not liked or used by body
- ie oxidised form
- Fe 3+ + e- → Fe 2+ (reduction, occurs at low pH)
- therefore acid in stomach promotes ferric → ferrous
haem vs non-haem iron
haem
- Fe 2+
- best source
- animal foods eg liver, kidney, beef steak, chicken, duck, pork, salmon, tuna
non haem
- Fe 2+ and 3+
- ferric iron must be reduced to Fe 2+ before it can be absorbed from the diet
- plant based foods eg fortified cereals, beans, oats, rice, raisins, barley
where does absorbtion occur for iron
duodenum and upper jejunum
→ acid in stomach promotes reduction of ferric to ferrous due to low pH
how much iron is required per day in the diet
need 10-15 mg per day in diet… in reality will actually absorb much less than this
how is iron absorbed from the diet
- proteins and enzymes on the brush border of apical surface of enterocytes are in contact with the chyme
- Fe3+ is reduced to Fe2+ using enzyme reductase (on apical surface of enterocyte) and an electron donated by vitamin C
- Fe2+ enters enterocyte via DMT1 (allows only Fe2+ to enter)
- Fe2+ can be stored using ferritin (on sep card)
- can exit enterocyte and enter bloodstream by ferroportin
- hephaestin converts Fe2+ → Fe3+ so that it can bind to transferrin to be transported around the body
note: haem can also enter enterocyte, and be converted to Fe2+ inside cell by haem oxygenase
how is iron stored
- by ferritin
- ferritin serves as a storage molecule for iron in 3+ form only
- has pores
- Fe2+ is oxidised → Fe3+ inside enterocyte
what is chyme
the pulpy acidic fluid which passes from the stomach to the small intestine, consisting of gastric juices and partly digested food
what does transferrin do
once Fe2+ is transported out of enterocyte via ferroportin into the bloodstream, hephaestin oxidises Fe2+ → Fe3+
transferrin binds 2 x Fe3+ to be transported around the body
what is hepicidin and what does it do
- peptide produced by the liver
- inhibits ferroportin by binding to it
- iron is trapped inside the enterocyte rather than be exported out
- hepicidin synthesis is increased in iron overload
- decreased by high erythropoietic activity
- hepicidin induces internalisation and degradation of ferroportin
factors affecting absorption of non-haem iron from food
negative influence
- tannins in tea
- phylatates (eg chapattis, pulses)
- fibre
… these can bind non-haem iron in the intestine, causing iron to be excreted rather than absorbed
- antiacids (raises pH so limits reduction of Fe3+ → Fe2+
positive influence
vitamin C and citrate
- prevent formaiton of insoluble iron compounds
- vit C also helps to reduce ferric to ferrous iron
functional vs stored iron
functional
- haemoglobin
- myoglobin
- enzymes eg cytochromes
- transported iron
stored
FERRITIN
- soluble
- globular protein complex with hollow core
- pores allow iron to enter and be released
HAEMOSIDERIN
- insolulbe
- builds up with age
- aggregates of clumped ferritin particles, denatured protien and lipid
- accumulates in macrophages, particularly in liver, spleen and marrow
cellular iron uptake
- Fe3+ bound transferring binds to transferrin receptor
- enters the cytosol via receptor mediated endocytosis
- Fe3+ within endosome is released by acidic microenvironment
- Fe3+ reduced to Fe2+
- the Fe2+ is transported to the cytosol via DMT1
once in cytosol…
- Fe2+ can be stored in ferritin
- exported by ferroportin (FPN1)
- taken up by mitochondria for use in cytochrome enzymes
