Iron deficiency

• Iron absorption =

  Location = duodenum

  Enhanced by -

  • Haem (from meat) absorbed better due to haem iron transporter
  • Ascorbic acid - reduces iron
  • Alcohol

  Inhibited by -

  • tannins - tea
  • phyates - cereals + seeds
  • calcium - dairy
• Ferroportin =

  Facilitates iron export from enterocyte

  Passed onto transferrin
• Mechanisms of iron absorption =

  duodenal cytochrome B

  DMT

  Ferroportin
• Hepcidin = major negative regulator of iron uptake

  Produced in liver in response to increased iron load + inflammation

  Binds to ferroportin
• Transferrin = transport molecule for Fe in plasma

  Protein with 2 binding sites for iron

  Transports iron from donor tissues to tissues with transferrin receptors (erythromycin marrow)

  Measured in % saturation of transferrin with iron
• Ferritin =

  spherical intracellular protein

  Indirect measure of storage iron

  Increased in infection and malignancy
• Epithelial changes with iron deficiency =

  Skin - pallor

  Koilonychia

  Angular stomatitis
• Hypochromic microcytic anaemias = deficient haemoglobin synthesis
• Iron deficiency can be confirmed by =

  Anaemia - decreased haemoglobin iron

  Reduced storage iron - low serum ferritin
• Reasons for iron deficiency =

  Diet

  Bleeding

  Malabsorption
• Anaemia of chronic disease =

  1. increased transcription of ferritin mRNA - stimulated by inflammatory cytokines - increased ferritin synthesis
  2. Increased plasma hepcidin - blocks ferroportin release of iron
  3. Results in impaired iron supply to marrow erythroblasts - hypochromic red cells

  Occurs due to protective mechanisms to reduce supply of iron to pathogens
• Iron deficiency vs anaemia of chronic disease

  A) reduced

  B) reduced

  C) normal or increased

  D) normal or reduced

  E) reduced

  F) reduced

  G) reduced

  H) normal or increased

  I) reduced

  J) normal

  
• Causes of iron overload =

  Primary - hereditary haemochromatosis

  Secondary - transfusions + iron loading anaemias
• Heredigary haemochromatosis =

  Primary iron overload (over 5g) - long term excess iron absorption with parenchymal rather than macrophage iron loading

  Commonest form due to HFE gene mutation

  • decreases synthesis of hepcidin
  • increased iron absorption
  • results in gradual iron accumulation - risk of end-organ damage
• Clinical features of hereditary haemochromatosis =

  • fatigue
  • joint pain
  • arthritis
  • cirrhosis
  • diabetes
  • cardiomyopathy

  Presents in middle age or later
• Diagnosis of hereditary haemochromatosis =

  Transferrin saturation >50%

  Serum ferritin >300/>200(women)

  Liver biopsy

  Genetic testing
• Treatment for hereditary haemochromatosis =

  Weekly venesection - exhaust iron stores
• Iron loading anaemias

  Source

  • repeated red cell transfusions
  • excessive iron absorption - overactive erythropoiesis

  Disorders

  Massive ineffective erythropoiesis

  • thalassemia
  • sideroblastic anaemias

  Refractory hypoplastic anaemias

  • red cell aplasia
  • myelodysplasia
• Treatment of secondary iron overload =

  Venesection - not an option for anaemia

  Iron chelating agents