Anaemia caused by deficient haemoglobin synthesis (cytoplasmic defect)

Aetiology

• Haem deficiency
  • Lack of iron for erythropoiesis
    • Iron deficiency - most common cause of microcytic anaemia
    • Anaemia of chronic disease - IL-6 is released due to chronic diseases and increases production of hepcidin, which subsequently down regulates ferroportin expression, reducing iron absorption and precipitating anaemia of chronic disease
  • Problems with porphyrin synthesis
    • Sideroblastic anaemia: excess iron buildup in mitochondria due to failure to incorportae iron into haem, can be hereditary (congenital sidoblastic anaemias) or aquired e.g. MDS, lead poisoning, alcohol excess
• Globin deficiency
  • Thalassaemia (trait, intermedia, major)

Causes of iron deficiency

• Insufficient intake to meed physiological need
  • More likely in women and children due to greater requirements
  • Dietary factors
• Losing too much - bleeding
  • Causes of chronic blood loss: menorrhagia, gastrointestinal (tumours, ulcers, NSAIDs, parasitic infection), haematuria
• Not absorbing enough - malabsorption e.g. coeliac disease (less common)

Pathophysiology

• In microcytic anaemia, one of the building blocks needed to synthesize Hb in the cytoplasm is lacking
• However the nuclear machinery is intact, so the cells can keep dividing
• This results in microcytic (small) cells, and as they contain little Hb they are hypochromic (lacking in colour)

Iron metabolic pathway

• ‘Closed’ system - only able to absorb a small amount of iron, with a tiny amount in circulation moving to/from storage
• Iron turnover in plasma pool is fast
• Circulating iron is bound to transferrin, a protein which transports iron from donor tissues (macrophages, intestinal cells and hepatocytes) to tissues expressing transferrin receptors (especially erythroid marrow)
• % saturation of transferrin with iron measures iron supply
  • Reduced in iron deficiency, but also in anaemia of chronic disease
  • Increased in genetic haemachromatosis
• Iron is stored in ferritin mainly in the liver
  • Ferritin is a large spherical intracellular protein which stores up to 4000 ferric ions
  • Serum ferritin is an easily measured indirect measure of storage iron (reflects intracellular ferritin sythesis in response to iron status of the host)
    • Low ferritin means iron deficiency

Anaemia of chronic disease

Protective mechanism to reduce supply of iron to pathogens: