Iron in Health and Disease Flashcards
Name 2 things that Iron helps transport?
Oxygen
Electron (Mitochondrial production of ATP)
What is Iron present in?
Haemoglobin
Myoglobin
Enzymes e.g. cytochromes
How is Iron dangerous?
Causes oxidative stress
No mechanism for excretion
Where in the structure of haemoglobin does Iron sit?
In the porphyrin ring
What are the 3 status’ of iron?
Functional iron
transport iron/iron supply to tissues
Storage iron
What is functional iron?
Haemoglobin concentration
What is Transport iron/iron supply to tissues?
% saturation of transferrin with iron
What is storage iron>
Serum ferritin Tissue biopsy (bone marrow for Fe deficiency, liver for iron overload)
Describe transferrin?
Protein with 2 binding sites for iron atoms
Transports iron from donor tissues (macrophages, intestinal cells and hepatocytes) to tissues expressing transferrin receptors (especially erythroid marrow)
What is holotransferrin and apotransferrin?
Halo = iron bound to transferrin Apo = Unbound transferrin
What happens to transferrin saturation in iron overload and in iron deficiency?
Overload = Increases Deficiency = Decreases
How is transferrin saturation measured?
Serum iron / total iron binding capacity (to transferrin) X 100%
Describe ferritin?
Large intracellular protein (450kDa)
Spherical proteins; stores up to 4000 ferric ions
Stores iron in Fe3+ form
What does a tiny amount in serum ferritin reflect?
Intracellular ferritin synthesis synthesis in response to iron - indirect measure of storage iron.
What does serum ferritin act as ?
An acute phase protein so also goes up with infection, malignancy etc.
In situations such as inflammation, sepsis, malignancy, liver disease etc. does serum ferritin levels increase or decrease?
Increase (not quite overload)
How is iron absorption regulated?
Intraluminal factors
Mucosal factors
Systemic factors (Hepcidin)
What are the intraluminal factors?
Solubility of ionrganic iron
haem iron easier to absorb
Reduction of ferric (Fe3+ to ferrous Fe2+)
What are the mucosal factors?
DMT-1 (divalent metal transporter) at the mucosal surface
Ferroportin at serosal surface
What are the systemic factors (Hepcidin)?
The major negative regulator of iron uptake
Produced in liver in response to iron overload and inflammation
Down-regulated ferroportin
What does DMT-1 do?
Transports iron into the duodenal enterocyte
What does Ferroportin do?
Facilitates iron export from the enterocyte
Passed on to transferrin for transport elsewhere
What does Hepcidin do?
Down-regulate ferroportin
What epithelial changes can be caused by low iron?
Skin changes
Koilonychia
Angular stomatits
What can cause a hypochromatic microcytic anaemia?
Haem deficiency
Globin deficiency
Describe haem deficiency?
Lack of iron for erythropoiesis
Iron deficiency
Anaemia of chronic disease
Congenitcal sideroblastic anaemia
Describe gobin deficiency?
Thalassaemia
What are causes of chronic blood loss?
Menorrhagia
GI: Tumours, Ulcers, NSAIDs, Parasites
Haematuria
What is the maximum dietary absorption of iron?
4-5mg per day
What stimulates increased transcription of ferritin mRNA?
Inflam cytokines so ferratin synthesis is increased
What blocks ferroportin-mediated release of iron?
Increased plasma hepcidin
What are clinical features of hereditary haemochromatosis?
Weakness/fatigue Joint pain Impotence Arthritis Cirrhosis Diabetes Cardiomyopathy
What are the genetics of hereditary haemochromatosis?
Mutations of HFE gene
Mutation is C282Y
Main effect likely to be via reduced hepcidin synthesis
What is the treatment for hereditary haemochromatosis?
Weekly phlebotomy - 450-500ml + 200-250mg iron
Keep ferritin below 50ug/l
How do you diagnose hereditary haemochromatosis?
Serum ferritin >300ug/l in men, 250ug in pre-menopausal women
Liver biopsy if unsure about iron loading
What is the risk in first degree relatives for hereditary haemochromatosis?
1 in 4
When may haemochromatosis be asymptomatic?
Until irreversible organ damage has occured
What disorders may cause iron-loading anaemias?
Massive ineffective eryhtropoiesis - Thalassaemia syndromes + sideroblastic anaemias
Refractory hypoplastic anaemias - red cell aplasia + myelodysplasia (MDS)
How much iron does each unit of transfused blood contain?
200-250 mg iron
In thalassaemia patients, how often do they require transfusions?
Lifelong, every 2-3 weeks
How do you treat secondary iron overload?
Venesection not an option in already anaemic patients
Iron chelating agents - Desferrioxamine (s.c. or IV infusion)
Oral agents such as Deferiprone or Deferasirox
