Iron Absorption, Overload & Malnutrition (AOCD) Flashcards
Name the two states of iron
Ferric (Fe3+ ) and ferrous forms ( Fe2+ )
Name 3 molecules that require iron
- Haemoglobin (most common)
- Myoglobin
- Enzymes eg cytochromes
Why is iron dangerous
Can cause oxidative damage & free radical production
How is iron excreted
No specific mechanism for excretion.
Passive excretion only e.g. RBC destruction
How does iron absorption compare to iron loss in a healthy person
Iron absorption = Iron loss
Where is most iron found in the body
RBC Hb
Name 3 dietary factors that can enhance iron absorption
- Meat (HEAM iron - has own transporter)
- Ascorbic acid/ Vit C (reduces iron to Fe2+)
- Alcohol
Name 3 dietary factors that can inhibit iron absorption
- Tannins e.g. tea
- Phytates e.g. cereals, bran, nuts & seeds
- Calcium e.g. dairy products
Where does iron absorption occur
Mainly absorbed into cells of duodenal mucosa
How is iron absorbed
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
What molecule regulates iron absorption, when is this molecule produced and how does it work
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
Name 3 measurements used to assess iron status
- Hb concentration (functional iron)
- Transferrin iron saturation (transport iron/ iron supply)
- Serum ferritin (storage iron)
How many iron binding sites do transferrin have
2
Where do transferrin molecules bind to
Tissues expressing transferrin receptors.
Particularly erythroid marrow.
Also macrophages and hepatocytes etc
What is holotransferrin vs apotransferrin
Holotransferrin - iron-bound transferrin
Apotransferrin - unbound transferrin
ratio allows transferrin saturation to be calculated
What is the use of ferritin in assessing iron status and why can it be unreliable
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
What are three main iron metabolism disorders
- iron deficiency
- iron malutilisation (anaemia of chronic disease)
- iron overload
Iron deficiency pathophysiology
1) exhaustion of iron stores =>
2) Iron deficient erythropoiesis =>
3) microcytic anaemia =>
4) anaemia symptoms & epithelial changes (severe deficiency )
What is anaemia of chronic disease and how would you differentiate it from iron deficiency anaemia
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
Anaemia of chronic disease consequences/ pathophysiology
- 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
Why is ferritin an acute phase protein
It is a protective mechanism to reduce supply of iron to pathogens
Anaemia of chronic disease investigations & findings
- 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)
Anaemia of chronic disease treatment
Treat the cause of inflammation!
Iron overload aetiology
Primary - hereditary haemochromatosis
Secondary - transfusional, iron overload anaemias
Hereditary haemochromatosis aetiology & pathophysiology
- usually due to mutation in HFE gene
- decreases synthesis of hepcidin
- increases iron absorption
- gradual iron accumulation
- end-organ damage
Hereditary haemochromatosis clinical presentation
- iron overload > 5g @ middle age
- Weakness & fatigue
- Joint pains & arthritis (joints)
- Impotence (pituitary gland -> low sex hormones)
- Cirrhosis (liver)
- Diabetes (pancreas)
- cardiomyopathy (heart)
Hereditary haemochromatosis investigations
- genetic testing
- blood iron status (high transferrin & ferritin)
- fibroscan or liver biopsy to assess for cirrhosis
Hereditary haemochromatosis management
Weekly venesection
What types of anaemia can cause iron overload
- Massive ineffective erythropoiesis - thalassaemia, sideroblastic anaemias
- Refractory hypoplastic anaemias - red cell aplasia, myelodysplasia (MDS)
Secondary iron overload treatment
Iron chelating drugs e.g. desferrioxamine
Iron overload can be classified into parenchymal overload and macrophage overload. Which is HH (primary) and which is transfusional/anaemia related (secondary)
HH (primary) - parenchymal
Transfusional/anaemia related (secondary) - macrophage
