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Haematology > Iron in Health and Disease > Flashcards

Iron in Health and Disease Flashcards

1
Q

Name 2 things that Iron helps transport?

A

Oxygen

Electron (Mitochondrial production of ATP)

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2
Q

What is Iron present in?

A

Haemoglobin
Myoglobin
Enzymes e.g. cytochromes

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3
Q

How is Iron dangerous?

A

Causes oxidative stress

No mechanism for excretion

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4
Q

Where in the structure of haemoglobin does Iron sit?

A

In the porphyrin ring

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5
Q

What are the 3 status’ of iron?

A

Functional iron
transport iron/iron supply to tissues
Storage iron

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6
Q

What is functional iron?

A

Haemoglobin concentration

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7
Q

What is Transport iron/iron supply to tissues?

A

% saturation of transferrin with iron

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8
Q

What is storage iron>

A 
Serum ferritin
Tissue biopsy (bone marrow for Fe deficiency, liver for iron overload)
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9
Q

Describe transferrin?

A

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)

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10
Q

What is holotransferrin and apotransferrin?

A 
Halo = iron bound to transferrin
Apo = Unbound transferrin
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11
Q

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

A 
Overload = Increases
Deficiency = Decreases
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12
Q

How is transferrin saturation measured?

A

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

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13
Q

Describe ferritin?

A

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

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14
Q

What does a tiny amount in serum ferritin reflect?

A

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

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15
Q

What does serum ferritin act as ?

A

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

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16
Q

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

A

Increase (not quite overload)

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17
Q

How is iron absorption regulated?

A

Intraluminal factors
Mucosal factors
Systemic factors (Hepcidin)

18
Q

What are the intraluminal factors?

A

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

19
Q

What are the mucosal factors?

A

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

Ferroportin at serosal surface

20
Q

What are the systemic factors (Hepcidin)?

A

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

21
Q

What does DMT-1 do?

A

Transports iron into the duodenal enterocyte

22
Q

What does Ferroportin do?

A

Facilitates iron export from the enterocyte

Passed on to transferrin for transport elsewhere

23
Q

What does Hepcidin do?

A

Down-regulate ferroportin

24
Q

What epithelial changes can be caused by low iron?

A

Skin changes
Koilonychia
Angular stomatits

25
Q

What can cause a hypochromatic microcytic anaemia?

A

Haem deficiency

Globin deficiency

26
Q

Describe haem deficiency?

A

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

27
Q

Describe gobin deficiency?

A

Thalassaemia

28
Q

What are causes of chronic blood loss?

A

Menorrhagia
GI: Tumours, Ulcers, NSAIDs, Parasites
Haematuria

29
Q

What is the maximum dietary absorption of iron?

A

4-5mg per day

30
Q

What stimulates increased transcription of ferritin mRNA?

A

Inflam cytokines so ferratin synthesis is increased

31
Q

What blocks ferroportin-mediated release of iron?

A

Increased plasma hepcidin

32
Q

What are clinical features of hereditary haemochromatosis?

A 
Weakness/fatigue
Joint pain
Impotence
Arthritis
Cirrhosis
Diabetes
Cardiomyopathy
33
Q

What are the genetics of hereditary haemochromatosis?

A

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

34
Q

What is the treatment for hereditary haemochromatosis?

A

Weekly phlebotomy - 450-500ml + 200-250mg iron

Keep ferritin below 50ug/l

35
Q

How do you diagnose hereditary haemochromatosis?

A

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

36
Q

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

A

1 in 4

37
Q

When may haemochromatosis be asymptomatic?

A

Until irreversible organ damage has occured

38
Q

What disorders may cause iron-loading anaemias?

A

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

39
Q

How much iron does each unit of transfused blood contain?

A

200-250 mg iron

40
Q

In thalassaemia patients, how often do they require transfusions?

A

Lifelong, every 2-3 weeks

41
Q

How do you treat secondary iron overload?

A

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

Haematology (27 decks)

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