Iron Studies

Question 1

In normal physiology, where is Fe absorbed and also lost?

Answer 1

Gut - absorbs app 1-2mg/day

as the epithelial cells turn over 1-2mg/day is lost

Question 2

Is Fe stored in after absorption through gut lumen to the blood?

Answer 2

It is not stored after reabsorption, rather it is stored in the enterocyte and can be sloughed off if in excess. There is no absorption in the rest of the body

Question 3

What is the normal saturation level of transferrin?

Answer 3

40%

Question 4

How is transferrin and transferring receptor produced? Compare situations between low and high iron.

Answer 4

Fe controls the transferrin and transferring receptor proteins that it needs:
Low Fe in enterocyte: IRE BP (iron responsive binding protein) binds to IRE on mRNA, therefore transferrin receptor produced

High Fe in enterocyte: IRE-BP cannot bind to IRE on transferrin mRNA, therefore transferrin mRNA is destabilised and less production

Question 5

How is transferrin and transferring receptor produced? Compare situations between low and high iron.

Answer 5

Fe controls the transferrin and transferring receptor proteins that it needs:
Low Fe in enterocyte: IRE BP (iron responsive binding protein) binds to IRE on mRNA, therefore transferrin receptor produced

High Fe in enterocyte: IRE-BP cannot bind to IRE on transferrin mRNA, therefore transferrin mRNA is destabilised and less production

Question 6

What are the complications of haemochromatosis?

Answer 6

Fe causing damage directly:

1. Liver disease
2. DM: Fe damage pancreatic islets
3. Cardiac dysfunction
4. Skin pigmentation
5. Athropathy: Fe oxidizes joint tissue and destroys it
6. Gonadal Dysfunction
7. FHx

Question 7

Prevalence of haemachromatosis?

Answer 7

1/400 people

even though gene is 1/200 people the gene is only 50% penetrance

Question 8

How many grams of body Fe required until organ damage?

Answer 8

0-20g asymptomatic, non-specific symptoms
20g signs of organ damage (liver)
>20g early death

Question 9

What mutations are associated with haemochromatosis?

Answer 9

H63D

C282Y

Question 10

What level of ferritin leads to an increase in ALT?

Answer 10

1000 - i.e. liver damage

Question 11

Effect of pregnancy on Fe studies

Answer 11

Transferrin will high (even in anaemia), as estrogen increases production.
Why? As you want to send Fe to baby

Question 12

What are the physiological Fe losses?

Answer 12

Sweat, skin, gut (mostly) = 1mg/day
Menses leads to additional 1-2 mg/day
Pregnancy, breast feeding, delivery (give to baby)

Question 13

Sx of Fe deficiency

Answer 13

Weakness, fatigue, headache, irritability, sore tongue, angular chelitis, nail changes

Question 14

‘Too little in’ causes of Fe deficiency?

Answer 14

a. Dietary deficiency

b. Malabsorption: coeliac, achlorhydria (PPI not associated) as low pH needed in reabsorption of Fe, bowel resection

Question 15

‘Too much out’ causes of FE deficiency?

Answer 15

a. Gut ulceration - reflux, peptic ulceration, Crohn’s
b. Tumours - GIT, kidney, uterus
c. Infection - hookworm, malaria
d. Rare: intravascular haemolysis, dialysis

Question 16

How do bacteria attempt to take our body Fe?

Answer 16

Bacteria require Fe for their own growth and use haemolysins and siderophores

Question 17

What form of iron is absorbed from gut lumen -> enterocyte, enterocyte -> blood?

Answer 17

gut lumen -> enterocyte: ferric Fe3+ becomes ferrous Fe2+ and is STORED in enterocyte as FERRITIN (can then be sloughed off)

enterocyte -> blood: Fe2+ via ferroportin to blood stream becomes Fe3+ then transported around blood with TRANSFERRIN (that relies on transferrin R)

Question 18

Is Fe stored after absorption through gut lumen to the blood?

Answer 18

No, it is not stored after reabsorption, rather it is stored in the enterocyte as ferritin and is then sloughed off if in excess or released if deficient in Fe. There is no absorption in the rest of the body

Question 19

How many grams of body Fe is needed until it causes organ damage?

Answer 19

0-20g asymptomatic, non-specific symptoms
20g signs of organ damage (liver)
>20g early death

Question 20

What are the markers of Fe studies?

*important

Answer 20

1. Serum Fe: Fe in blood
2. TIBC (total binding capacity): amount of Fe that can be bound to Fe protein
3. % Transferrin Saturation: extent which Fe binding sites on transferrin are occupied by Fe
4. Serum ferritin: iron stores in body

Question 21

What is the normal serum transferrin level

Answer 21

Normal serum transferrin: 2-3.5

Question 22

What are the effects of pregnancy of Fe studies?

Answer 22

Transferrin will high (even in anaemia), as estrogen increases production.
Why? As you want to send Fe to baby

Question 23

What are the mechanisms in which bacteria attempt to take our body Fe?

Answer 23

Bacteria require Fe for their own growth; they use haemolysins and siderophores

Question 24

Fe study of inflammation:

Answer 24

Serum Fe: low
Transferrin: low
Saturation % transferrin: low
Serum Ferritin: high

Question 25

What is the role of haptoglobin?

Answer 25

Haptoglobin is an acute phase protein that binds to Hb in attempt to conserve it in the bloodstream (away from bacteria) during inflammation.

Therefore with no inflammation, Haptoglobin is low; inflammation, haptoglobin is high

Question 26

What is the effect of inflammation on Fe studies?

Answer 26

Inflammation leads to the body attempting to retain and protect its Fe from bacteria. Therefore cytokines signal the liver to produce: haemopexin and haptoglobin.

Fe: Low (decrease release)
Transferrin: Low (acute phase response)
Saturation: Low
Ferritin: high (increase storage)
MCV: does not change (anaemia of chronic disease

Question 27

Fe study of iron excess:

Answer 27

Fe: high
Transferrin: low
Saturation: high
Ferritin: high

Question 28

Fe study of iron deficiency:

Answer 28

Fe: low
Transferrin: high
Saturation: low
Ferritin: low

Question 29

Fe study of inflammation:

Answer 29

Fe: low
Transferrin: low
Saturation: low
Ferritin: high