Iron Absorption, Overload & Malnutrition (AOCD)

Question 1

Name the two states of iron

Answer 1

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

Question 2

Name 3 molecules that require iron

Answer 2

• Haemoglobin (most common)
• Myoglobin
• Enzymes eg cytochromes

Question 3

Why is iron dangerous

Answer 3

Can cause oxidative damage & free radical production

Question 4

How is iron excreted

Answer 4

No specific mechanism for excretion.
Passive excretion only e.g. RBC destruction

Question 5

How does iron absorption compare to iron loss in a healthy person

Answer 5

Iron absorption = Iron loss

Question 6

Where is most iron found in the body

Answer 6

RBC Hb

Question 7

Name 3 dietary factors that can enhance iron absorption

Answer 7

• Meat (HEAM iron - has own transporter)
• Ascorbic acid/ Vit C (reduces iron to Fe2+)
• Alcohol

Question 8

Name 3 dietary factors that can inhibit iron absorption

Answer 8

• Tannins e.g. tea
• Phytates e.g. cereals, bran, nuts & seeds
• Calcium e.g. dairy products

Question 9

Where does iron absorption occur

Answer 9

Mainly absorbed into cells of duodenal mucosa

Question 10

How is iron absorbed

Answer 10

Duodenal cytochrome B
- Found in luminal surface
- Reduces ferric iron (Fe3+) to ferrous form (Fe2+)

DMT (divalent metal transporter) -1
- Transports ferrous iron into the duodenal enterocyte

Ferroportin
- Facilitates iron export from the enterocyte

Transferrin
- ferrous form (Fe2+) is oxidised to ferric iron (Fe3+)
- Fe3+ is passed on to transferrin for transport elsewhere

Question 11

What molecule regulates iron absorption, when is this molecule produced and how does it work

Answer 11

Hepcidin (decreases Iron absorption)

• Produced by liver in response to increased iron load & inflammation
• Binds to ferroportin and causes its degradation
• Iron is then trapped in duodenal cells & macrophages

Question 12

Name 3 measurements used to assess iron status

Answer 12

• Hb concentration (functional iron)
• Transferrin iron saturation (transport iron/ iron supply)
• Serum ferritin (storage iron)

Question 13

How many iron binding sites do transferrin have

Answer 13

2

Question 14

Where do transferrin molecules bind to

Answer 14

Tissues expressing transferrin receptors.
Particularly erythroid marrow.
Also macrophages and hepatocytes etc

Question 15

What is holotransferrin vs apotransferrin

Answer 15

Holotransferrin - iron-bound transferrin
Apotransferrin - unbound transferrin

ratio allows transferrin saturation to be calculated

Question 16

What is the use of ferritin in assessing iron status and why can it be unreliable

Answer 16

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

Question 17

What are three main iron metabolism disorders

Answer 17

• iron deficiency
• iron malutilisation (anaemia of chronic disease)
• iron overload

Question 18

Iron deficiency pathophysiology

Answer 18

1) exhaustion of iron stores =>
2) Iron deficient erythropoiesis =>
3) microcytic anaemia =>
4) anaemia symptoms & epithelial changes (severe deficiency )

Question 19

What is anaemia of chronic disease and how would you differentiate it from iron deficiency anaemia

Answer 19

AOCD
- Chronic infection/ malignancy/ autoimmune disease
- leading to inflammatory cytokines
- that increase hepcidin and ferritin synthesis
- and decrease erythropoiesis & ferroportin-mediated iron release
- leading to normocytic and then hypochromic, microcytic anaemia

AOCD - normal/ high ferritin, Iron deficiency - low ferritin

Question 20

Anaemia of chronic disease consequences/ pathophysiology

Answer 20

• increases synthesis of ferritin & increased iron storage
• increases hepcidin & so inhibits ferroportin-mediated iron release
• inhibits erythropoietin release & erythroid proliferation

=> limited iron availability & so eventually hypochromic, microcytic cells & reduced RBC survival

Question 21

Why is ferritin an acute phase protein

Answer 21

It is a protective mechanism to reduce supply of iron to pathogens

Question 22

Anaemia of chronic disease investigations & findings

Answer 22

• Increased inflammatory markers (inflammation)
• Anaemia (low Hb)
• Reduced transferrin saturation and serum iron (low iron availability)
• Normal or increased serum ferritin (iron ‘stuck’)
• Reduced reticulocytes & erythropoietin (decreased erythropoiesis)
• Normal or reduced MCV (normocytic or microcytic)

Question 23

Anaemia of chronic disease treatment

Answer 23

Treat the cause of inflammation!

Question 24

Iron overload aetiology

Answer 24

Primary - hereditary haemochromatosis
Secondary - transfusional, iron overload anaemias

Question 25

Hereditary haemochromatosis aetiology & pathophysiology

Answer 25

• usually due to mutation in HFE gene
• decreases synthesis of hepcidin
• increases iron absorption
• gradual iron accumulation
• end-organ damage

Question 26

Hereditary haemochromatosis clinical presentation

Answer 26

• iron overload > 5g @ middle age
• Weakness & fatigue
• Joint pains & arthritis (joints)
• Impotence (pituitary gland -> low sex hormones)
• Cirrhosis (liver)
• Diabetes (pancreas)
• cardiomyopathy (heart)

Question 27

Hereditary haemochromatosis investigations

Answer 27

• genetic testing
• blood iron status (high transferrin & ferritin)
• fibroscan or liver biopsy to assess for cirrhosis

Question 28

Hereditary haemochromatosis management

Answer 28

Weekly venesection

Question 29

What types of anaemia can cause iron overload

Answer 29

• Massive ineffective erythropoiesis - thalassaemia, sideroblastic anaemias
• Refractory hypoplastic anaemias - red cell aplasia, myelodysplasia (MDS)

Question 30

Secondary iron overload treatment

Answer 30

Iron chelating drugs e.g. desferrioxamine

Question 31

Iron overload can be classified into parenchymal overload and macrophage overload. Which is HH (primary) and which is transfusional/anaemia related (secondary)

Answer 31

HH (primary) - parenchymal
Transfusional/anaemia related (secondary) - macrophage