Iron in health and disease

Question 1

Why is iron essential in health?

Answer 1

Oxygen transport and electron transport. It is present in haemoglobin, myoglobin and enzymes such as cytochromes

Question 2

What makes iron potentially dangerous?

Answer 2

Chemical reactivity - oxidative stress and free radical production No mechanism for excretion of iron!

Question 3

Where is the majority of iron present in the body found?

Answer 3

Majority found in haem

Question 4

What makes up haem?

Answer 4

Porphyrin ring + Fe2+

Question 5

Where is iron absorbed?

Answer 5

Occurs mainly in the duodenum, uptake into cells of duodenal mucosa, influenced by dietary factors

Question 6

What enhances and inhibits iron absorption?

Answer 6

Enhances - haem iron transporter, ascorbic acid (reduces iron to Fe2+ form), alcohol Inhibits - tannins e.g. tea, phytates e.g. cereal, nuts., calcium e.g. dairy produce

Question 7

Describe the mechanism for iron absorption

Answer 7

Duodenal cytochrome B - found in luminal surfcace, reduces ferric iron (Fe3+) to ferrous form (Fe2+) DMT-1 - transports ferrous iron into the duodenal enterocyte Ferroportin - facilitates iron export from the enterocyte and passes it on to transferrin for transport elsewhere

Question 8

How is iron absorption regulated?

Answer 8

Hepcidin - major negative regulator of iron uptake, produced in liver in response to iron overload and inflammation, binds to ferroportin and causes its degradation. Iron is ‘trapped’ in duodenal cells and macrophages

Question 9

What happens to levels of hepcidin during iron deficiency?

Answer 9

Levels of hepcidin decrease when iron deficient

Question 10

How is functional iron level assessed?

Answer 10

Haemoglobin concentration

Question 11

How is transport iron/iron supply to tissues assessed?

Answer 11

% saturation of transferrin with iron

Question 12

How is storage iron level assessed?

Answer 12

Serum ferritin - tiny amount of serum ferritin reflects intracellular ferritin synthesis (indirect measure of storage iron). Serum ferritin also acts as an acute phase protein so goes up with infection, malignancy, etc. Tissue biopsy can be used if needed

Question 13

Where does transferrin transport iron to and from?

Answer 13

Transports iron from donor tissues (macrophages, hepatocytes and duodenal enterocytes) to tissues expressing transferrin receptors. Erythroid marrow especially rich in transferrin receptors

Question 14

What are the consequences of negative iron balance?

Answer 14

Exhaustion of iron stores, iron deficient erythropoiesis (falling red cell MCV), microcytic anaemia, epithelial changes (skin, angular stomatitis, koilonychia)

Question 15

What is the cause of hypochromic microcytic anaemia?

Answer 15

Deficient haemoglobin synthesis either due to haem or globin deficiency. Haem deficiency - lack of iron for erythropoiesis e.g. iron deficiency or anaemia of chronic disease, congenital sideroblastic anaemia Globin deficiency - thalassaemias

Question 16

What confirms iron deficiency?

Answer 16

A combination of anaemia (decreased Hb) and reduced storage iron (low serum ferritin)

Question 17

Name some causes of iron deficiency

Answer 17

Insufficient intake to meet needs - pregnant women, vegans, children Losing too much i.e. bleeding Not absorbing enough i.e. malabsorption e.g. coeliac disease

Question 18

What are some causes of chronic blood loss?

Answer 18

Menorrhagia, GI -tumours, ulcers, NSAIDs, parasitic infection., haematuria

Question 19

What can happen as a result of occult blood loss?

Answer 19

GI blood loss of 8-10 ml per day can occur without any symptoms or signs of bleeding. The maximum dietary iron absorption is around 4-5mg per day therefore negative iron balance can occur

Question 20

Iron deficiency anaemia is a diagnosis not a symptom (T/F)?

Answer 20

False - iron deficiency is a symptom NOT a diagnosis

Question 21

What is the mechanism behind anaemia of chronic disease?

Answer 21

Inflammatory macrophage iron block: 1. increased transcription of ferritin mRNA stimulated by inflammatory cytokines so ferritin synthesis increases 2. increased plasma hepcidin blocks ferroportin mediated release of iron 3. results in impaired iron supply to marrow erythrocytes and eventually hypochromic red cells

Question 22

What are the primary and secondary causes of iron overload?

Answer 22

Primary - hereditary haemochromatosis Secondary - Transfusional, iron loading anaemias

Question 23

What is hereditary haemochromatosis?

Answer 23

Most common form is due to mutations in HFE gene Decreases synthesis of hepcidin Increased iron absorption Results in gradual iron accumulation with risk of end-organ damage

Question 24

What are the clinical features of hereditary haemochromatosis?

Answer 24

Weakness/fatigue, joint pains, impotence, arthritis, CIRRHOSIS, diabetes, cardiomyopathy Presents usually in middle age or later Iron overload of >5g

Question 25

How is hereditary haemochromatosis diagnosed?

Answer 25

Mutations of HFE gene account for 95%. Risk of iron loading - Transferrin saturation >50% Increased iron stores - serum ferritin >300ug/L in men or >200ug/L in pre-menopausal women Liver biopsy - rarely needed

Question 26

How is hereditary haemochromatosis treated?

Answer 26

Weekly venesection 450-500ml/200-250mg iron Initial aim to exhaust iron stores (ferritin <20ug/L) thereafter keep ferritin below 50ug/L

Question 27

How is hereditary haemochromatosis screened for?

Answer 27

Family screening - first degree relatives of cases, esp siblings

Question 28

What can cause secondary iron-loading anaemias?

Answer 28

Sources - Repeated red cell transfusions and excessive iron absorption related to over-active erythropoiesis Disorders - Massive ineffective erythropoiesis e.g. thalassaemias, sideroblastic anaemias or refractory hypoplastic anaemias e.g. red cell aplasia, myelodysplasia

Question 29

How is secondary iron overload treated?

Answer 29

Treatment by venesection NOT an option in already anaemic patients! Iron chelating agents such as desferrioxamine are used