Iron in Health and Disease

Question 1

Name 2 things that Iron helps transport?

Answer 1

Oxygen

Electron (Mitochondrial production of ATP)

Question 2

What is Iron present in?

Answer 2

Haemoglobin
Myoglobin
Enzymes e.g. cytochromes

Question 3

How is Iron dangerous?

Answer 3

Causes oxidative stress

No mechanism for excretion

Question 4

Where in the structure of haemoglobin does Iron sit?

Answer 4

In the porphyrin ring

Question 5

What are the 3 status’ of iron?

Answer 5

Functional iron
transport iron/iron supply to tissues
Storage iron

Question 6

What is functional iron?

Answer 6

Haemoglobin concentration

Question 7

What is Transport iron/iron supply to tissues?

Answer 7

% saturation of transferrin with iron

Question 8

What is storage iron>

Answer 8

Serum ferritin
Tissue biopsy (bone marrow for Fe deficiency, liver for iron overload)

Question 9

Describe transferrin?

Answer 9

Protein with 2 binding sites for iron atoms
Transports iron from donor tissues (macrophages, intestinal cells and hepatocytes) to tissues expressing transferrin receptors (especially erythroid marrow)

Question 10

What is holotransferrin and apotransferrin?

Answer 10

Halo = iron bound to transferrin
Apo = Unbound transferrin

Question 11

What happens to transferrin saturation in iron overload and in iron deficiency?

Answer 11

Overload = Increases
Deficiency = Decreases

Question 12

How is transferrin saturation measured?

Answer 12

Serum iron / total iron binding capacity (to transferrin) X 100%

Question 13

Describe ferritin?

Answer 13

Large intracellular protein (450kDa)
Spherical proteins; stores up to 4000 ferric ions
Stores iron in Fe3+ form

Question 14

What does a tiny amount in serum ferritin reflect?

Answer 14

Intracellular ferritin synthesis synthesis in response to iron - indirect measure of storage iron.

Question 15

What does serum ferritin act as ?

Answer 15

An acute phase protein so also goes up with infection, malignancy etc.

Question 16

In situations such as inflammation, sepsis, malignancy, liver disease etc. does serum ferritin levels increase or decrease?

Answer 16

Increase (not quite overload)

Question 17

How is iron absorption regulated?

Answer 17

Intraluminal factors
Mucosal factors
Systemic factors (Hepcidin)

Question 18

What are the intraluminal factors?

Answer 18

Solubility of ionrganic iron
haem iron easier to absorb
Reduction of ferric (Fe3+ to ferrous Fe2+)

Question 19

What are the mucosal factors?

Answer 19

DMT-1 (divalent metal transporter) at the mucosal surface

Ferroportin at serosal surface

Question 20

What are the systemic factors (Hepcidin)?

Answer 20

The major negative regulator of iron uptake
Produced in liver in response to iron overload and inflammation
Down-regulated ferroportin

Question 21

What does DMT-1 do?

Answer 21

Transports iron into the duodenal enterocyte

Question 22

What does Ferroportin do?

Answer 22

Facilitates iron export from the enterocyte

Passed on to transferrin for transport elsewhere

Question 23

What does Hepcidin do?

Answer 23

Down-regulate ferroportin

Question 24

What epithelial changes can be caused by low iron?

Answer 24

Skin changes
Koilonychia
Angular stomatits

Question 25

What can cause a hypochromatic microcytic anaemia?

Answer 25

Haem deficiency | Globin deficiency

Question 26

Describe haem deficiency?

Answer 26

Lack of iron for erythropoiesis Iron deficiency Anaemia of chronic disease Congenitcal sideroblastic anaemia

Question 27

Describe gobin deficiency?

Answer 27

Thalassaemia

Question 28

What are causes of chronic blood loss?

Answer 28

Menorrhagia GI: Tumours, Ulcers, NSAIDs, Parasites Haematuria

Question 29

What is the maximum dietary absorption of iron?

Answer 29

4-5mg per day

Question 30

What stimulates increased transcription of ferritin mRNA?

Answer 30

Inflam cytokines so ferratin synthesis is increased

Question 31

What blocks ferroportin-mediated release of iron?

Answer 31

Increased plasma hepcidin

Question 32

What are clinical features of hereditary haemochromatosis?

Answer 32

``` Weakness/fatigue Joint pain Impotence Arthritis Cirrhosis Diabetes Cardiomyopathy ```

Question 33

What are the genetics of hereditary haemochromatosis?

Answer 33

Mutations of HFE gene Mutation is C282Y Main effect likely to be via reduced hepcidin synthesis

Question 34

What is the treatment for hereditary haemochromatosis?

Answer 34

Weekly phlebotomy - 450-500ml + 200-250mg iron | Keep ferritin below 50ug/l

Question 35

How do you diagnose hereditary haemochromatosis?

Answer 35

Serum ferritin >300ug/l in men, 250ug in pre-menopausal women Liver biopsy if unsure about iron loading

Question 36

What is the risk in first degree relatives for hereditary haemochromatosis?

Answer 36

1 in 4

Question 37

When may haemochromatosis be asymptomatic?

Answer 37

Until irreversible organ damage has occured

Question 38

What disorders may cause iron-loading anaemias?

Answer 38

Massive ineffective eryhtropoiesis - Thalassaemia syndromes + sideroblastic anaemias Refractory hypoplastic anaemias - red cell aplasia + myelodysplasia (MDS)

Question 39

How much iron does each unit of transfused blood contain?

Answer 39

200-250 mg iron

Question 40

In thalassaemia patients, how often do they require transfusions?

Answer 40

Lifelong, every 2-3 weeks

Question 41

How do you treat secondary iron overload?

Answer 41

Venesection not an option in already anaemic patients Iron chelating agents - Desferrioxamine (s.c. or IV infusion) Oral agents such as Deferiprone or Deferasirox