Session 4- Iron Metabolism and microcytic anemias Flashcards
what is iron required for?
Required for:
• Oxygen carriers:
Haemoglobin in red cells
Myoglobin in myocytes
- Co-factor in many enzymes:
- Free iron potentially very toxic to cells
• Complex regulatory systems to ensure the safe
absorption, transportation & utilisation
• Body has no mechanism for excreting iron
ferrous
Fe2+
ferric
Fe3+
what form is dietary iron in
haem iron and non-haem (mix of ferrous and feric)
Ferric iron must be reduced to
ferrous iron (Fe2+) before it can be absorbed from diet
where does haem absorption occur
duodenum
upper jejenum
dietary absorption of iron
Fe2+ transported via DMT1
Fe3+ reduced to Fe2+ by reductase then transported into cell via DMT1.
FE2+ move into blood via ferroportin this can be prevented by hepcidin from liver
Hephaestin converts Fe2+ Into Fe3+
Fe3+ transported around the body using trasnferrin
negative influence on absorption of non-haem iron
• Tannins (in tea)
• Phytates (e.g. Chapattis, pulses)
• Fibre
these three can bind non-haem iron in the intestine. Reduces absorption
• Antacids (e.g. Gaviscon)
positive influence on absorption of non-haem iron
Vitamin C & Citrate • Prevent formation of insoluble iron compounds • Vit C also helps reduce ferric to ferrous iron
stored iron
Ferritin
• Globular protein complex with hollow core
• Pores allow iron to enter and be released.
soluble
Haemosiderin
• Aggregates of clumped ferritin particles,
denatured protein & lipid.
• Accumulates in macrophages,
particularly in liver, spleen and marrow.
insoluble
cellular iron uptake
1) Fe3+ bound transferrin binds transferrin receptor and enters the cytosol receptor-mediated endocytosis. 2) Fe3+ within endosome released by acidic microenvironment and reduced to Fe2+ . 3) The Fe2+ transported to the cytosol via DMT1. 4) Once in the cytosol, Fe2+ can be stored in ferritin, exported by ferroportin (FPN1), or taken up by mitochondria for use in cytochrome enzymes
iron recycling
• Most (>80%) of iron requirement met from recycling damaged or senescent red blood cells • Old RBCs engulfed by macrophages (phagocytosis) • Mainly by splenic macrophages and Kupffer cells of liver • Macrophages catabolise haem released from red blood cells • Amino acids reused and Iron exported to blood (transferrin) or returned to storage pool as ferritin in macrophage
hepcidin: a negative regukar of iron absorption
• Hepcidin synthesis is increased
in iron overload.
• Decreased by high erythropoietic
activity
it induces internalisation and degradation of ferroportin
anaemia of chronic disease
inflammatory condition
cytokines released by immune cells
increased production of Hepcidin by liver
inhibition of ferroportin
decreased iron release from reticuloendothelial system
decreased iron absorption in gut
plasma iron reduced
inhibition of erythropoesis
causes of iron deficiency
Insufficient iron in diet
e.g. Vegan & vegetarian diets
Malabsorption of iron
e.g. Vegan & vegetarian diets
Bleeding
e.g. Menstruation, gastric bleeding
due to chronic NSAID usage
Increased requirement
e.g. Pregnancy, rapid growth
Anaemia of chronic disease
e.g. Inflammatory bowel disease
iron deficiency signs and symptoms
• Tiredness • Pallor • Reduced exercise tolerance (due to reduced oxygen carrying capacity) • Cardiac – angina, palpitations, development of heart failure • Increased respiratory rate • Headache, dizziness, light-headedness
Pica (unusual cravings for non-nutritive
substances e.g. dirt, ice)
Cold hands and feet
Epithelial changes
testing for iron deficiency
plasma ferritin
reduced plasma ferritin
Chr (low reticulocyte Haemoglobin Content) remains low during inflammation
treatment of iron deficiency
- Dietary advice
- Oral iron supplements
- Intramuscular iron injections
- Intravenous iron
- Blood transfusion if severe
why is excess iron dangerous
• Excess iron can exceed binding capacity of transferrin • Excess iron deposited in organs as haemosiderin • Iron promotes free radical formation & organ damage
transfusion associated haemosiderosis
• Repeated blood transfusions
give gradual accumulation of
iron
• Problem with transfusion
dependent anaemias such as
thalassaemia & sickle cell
anaemia
• Iron chelating agents such as
desferrioxamine can delay but
do not stop inevitable effects of
iron overload
heriditary haemochromatosis
autosomal recessive disease caused by mutation in HFE gene
HFE protein normally interacts with transferrin receptor reducing its affinity for iron-bound transferrin
HFE promotes hepcidin expression through activation of signalling pathways in liver
mutatted HFE therefore results in loss of negative influences on iron uptake and absorption
too much iron enters cells and accumulates in end organ damage
treat with venesection
how does the body adapt to anaemia
increased 2,3 DPG production shifts oxygen dissociation curve to the right meaning that Hb gives up oxygen more readily in the tissues
the blood becomes more visous which reduces systemic vascular resistance which increases cardiac output
Name two intracellular protein-iron complexes that are used to store iron.
Ferritin and haemosiderin
Ferritin
Ferritin is a universal intracellular protein that stores iron and releases it in a controlled fashion. Ferritin is found in most tissues as a cytosolic protein, but small amounts are secreted into the serum where it functions as an iron carrier. A ferritin blood test is therefore a useful diagnistic.
haemosiderin
aemosiderin is also an iron-storage complex and is only found within cells. Haemosiderin is complex of ferritin, denatured ferritin and other material. Unlike ferritin, the iron within deposits of haemosiderin is very poorly available.
treatment of hereditary haemochromatosis
therapeutic phlebotomy to remove excess iron
