Iron in health and disease Flashcards
What is iron required for in the body?
Oxygen transport (reversible oxygen binding by haemoglobin) Electron transport (mitochondrial production of ATP)
What substances in the body contain iron?
Haemoglobin
Myoglobin
Enzymes e.g. cytochromes
How can iron harm the cells?
Oxidative stress
How is iron excreted by the body?
There is no mechanism for active excretion
There is passive loss through old cells being shed e.g. skin cells, menstruation
How are iron levels controlled by the body?
By controlling iron absorption
Where is most of the body’s iron found?
In haemoglobin
How much iron is absorbed and lost a day from the body?
1mg
How much iron is present in a) the plasma b) the erythroid marrow c) red cell haemoglobin d)macrophage stores and e) parenchymal tissues?
a) 4mg
b) 150mg
c) 2500 mg
d) 500mg
e) 500mg
What are the three components of assessment of iron status, and how are they measured?
- Functional iron, measured by haemoglobin concentration
- Transport iron/iron supply to the tissues, measured by Transferrin saturation
- Storage iron, measured by serum ferritin and tissue biopsy (Bone marrow for Fe deficiency, liver for Fe overload)
What is transferrin?
A protein with 2 binding sites for iron atoms
It transports iron from donor tissues (macrophages, intestinal cells and hepatocytes) to tissues expressing transferrin receptors (especially erythroid marrow).
What does % transferrin saturation measure?
Iron supply
How is % transferrin saturation calculated?
Serum iron/transferrin x 100
What is ferritin?
A large spherical intracellular protein
It can store up to 4000 ferric ions
What is an indirect measure of storage iron?
What can it tell you?
Serum ferritin
Low serum ferritin always indicated iron deficiency but a normal level does not guarantee normal stores as ferritin is increased in chronic inflammation and liver disease.
Name three groups of factors that regulate iron absorption.
Intraluminal factors
Mucosal factors
Systemic factors
What intraluminal factors regulate iron absorption?
Solubility of inorganic iron
Reduction of ferric (Fe3+) to ferrous (Fe2+)
What mucosal factors regulate iron absorption?
Expression of iron transporters:
- DMT-1 (divalent metal transporter) at mucosal surface which transports iron into the duodenal enterocyte
- Ferroportin at mucosal surface which facilitates iron export from the enterocyte, which is passed on to transferrin.
What systemic factor regulates iron absorption?
How does it do this?
Hepcidin
It is the major negative regulator of iron uptake.
It is produced in the liver in response to iron load and inflammation.
It down regulates ferroportin, which transports iron from the enterocyte into the systemic circulation.
What types of disorders of iron metabolism can we have?
Iron deficiency
Iron malutilisation
Iron overload
What are the consequences of a negative iron balance?
Exhaustion of iron stores
Iron deficient erythropoiesis
Microcytic anaemia
Epithelial changes (skin, koilonychia, angular stomatitis)
Name some causes of iron deficiency
Insufficient dietary intake (particularly women and children, vegetarian diets)
Losing too much - bleeding
Malabsorption - relatively uncommon
Give an example of a cause of iron malutilisation
Anaemia of chronic disease
Is haem iron or non-haem iron better absorbed? Why?
Haem iron is better absorbed because there is a specific pathway for this process.
Describe the mechanism of inflammatory macrophage iron block ad how it leads to anaemia.
There is increased transcription of ferritin mRNA stimulated by inflammatory cytokines.
As old red blood cells are broken down the iron is taken up by macrophages and stored in ferritin.
There is increased plasma hepcidin which blocks ferroportin mediated release of iron from the macrophages.
This results in impaired iron supply to marrow erythroblasts and eventually hypochromic red cells.
