Iron in Health and Disease

Question 1

What is iron present in throughout the body?

Answer 1

Haemoglobin
Myoglobin
Enzymes eg cytochromes

Question 2

Why is iron important?

Answer 2

Used for oxygen transport - haemoglobin

Electron transport eg mitochondrial production of ATP

Question 3

Why can iron be dangerous?

Answer 3

It contributes to oxidative stress but cannot be actively excreted from the body

Question 4

what adaptive mechanisms are there

Answer 4

Safe transport
safe storage
regulation of iron absoption

Question 5

What is oxidative stress?

Answer 5

Oxidative stress reflects an imbalance between the systemic manifestation of reactive oxygen species and a biological system’s ability to readily detoxify the reactive intermediates or to repair the resulting damage.

Question 6

Where is most of the iron in the body

Answer 6

In haemoglobin

Question 7

Describe the structure of haemoglobin

Answer 7

Four haem groups in a globin chain.

Haem group made up of iron sitting in a prophyrin ring.

Question 8

How is the haem group made

Answer 8

Iron and protoporphyrin come together in the mitochondria to make haem which is deposited in the cytoplasm

Question 9

What assesses functional iron

Answer 9

Hb concentration

Question 10

What assesses transport iron/iron supply to the tissues

Answer 10

Percentage saturation of transferrin with iron

Question 11

What assesses storage iron

Answer 11

serum ferritin
tissue biopsy (bone marrow for iron deficiency; liver for iron overload)

Question 12

What is the function of transferrin.

Answer 12

Transports iron from donor tissues (macrophages, intestinal cells and hepatocytes) to tissues expressing transferrin receptors (erythroid marrow).
It has two binding sites for iron atoms.

Question 13

How is the percentage saturation of transferrin measured and what does it indicate

Answer 13

Serum iron/transferrin x 100

• measures iron supply
• reflects proportion of diferric transferrin

Question 14

How is iron absoption regulated

Answer 14

Intraluminal factors - solubility of inorganic iron, reduction of ferric to ferrous.
Mucosal factors - expression of iron transporters (DMT-1) at mucosal surface and ferroportin at serosal surface
Systemic factors- hepcidin

Question 15

Why is it important that ferric iron is reduced to ferrous iron to be absorbed

Answer 15

ferric iron is insoluble and must be reduced to ferrous before crossing the bowel lumen

Question 16

why is hepcidin important in the regulation of iron absoption

Answer 16

Hepcidin is produced in the liver in response to iron load and inflammation.
It down regulates ferroportin

Question 17

What is ferroportin

Answer 17

It is a transmembrane protein that regulates the exit of iron from enterocytes and macrophages. Where is is then passed on to transferrin and transported elsewhere.

Question 18

What do DMT1 transporters do

Answer 18

Transports iron into the duodenal enterocyte

Question 19

How much iron do we need?

Answer 19

About 4g in an adult

2-5g can be normal depending on the adult and circumstances

Question 20

What are the three main groups of disorders of iron metabolism

Answer 20

Iron deficiency
Iron malutilisation
iron overload

Question 21

what type of anaemia is caused be iron malutilisation

Answer 21

Anaemia of chronic disease (which can be microcytic or normocytic)

Question 22

What is the mechanism of anaemia of chronic disease?

Answer 22

1. Increased transcription of ferritin mRNA occurs due to stimulation by inflammatory cytokines –> ferritin synthesis increases
2. Increases plasma hepcidin (due to increases ferritin) blocks ferroportin-mediated release of iron from cells
3. Results in impaired iron supply to marrow erythroblasts and eventually hypochromic red cells

In a nutshell = iron is trapped in cells

Question 23

What are the blood measurements of iron in anaemia of chronic disease

Answer 23

Ferritin = high/normal
Transferrin= low
Serum transferrin receptors = low

Question 24

what is primary iron overload

Answer 24

Long term excess iron absorption with parenchymal rather than macrophage iron loading and eventual organ damage

Question 25

What groups of patients does iron overload occur in

Answer 25

1. those who chronically absorb increased quantities of iron | 2. those recieving repeated blood transfusions to treat conditions such as thalassaemia, aplastic anaemia

Question 26

What is hereditary haemochromatosis

Answer 26

A condition in which iron absorption from a normal diet is inappropriately increased from birth It an is inherited conditon

Question 27

what is the mode of inheritance of haemochromatosis

Answer 27

autosomal recessive

Question 28

What are the clinical features of hereditary haemochromatosis

Answer 28

``` Weakness/fatigue joint pain impotence arthritis cirrhosis diabetes cardiomyopathy ``` Usually presents in middle age or later with iron overload >5mg

Question 29

What gene is mutated in herediatory haemochromatosid

Answer 29

HFE gene Main effect likely to be via reduced hepcidin synthesis Accounts for 95 percent of cases Incomplete penetrance

Question 30

How is hereditary haemochromatosis diagnosed

Answer 30

Genes - HFE Phenotype- Transferrin sats more than fifty percent serum ferritin more than 300ug in men or 200 in premenpausal women Liver biopsy only if uncertain or to asses tissue damage

Question 31

what is the treatment of haemochromatosis?

Answer 31

weekly phlebotomy (450-500ml, 200-250ml of iron) Initial aim to exhaust iron stored (ferritin less than 20ug) Therefore keep ferritn below 50ug

Question 32

What are possible complications of haemochromatosis

Answer 32

``` Diabetes infection Cardiac failure Hepatic failure Varices Hepatoma ```

Question 33

What is the most common cause of death after the introduction of phlebotomy in pts with haemochromatosis

Answer 33

Hepatoma

Question 34

What is the risk for first degree relatives of pts with hereditaoty haemochromatosis

Answer 34

1 in 4

Question 35

Why is family screening important

Answer 35

Haemochromatosis may be asymptomatic until irreversible organ damage has occurred.

Question 36

What is secondary iron overload

Answer 36

Overload due to treatment for anaemias

Question 37

What is the cause of secondary iron overload

Answer 37

Repeated red cell transfusions | excessive iron absoption related to over-actve erythropoiesis

Question 38

What disorders can iron-loading anaemias (iron overload) occur in

Answer 38

Thalassaemias and sideroblastic anaemia - due to massive ineffective erythropoiesis Red cell aplasia and myelodysplasia - refractory hypoplastic anaemias

Question 39

How much iron is in a unit of blood usually

Answer 39

200-250mg

Question 40

What can result from iron overload

Answer 40

Damage to liver, heart and endocrine glands

Question 41

What is the treatment for secondary iron overload

Answer 41

Treatment by venesection NOT an option in already anaemic patients Iron chelatin drugs are used

Question 42

Name iron chelating drugs

Answer 42

Desferrioxamine (sc or iv) New oral agents - deferoprone, deferasirox