Iron Homeostasis

Question 1

Why do we need Iron?

Answer 1

• Essential part of Heme in Haemoglobin
• Maximises gas exchange
• Allows RBCs to deform/distort

Question 2

What is iron’s total body content?

Answer 2

4G

Question 3

How much iron is in Bone marrow and RBCs?

Answer 3

3G

Question 4

How much iron is for the RES (reticuloendothelial system)?

Answer 4

200-500mg

Question 5

How much iron content for myoglobins?

Answer 5

200-300mg

Question 6

How much iron for essential iron containing enzymes?

Answer 6

100mg

Question 7

Give examples of essential iron containing enzymes

Answer 7

cytochromes
peroxidases
Xanthine oxidase 
Catalases 
RNA reductase

Question 8

What is the principal form of iron storage?

Answer 8

Ferritin

Question 9

What other complex stores iron?

Answer 9

Haemosiderin

Question 10

what are the differences between ferritin and haemosiderin? (solubility, iron availability)

Answer 10

Ferritin:

• soluble iron
• iron readily available from RES

Haemoseridin:

• insoluble conglomerates/clumps of ferritin
• iron slowly available

Question 11

What is iron bound to for plasma transport?

Answer 11

Transferrin

Question 12

What class of proteins does transferrin belong to?

Answer 12

glycoprotein

Question 13

where is transferrin synthesised

Answer 13

hepatocytes (liver)

Question 14

what is the relationship between transferrin and iron levels?

Answer 14

low iron -> high Tf

high iron -> low Tf

Question 15

how many iron binding domains does transferrin have

Answer 15

2 (Y shaped, iron binds to the end of v)

each transferrin molecule can bind to 2 iron atoms

Question 16

What is plasma iron saturation?

Answer 16

30%, so 70% of plasma is free with iron

Question 17

How much iron do we need to absorb in a day?

Answer 17

1-2mg/day

Girls need 2mg/day due to iron loss coz of menstruation

Question 18

How much iron is absorbed due to the western diet

Answer 18

15-20mg/day

Question 19

does diet play a big part in iron in plasma?

Answer 19

No, most iron in plasma comes from body stores (macrophages)

only a little amount comes from the diet

Question 20

What are the two types of iron and what food are they found in?

Answer 20

haem iron- red meat (easily absorbed)

non haem iron- white meat, cereals, veggies (not easily absorbed)

Question 21

is there an excretory mechanism for iron

Answer 21

no excretory mechanism for excess iron

Question 22

where does iron absorption predominantly occur

Answer 22

duodenal enterocytes

Question 23

Describe the process of non-haem iron absorption

Answer 23

• 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

Question 24

What is ferroportin and where is it found and not found in

Answer 24

Transmembrane protein
Found in duodenal enterocytes, macrophages of RES and hepatocytes
Not found in developing eythroblasts

Question 25

What are the principal regulators of GI Iron absorption

Answer 25

INTERACTION between Ferroportin and Hepcidin

Question 26

When would upregulation of DMT1 expression occur

Answer 26

Iron deficiency (this would allow increase iron absorption)

Question 27

How does the RES acquire iron

Answer 27

RES macrophages acquire iron from effete RBCs | effete RBCs are Haem broken down to iron+bilirubin and globin to the amino acid pool

Question 28

How does the RES store iron

Answer 28

Stores iron as ferritin or haemosiderin

Question 29

How does RES release iron

Answer 29

iron released from RES macrophages to Transferrin in plasma

Question 30

What controls RES release of iron

Answer 30

Ferroportin and Hepcidin

Question 31

what is the maximum mg of iron that can bind to transferrin

Answer 31

4mg of iron bound to transferrin

Question 32

how is iron delivered to tissues

Answer 32

transferrin-iron complex binds to transferrin receptors found on the cell surface

Question 33

what cell type has the highest concentration of Transferrin receptors

Answer 33

1. erythroblasts | 2. hepatocytes

Question 34

what are the disorders related to iron metabolism

Answer 34

iron deficiency anaemia (IDA)- too little | Haemochromatosis- too much

Question 35

What are the characteristic features of IDA RBC compared to normal RBC

Answer 35

Hypochromic (paler) | microcytosis (smaller)

Question 36

WHat commonly causes IDA in males and post-menopausal women

Answer 36

GI blood loss

Question 37

What causes IDA in young women

Answer 37

menstrual blood loss | pregnancy

Question 38

what haematinic deficiencies are common in coeliac disease

Answer 38

1. folate deficiency 2. iron deficiency 3. Vitamin B12 deficiency (in this order)

Question 39

what is the role of hepcidin in iron regulation

Answer 39

'low iron hormone' | reduces the levels of iron in plasma

Question 40

What actions does hepcidin carry out to reduce iron plasma levels

Answer 40

Binds to ferroportin and degrades it , causing: - reduces GI iron absorption through enterocytes - reduces macrophage iron release from RES

Question 41

What is Hereditary Haemochromatosis (HH)

Answer 41

autosomal recessive disorder of iron metabolism causing iron overload

Question 42

What is the main cause of HH and what effect does it have on hepcidin

Answer 42

Homozygous C282Y mutation of the HFE gene. | reduces hepcidin production

Question 43

why is HH more severe in males

Answer 43

females lose the exccesive iron through mesntruation and child birth whereas males dont

Question 44

what happens to transferrin binding site in HH

Answer 44

more Fe and not enough transferrin binding sites for Fe | non-transferrin bound Fe can lead to lipid oxidation and tissue damage

Question 45

list complications of HH

Answer 45

``` liver->cirrhosis pancreas->diabetes skin->bronzing joints->arthritis (common in 2nd and 3rd metacarpophalangeal joints) heart-> restrictive cardiomyopathy ```

Question 46

What is the treatment for HH

Answer 46

venesection (withdrawal of blood) monitor ferritin and transferrin saturation prevent organ damage