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Year 3 - Haematology > Iron in health & disease > Flashcards

Iron in health & disease Flashcards

1
Q

What is iron present in?

A

Haemoglobin
Myoglobin
Enzymes e.g. cytochromes

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2
Q

What is iron essential for?

A

Oxygen transport - reversible oxygen binding to haemoglobin
Electron transport (e.g. mitochondrial production of ATP) - Ferric (Fe3+) and ferrous forms (Fe2+)

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3
Q

Why is iron dangerous?

A

Chemical reactivity (Fenton reaction: Fe2+ + H2O2 -> Fe3+ + HO. + OH-

Oxidative stress and free radical production

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4
Q

Haem grop is where in Hb?

A

Haem group in each globin chain

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5
Q

Fe2+ ions sit in what?

A

Porphyin ring

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6
Q

The majority of body iron is found in?

A

Haem

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7
Q

Porphyrin ring + Fe = ?

A

Haem

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8
Q

Iron absorption occurs where?

A

Mainly in duodenum
Uptake into cells of duodenal mucosa

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9
Q

Iron absorption is enhanced by?

A

Haem vs non haem iron
- Dedicated haem iron transporter

Ascorbic acid (reduces iron to Fe2+ form)
Alcohol

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10
Q

Iron absorption is inhibited by?

A

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

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11
Q

Describe the mechanisms of iron absorption

A
  1. Duodenal cytochrome B
    - Found in luminal surface
    - Reduces ferric iron (Fe3+) to ferrous form (Fe2+)
  2. DMT (divalent metal transporter)-1
    - Transports ferrous iron into the duodenal enterocyte
  3. Ferroportin
    - Facilitates iron export from the enterocyte
    - Passed on to transferrin for transport elsewhere
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12
Q

What is hepcidin?

A

Major negative regulator of iron uptake
Produced in liver in response to increased iron load and inflammation
Binds to ferroportin and causes its degradation
Iron therefore trapped in duodenal cells and macrophages

Hepcidin levels decrease when iron deficient

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13
Q

What are the 3 compartments to assessment of iron status?

A

Functional iron
Transport iron / iron supply to tissues
Storage iron

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14
Q

Describe functional iron

A

Haemoglobin concentration

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15
Q

Describe transport iron / iron supply to tissues

A

% saturation of transferrin with iron

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16
Q

Describe storage iron

A

Serum ferritin

Tissue biopsy (rarely needed)

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17
Q

What is transferrin and what does it do?

A

Protein with two binding sites for iron atoms

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

Erythroid marrow especially rich in transferrin receptors

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18
Q

How many binding sites for iron is there on transferrin?

A

2

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19
Q

What does transferrin do?

A

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

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20
Q

What does transferrin saturation measure?

A

Iron supply

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

Reflects proportion of diferric transferrin (high affinity for cellular transferrin receptors)

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21
Q

In iron overload, what happens to transferrin?

A

Transferrin saturation elevated

22
Q

What happens to transferrin in iron deficiency?

A

Transferrin saturation decreased

23
Q

What is ferritin?

A

A spherical intracellular protein that stores up to 4000 ferric ions (Fe3+)

24
Q

What does a tiny amount of serum ferritin reflect?

A

Intracellular ferritin synthesis - indirect measure of storage iron

25
Q

Why does serum ferritin go up in infection and malignancy?

A

It acts as an acute phase protein

26
Q

Describe ferritin levels in iron deficiency, iron overload and in inflammation(sepsis, malignancy, liver injury)

A
27
Q

Describe examples of disorders of iron metabolism

A

Iron deficiency
Iron malutilisation (anaemia of chronic disease)
Iron overload

28
Q

What are consequences of negative iron balance?

A

Exhaustion of iron stores
Iron deficient erythropoiesis (falling red cell MCV)
Microcytic anaemia
Epithelial changes - skin, koilonychia, angular stomatitis

29
Q

What are causes of hypo chromic microcytic anaemias?

A
30
Q

What do hypochromic microcytic anaemias mean?

A

Deficient haemoglobin synthesis

31
Q

What is sideroblastic anaemia?

A

Excess iron build up in mitochondria (blue granules around nucleus) due to failure to incorporate iron into haem

Can be hereditary or acquired e.g. MDS, lead poisoning, alcohol excess

32
Q

Iron deficiency can be confirmed by a combination of ?

A

Anaemia (decreased haemoglobin iron) + reduced storage iron (low serum ferritin)

33
Q

What are causes of iron deficiency?

A

Dietary insufficiency
Bleeding
Malabsorption (coeliac disease)

34
Q

What are causes of chronic blood loss?

A

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

35
Q

Describe occult blood loss and how this can cause negative iron balance

A
36
Q

Describe normal haemoglobin recycling

A
37
Q

Describe anaemia of chronic disease and how this affects iron recycling

A
38
Q

Why does anaemia of chronic disease iron deficiency occur?

A

Protective mechanism to reduce supply of iron to pathogens

39
Q

What are primary causes of iron overload?

A

Hereditary haemochromatosis

40
Q

What are secondary causes of iron overload?

A

Transfusional
Iron loading anaemias

41
Q

What is primary iron overload?

A

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

42
Q

What is hereditary haemochromatosis?

A

A genetic disease which causes decreased synthesis of hepcidin and increases iron absorption

Results in gradual iron accumulation with risk of end organ damage

43
Q

What causes hereditary haemochromatosis?

A

Mutations in HFE gene

44
Q

What are clinical features of hereditary haemochromatosis?

A

Weakness / fatigue
Joint paints
impotence
Arthritis
Cirrhosis
Diabetes
Cardiomyopathy

Presentation usually in middle age or later
Iron overload >5g

45
Q

How do you diagnose hereditary haemochromatosis?

A
46
Q

How do you diagnose hereditary haemochromatosis based off of phenotype?

A
47
Q

What is the treatment for hereditary haemochromatosis?

A

Weekly venesection - 400-500ml (200-250mg iron)

Initial aim is to exhaust iron stores (ferritin <20 micrograms / L)

Thereafter keep ferritin below 50 micrograms/L

48
Q

What are causes of secondary iron overload?

A
49
Q

Why can iron overload occur in thalassaemia patients?

A

Each unit of blood contains about 250mg iron

Patients with thalassaemia may require transfusion every 2-3 weeks lifelong

50
Q

So why is iron overload a problem?

A
51
Q

What are treatments for secondary iron overload?

A

Treatment by venesection not an option in already anaemic patients

Iron chelating agents!!!
- Desferrioxamine (subcutaneous or IV infusion)
Newer oral agents - deferiprone, deferasirox

Year 3 - Haematology (35 decks)

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