CL4 Anaemia

Reduced synthesis of α or β globin chains.

Autosomal recessive inheritance

1. Decreased production

• Ineffective erythropoiesis

➢ Deficiency of B12/folate/iron

➢ Abnormal synthesis of haemoglobin (thalassaemia)

• Decreased effective erythropoiesis

➢ Aplastic anaemia/marrow failure

• Decreased production of erythropoietin

➢ Renal disease

2. Increased blood loss

➢ Gastrointestinal bleeding

➢ Motor-vehicleaccident (MVA)

3. Increased destruction

➢ Haemolysis (intra or extravascular) eg. malaria infection

➢Vitamin B12 deficiency

➢Folate deficiency

1. Morphological

– Based on red cell indices and blood film

• Hypochromic microcytic anaemia (MCV decrease, MCH decrease)

• Normocytic normochromic anaemia (MCV normal, MCH normal)

• Normochromic macrocytic anaemia (MCV increase, MCH normal)

2. Pathophysiological

– Based on causes of anaemia

• Iron deficiency anaemia

• Megaloblastic anaemia

• Haemolytic anaemia

Cobalamin & folate deficiency affect rapidly growing tissues (that require large amount of DNA synthesis for cell division and growth):

• Megaloblastic anaemia in bone marrow

• Macrocytosis of epithelial cell surfaces (in mouth, stomach, small intestine, respiratory, urinary & female genital tracts

• Prematurity/ Premature birth 早产 due to maternal folate deficiency

• Neural tube defects due to folate deficiency in early pregnancy

• Also known as gluten-sensitive enteropathy or coeliac sprue, is disease of small intestine

• Caused by consumption of gluten (substance found in wheat, barley and rye) > gluten activates the immune system and causing damage to delicate lining of the small intestine (that is responsible for absorbing nutrients and vitamins)

• Histological section of jejunal biopsy shows villous atrophy with absence/flattening of vili and hypertrophy of the mucosal crypts

• Normal RBC lifespan is 120 days, after which they are removed by reticuloendothelial system (in marrow, liver, spleen)

• While in haemolytic anaemia, red cell survival is less than 30 days

• Mechanism:

  • Intravascular: haemolysis occur in blood circulation

  • Extravascular: removal of RBC in reticuloendothelial system

Pernicious anaemia is due to severe lack of intrinsic factor, lack of IF can be caused by autoimmune or congenital.

1) Autoimmune

• Occur in 50% of cases

• IF antibody inhibit IF function in gastric juice

• May a/w myxoedema, Hashimoto’s ds, Addison’s ds, vitiligo, hypoparathyroidism & hypogammaglobulinaemia

• Occur in families, F > M, 60 years old, blood group A

• Increase incidence of stomach cancer.

• It will cause gastric atrophy (thin stomach wall, plasma cell & lymphoid infiltrate of lamina propria, loss of gastric glands & parietal cells)

2) Congenital PA

• Congenital lack of IF

• presentation develop after age of 2

Anaemia is reduction of haemoglobin (Hb) concentration in blood below normal for age and sex.

• Vitamin B12 Neuropathy is also known as Subacute combined degeneration of the cord

• Manifestations:

  • bilateral peripheral neuropathy / degeneration of posterior & pyramidal tracts of the spinal cord

  • Rarely: optic atrophy and mental abnormalities

  • Long term deficiency in infancy leads to poor brain development & impaired intellectual development

  • demyelination of the lateral & posterior columns

  • patient may die

• Cause: accumulation of S-adenosylhomocysteine (SAH) (excessive homocysteine, but lack of B12 to convert to methionine)

beta thalassemia major, Hb Barts disease (=hydrops fetalis) and HbH disease