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Y2 GI block > Iron Homeostasis > Flashcards

Iron Homeostasis Flashcards

1
Q

Why do we need Iron?

A
  • Essential part of Heme in Haemoglobin
  • Maximises gas exchange
  • Allows RBCs to deform/distort
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2
Q

What is iron’s total body content?

A

4G

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3
Q

How much iron is in Bone marrow and RBCs?

A

3G

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4
Q

How much iron is for the RES (reticuloendothelial system)?

A

200-500mg

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5
Q

How much iron content for myoglobins?

A

200-300mg

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6
Q

How much iron for essential iron containing enzymes?

A

100mg

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7
Q

Give examples of essential iron containing enzymes

A 
cytochromes
peroxidases
Xanthine oxidase 
Catalases 
RNA reductase
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8
Q

What is the principal form of iron storage?

A

Ferritin

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9
Q

What other complex stores iron?

A

Haemosiderin

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10
Q

what are the differences between ferritin and haemosiderin? (solubility, iron availability)

A

Ferritin:

  • soluble iron
  • iron readily available from RES

Haemoseridin:

  • insoluble conglomerates/clumps of ferritin
  • iron slowly available
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11
Q

What is iron bound to for plasma transport?

A

Transferrin

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12
Q

What class of proteins does transferrin belong to?

A

glycoprotein

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13
Q

where is transferrin synthesised

A

hepatocytes (liver)

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14
Q

what is the relationship between transferrin and iron levels?

A

low iron -> high Tf

high iron -> low Tf

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15
Q

how many iron binding domains does transferrin have

A

2 (Y shaped, iron binds to the end of v)

each transferrin molecule can bind to 2 iron atoms

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16
Q

What is plasma iron saturation?

A

30%, so 70% of plasma is free with iron

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17
Q

How much iron do we need to absorb in a day?

A

1-2mg/day

Girls need 2mg/day due to iron loss coz of menstruation

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18
Q

How much iron is absorbed due to the western diet

A

15-20mg/day

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19
Q

does diet play a big part in iron in plasma?

A

No, most iron in plasma comes from body stores (macrophages)

only a little amount comes from the diet

20
Q

What are the two types of iron and what food are they found in?

A

haem iron- red meat (easily absorbed)

non haem iron- white meat, cereals, veggies (not easily absorbed)

21
Q

is there an excretory mechanism for iron

A

no excretory mechanism for excess iron

22
Q

where does iron absorption predominantly occur

A

duodenal enterocytes

23
Q

Describe the process of non-haem iron absorption

A
  • it is reduced from the ferric (Fe3+) to the ferrous form (Fe 2+) by duodenal cytochrome b1(dCytb1). this process is influenced by Vitamin C
  • Fe2+ transported to enterocyte through divalent metal transporter 1 (DMT1)
  • Fe2+ exported from enterocyte to circulating plasma through ferroportin and Hepcidin
24
Q

What is ferroportin and where is it found and not found in

A

Transmembrane protein
Found in duodenal enterocytes, macrophages of RES and hepatocytes
Not found in developing eythroblasts

25
Q

What are the principal regulators of GI Iron absorption

A

INTERACTION between Ferroportin and Hepcidin

26
Q

When would upregulation of DMT1 expression occur

A

Iron deficiency (this would allow increase iron absorption)

27
Q

How does the RES acquire iron

A

RES macrophages acquire iron from effete RBCs

effete RBCs are Haem broken down to iron+bilirubin and globin to the amino acid pool

28
Q

How does the RES store iron

A

Stores iron as ferritin or haemosiderin

29
Q

How does RES release iron

A

iron released from RES macrophages to Transferrin in plasma

30
Q

What controls RES release of iron

A

Ferroportin and Hepcidin

31
Q

what is the maximum mg of iron that can bind to transferrin

A

4mg of iron bound to transferrin

32
Q

how is iron delivered to tissues

A

transferrin-iron complex binds to transferrin receptors found on the cell surface

33
Q

what cell type has the highest concentration of Transferrin receptors

A
  1. erythroblasts

2. hepatocytes

34
Q

what are the disorders related to iron metabolism

A

iron deficiency anaemia (IDA)- too little

Haemochromatosis- too much

35
Q

What are the characteristic features of IDA RBC compared to normal RBC

A

Hypochromic (paler)

microcytosis (smaller)

36
Q

WHat commonly causes IDA in males and post-menopausal women

A

GI blood loss

37
Q

What causes IDA in young women

A

menstrual blood loss

pregnancy

38
Q

what haematinic deficiencies are common in coeliac disease

A
  1. folate deficiency
  2. iron deficiency
  3. Vitamin B12 deficiency
    (in this order)
39
Q

what is the role of hepcidin in iron regulation

A

‘low iron hormone’

reduces the levels of iron in plasma

40
Q

What actions does hepcidin carry out to reduce iron plasma levels

A

Binds to ferroportin and degrades it , causing:

  • reduces GI iron absorption through enterocytes
  • reduces macrophage iron release from RES
41
Q

What is Hereditary Haemochromatosis (HH)

A

autosomal recessive disorder of iron metabolism causing iron overload

42
Q

What is the main cause of HH and what effect does it have on hepcidin

A

Homozygous C282Y mutation of the HFE gene.

reduces hepcidin production

43
Q

why is HH more severe in males

A

females lose the exccesive iron through mesntruation and child birth whereas males dont

44
Q

what happens to transferrin binding site in HH

A

more Fe and not enough transferrin binding sites for Fe

non-transferrin bound Fe can lead to lipid oxidation and tissue damage

45
Q

list complications of HH

A 
liver->cirrhosis
pancreas->diabetes
skin->bronzing
joints->arthritis (common in 2nd and 3rd metacarpophalangeal joints)
heart-> restrictive cardiomyopathy
46
Q

What is the treatment for HH

A

venesection (withdrawal of blood)
monitor ferritin and transferrin saturation
prevent organ damage

Y2 GI block (25 decks)

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