Megaloblastic anaemia Flashcards
What is required for normal red cell production?
- Drive for erythropoiesis (erythropoietin)
- Genes coding erythropoiesis
- Essential components for erythropoiesis: Iron, B12, folate and minerals
- Functioning bone marrow
In very generalised terms, explain anaemia
Reduced production of red cells or increased destruction of red cells
In very generalised terms, explain polycythaemia
Increased red cell production or decreased red cell destruction/loss
What are vitamin B12 and Folate needed for?
DNA synthesis and nuclear maturation, they are required in all dividing cells
In which cells is the deficiency of B12/folate first noted?
Red cells
What is the result of a deficiency of B12/folate?
Megaloblastic (abnormally large red cells) anaemia, it will eventually effect other organs
What 2 process is B12 necessary for?
- Methylation of homocysteine to methionine (involved in DNA production)
- Methylmalonyl-CoA isomerisation (involved in the breakdown of fatty acids/proteins)
What are the sources of B12?
Dietary sources:
•Synthesised soley by microorganisms
•Meat (especially liver and kidney)
•Small amount in dairy products
What is the daily requirement of B12?
1 microgram a day
Describe the absorption of B12
- B12 ingested in form of animal protein
- Gastric parietal cells produce intrinsic factor
- B12 is released by enzymes and acid in the stomach and duodenum
- Intrinsic factor binds to B12
- The intrinsic factor- B12 complex binds to cubulin (a specific receptor in the ileum)
- B12 is absorbed into the blood and binds to transcobalamin
What makes intrinsic factor?
Gastric parietal cells in the fungus/body of the stomach
What is the daily loss of B12?
1-2 micrograms are lost each day in the urine/faeces
How long do the stores of B12 last?
3-4 years
What are the sources of folate?
Green veg (but the folate is destroyed by cooking)
Describe the absorption of folate
Mostly in the small bowel, no carrier molecule is required
How long do the stores of folate last?
A few days - quickly used up if there is increased demand e.g. increased cell turnover
Explain what happens if there is not enough folate or B12
- Disparity in the rate of synthesis of the precursors of DNA (deoxyribonucleoside triphosphates)
- Abnormality of cell division
- If no dietary folate, no methyl THF
- If no B12, Methyl THF can’t be converted to THF
Explain the blood film of someone with a B12/folate deficiency
- Dissociation between nuclear and cytoplasmic development (nucleus not mature)
- Abnormal cells e.g. too many lobes in a neutrophil due to failure of division
- Microcytic red cells, often oval shaped
Why may there be increased bilirubin or LDH with megaloblastic anaemia?
Because of ineffective erythropoiesis, there is death of mature cells whilst still in the bone marrow as they are abnormal. This breakdown results in raised bilirubin and lactate dehydrogenase
Describe the tissues affected in B12 or folate deficiency
All rapidly growing, DNA synthesising cells, especially therefore the bone marrow and epithelial surfaces (mouth, stomach, small intestine, urinary and female genital tracts)
What are the blood abnormalities in a B12 deficiency?
Megaloblastic anaemia with leucopenia and thrombocytopenia
What is leucopenia
Low white blood cell count
What is thrombocytopenia?
Low platelet count
What are the neurological manifestations of B12 deficiency?
Bilateral peripheral neuropathy or demyelination of the posterior and pyramidal tracts of the spinal cord
What are the blood abnormalities of folate deficiency?
Megaloblastic anaemia, potentially leucopenia and thrombocytopenia
What is the effect of folate deficiency on a growing foetus?
If in the first 12 weeks, deficiency can cause neural tube defects
How do patients with a folate or B12 deficiency present?
- Symptoms of anaemia/cytopenia: tired, easy bruising (due to thrombocytopenia (rare))
- Mild jaundice “lemon yellow tint” due to haemolysis
- Neurological problems with gait and vibration sense due to B12 deficiency (subacute combined degeneration of cord
What are the causes of B12 deficiency?
- Dietary - B12 not ingested
- Pernicious anaemia
- Gastrectomy/ achlorhydria
- Terminal ileum problem e.g. Chron’s, resection
Explain how pernicious anaemia leads to B12 deficiency
Autoimmune reaction to the gastric parietal cells, resulting in less intrinsic factor so no binding to B12 so it cannot be absorbed into the blood
Explain how a gastrectomy/achlorhydria leads to B12 deficiency
Removal of the stomach, therefore lacks the acid and therefore ability to release B12
What are the causes of folate deficiency?
- Dietary (majority)
- Extenisve small bowel disease e.g. coeliac/chrons
- Increased cell turnover e.g. haemolysis or severe skin disorders such as psoriasis
Other than folate/B12 deficiency (megaloblastic anaemia), what are the other causes of macrocytosis?
- Reticulocytosis
- Red cell membrane abnormality (made of lipids) due to alcohol/liver disease/ hypothyroidism
- In anaemia with bone marrow failure syndromes - congenital or myelodysplasia
