Iron Homeostasis

Question 1

How is iron stored in cells?

Answer 1

As Ferririn;

• Soluable.
• Iron is readily available from the Recticuloendothelial System.
• Small amount also in serum, which is related to RES storage.

As Haemosiderin;

• Insoluable conglomerates of ferritin.
• Iron only slowly available.

Question 2

Would serum ferritin be increased/decreased in iron deficient anaemia?

Answer 2

Decreased.

Question 3

Would serum ferritin be increased/decreased in iron overload?

Answer 3

Increased.

Question 4

Would serum ferritin be increased/decreased in tissue inflammation?

Answer 4

Increased.

Question 5

How is iron transported in the plasma?

Answer 5

With transferrin.

Question 6

What kind of molecule is transferrin? Describe its structure.

Answer 6

A glycoprotein. Has 2 binding sites usually 30% saturated with iron.

Question 7

Where is tranferrin made? What controls the rate of its production?

Answer 7

Made by hepatocytes.

Iron levels control the rate of its production.

Question 8

How is iron delivered to tissues?

Answer 8

Transported on transferrin in the blood as a transferrin-iron complex. This binds to transferrin receptors on cell surfaces.

Question 9

Where is the highest concentration of transferrin cell surface receptors found?

Answer 9

On RBC precursors in the liver (80% of receptors).

Question 10

What iron is obtained from the diet?

Answer 10

Haem iron in red meat.

Non-haem iron in white meat, green veg.

Question 11

How is iron excreted?

Answer 11

No excretory mechanism - only iron lost is via cell sloughing in the GI tract or in the menstrual cycle.

Question 12

Where is iron mainly absorbed in digestion?

Answer 12

In the duodenum.

Question 13

How is haem iron absorbed?

Answer 13

Easily..
Taken into enterocyte by DMT1 transporter.
Goes into the blood through the Ferroportin transporter.

Question 14

How is non-haem iron absorbed?

Answer 14

Released from food stuffs by acid digestion and proteolytic enzymes.
Must then be reduced from ferric to ferrous form by duodenal cytochrome b1 (DCytb1).
This process is influenced by vitamin C.

Taken into enterocyte by DMT1 transporter.
Goes into the blood through the Ferroportin transporter.

Question 15

How is iron released from the RES?

Answer 15

RES macrophages get iron from effate RBC’s when haem is broken down to iron and bilirubin.
Iron is stored in the RED as ferritin or haemosidrin (Can store 500mg).
Ferroportin transporter allows its release, this happens in the presence of Hepcidin. .

Question 16

What is Hepcidin?

Answer 16

A hormone made in the liver . It controls the ferroportin transporter on enterocytes and degrades it when there is too much iron.

Question 17

When is DMT1 transporter upregulated?

Answer 17

In IDA.

Question 18

How do erythroblasts use iron?

Answer 18

Tf-iron transports iron to the erythroblast, where iron is taken in via the Tf-receptor.
Inside it can be stored as ferritin OR
Converted to haem in the mitochondria via enzyme ALA-S2.

Question 19

What is haemochromatosis?

Answer 19

Herititary haemochromatosis is an autosomal recessive disorder of iron metabolism causing iron overload.

Question 20

What causes hereditary haemochromatosis?

Answer 20

Abnormalities of the HFE gene though to cause reduced hepcidin production soferroportin cant be switched off. Homoxygous C28Y mutation thought to be most common.

Question 21

Why is HH more severe in males than females?

Answer 21

As females can lose some iron via menstruation and childbirth?

Question 22

How many grams of iron are there in the body?

How many in RBC’s and how many in other tissues?

Answer 22

4g

3g in RBC’s and 1g in other tissues (liver, pancreas, skin, joints).

Question 23

How does HH affect other tissues?

Answer 23

Hepcidin loss causes more iron to be absorbed and taken on transferrin to organs and joints - so 20g of iron can be found in other tissues.

Can lead to cirrhosis, diabetes, bronzed skin and arthritis.

Question 24

How is HH treated?

Answer 24

Venesection.

Monitor ferritin and Tf saturation.

Question 25

What is sidroblastic anaemia?

Answer 25

RBC’s take in iron, but dont transfer it to haem. Instead it is locked away as haemosidrin.

Question 26

What is Iron deficient anaemia?

Answer 26

Not enough iron.

Can be due to malabsorption e.g. in coeliac disease.