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Haematology > Iron in Health and Disease > Flashcards

Iron in Health and Disease Flashcards

1
Q

What are the different forms of iron?

A

Ferric (Fe3+)

Ferrous (Fe 2+)

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2
Q

Where is iron present in the body?

A

Haemaglobin
Myoglobin
Cytochromes

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3
Q

Why can iron be dangerous?

A

Chemical reactivity; oxidative stress and free radical production
Adaptive requirements for safe transport, storage and absorption required
We have no mechanism to excrete iron

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4
Q

What is the fenton reaction?

A

Formation of free radicals from iron

Ferrous + Water = Ferric + free radical + hydroxyl group

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5
Q

Where is haem synthesised?

A

Cytoplasm of cell

Some of it occurs in the mitochondrion

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6
Q

How much iron is absorbed a day?

A

1mg/ day

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7
Q

How much iron is present in the plasma?

A

4mg

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8
Q

How much iron is found in the erythroid marrow?

A

150mg

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9
Q

How much iron is found in the haemaglobin of red cells?

A

2500 mg

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10
Q

How much iron is found in the macrophages?

A

500mg

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11
Q

How much iron is found in parenchymal tissues (liver)?

A

500mg

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12
Q

How much iron is lost a day?

A

1mg / day

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13
Q

Where does iron absorption occur?

A

Duodenum

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14
Q

What will enhance iron absorption?

A

Haem vs non-haem iron (dedicated haem iron transporter)
Ascorbic acid (reduces iron to Fe2+ form)
Alcohol

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15
Q

What will inhibit iron absorption?

A

Tannins e.g. tea
Phytates e.g. cereals, bran, nuts, seeds
Calcium e.g. dairy produce

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16
Q

What is the function of duodenal cytochrome B?

A

Found on luminal surface of duodenum

Reduces ferric iron (3+) to ferrous form (2+)

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17
Q

What is the function of DMT?

A

Transports ferrous iron into the duodenal enterocyte

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18
Q

What is the function of ferroportin?

A

Facilitates iron export from enterocyte

Passed onto transferrin for transport elsewhere

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19
Q

How is iron absorption regulated?

A

Hepcidin:
Major negative regulator or iron uptake
Produced in liver in response to increased iron load and inflammation
Will bind to ferroportin to result in degradation and therefor iron is “trapped” in the duodenum cells and macrophages

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20
Q

How is iron transported within transferrin?

A

Fe3+

This occurs via hephaestin present on the duodenal enterocyte

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21
Q

How is functional iron assessed?

A

Hb conc

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22
Q

How is transport iron/ supply to tissues assessed?

A

% saturation of transferrin with iron

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23
Q

How is storage iron assessed?

A 
Serum ferritin
Tissue biopsy (rarely needed)
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24
Q

How many ion of iron can transferrin carry?

A

2 binding sites

25
Q

What is the function of transferrin?

A

Transports iron from donor tissues (macrophages, interstitial cells and hepatocytes) to tissues expressing transferrin receptors

26
Q

What is a structure especially rich in transferrin receptors?

A

Erythroid marrow

27
Q

What measures iron supply?

A

Transferrin saturation
Serum iron/ total binding capacity x 100%
Reflects proportion of diferric transferrin

28
Q

What is a normal transferrin saturation?

A

20-50%

29
Q

What is holotransferrin?

A

Iron bound to transferrin

30
Q

What is apotransferrin?

A

Unbound transferrin

31
Q

What will happen to transferrin saturation in iron overload?

A

Increased (and vice versa)

32
Q

How many ferric ions can ferritin store?

A

4000

33
Q

What can cause high levels of ferritin outwith iron stores?

A

Acts as an acute phase protein so increased in infection, malignancy etc

34
Q

What are disorders of iron metabolism?

A

Iron deficiency
Iron malutilisation - anaemia of chronic disease
Iron overload

35
Q

What are the consequences of a negative iron balance?

