Iron Flashcards
Function of iron
Many enzymes and proteins, including haemoglobin
Free iron is toxic to cells because..
It acts as a catalyst in the formation of free radicals
Absorption of iron occurs in the..
Duodenum and upper jejunum
What facilitates the uptake of non-haem ferrous iron (Fe2+) from the intestinal lumen?
The transporter protein Divalent Metal Transporter 1 (DMT1), located on the apical surface of enterocytes
Fe3+ in the intestinal lumen must be reduced to Fe2+ by ___________ before uptake by DMT1
Duodenal cytochrome B reductase (DcytB)
The iron within enterocytes can either be stored as ________, or transferred into the bloodstream via the protein ________
The iron within enterocytes can either be stored as ferritin, or transferred into the bloodstream via the protein ferroportin
Once in the blood, iron is bound to the transport protein ____________, and is mostly transported to bone marrow for ____________
Once in the blood, iron is bound to the transport protein transferrin, and is mostly transported to bone marrow for erythropoiesis
Some iron is taken up by __________ in the reticuloendothelial system as a storage pool
Macrophages
The absorption of iron is primarily regulated by a peptide called _________, which is expressed by the liver
The absorption of iron is primarily regulated by a peptide called hepcidin, which is expressed by the liver
Function of hepcidin
Directly binds to ferroportin, resulting in its degradation and therefore preventing iron from leaving the cell
Inhibits transcription of the DMT1 gene, thus reducing iron absorption
T or F: The human body has no specific mechanism for iron excretion, and therefore regulating iron absorption to match the natural losses, is a crucial part of iron metabolism
True
Approximately 1-2mg of iron is lost from the body each day from the..
Skin and gastrointestinal mucosa
A well-balanced diet contains sufficient iron to balance this loss, as approximately 10% of the 10-20 mg of dietary iron in a balanced diet is absorbed each day
Haem iron is from ________ sources, but non-haem iron is from..
Haem iron is from animal sources, but non-haem iron is from whole grains, nuts, seeds, legumes, and leafy greens.
Haem iron is more readily absorbed than inorganic iron which consists of both..
Ferric (Fe3+) and ferrous (Fe2+) iron
Ferric iron must first be reduced to the ________ form before it is absorbed
Ferrous
On a daily basis, only a small fraction of the total iron requirement is gained from the diet. Most of the iron requirement is met from..
Recycling of iron within the reticuloendothelial system, which is released from storage and returned to the active pool
Iron is stored in two forms..
Ferritin and its insoluble derivative haemosiderin
T or F: All cells have the ability to sequester iron as either ferritin or haemosiderin
True
The highest concentrations of stored iron are in the..
Liver, spleen, and bone marrow
What is HHC?
Autosomal recessive disease characterised by excessive absorption of dietary iron
In HHC, the defective gene resides on chromosome ___ and codes for a protein called ____
In HHC, the defective gene resides on chromosome 6 and codes for a protein called HFE
Summary of iron metabolism and storage
Iron is present in which three things?
Haemoglobin
Myoglobin
Enzymes eg cytochromes
Fe2+ ion sits in the ________ ring
Prophyrin
Iron absorption is enhanced by..
Haem vs non-haem iron
Ascorbic acid (reduces iron to Fe2+ form)
Alcohol
Iron absorption is inhibited by..
Tannins eg tea
Phytates eg cereals, bran, nuts and seeds
Calcium eg dairy produce
Function of Duodenal cytochrome B
Reduces ferric iron (Fe3+) to ferrous form (Fe2+)
Function of DMT-1
Transports ferrous iron into the duodenal enterocyte
Function of Ferroportin
Facilitates iron export from the enterocyte
Passed on to transferrin for transport elsewhere
The major negative regulator of iron uptake of iron is..
Hepcidin. It binds to ferroportin and causes its degradation so Iron is ‘trapped’ in duodenal cells and macrophages
Where is Hepcidin produced?
Liver
T or F: Hepcidin levels decrease when iron deficient
True
Summary of iron
Assessment of iron status: three compartments
Functional iron - haemoglobin concentration
Transport iron/iron supply to tissues – % saturation of transferrin with iron
Storage iron – serum ferritin, tissue biopsy (rarely needed)
Function of transferrin
Transports iron from
donor tissues (macrophages, intestinal cells and hepatocytes) to tissues expressing transferrin receptors
__________ is rich in transferrin receptors
Erythroid marrow
How can you measure the iron supply?
What would be an indirect measure of storage iron?
Tiny amount of serum ferritin as it reflects intracellular
ferritin synthesis
Serum ferritin also acts as an acute phase protein so goes up with..
Infection, malignancy etc
Ferriten levels in health & disease
Conditions that cause haem deficiency
Iron deficiency (low body iron)
Anaemia of Chronic Disease (normal body iron)
Sideroblastic anaemias (rare)
Conditions that cause globin deficiency
Thalassaemias
Iron deficiency can be confirmed by a combination of…
Anaemia (decreased haemoglobin iron) and reduced storage iron (low serum ferritin)
The maximum dietary iron absorption of iron is around 4-5 mg per day. Therefore negative _________ can occur
Iron balance
How would an inflammatory condition (cytokines) affect the transport of iron?
What are the primary causes of iron overload?
Hereditary haemochromatosis
What are the secondary causes of iron overload?
Transfusional
Iron loading anaemias
What is Primary Iron Overload?
Long-term excess iron absorption with parenchymal rather than macrophage iron loading
How does Hereditary
Haemochromatosis affect iron cycle?
Decreases synthesis of hepcidin
Increased iron absorption
Results in gradual iron accumulation with risk
of end-organ damage
Give examples of secondary iron overload anaemias
Massive ineffective erythropoiesis
* Thalassaemia
* Sideroblastic anaemias
Refractory hypoplastic anaemias
* Red cell aplasia
* Myelodysplasia (MDS)
Tx of secondary iron overload
Iron chelating agents:
Desferrioxamine (subcut or IV infusion)
Deferiprone/ Deferasirox
The best test to see whether iron overload is present is..
Transferrin saturation
Typically, normal values of < 45% in females and < 50% in males exclude iron overload
Haemochromatosis usually presents after age..
40 when the iron overload becomes symptomatic
What does the following clinical presentation show?
Haemochromatosis
Ix for Haemochromatosis
Serum ferritin
Transferrin saturation
Genetic testing
Liver biopsy with Perl’s stain
MRI
Mx for Haemochromatosis
Venesection (regularly removing blood to remove excess iron – initially weekly)
Monitoring serum ferritin
Monitoring and treating complications
