Iron

Question 1

Where does most iron reside in the body?

Answer 1

Ferrous (Fe2+) iron sits in porphyrin ring of Hb

Question 2

What are the 3 compartments from which iron status is assessed?

Answer 2

Functional iron (bound to Hb)
Transport iron (bound to transferrin)
Stored iron (ferritin in liver)

Question 3

How many binding sites are on transferrin for iron?

Answer 3

2

Question 4

What does transferrin do?

Answer 4

Transport iron from donor tissue (macrophages, intestines, liver) to tissues (erythroid marrow)

Question 5

What are holotransferrin and apotransferrin?

Answer 5

Holotransferrin: bound transferrin
Apotransferrin: unbound transferrin

Question 6

Serum ferritin can also act as an acute phase protein. What is the implication of this?

Answer 6

Levels rise in infection, malignancy etc.

Question 7

What are the 2 main mucosal iron transporters that affect iron absorption?

Answer 7

DMT-1 on mucosal surface (transports ferrous iron)

Ferroportin on serosal surface (facilitates iron export from enterocyte via transferrin)

Question 8

What is hepcidin and what effect does it have on iron absorption?

Answer 8

Produced in liver in response to iron overload

Down-regulates ferroportin to decrease iron absorption

Question 9

Where in the body does iron absorption/pick-up occur?

Answer 9

Duodenum

Question 10

What are the consequences of a negative iron balance?

Answer 10

Iron-deficient erythropoiesis
Decreasing MCV
Microcytic anaema
Epithelial changes (koilonychia, angular stomatitis)

Question 11

List the main disorders of iron metabolism

Answer 11

Iron deficiency
Iron malutilisation (anaemia of chronic disease)
Iron overload (primary or secondary)

Question 12

How does iron overload (haemochromatosis) arise? What effect does it have on erythroid marrow?

Answer 12

Increased ferritin storage with decreased iron release (due to hepcidin), resulting in iron overload and impaired iron supply to erythroid marrow

Question 13

List some clinical features of hereditary haemochromatosis

Answer 13

Weakness, fatigue
Joint pain
Impotence
Arthritis
Cirrhosis
Diabetes
Cardiomyopathy

Question 14

Mutation in which gene accounts for 95% of hereditary haemochromatosis?

Answer 14

HFE gene encoding hepcidin

Question 15

What are the diagnostic levels for iron overload?

Answer 15

Over 50% transferrin saturations
Over 300 micrograms/l serum ferritin in men
Over 200 micrograms/l serum ferritin in pre-menopausal women

Question 16

When is a liver biopsy for haemochromatosis warranted?

Answer 16

If uncertain about iron overload

Assess tissue damage

Question 17

How is hereditary haemochromatosis treated?

Answer 17

Weekly venesection to exhaust iron stores

Family screening

Question 18

What are the typical causes of secondary iron overload?

Answer 18

IRON-LOADING ANAEMIAS
Repeated blood transfusion
Excessive iron absorption (overactive erythropoeisis)
Inefffective erythropoeisis (thalassaemia)
Refractory hypoplastic anaemias (myelodysplasia)

Question 19

What is the treatment option for secondary iron overload?

Answer 19

Iron-chelating agents: desferrioxamine, deferiprone

Venesection contraindicated due to anaemia

Question 20

How do iron-chelating agents work?

Answer 20

Bind iron to form complexes that are secreted in urine

Question 21

Which system found on the luminal surface of the small bowel reduces Fe3+?

Answer 21

Duodenal cytochrome B

Question 22

List the main causes of iron deficiency

Answer 22

Dietary insufficiency
Bleeding
Malabsorption

Question 23

Outline the pathophysiology of irom malutilisation

Answer 23

Increased transcription of ferritin mRNA due to inflammatory cytokines
Increased plasma hepcidin blocks ferriportin mediated iron release
Impaired iron supply to marrow erythroblasts