Iron in Health and Disease Flashcards
What is iron present in throughout the body?
Haemoglobin
Myoglobin
Enzymes eg cytochromes
Why is iron important?
Used for oxygen transport - haemoglobin
Electron transport eg mitochondrial production of ATP
Why can iron be dangerous?
It contributes to oxidative stress but cannot be actively excreted from the body
what adaptive mechanisms are there
Safe transport
safe storage
regulation of iron absoption
What is oxidative stress?
Oxidative stress reflects an imbalance between the systemic manifestation of reactive oxygen species and a biological system’s ability to readily detoxify the reactive intermediates or to repair the resulting damage.
Where is most of the iron in the body
In haemoglobin
Describe the structure of haemoglobin
Four haem groups in a globin chain.
Haem group made up of iron sitting in a prophyrin ring.
How is the haem group made
Iron and protoporphyrin come together in the mitochondria to make haem which is deposited in the cytoplasm
What assesses functional iron
Hb concentration
What assesses transport iron/iron supply to the tissues
Percentage saturation of transferrin with iron
What assesses storage iron
serum ferritin tissue biopsy (bone marrow for iron deficiency; liver for iron overload)
What is the function of transferrin.
Transports iron from donor tissues (macrophages, intestinal cells and hepatocytes) to tissues expressing transferrin receptors (erythroid marrow).
It has two binding sites for iron atoms.
How is the percentage saturation of transferrin measured and what does it indicate
Serum iron/transferrin x 100
- measures iron supply
- reflects proportion of diferric transferrin
How is iron absoption regulated
Intraluminal factors - solubility of inorganic iron, reduction of ferric to ferrous.
Mucosal factors - expression of iron transporters (DMT-1) at mucosal surface and ferroportin at serosal surface
Systemic factors- hepcidin
Why is it important that ferric iron is reduced to ferrous iron to be absorbed
ferric iron is insoluble and must be reduced to ferrous before crossing the bowel lumen
why is hepcidin important in the regulation of iron absoption
Hepcidin is produced in the liver in response to iron load and inflammation.
It down regulates ferroportin
What is ferroportin
It is a transmembrane protein that regulates the exit of iron from enterocytes and macrophages. Where is is then passed on to transferrin and transported elsewhere.
What do DMT1 transporters do
Transports iron into the duodenal enterocyte
How much iron do we need?
About 4g in an adult
2-5g can be normal depending on the adult and circumstances
What are the three main groups of disorders of iron metabolism
Iron deficiency
Iron malutilisation
iron overload
what type of anaemia is caused be iron malutilisation
Anaemia of chronic disease (which can be microcytic or normocytic)
What is the mechanism of anaemia of chronic disease?
- Increased transcription of ferritin mRNA occurs due to stimulation by inflammatory cytokines –> ferritin synthesis increases
- Increases plasma hepcidin (due to increases ferritin) blocks ferroportin-mediated release of iron from cells
- Results in impaired iron supply to marrow erythroblasts and eventually hypochromic red cells
In a nutshell = iron is trapped in cells
What are the blood measurements of iron in anaemia of chronic disease
Ferritin = high/normal
Transferrin= low
Serum transferrin receptors = low
what is primary iron overload
Long term excess iron absorption with parenchymal rather than macrophage iron loading and eventual organ damage
What groups of patients does iron overload occur in
- those who chronically absorb increased quantities of iron
2. those recieving repeated blood transfusions to treat conditions such as thalassaemia, aplastic anaemia
What is hereditary haemochromatosis
A condition in which iron absorption from a normal diet is inappropriately increased from birth
It an is inherited conditon
what is the mode of inheritance of haemochromatosis
autosomal recessive
What are the clinical features of hereditary haemochromatosis
Weakness/fatigue joint pain impotence arthritis cirrhosis diabetes cardiomyopathy
Usually presents in middle age or later with iron overload >5mg
What gene is mutated in herediatory haemochromatosid
HFE gene
Main effect likely to be via reduced hepcidin synthesis
Accounts for 95 percent of cases
Incomplete penetrance
How is hereditary haemochromatosis diagnosed
Genes - HFE
Phenotype-
Transferrin sats more than fifty percent
serum ferritin more than 300ug in men or 200 in premenpausal women
Liver biopsy only if uncertain or to asses tissue damage
what is the treatment of haemochromatosis?
weekly phlebotomy (450-500ml, 200-250ml of iron)
Initial aim to exhaust iron stored (ferritin less than 20ug)
Therefore keep ferritn below 50ug
What are possible complications of haemochromatosis
Diabetes infection Cardiac failure Hepatic failure Varices Hepatoma
What is the most common cause of death after the introduction of phlebotomy in pts with haemochromatosis
Hepatoma
What is the risk for first degree relatives of pts with hereditaoty haemochromatosis
1 in 4
Why is family screening important
Haemochromatosis may be asymptomatic until irreversible organ damage has occurred.
What is secondary iron overload
Overload due to treatment for anaemias
What is the cause of secondary iron overload
Repeated red cell transfusions
excessive iron absoption related to over-actve erythropoiesis
What disorders can iron-loading anaemias (iron overload) occur in
Thalassaemias and sideroblastic anaemia - due to massive ineffective erythropoiesis
Red cell aplasia and myelodysplasia - refractory hypoplastic anaemias
How much iron is in a unit of blood usually
200-250mg
What can result from iron overload
Damage to liver, heart and endocrine glands
What is the treatment for secondary iron overload
Treatment by venesection NOT an option in already anaemic patients
Iron chelatin drugs are used
Name iron chelating drugs
Desferrioxamine (sc or iv)
New oral agents - deferoprone, deferasirox
