Iron in health and disease Flashcards
Why is iron essential in health?
Oxygen transport and electron transport. It is present in haemoglobin, myoglobin and enzymes such as cytochromes
What makes iron potentially dangerous?
Chemical reactivity - oxidative stress and free radical production No mechanism for excretion of iron!
Where is the majority of iron present in the body found?
Majority found in haem
What makes up haem?
Porphyrin ring + Fe2+
Where is iron absorbed?
Occurs mainly in the duodenum, uptake into cells of duodenal mucosa, influenced by dietary factors
What enhances and inhibits iron absorption?
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
Describe the mechanism for iron absorption
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
How is iron absorption regulated?
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
What happens to levels of hepcidin during iron deficiency?
Levels of hepcidin decrease when iron deficient
How is functional iron level assessed?
Haemoglobin concentration
How is transport iron/iron supply to tissues assessed?
% saturation of transferrin with iron
How is storage iron level assessed?
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
Where does transferrin transport iron to and from?
Transports iron from donor tissues (macrophages, hepatocytes and duodenal enterocytes) to tissues expressing transferrin receptors. Erythroid marrow especially rich in transferrin receptors
What are the consequences of negative iron balance?
Exhaustion of iron stores, iron deficient erythropoiesis (falling red cell MCV), microcytic anaemia, epithelial changes (skin, angular stomatitis, koilonychia)
What is the cause of hypochromic microcytic anaemia?
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
What confirms iron deficiency?
A combination of anaemia (decreased Hb) and reduced storage iron (low serum ferritin)
Name some causes of iron deficiency
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
What are some causes of chronic blood loss?
Menorrhagia, GI -tumours, ulcers, NSAIDs, parasitic infection., haematuria
What can happen as a result of occult blood loss?
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
Iron deficiency anaemia is a diagnosis not a symptom (T/F)?
False - iron deficiency is a symptom NOT a diagnosis
What is the mechanism behind anaemia of chronic disease?
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
What are the primary and secondary causes of iron overload?
Primary - hereditary haemochromatosis Secondary - Transfusional, iron loading anaemias
What is hereditary haemochromatosis?
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
What are the clinical features of hereditary haemochromatosis?
Weakness/fatigue, joint pains, impotence, arthritis, CIRRHOSIS, diabetes, cardiomyopathy Presents usually in middle age or later Iron overload of >5g