A

Exhaustion of iron stores
Iron deficiency erythropoiesis; falling red cell MCV
Microcytic anaemia
Epithelial changes; dry skin, koilonychia, angular stomatitis

36
Q

What does hypochromic microcytic anaemia suggest?

A

Deficiency haemaglobin synthesis

37
Q

What can cause a haem deficiency?

A

Lack of iron for erythropoiesis - iron deficiency, anaemia of chronic disease
Congenital sideroblastic anaemia

38
Q

What can cause a globin deficiency?

A

Thalassaemia

39
Q

What can cause an iron deficiency?

A

Insufficient intake to meet physiological needs
Bleeding
Malabsorption; coeliac

40
Q

What can cause chronic blood loss?

A

Menorrhagia
GI; tumours, ulcers, NSAIDs, parasitic infection
Haematuria

41
Q

What can cause occult blood loss?

A

GI blood loss of 8-10 ml a day (4-5mg of iron) without any symptoms or signs
Max dietary iron absorption is 4-5mg a day

42
Q

How pathologically, will chronic disease lead to iron deficiency anaemia?

A

AOCD; inflammatory macrophage iron block
Increased transcription of ferritin mRNA by inflam cytokines so ferritin synthesis increased
Increased plasma hepcidin blocks ferroportin mediated release of iron
This results in an impaired iron supply to marrow erythroblasts and eventually hypochromic red cells

43
Q

Why does inflammatory macrophage iron block occur?

A

Protective mechanism to reduce supply of iron to pathogens

44
Q

What are the primary and secondary causes of iron overload?

A

Primary; hereditary haemochromatosis

Secondary: transfusional, iron loading anaemia

45
Q

What is primary iron overload?

A

Long term excess iron absorption with parenchymal rather than macrophage iron loading

46
Q

Describe hereditary haemochromatosis

A

Commonest form due to mutations in HFE gene
Decreases synthesis of hepcidin
Increased iron absorption
Results in gradual iron accumulation with risk of end-organ damage

47
Q

What are the clinical features of hereditary haemochromatosis?

A 
Weakness/ fatigue
Joint pains
Impotence
Arthritis
Cirrhosis
Diabetes
Cardiomyopathy
48
Q

What is defined as iron overload?

A

> 5g

49
Q

How is haemochromatosis diagnosed molecularly?

A

Mutations of HFE gene

Mutations of other iron regulatory proteins e.g. transferrin receptor, hepcidin, ferroportin

50
Q

What is the phenotype of haemochromatosis?

A

Transferrin saturation >50%
Serum ferritin >300 microgram/l in men or >200 microgram/l in pre-menopausal women
Liver biopsy; rarely needed as fibroscan available now to assess cirrhosis

51
Q

How is haemochromatosis treated?

A

Weekly venesection; 450-500ml (200-250 mg iron)
Initial aim to exhaust iron stores (ferritin <20 microgram/l)
Maintenance <50 microgram/l

52
Q

What causes the most deaths in haemochromatosis?

A

Hepatic failure

Hepatoma

53
Q

Is family screening indicated in haemochromatosis?

A

First degree relatives esp siblings
Children; wait until adults for informed consent
HFE genotype and iron status

54
Q

Why are family studies so important in haemochromatosis?

A

May be asymptomatic until irreversible organ damage has occured

55
Q

What can cause iron loading anaemia?

A

Repeated red cell transfusions
Excessive iron absorption related to over active erythropoiesis
Thalassaemia
Sideroblastic anaemia
Refractory hypoplastic anaemia; red cell aplasia, myelodysplasia

56
Q

How much iron does each unit of blood contain?

A

250 mg

Beta thal maj - transfusion every 2-3 weeks

57
Q

How is secondary iron overload treated?

A

Venesection not an option in already anaemic patients

Iron chelating agents; desferrioxamine, deferiprone, deferaasirox

58
Q

What is sideroblastic anaemia?

A

Failure to incorporate iron into haem

Can be hereditary or acquired (MDS, lead poisoning, alcohol excess)

Haematology (31 decks)

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