Iron Flashcards
what is iron essential for
oxygen transport electron transport (e.g. mitochondrial production of ATP)
present in = haemoglobin, myoglobin, enzymes
what can chemical reactivity cause in iron
oxidative stress
why is it difficulty to get rid of iron in the body
there is no mechanism for excretion
where does iron sit on Hb
prophyrin ring
- where most body iron resides
where does the body have most of its iron
Hb - 2500mg Macrophage stores - 500mg Liver stores - 500mg Erythroid marrow - 150mg Plasma - 4mg
what is the only way to influence iron levels
through absorption
how can assess iron status
Functional iron:
- haemoglobin concentration
Transport iron/iron supply to tissues:
- % saturation of transferrin with iron
Storage iron:
- serum ferritin
- tissue biopsy (bone marrow for Fe deficiency; liver for iron overload)
what is the role of transferrin
Transports iron from donor tissues (macrophages, intestinal cells where iron is being absorbed and hepatocytes) to tissues expressing transferrin receptors i.e. tissues that need it
how does transferrin work
binds to iron in the Fe3+ state and takes it to where it is needed
what does transferrin saturation measure
iron supply
what is holo- and app-transferrin
holotransferrin = iron bound to transferrin
apotransferrin = unbound transferrin
what is ferritin
large protein, that stores iron in Fe3+ form
what does serum ferritin levels show
indirect measure of storage iron
why does an increased ferritin level not necessarily have anything to do with iron
acts as an acute phase protein
also goes up with infection, malignancy etc
when would serum ferritin levels be low
iron deficiency
how is iron absorption regulated
Ferroportin
Hepcidin
what is Hepcidin
The major negative regulator of iron uptake
Produced in liver in response to iron load and inflammation
Down-regulates ferroportin
where is iron absorbed
duodenum
through what mechanism is iron absorbed
DMT-1
- transports iron into the duodenal enterocyte
Ferroportin
- Facilitates iron export from the enterocyte
- Passed on to transferrin for transport elsewhere
what are consequences of negative iron balance
1 - Exhaustion of iron stores
2 - Iron deficient erythropoiesis
= Falling red cell MCV
3 - Microcytic Anaemia
4 - Epithelial changes:
> skin
> Koilonychia
> Angular stomatitiswhat are causes of a hypochromic microcytic anaemia
haem deficiency
- lack of iron
- congential sideroblastic anaemia
globin deficiency
- thalassaemia
what are causes of a lack of iron
iron deficiency
anaemia of chronic disease
how could you tell apart hypochromic microcytic anaemia caused by iron deficiency or anaemia of chronic disease
iron deficiency
= low body iron
anaemia of chronic disease
= normal body iron
what test results are indicative of iron deficiency
anaemia (decreased haemoglobin iron)
reduced storage iron (low serum ferritin)
what are causes of iron deficiency
Insufficient dietary intake
- particularly women and children
- vegetarian diets
Losing too much - bleeding (from any source i.e. GI bleeding)
Not absorbing enough – malabsorption
what are causes of chronic blood loss
Menorrhagia
Gastrointestinal
- Tumours, Ulcers, NSAIDs, Parasitic infection
Haematuria
what is important to remember about iron deficiency anaemia
it is a symptom not a diagnosis
requires investigation for an underling cause
what does anaemia of chronic disease interfere with
red cell breakdown in the macrophage
what happens in anaemia of chronic disease
- Increased transcription of Ferritin mRNA stimulated by inflammatory cytokines so ferritin synthesis increased
- Increased plasma Hepcidin blocks ferroportin-mediated release of iron
- Results in impaired iron supply to marrow erythroblasts and eventually hypochromic red cells
what is primary iron overload
Long-term excess iron absorption with parenchymal rather than macrophage iron loading, and eventual organ damage
what are clinical features of hereditary haemochromatosis
Weakness/fatigue Joint pains Impotence Arthritits Cirrhosis Diabetes Cardiomyopathy Bronze skin
how does hereditary haemochromatosis present
Presentation usually in middle age or later
Iron overload > 5g
what is affected in haemochromatosis
Mutations of HFE gene on chromosome 6
- Main effect likely to be via reduced hepcidin synthesis
- causes iron accumulation
- autosomal recessive
what blood results are seen in haemochromatosis
increased LFT
increased serum ferritin
transferrin saturation >50%
what other diagnostic test can be done in haemochromatosis
liver biopsy
Tx for hereditary haemochromatosis
Weekly phlebotomy
Initial aim to exhaust iron stores (ferritin <20 µg/l)
Thereafter keep ferritin below 50 µg/l
Insulin
what is secondary haemochromatosis also known as
iron-loading anaemias
what causes iron-loading anaemia
Repeated red cell transfusions
Excessive iron absorption related to over-active erythropoiesis
what conditions and their treatment may lead to iron-loading anaemia
Thalassaemia syndromes
Sideroblastic anaemias
Red cell aplasia
Myelodysplasia (MDS)
what is treatment of secondary iron overload
Treatment by venesection not an option in already anaemic patients
Iron chelating agents:
Desferrioxamine (s.c. or IV infusion)
