Flashcards in Iron Metabolism Deck (44):
What enzymes contain iron? (The essential enzymes)
What are the two ways iron can be stored?
Heamosiderais or (more commonly) Ferritin
What is heamosiderais?
It's insoluble conglomerates of ferritin
Iron is only slowly available
What is ferritin?
Ferritin is a soluble, readily available iron source found intracellularly.
Tiny amounts can be found in the serum (proportional to the RES iron stores)
What does ferritin being an acute phase protein mean?
It increases in the plasma during tissue inflammation, so it can cause inaccurate RES iron store estimation.
Where is the iron transporter transferrin synthesised?
What happens to transferrin when iron absorption decreases or increases?
When iron decreases, transferrin increases
When iron increases, transferrin decreases
How many of Tf's binding sites are saturated at any one time?
How much iron do men and women need daily?
Men need 1mg a day and women need 2mg a day (because of menstruation).
The typical western diet provides 15-20mg/day
Describe the locked system that iron is trapped in.
It enters the body via the GI tract, and becomes transferrin.
This is then stored in myoglobin, RBC, enzymes and bone marrow
Iron is then lost from the RBCs as menstrual blood or stored in the RES.
From the RES, iron can be transported back to the myoglobin etc. via transferrin, and then it circles again.
Name the two forms dietary iron.
Heam iron in red meat.
Non-heam iron in white meat, green vegetables and cereals
We have one physiological mechanism to absorb iron to maintain iron balance. Do we have a mechanism to excrete excess iron?
No, iron is either used up by the body or lost in menstruation (in women)
Where is the primary site for iron absorption?
Haem iron is easily absorbed. How is non-heam iron absorbed?
Its released from foodstuffs by acid digestion and proteolysis in the stomach.
Then it must be reduced from the ferric form to the ferrous form by detached cytochrome b1 (dCytb1).
This process is upregulated by vitamin C.
How is iron taken into the enterocyte?
Through the electrogenic divalent metal transporter 1 (DMT1). The expression of this is regulated by the amount of iron in the body.
How does iron get transported from the enterocyte to the plasma?
A transmembrane protein called ferroportin.
This is also needed for the release of iron from macrophages
Describe the whole process of iron transport from the gut lumen to the circulating plasma.
Non-heam iron is reduced to the ferrous form by dCytb1. This and heam iron enters the enterocyte through DMT1. The non-heam iron and heam iron (now heam oxygenase) is added to the labile pool of iron inside the cell.
To exit the cell, the iron must travel through ferroportin, and once outside, it attaches to transferrin.
Describe the action of hepcidin.
Hepcidin inhibits the action of ferroportin, and is downregulated in response to low iron levels.
The higher the iron levels, the more the hepcidin acts.
How many iron ions can transferrin bind?
2, one on each arm
How much iron is transported around the body everyday?
50mg, despite there only being 4mg bound to Tf at any one time
How is iron is delivered from Tf to tissue?
The Tf iron complex binds to Tf receptors found on the surface of target tissues.
What cells have the most Tf receptors on their surface?
Red blood cell precurosors (around 80% of them)
Followed by the liver
Once iron has entered a red blood cell, what two things could happen to it?
The mitochondria can convert it to heam or it can be stored as ferritin
How is heam useful in RBCs?
It can reversibly bind to oxygen without undergoing oxidation or reduction?
What is IDA blood like compared to normal blood?
It's hyperchromic and macrocytic
Name some possible causes of iron deficiency anaemia.
In women its commonly menstruation. In males and post-menopausal women its normally GI blood loss. The most common non-GI cause is malabsorption (e.g. Coeliac disease)
Name the three types of heamatinic deficiencies in coeliac disease.
Folate, iron and vitamin B12 deficiency. One person can have any mixture of these.
Describe folate deficiency.
Folate is found in green vegetables and liver. You need 150micrograms/day and your body can store 15mg. This will only last you for three months (it isn't stored well)
Describe iron deficiency.
Found in heam and non-heam forms. We need 1mg a day and the body can store 200-500mg.
Describe vitamin B12 deficiency.
This is found in meat and dairy products. We need 1-3micrograms/day, while the body stores 3mg. This will last us 3-5 years.
At what age do the macrophages remove RBCs?
What is the most important influence on iron regulation?
Hepcidin - the 'low iron' hormone.
This is because it reduces plasma levels of iron by binding to and degrading ferroportin (on enterocytes and macrophages)
What is the HFE gene?
The 'high iron' gene. Its expression is required to synthesis hepcidin. This relationship balances the iron levels.
What regulates the stimulation of the HFE gene?
Circulating Tf and liver iron stores
Describe HFE action.
If there is less TF in the blood, there is less expression of HFE, so then there is less hepcidin, so less ferroportin is inhibited and more iron can enter the body.
What causes HHC?
This is an autosomal recessive disorder caused by an abnormality in the HFE gene (homozygous C28 2Y is the most common)
What are the effects of HHC?
A reduction in HFE (so less hepcidin is produced) leads to an iron influx and increased iron stores.
Who is more likely to get HHC and why?
Males, because women are protected by menstruation and iron loss in child birth.
It also more common in Scotland and Northern England.
How much transferrin is typically saturated in IDA?
Less than 15%
How much iron is absorbed and stored in HHC?
4-5mg is absorbed per day and around 23g is stored in total in the body (the 3g in RBCs remains constant)
Name problems caused by excess iron in the following tissues; liver, pancreas, skin, joints and the heart.
Liver - Cirrhosis/Fibrosis
Pancreas - Diabetes
Skin - Bronzing
Joints - Arthritis
Heart - Restrictive cardiomyopathy
How is HHC treated?
- initially weekly
- for every 500mls of whole blood drained, 250mg of iron is removed
- ferritin and Tf saturation monitored
What is sideroblastic anaemia?
The accumulation of iron in RBCs trapping the mitochondria around the nucleus and so trapping the iron in the cell.