Iron Flashcards
what is iron essential for
oxygen transport
electron transport
present in: Hb, myoglobin, enzymes
what mitochondrial process is iron needed for
ATP production
what can chemical reactivity with iron cause
oxidative stress
why is iron difficult to get rid of in the body
there is no mechanism for excretion
where is the major of the body iron found
haem (2500mg)
where does iron sit in haem
porphyrin ring
where else is iron stored in the body
macrophage stores (500mg) liver stores (500mg) erythroid marrow (150mg) plasma (4mg)
what is the only way to influence iron levels
through absorption
where is iron absorbed
duodenum
what transports iron into duodenal enterocyte
DMT
what facilitates iron export from duodenal enterocyte
ferroportin
passes it on to transferrin
what transports iron around the body
transferrin
what down regulates ferroportin to decrease iron uptake
hepcidin
where is hepcidin produced
liver in response to iron load and inflammation
how can iron status be assessed
- function iron: Hb concentration
- transport iron/iron supply to tissue: % transferrin saturation with iron
- storage iron: serum ferritin/tissue biopsy
where do you take a tissue biopsy to look for iron deficiency
bone marrow
where do you take a tissue biopsy to look for iron overload
liver
role of transferrin
transports iron from donor tissues (macrophage/intestinal cells and hepatocytes) to tissues expressing transferrin receptors
i.e. tissues that need it
how many binding sites for iron does transferrin have
2
what form of iron does transferrin bind to
Fe3+
what does transferrin saturation measure
iron supply
what is holotransferrin
transferrin bound to iron
what is apotransferrin
unbound transferrin
how is transferrin affected in iron overload
the transferrin saturation is increased
what is ferritin
large protein, stores iron in Fe 3+ form
what do serum ferritin levels show
indirect measure of iron storage
why does an increase in ferritin level not necessarily have anything to do with iron
acts as an acute phase protein and will be increased with infection, malignancy ect
when would serum ferritin levels be low
iron deficiency
consequences of a negative iron balance
- exhaustion of iron stores
- iron deficient erythropoiesis – falling MCV
- Microcytic anaemia
- epithelial changes - koilonychia, angular stomatitis
disorders of iron metabolism
iron deficiency
iron overload
iron malutilisation- anaemia of chronic disease
causes of microcytic hypochromic anaemia
iron deficiency
globin deficiency
- thalassaemia
difference between iron deficiency anaemia and anaemia of chronic disease
ferritin is low in iron deficiency
causes of iron deficiency
insufficient intake- dietary factors
losing too much- bleeding
not absorbing enough- malabsorption
causes of chronic blood loss that can result in iron deficiency
menorrhagia
GI- tumours, ulcers, NSAIDs, parasitic infection
Haematuria
maximun daily absorption of iron
4-5mg
what happens in anaemia of chronic disease
- increased transcription of ferritin mRNA stimulated by inflammatory cytokines (ferritin synthesis increased)
- increased plasma hepcidin blocks ferroportin - mediated release of iron
- results in impaired iron supply to marrow erythroblasts and eventually hypo chromic red cells
what is primary iron overload
long term excess iron absorption
parenchymal iron loading – organ damage
what is hereditary haemochromatosis
mutations in HFE gene on chromosome 6
decreased hepcidin synthesis – increased iron absorption
presents around middle age
features of hereditary haemochromatosis
weakness fatigue joint pains impotence arthritis cirrhosis diabetes cardiomyopathy bronze skin
blood results in haemochromatosis
increased LFT’s
increased serum ferritin
transferrin saturation >50% (high)
treatment of hereditary haemochromatosis
weekly venesection (blood removal)
- 450-500ml
- initial aim to exhaust iron stores
- keep ferritin under 50
what causes iron loading anaemia
repeated red cell transfusions
excessive iron absorption related to over-active erythropoiesis
conditions and their treatments that may cause iron loading anaemia
thalassaemia
sideroblastic anaemia
red cell aplasia
myelodysplasia
treatment of patients with iron loading anaemia
NOT VENESECTION: already anaemic so do not want to remove blood
iron chelating agents: desferrioxamine (SC/IV)
