Iron Metabolism, Microcytic Anaemias

Question 1

Describe the causes of Microcytic Anaemia

Answer 1

TAILS

Thalasaemia (Alpha or Beta)

Anaemia of Chronic Disease- Hepcidin-> Functional iron deficiency

Iron deficiency- Insufficient iron for haem synthesis

Lead poisoning- Lead inhibits enzymes involved in haem synthesis

Sideroblastic anaemia- Inherited defect in haem synthesis

Question 2

How does the body regulate iron excretion

Answer 2

It doesn’t

Question 3

Compare the 2 components of dietary iron

Answer 3

Haem iron (Fe2+) + Non-haem iron (Fe2+ and Fe3+)

Question 4

What is Fe2+ iron called
What is Fe3+ iron called
In what form can iron be absorbed

Answer 4

Fe2+ is called Ferrous iron
Fe3+ is called Ferric iron

Must be converted to Fe2+ for absorption

Question 5

How much iron is needed per day in diet
Where does absorption occur

Name 3 good sources of Haem iron
Name 3 good sources of Non-haem iron

Answer 5

10-15mg per day
Duodenum + Upper Jejunum

Haem: Chicken, Liver, Kidney (Meats)
Non-haem: Fortified cereals, Rice, Potatoes

Question 6

Compare absorption of Haem and Non-haem iron into the enterocyte from intestinal lumen

Answer 6

Haem: Directly taken up by enterocyte

Non-haem: Fe2+ is taken up by DMT1 on apical surface. Ferric iron is reduced to ferrous iron by Reductase

Question 7

Once in enterocyte, what 2 things can happen to iron and how?

Answer 7

1. Stored in ferric form as Ferritin
2. Enter bloodstream through Ferroportin, then converted to Ferric form by Hephaestin. Bound to Transferrin for transport

Question 8

What substances have a Negative Influence on iron absorption and how

Answer 8

• Fibre
• Antacids (Inhibit Ferrous iron formation)
• Tannins (In tea)
• Phytates (In chapattis)
  These two bind non-haem iron in intestine

Question 9

What substances have a Positive Influence on iron absorption and how

Answer 9

Vit C and Citrate prevent formation of insoluble iron compounds

Vit C also helps reduce ferric to ferrous iron

Question 10

What is the primary regulation of iron absorption? How does it work

Answer 10

Hepcidin expressed by liver, binds to and inhibits Ferroportin

Question 11

Compare the 2 forms of iron storage

Answer 11

1. Ferritin: Soluble protein-iron complex

2. Haemosiderin: Aggregate of clumped ferritin, Accumulates in Macrophages, particularly in Liver/Spleen/Marrow

Question 12

Describe cellular ion uptake in 4 steps

Answer 12

1. Ferric iron bound transferrin binds transferrin receptor, enters cytosol via Receptor Mediated Endocytosis
2. Fe3+ within endosome released by acidic environment, reduced to Ferrous iron
3. Fe2+ transported to cytosol via DMT1
4. Stored in Ferritin/ Exported out of cell by Ferroportin/ Taken up by mitochondria for use in cytochrome enzymes

Question 13

Where is most of the daily iron requirement from?

Answer 13

Recycling of damaged/ senescent RBCs by Macrophages (Mainly Splenic and Kupffer cells)

Question 14

Outline 2 ways in which inflammation can lead to anaemia

Answer 14

1. Cytokines inhibit EPO production-> Inhibited erythropoiesis in marrow-> Anaemia
2. Cytokines increase Hepcidin production-> Ferroportin inhibited-> Decreased Fe absorption and release from RES-> Reduced plasma iron-> Inhibition of erythropoiesis in marrow

Question 15

Identify 5 causes of Iron Deficiency

Answer 15

• Insufficient iron in diet
• Malabsorption of iron
• Bleeding
• Increased requirement
• Anaemia of Chronic Disease

Question 16

Other than those of generic Anaemia, identify 3 sets of symptoms of Iron Deficiency

Answer 16

Pica (Cravings for non-nutritive substances)
Cold hands and Feet

Epithelial changes (Angular Stomatitis/ Koilonychia/ Glossitis)

Question 17

In iron deficiency, how do RBCs appear in 4 ways

Answer 17

Microcytic
Hypochromic
Anisopoikilocytosis
Sometimes Pencil and Target cells

Question 18

What are 2 tests for Iron deficiency

When can one these not be used

Answer 18

• Plasma ferritin (Low= Iron deficiency, but normal/ high doesn’t rule out iron deficiency)
• Reticulocyte Haemoglobin count (CHr) (Low during Iron deficiency)
• CHr is already low in Thalassemia patients, so can’t be used

Question 19

What are the 3 stages of Treating iron deficiency
Why is the first stage not suitable sometimes
When is the last stage used

Answer 19

1. Dietary advice and Oral supplements (These can cause GI side effects)
2. IM and IV iron injections
3. Blood transfusion (Severe anaemia with imminent cardiac compromise)

Question 20

What are 2 expected responses to Treating Iron Deficiency

Answer 20

1. Improvement in symptoms

2. 20g/L rise in Hb over 3 weeks

Question 21

Why is Iron Excess dangerous in 3 steps

Name 2 conditions where this happens

Answer 21

1. Iron exceeds binding capacity of Transferrin
2. Iron deposited in organs as Haemosiderin
3. Promotes Free radical damage + Organ damage

Transfusion Associated Haemosiderosis
Hereditary Haemochromostosis (HH)

Question 22

What is Transfusion Associated Haemosiderosis

What kind of drugs can be given, how do they help? Give 1 example

How does this condition affect skin colour?

Answer 22

Repeated blood transfusions-> Iron accumulation

Iron chelating agents (Desferrioxamine) can DELAY effects

Skin-> Slate grey colour

Question 23

What is Hereditary Haemochromostosis

Answer 23

Mutation in HFE protein, which normally interacts with the Transferrin Receptor to reduce its affinity for Fe-bound Transferrin

HFE also inhibits Hepcidin production

This mutation causes too much iron to be taken into cells

Question 24

How is Hereditary Haemochromostosis treated

Answer 24

Venesection/ Phlebotomy (Removal of blood)