Iron Metabolism

Question 1

What is iron used for in the body?

Answer 1

– Transports and stores oxygen
– Integral part of many enzymes
including energy metabolism, neurotransmitter production, collagen formation and immune system function

Question 2

Why is iron content in the body carefully controlled?

Answer 2

Have no mechanism for excreting iron – must maintain a fine balance between absorption and loss

Question 3

Name the sites containing active iron in the body

Answer 3

��-- Haemoglobin
�-- Myoglobin: oxygen
reserve in muscles
��--Tissue Iron:
 enzyme systems, cytochromes
��-- Transported iron-’serum iron’

Question 4

Give two inactive stores of iron

Answer 4

�Ferritin – soluble

��Haemosiderin – Macrophage iron, Insoluble

Question 5

Where do you find the majority of iron in the body?

Answer 5

Most in haemoglobin
Stores of iron (liver)
Less in myoglobin

Question 6

Where is haem iron and non-heam iron found in the diet?

Answer 6

Haem iron – meat

Non-haem iron – cereal and vegetables

Question 7

What are the two form of iron and which is the correct form to be absorbed by the body?

Answer 7

Fe2+ – ferrous form in meat, easier to absorb

Fe3+ – ferric form in veg and cereals must be reduced by stomach acid to be absorbed

Question 8

Where does the majority of iron absorption take place?

What facilitates this in the apical surface?

Answer 8

Duodenum and upper jejunum by enterocytes (epithelial cells in jejunum and duodenum)

Transferrin brings two Fe molecules in per transferrin

Question 9

What protein exports iron out of the blood?

Answer 9

ferrroportin

Question 10

Describe the process of iron absorption into enterocytes

Answer 10

Stomach acid reduces Fe3+ to Fe2+
Transferrin transports two Fe2+ into enterocytes by endocytosis. Can be stored in RBC as ferritin.
Then enters blood by ferroportin, where it is transported to the liver for storage or used by Hb

Question 11

What affect does vitamin C have on iron absorption?

Answer 11

Enhances iron absorption

Question 12

How is iron taken into red blood cells?

Answer 12

by binding of Iron-transferrin complex to transferrin receptor (TfR)
Erythroid cells contain the highest number of TfRs

Question 13

What can be used as a good level of functional iron levels?

Answer 13

soluble TfR (sTfR) is a good indicator of functional iron levels

Question 14

What does the regulation of iron absorption depend on?

Answer 14

dietary factors, body iron stores and erythropoiesis

Question 15

What are the major mechanisms for the control of iron absorption?

Answer 15

Transporter regulation (can be up or down regulated)
Receptor expression
Crosstalk between epithelial cells and macrophages (other cells)
Hepcidin – tissue derived factor

Question 16

What does hepcidin do?

Answer 16

– negative regulator of iron absorption
by degrading ferroportin, a protein involved in moving iron out of cells
This prevents iron absorption from gut ane iron release from macrophages

Question 17

Describe hepcidin synthesis

Answer 17

– Secreted by the liver and excreted by the kidneys
�– Synthesis increased in iron overload
��– Transgenic mice constructed to over-express hepcidin died shortly after birth with iron deficiency (negative regulator)
��– Hepcidin production is decreased by high erythropoietic activity

Question 18

Where dose the majority of the iron in the body come from?

Answer 18

Recycling of iron in body (RBC) accounts for about 80%

Question 19

How do macrophages acquire iron?

Answer 19

Macrophages ‘eat’ old senescent RBCs

Question 20

Why are iron deficiencies important to recognise?

Answer 20

Most common nutritional disorder worldwide
Is a symptom of:
1. Insufficient intake/poor absorption 
2. Increased use
-- physiological eg pregnancy 
-- pathological eg bleeding

Question 21

What are some physiological affects of anaemia?

Answer 21

tiredness
reduced oxygen carrying capacity (pallour, reduced exercise tolerance)
CCF
shortness of breath
palpitations

Question 22

How can you confirm iron deficiency?

Answer 22

– Low Hb
– Small RBC and low MCV (mean cell volume)
��– Pencil cells, hypchromia, microcytosis, target cells
��– Low serum ferritin, serum iron (transferrin bound iron) and %transferrin saturation, raised TIBC (total iron binding capacity, measures transferrin levels)

Question 23

Why is serum ferritin important to look at?

Answer 23

Correlates with stores of iron in the body

Question 24

What is the most important thing to measure in iron deficiency?

Answer 24

Ferritin is the single most important measure of iron status
Reduced levels –> iron deficiency
High/normal levels –> don’t rule out iron deficiency

Question 25

When can ferritin levels be increased?

Answer 25

ferritin increased with acute or chronic
inflammation, malignancy, liver disease, and
alcoholism

Question 26

What are the main methods of iron replacement?

Answer 26

– Oral, Diet
– Supplements……
Iron replacement
����– Intravenous – anaphylaxis
����– Intramuscular

Question 27

Describe the pathology of iron excess

Answer 27

Exceeds binding capacity of transferrin
– increased free iron in the blood which is dangerous as it can produce free radical which damage lipid, protein, DNA etc

Question 28

Define haemachromotosis

Answer 28

– Disorder of iron excess resulting in end organ damage
Causes c��irrhosis, diabetes mellitus, hypogonadism, cardiomyopathy, and arthropathy and skin pigmentation
��– Normal body iron 2-3g; damage when reaches 10-15g

Question 29

Describe hereditary haemochromotosis

Answer 29

Autosomal recessive
Four genes can cause it while three interact normally
Treat with venesection (remove blood to remove iron then retransfuse in)

Question 30

What is transfusion associated aemosiderosis?

Answer 30

Transfusion dependent anaemias such as
thalassaemia, myelodysplasia
There is a gradual accumulation of iron
Treat with iron chelating agents eg desferrioxamine which delay but don’t stop inevitable effects of iron overload

Question 31

Give some tests which can confirm iron overload

Answer 31

– Raised serumferritin
��– Increased % transferrin saturation
����– Genetic testing for mutations of HFE gene
��– Evidence parenchymal iron overload on liver biopsy
��– Amount of iron removed by venesection