Iron in Health and Disease Flashcards
(32 cards)
What does transferrin do?
Transports iron from donor tissues (macrophages, intestinal cells and hepatocytes) to tissues expressing transferrin receptors (especially erythroid marrow)
What is transferrin?
Protein with two binding sites for iron atoms
What does transferrin saturation measure?
Iron supply
What is holo- and apotransferrin?
Holo- iron bound to transferrin
Apo- unbound
What is ferritin?
Large intracellular protein
Stores up to 4000 ferric ions in Fe3+ form
What does a tiny amount of serum ferritin reflect?
Intracellular ferritin synthesis in response to iron- indirect measure of storage of iron
What does serum ferritin levels rise in?
Infection, malignancy etc
Acts as an acute phase protein
What intraluminal factors regulate iron absorption?
Solubility of inorganic iron
Haem iron easier to absorb
Reduction of ferric (Fe3+) to ferrous (Fe2+)
What mucosal factors (expression of iron transporters) regulate iron absorption?
DMT-1 (divalent metal transporter) at mucosal surface
Ferroportin at serosal surface
What systemic factors regulate iron absorption?
Hepcidin:
The major negative regulator of iron uptake
Produced in liver in response to iron load and inflammation
Down-regulates ferroportin
Describe iron absorption in the duodenum
DMT 1- Transports iron into the duodenal enterocyte
Ferroportin: facilitates iron export from enterocyte, passed onto transferrin for transport elsewhere
Hepcidin: down-regulates ferroportin
What are the consequences of -ve iron balance?
Exhaustion of iron stores Iron deficient erythropoiesis Falling red cell MCV Microcytic Anaemia Epithelial changes- skin, Koilonychia, Angular stomatitis
What does a hypochromic microcytic mean?
Deficient Hb synthesis
What can iron deficiency be confirmed by?
A combination of anaemia (decreased haemoglobin iron) and reduced storage iron (low serum ferritin)
What are the causes of iron deficiency?
Insufficient dietary intake to meet physiological requirements: particularly women and children, vegetarian diets
Losing too much - bleeding
Not absorbing enough – malabsorption (relatively uncommon)
What are the causes of chronic blood loss?
Menorrhagia
Gastrointestinal- Tumours, Ulcers, NSAIDs, Parasitic infection
Haematuria
What is iron malutilisation?
Anaemia of chronic disorders
What occurs in red cell breakdown in inflammatory macrophage iron block?
Increased transcription of Ferritin mRNA stimulated by inflammatory cytokines so ferritin synthesis increased
Increased plasma Hepcidin blocks ferroportin-mediated release of iron
Results in impaired iron supply to marrow erythroblasts and eventually hypochromic red cells
What is primary iron overload?
Long-term excess iron absorption with parenchymal rather than macrophage iron loading, and eventual organ damage
What are the clinical features of hereditary haemochromatosis?
Weakness/fatigue Joint pains Impotence Arthritits Cirrhosis Diabetes Cardiomyopathy
When does hereditary haemochromatosis usually present?
Middle age or later
Describe mutations in HFE gene
1 in 8 of population carry C282Y mutation; 1 in 4 the H63D mutation
Patients are usually C282Y homozygotes; occasionally C282Y/H63D double heterozygotes
Main effect likely to be via reduced hepcidin synthesis
Account for 95% of hereditary haemochromatosis
Incomplete penetrance
How is hereditary haemochromatosis diagnosed based on phenotype?
Risk of iron loading: transferrin saturation >50% (sustained on repeat fasting sample)
Iron load: serum ferritin >300 g/l in men or >200 g/l in pre-menopausal women
Liver biopsy: only if uncertain about iron loading or to assess tissue damage
What can cause hereditary haemochromatosis?
Mutations in HFE gene
Mutations of other iron regulatory proteins, e.g.
Transferrin receptor, hepcidin, ferroportin very rare
