Iron Homeostasis Flashcards
Why do we need Iron?
- Essential part of Heme in Haemoglobin
- Maximises gas exchange
- Allows RBCs to deform/distort
What is iron’s total body content?
4G
How much iron is in Bone marrow and RBCs?
3G
How much iron is for the RES (reticuloendothelial system)?
200-500mg
How much iron content for myoglobins?
200-300mg
How much iron for essential iron containing enzymes?
100mg
Give examples of essential iron containing enzymes
cytochromes peroxidases Xanthine oxidase Catalases RNA reductase
What is the principal form of iron storage?
Ferritin
What other complex stores iron?
Haemosiderin
what are the differences between ferritin and haemosiderin? (solubility, iron availability)
Ferritin:
- soluble iron
- iron readily available from RES
Haemoseridin:
- insoluble conglomerates/clumps of ferritin
- iron slowly available
What is iron bound to for plasma transport?
Transferrin
What class of proteins does transferrin belong to?
glycoprotein
where is transferrin synthesised
hepatocytes (liver)
what is the relationship between transferrin and iron levels?
low iron -> high Tf
high iron -> low Tf
how many iron binding domains does transferrin have
2 (Y shaped, iron binds to the end of v)
each transferrin molecule can bind to 2 iron atoms
What is plasma iron saturation?
30%, so 70% of plasma is free with iron
How much iron do we need to absorb in a day?
1-2mg/day
Girls need 2mg/day due to iron loss coz of menstruation
How much iron is absorbed due to the western diet
15-20mg/day
does diet play a big part in iron in plasma?
No, most iron in plasma comes from body stores (macrophages)
only a little amount comes from the diet
What are the two types of iron and what food are they found in?
haem iron- red meat (easily absorbed)
non haem iron- white meat, cereals, veggies (not easily absorbed)
is there an excretory mechanism for iron
no excretory mechanism for excess iron
where does iron absorption predominantly occur
duodenal enterocytes
Describe the process of non-haem iron absorption
- it is reduced from the ferric (Fe3+) to the ferrous form (Fe 2+) by duodenal cytochrome b1(dCytb1). this process is influenced by Vitamin C
- Fe2+ transported to enterocyte through divalent metal transporter 1 (DMT1)
- Fe2+ exported from enterocyte to circulating plasma through ferroportin and Hepcidin
What is ferroportin and where is it found and not found in
Transmembrane protein
Found in duodenal enterocytes, macrophages of RES and hepatocytes
Not found in developing eythroblasts
What are the principal regulators of GI Iron absorption
INTERACTION between Ferroportin and Hepcidin
When would upregulation of DMT1 expression occur
Iron deficiency (this would allow increase iron absorption)
How does the RES acquire iron
RES macrophages acquire iron from effete RBCs
effete RBCs are Haem broken down to iron+bilirubin and globin to the amino acid pool
How does the RES store iron
Stores iron as ferritin or haemosiderin
How does RES release iron
iron released from RES macrophages to Transferrin in plasma
What controls RES release of iron
Ferroportin and Hepcidin
what is the maximum mg of iron that can bind to transferrin
4mg of iron bound to transferrin
how is iron delivered to tissues
transferrin-iron complex binds to transferrin receptors found on the cell surface
what cell type has the highest concentration of Transferrin receptors
- erythroblasts
2. hepatocytes
what are the disorders related to iron metabolism
iron deficiency anaemia (IDA)- too little
Haemochromatosis- too much
What are the characteristic features of IDA RBC compared to normal RBC
Hypochromic (paler)
microcytosis (smaller)
WHat commonly causes IDA in males and post-menopausal women
GI blood loss
What causes IDA in young women
menstrual blood loss
pregnancy
what haematinic deficiencies are common in coeliac disease
- folate deficiency
- iron deficiency
- Vitamin B12 deficiency
(in this order)
what is the role of hepcidin in iron regulation
‘low iron hormone’
reduces the levels of iron in plasma
What actions does hepcidin carry out to reduce iron plasma levels
Binds to ferroportin and degrades it , causing:
- reduces GI iron absorption through enterocytes
- reduces macrophage iron release from RES
What is Hereditary Haemochromatosis (HH)
autosomal recessive disorder of iron metabolism causing iron overload
What is the main cause of HH and what effect does it have on hepcidin
Homozygous C282Y mutation of the HFE gene.
reduces hepcidin production
why is HH more severe in males
females lose the exccesive iron through mesntruation and child birth whereas males dont
what happens to transferrin binding site in HH
more Fe and not enough transferrin binding sites for Fe
non-transferrin bound Fe can lead to lipid oxidation and tissue damage
list complications of HH
liver->cirrhosis pancreas->diabetes skin->bronzing joints->arthritis (common in 2nd and 3rd metacarpophalangeal joints) heart-> restrictive cardiomyopathy
What is the treatment for HH
venesection (withdrawal of blood)
monitor ferritin and transferrin saturation
prevent organ damage
