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3MB Haematology > Iron > Flashcards

Iron Flashcards

1
Q

Function of iron

A

Many enzymes and proteins, including haemoglobin

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2
Q

Free iron is toxic to cells because..

A

It acts as a catalyst in the formation of free radicals

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3
Q

Absorption of iron occurs in the..

A

Duodenum and upper jejunum

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4
Q

What facilitates the uptake of non-haem ferrous iron (Fe2+) from the intestinal lumen?

A

The transporter protein Divalent Metal Transporter 1 (DMT1), located on the apical surface of enterocytes

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5
Q

Fe3+ in the intestinal lumen must be reduced to Fe2+ by ___________ before uptake by DMT1

A

Duodenal cytochrome B reductase (DcytB)

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6
Q

The iron within enterocytes can either be stored as ________, or transferred into the bloodstream via the protein ________

A

The iron within enterocytes can either be stored as ferritin, or transferred into the bloodstream via the protein ferroportin

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7
Q

Once in the blood, iron is bound to the transport protein ____________, and is mostly transported to bone marrow for ____________

A

Once in the blood, iron is bound to the transport protein transferrin, and is mostly transported to bone marrow for erythropoiesis

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8
Q

Some iron is taken up by __________ in the reticuloendothelial system as a storage pool

A

Macrophages

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9
Q

The absorption of iron is primarily regulated by a peptide called _________, which is expressed by the liver

A

The absorption of iron is primarily regulated by a peptide called hepcidin, which is expressed by the liver

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10
Q

Function of hepcidin

A

Directly binds to ferroportin, resulting in its degradation and therefore preventing iron from leaving the cell

Inhibits transcription of the DMT1 gene, thus reducing iron absorption

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11
Q

T or F: The human body has no specific mechanism for iron excretion, and therefore regulating iron absorption to match the natural losses, is a crucial part of iron metabolism

A

True

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12
Q

Approximately 1-2mg of iron is lost from the body each day from the..

A

Skin and gastrointestinal mucosa

A well-balanced diet contains sufficient iron to balance this loss, as approximately 10% of the 10-20 mg of dietary iron in a balanced diet is absorbed each day

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13
Q

Haem iron is from ________ sources, but non-haem iron is from..

A

Haem iron is from animal sources, but non-haem iron is from whole grains, nuts, seeds, legumes, and leafy greens.

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14
Q

Haem iron is more readily absorbed than inorganic iron which consists of both..

A

Ferric (Fe3+) and ferrous (Fe2+) iron

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15
Q

Ferric iron must first be reduced to the ________ form before it is absorbed

A

Ferrous

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16
Q

On a daily basis, only a small fraction of the total iron requirement is gained from the diet. Most of the iron requirement is met from..

A

Recycling of iron within the reticuloendothelial system, which is released from storage and returned to the active pool

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17
Q

Iron is stored in two forms..

A

Ferritin and its insoluble derivative haemosiderin

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18
Q

T or F: All cells have the ability to sequester iron as either ferritin or haemosiderin

A

True

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19
Q

The highest concentrations of stored iron are in the..

A

Liver, spleen, and bone marrow

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20
Q

What is HHC?

A

Autosomal recessive disease characterised by excessive absorption of dietary iron

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21
Q

In HHC, the defective gene resides on chromosome ___ and codes for a protein called ____

A

In HHC, the defective gene resides on chromosome 6 and codes for a protein called HFE

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22
Q

Summary of iron metabolism and storage

A
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23
Q

Iron is present in which three things?

A

Haemoglobin
Myoglobin
Enzymes eg cytochromes

24
Q

Fe2+ ion sits in the ________ ring

A

Prophyrin

25
Q

Iron absorption is enhanced by..

A

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

26
Q

Iron absorption is inhibited by..

A

Tannins eg tea
Phytates eg cereals, bran, nuts and seeds
Calcium eg dairy produce

27
Q

Function of Duodenal cytochrome B

A

Reduces ferric iron (Fe3+) to ferrous form (Fe2+)

28
Q

Function of DMT-1

A

Transports ferrous iron into the duodenal enterocyte

29
Q

Function of Ferroportin

A

Facilitates iron export from the enterocyte

Passed on to transferrin for transport elsewhere

30
Q

The major negative regulator of iron uptake of iron is..

A

Hepcidin. It binds to ferroportin and causes its degradation so Iron is ‘trapped’ in duodenal cells and macrophages

31
Q

Where is Hepcidin produced?

A

Liver

32
Q

T or F: Hepcidin levels decrease when iron deficient

A

True

33
Q

Summary of iron

A
34
Q

Assessment of iron status: three compartments

A

Functional iron - haemoglobin concentration

Transport iron/iron supply to tissues – % saturation of transferrin with iron

Storage iron – serum ferritin, tissue biopsy (rarely needed)

35
Q

Function of transferrin

A

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

36
Q

__________ is rich in transferrin receptors

A

Erythroid marrow

37
Q

How can you measure the iron supply?

A
38
Q

What would be an indirect measure of storage iron?

A

Tiny amount of serum ferritin as it reflects intracellular
ferritin synthesis

39
Q

Serum ferritin also acts as an acute phase protein so goes up with..

A

Infection, malignancy etc

40
Q

Ferriten levels in health & disease

A
41
Q

Conditions that cause haem deficiency

A

Iron deficiency (low body iron)
Anaemia of Chronic Disease (normal body iron)
Sideroblastic anaemias (rare)

42
Q

Conditions that cause globin deficiency

A

Thalassaemias

43
Q

Iron deficiency can be confirmed by a combination of…

A

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

44
Q

The maximum dietary iron absorption of iron is around 4-5 mg per day. Therefore negative _________ can occur

A

Iron balance

45
Q

How would an inflammatory condition (cytokines) affect the transport of iron?

A
46
Q

What are the primary causes of iron overload?

A

Hereditary haemochromatosis

47
Q

What are the secondary causes of iron overload?

A

Transfusional
Iron loading anaemias

48
Q

What is Primary Iron Overload?

A

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

49
Q

How does Hereditary
Haemochromatosis affect iron cycle?

A

Decreases synthesis of hepcidin
Increased iron absorption
Results in gradual iron accumulation with risk
of end-organ damage

50
Q

Give examples of secondary iron overload anaemias

A

Massive ineffective erythropoiesis
* Thalassaemia
* Sideroblastic anaemias

Refractory hypoplastic anaemias
* Red cell aplasia
* Myelodysplasia (MDS)

51
Q

Tx of secondary iron overload

A

Iron chelating agents:
Desferrioxamine (subcut or IV infusion)
Deferiprone/ Deferasirox

52
Q

The best test to see whether iron overload is present is..

A

Transferrin saturation

Typically, normal values of < 45% in females and < 50% in males exclude iron overload

53
Q

Haemochromatosis usually presents after age..

A

40 when the iron overload becomes symptomatic

54
Q

What does the following clinical presentation show?

A

Haemochromatosis

55
Q

Ix for Haemochromatosis

A

Serum ferritin
Transferrin saturation
Genetic testing
Liver biopsy with Perl’s stain
MRI

56
Q

Mx for Haemochromatosis

A

Venesection (regularly removing blood to remove excess iron – initially weekly)
Monitoring serum ferritin
Monitoring and treating complications

3MB Haematology (23 decks)

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