L9 Anaemia

• Anaemia


  Condition of low haemoglobin concentration
• Anaemia is not a final diagnosis: it is a sign of another problem
• Anaemia cases I see regularly


  • Young females with iron deficiency
  • Chronic colonic bleeding with iron deficiency
  • Upper GI bleeding without iron deficiency
  • Severe chronic inflammation (inflammatory arthritis)
  • Renal failure
  • Lymphoma
  • 2 year old with anaemia, neutropenia and thrombocytopenia
• Normal red blood cells (erythrocytes)

  • Biconcave discs, ~7 um diameter
  • Central pallor ~1/3 of the diameter
  • Contain haemoglobin (Hb)

  
• Red cells (and platelets) are made in the bone marrow

  
• Erythropoiesis


  1. Blood cell precursors

  2. Fat spaces

  3. Trabecular bone

  4. Marrow

  5. Blood

  
• Reticulocytes


  1 day old red cells that contain RNA – a marker of marrow production

  
• Developing red cells in the marrow surrounding a macrophage that supplies them with iron
• Anaemia


  Low haemoglobin concentration
• Normal haemoglobin (Hb) concentration varies with

  • Age
  • Sex
  • Pregnancy
• Adult reference intervals for Hb

  • Male (adult) 130 – 175 g/L
  • Female (adult) 120 – 155 g/L
• Red cells


  Bags of haemoglobin
• If there are fewer red cells or less Hb in each cell

  Reduced oxygen carrying capacity
• Reduced oxygen carrying capacity

  • Less oxygen in blood
  • Tissue hypoxia
• Haemoglobin molecule


  • Haem
  • Globin chain
• General clinical features of anaemia

  • Fatigue
  • Shortness of breath
  • 'Heart racing', palpitations
  • Angina (if vascular disease present)
  • Claudication (if vascular disease present)
• Pallor


  Sign of anaemia
• Anaemia classification by aetiology

  • Reduced red cell or haemoglobin production
  • Increased red cell destruction (haemolysis)
  • Blood loss
• Causes of reduced red cell or haemoglobin production


  • Deficiencies: iron, folate, vitamin B12
  • Globin gene defects (thalassaemia)
  • Lack of erythropoietin (small diseased kidneys)
  • Bone marrow disease

  
• Causes of increased red cell destruction (haemolysis)

  • Inherited
  • Acquired
• Mean cell volume (MCV)


  Used to classify anaemia
• Types of anaemia by cell size

  • Microcytic anaemia (small red cells on average)
  • Normocytic anaemia (normal sized red cells on average)
  • Macrocytic anaemia (large red cells on average)
• Microcytic anaemia


  Small pale red cells
• Causes of microcytic anaemia

  • Iron deficiency
  • Thalassaemias
  • Inflammation (iron is unavailable - sequestered in macrophages)
• Iron deficiency anaemia


  Unable to make enough haem for Hb
• Causes of iron deficiency

  • Excessive loss (Gastrointestinal, Excessive menstruation, Trauma/surgery)
  • Reduced absorption (Coeliac disease, Other small bowel diseases, Vegetarian with poor diet)
  • Increased demand (Pregnancy, Childhood growth)
• Thalassaemias


  Lack of protein production from the α globin genes (alpha thalassemia) or from the β globin genes (beta thalassaemia)
• The thalassaemias are the most common single gene disorders in humans
• Severity of thalassaemias


  • Mild
  • Severe
• Anaemia of inflammation


  • aka Anaemia of chronic disease
  • Due to "functional" iron deficiency
  • Iron is present but it is sequestered in macrophages and unavailable
• Inflammation causes


  • A block in iron availability
  • Hepcidin production which sequesters iron inside macrophages and stops absorption in the gut
  • Low circulating iron levels
  • Red cells are starved of iron
• Macrocytic anaemia


  • B12 or folate deficiency (the megaloblastic anaemias)
  • Vitamin B12 & folate needed for DNA synthesis
  • Deficiency leads to delayed & abnormal nuclear maturation & cell division
  • The few surviving cells are big

  
• Other causes of macrocytic anaemia

  • Liver disease
  • Alcohol
  • Elevated reticulocytes
  • Bone marrow disease
  • Cytotoxic drugs
• Normocytic anaemia


  • Chronic renal failure (low erythropoietin -EPO)
  • Acute blood loss followed by haemodilution
  • Bone marrow disease
  • Haemolysis
• Erythropoietin (EPO)


  Reduced production in chronic renal failure leads to reduced RBC production and shorter red cell survival
• Haemolytic Anaemia


  Reduced red cell survival in the circulation
• Causes of reduced red cell survival

  • Abnormal red cells (inherited)
  • Excessive destruction of normal red cells (acquired)
• Reticulocytosis


  Raised reticulocyte count - a marker of increased red cell production
• Inherited causes of Haemolytic Anaemia

  • Cell membrane abnormalities (e.g. Hereditary spherocytosis)
  • Haemoglobinopathies (e.g., Sickle cell anaemia)
  • Enzymopathies (e.g. Glucose-6-phosphate deficiency)
• Acquired haemolysis


  Autoimmune haemolytic anaemia - caused by autoantibodies against red cells due to dysregulation of the immune system