iron stuff Flashcards
Fe + ? -> haem
porphyrin ring + Fe -> haem
Fe + protoporophyrin leave mitochondrion to cytoplasm + form haem
when is iron absorbed
mainly duodenum
- uptake into cells of duodenal mucosa
- influenced by dietary factors
what enhances / inhibits iron absorption?
enhanced by -
- ascorbic acid (vit c) - reduces iron to Fe2+ form
- alcohol
inhibited by -
- higher gastric pHs
- tannins - teas
- cereals, bran, nuts, seeds (phytates)
- calcium - dairy produce
causes of elevated iron
beta thalassaemia major
sideroblastic anaemia
oral contraceptive pills
multiple transfusions
hereditary haemochromatosis
mechanism of iron absorption
duodenal cytochrome B - found on luminal surface, reduces ferric iron (Fe3+) to ferrous form (Fe2+)
DMT (divalent metal transporter) - transports ferrous iron into duodenal enterocyte
ferroportin - facilitates iron export from enterocyte, passed on to transferrin for transport elsewhere
how is iron absorption regulated
hepcidin
- major negative regulator of iron uptake
- produced in liver in response to increased iron load + inflammation
- binds to ferroportin + causes degradation
- iron therefore “trapped” in duodenal cells + macrohphages
hepcidin levels decrease when iron deficient
transferrin
protein with 2 binding sites
transports iron from donor tissues (macrophages, intestinal cells + hepatocytes) to tissues expressing transferrin receptors
erythroid marrow especially rich in transferrin receptors
how is iron supply measured
transferrin saturation measures iron supply
ferritin
spherical intracellular protein, stores up to 4000 ferric ions
tiny amount of serum ferritin reflects intracellular ferritin synthesis -> indirect measure of storage iron
*also acts as acute phase protein - goes up with infection, malignancy
pathophysio of anaemia of chronic disease
inflammatory cytokines + increase ferritin stimulates hepcidin release which is inhibitory to iron absorption (decreases activity of ferroportin)
-> results in impaired iron supply to marrow erythroblasts + eventually hypochromic red cells
sideroblastic anaemia
uncommon, microcytic anaemia refractory to intensive iron therapy
- assoc with an atypically high serum ferritin + iron
excess iron build up in mitochondria (blue granules around neucleus) due to failure to incorporate iron into haem
can be hereditary or acquired - MDS, lead poisoning, alcohol excess
causes of iron overload
primary
- long term excess iron absorption with parachymal rather than macrophage iron loading
- hereditary haemochromatosis
secondary
- transfusional
- iron loading anaemias
hereditary haemochromatosis
gradual iron accumulation + deposits in many organ with risk of end organ damage
due to mutations in HFE gene on both copies of chromosome 6 - autosomal recessive
- decreases synthesis of hepcidin -> increases iron absorption
hereditary haemochromatosis presentation
bronze skin
weakness/fatigue
joint pain
impotence
cirrhosis
diabetes
cardiomyopathy
presentation usually middle age or later iron overload >5g
may be asymptomatic until irreversible organ damage has occured
hereditary haemochromatosis investigations
transferrin saturation raised
serum ferritin raised
deranged LFTs
mutations of HFE gene (incomplete penetrance)
- autosomal recessive
- many carry the gene
Hereditary haemochromatosis phenotype diagnosis
transferrin saturation >50% - sustained on repeat fasting sample
increased iron stores - serum ferritin >300ug/l in men or >200 ug/l in premenopausal women
liver biopsy - rarely needed, fibroscan for liver cirrhosis
management of haemochromatosis
venesection
- aim to exhaust iron stores initially
- there after keep ferritin below 50ug/l + tranferrin <50%
2nd line = desferrioxamine
family screening for haemochromatosis
1st degree relative of cases - especially siblings (risk 1 in 4)
children - wait till they are adults able to give informed consent
iron loading anaemias
disorders
- massive ineffective erythropoiesis - thalassaemia, sideroblastic anaemia
- refractory hypoplastic anaemias - red cell aplasia, myelodysplasia
sources
- repeated red cell transfusions
- excessive iron absorption related to overactive erythropoiesis
treatment of secondary iron overload
venesection not an option in already anaemic patients
iron chelating agents
- desferrioxamine - subcut or IV
- newer oral agents - deferiprone, deferasirox
assessment of iron status
function iron -> haemoglobin
iron supply -> transferrin saturation
storage iron -> serum ferritin (beware of acute phase reaction)
iron overload with red cell transfusions
Iron overload is inevitable with regular red cell transfusions, but risk of excess intestinal iron absorption may be hidden until tissue damage becomes symptomatic
MCV vs MCH
MCV = cell size
MCH = cell Hb content
what to do if haemolytic anaemia suspected
look for evidence of red cell breakdown products + reticulocytosis
then consider cause - blood film + history review
causes of macrocytic anaemia
nuclear maturation defects - failure of cell division
- nutritional - B12/folate (megaloblastic)
- myelodysplasia
- drugs
apparent
- agglutination
- (reticulocytosis)
causes of macrocytosis without significant anaemia
hypothyroidism
alcohol
liver disease
renal anaemia =
anaemia of chronic disease - due to failure of erythropoietin production
why can anaemia of chronic disease sometimes be microcytic?
if the predominant mechanism through hepcidin stimulation in that individual
- reduced relase of iron from macrophages due to block of ferroportin
- low available iron even though iron stores adequate
- failure of haemoglobin synthesis so microcytosis
- explains low transferrin saturation despite normal/raised ferritin
