Iron in Health Disease

Question 1

What are the names given to the two states that iron can be found in the body?

Answer 1

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

Question 2

Why is iron dangerous?

Answer 2

• high chemical reactivity (easy to oxidise)

- no mechanism for excretion

Question 3

If the body cannot regulate excreting iron, how can iron be lost?

Answer 3

Through loss of mucosal cells - e.g. skin, bowel etc

Question 4

Where is iron absorbed?

Answer 4

duodenum

Question 5

What can enhance iron absorption?

Answer 5

• Haem iron (red meat) absorbs easier than non-haem iron
• Ascorbic acid (reduces iron to Fe2+ form)
• Alcohol

Question 6

WHat can inhibit iron absorption?

Answer 6

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

Question 7

How is iron absorbed?

Answer 7

• haem iron absorbed through specific haem transporter
• non-haem iron absorbed through Duodenal cytochrome B (Reduces Fe3+ to Fe2+)
• DMT transports Fe2+ into duodenal enterocyte
• Binds to Ferroportin => export from the enterocyte
• Passed on to transferrin for transport elsewhere

Question 8

How is iron absoprtion regulated?

Answer 8

• Hepcidin
• Produced in liver in response to iron load and inflammation
• Binds to ferroportin and causes degradation
• Iron ‘trapped’ in duodenal cells and macrophages

Question 9

How can iron status be assessed?

Answer 9

Functional iron:
- haemoglobin concentration

Transport iron:
- % saturation of transferrin

Storage iron:
- serum ferritin

Question 10

When may serum ferritin rise other than in iron overload/excess?

Answer 10

Serum ferritin also acts as an acute phase protein so goes up with infection, malignancy etc

Question 11

What can occur if patients have a negative iron balance?

Answer 11

• Use up iron stores
• Iron deficient erythropoiesis
• Decreased MCV
  => Microcytic Anaemia

Epithelial changes
- in skin and nails (Koilonychia - spooning)

Angular stomatitis at mouth

Question 12

What are the main causes of iron deficiency?

Answer 12

Insufficient intake
- pregnant women and children especially

Dietary factors

Losing blood

• menorrhagia
• GI bleed
• haematuria

malabsorption eg coeliac disease

Question 13

Why can iron in patients with an anaemia of chronic disease not be utilised properly?

Answer 13

• inflammation in chronic disease causes more ferritin to be made
  => hepcidin switches on to reduce iron and prevent overload
  => binds to ferroportin and stops iron leaving cells
  => iron is present just cant be used to make RBCs

Question 14

What are the primary and secondary causes of iron overload?

Answer 14

Primary
- Hereditary haemochromatosis

Secondary

• Transfusional (especially patients receiving many long term)
• Iron loading anaemias

Question 15

What is hereditary haemochromatosis?

Answer 15

• mutations in HFE gene (Usually homozygous for C282Y)
• Decreases hepcidin
  => Increased iron absorption
• iron accumulation in parenchyma rather than macrophages
  => risk of end-organ damage

Question 16

What are the main clinical features of hereditary haemochromatosis?

Answer 16

Weakness/fatigue
Joint pains
Impotence
Arthritis
Cirrhosis
Diabetes
Cardiomyopathy

Question 17

When does hereditary haemochromatosis usually present?

Answer 17

middle aged or later

Iron usually >5g

Question 18

How is haemochromatosis usually diagnosed by blood tests?

Answer 18

transferrin saturation >50%

Increased iron stores
=> serum ferritin >300 g/l in men
OR >200 g/l in pre-menopausal women

Question 19

HOw is haemochromatosis treated?

Answer 19

Weekly venesection to begin with
(to exhaust iron stores)

=> thereafter only 2-3 times per year

Question 20

How is iron overload treated in patients with transfusion related overload?

Answer 20

Iron chelating agents:
Desferrioxamine (s/c or IV)
OR new oral agents