Iron Studies

Question 1

What is the charge on ferrous iron?

Answer 1

2+ (reduced)

Question 2

What is the charge on ferric iron?

Answer 2

3+ (oxidised)

Question 3

What are the 4 main functions of iron?

Answer 3

Oxygen carriers
Oxygen storage
Energy production (cytochromes for ox phos, Krebs cycle enzymes)
Liver detoxification (cytochrome p450)

Question 4

How much iron is ingested daily on average? How much is absorbed?

Answer 4

10-20 mg

1-2 mg

Question 5

How is iron absorbed?

Answer 5

Reduced to ferrous form in low pH of stomach and separates from ligand
Converted back to ferric form in high pH of intestine and is absorbed
Reduced as it is absorbed

Question 6

How is iron stored?

Answer 6

In ferritin as the ferrous form
In haemosiderin (slow release form)

Question 7

How is iron transferred?

Answer 7

Transferrin

Question 8

What is the normal saturation of transferrin?

Answer 8

40%

Question 9

What are the roles of HFE?

Answer 9

Controls the rate at which transferrin can be absorbed into the body
Also has effects on hepcidin and therefore the release of iron from cells

Question 10

What is the classical mutation in haemochromatosis?

Answer 10

C282Y mutation in HFE

Can also have C282Y and H63D heterozygote

Question 11

Describe the role of the iron response element (IRE)

Answer 11

High iron
Iron binds to and represses action of IRE
IRE does not bind to the mRNA transcript for transferrin
mRNA is degraded
Less transferrin is produced
Opposite occurs with low iron, opposite is true for ferritin production

Question 12

List 7 morbidities associated with haemochromatosis

Answer 12

Liver disease
DM
Cardiac dysfunction
Skin pigmentation
Arthropathy
Gonadal dysfunction
FHx (can be passed on)

Question 13

When does iron start to accumulate in haemochromatosis?

Answer 13

After child (turnover is reduced)
Same is true in normal population (ferritin is higher in males than pre-menopausal females due to menstruation in both diseased and normal populations)

Question 14

What is the threshold for organ damage (esp liver) in iron excess?

Answer 14

20g

Question 15

What are the findings on iron studies in iron excess?

Answer 15

High ferritin
High iron saturation
Low transferrin (due to binding of IRE)

Question 16

Why is ferritin not a good test for haemochromatosis?

Answer 16

Level varies depending on type of mutation and whether pt is heterozygous or homozygous

Question 17

In what population is ferritin a good test for haemochromatosis?

Answer 17

In women

Question 18

Above what ferritin level does ALT start to rise?

Answer 18

1000

Question 19

What is the effect of oestrogen on transferrin?

Answer 19

Increases

Question 20

What is the cut-off for what is considered a “high transferrin” in a pregnant woman?

Answer 20

~6

Question 21

What is the difference between iron depletion and iron deficiency?

Answer 21

Iron depletion refers to low ferritin in a non-anaemic person
Iron deficiency is a clinical syndrome with symptoms and signs of microcytic anaemia

Question 22

List 7 signs of IDA

Answer 22

Weakness
Fatigue
Headache
Irritability
Sore tongue
Angular chelitis
Nail changes

Question 23

How is iron lost and how much is lost this way?

Answer 23

Sweat, skin, gut: 1 mg/day
Menses: additional 1-2 mg/day
+ more if pregnant, breast-feeding or antenatally

Question 24

List 8 causes of iron deficiency

Answer 24

Dietary deficiency
Malabsorption
Gut ulceration
Tumours
Infection
Menorrhagia
Other rarer causes

Question 25

What 3 malabsorption states are often associated with iron deficiency?

Answer 25

Coeliac disease Achlorhydria (not associated with PPI) Bowel resection

Question 26

When might gut ulceration occur?

Answer 26

Reflux PUD Crohn's

Question 27

List 3 sites for tumours which can cause iron deficiency

Answer 27

Gut Kidney Uterus

Question 28

List 2 infections which can cause iron deficiency

Answer 28

Hookworm | Malaria

Question 29

List 4 other rarer causes of iron deficiency

Answer 29

Intravascular haemolysis Pulmonary haemosiderosis EPO therapy Dialysis

Question 30

What are the findings on iron studies in IDA?

Answer 30

``` Low ferritin Low iron saturation High transferrin Anaemia (low Hb) Low MCV ```

Question 31

What ferritin level causes low Hb?

Answer 31

<10

Question 32

What ferritin level causes low MCV?

Answer 32

<10 to see microcytosis)

Question 33

What ferritin level causes high RDW?

Answer 33

<40

Question 34

Why can iron be normal in certain inflammatory conditions (e.g. UC)?

Answer 34

mm

Question 35

What can siderophore infusion be used to treat?

Answer 35

Iron overload

Question 36

What is the effect of fever on siderophore production?

Answer 36

Decreases

Question 37

How does the immune system respond to the detection of bacteria to prevent their access to iron?

Answer 37

White cell releases lactoferrin, which binds iron in acid environment (environment of inflammation) Cytokines induce APP production Caeruloplasmin oxidises iron Haemopexin removes heme from circulation Haptoglobin removes Hb from blood Hepcidin and ferroportin decrease iron release

Question 38

What is the effect of inflammation on iron studies results?

Answer 38

``` Decreased transferrin Decreased iron saturation Decreased iron Increased ferritin Reduced Hb Normal MCV ```