Megaloblastic Anaemias Flashcards
What can a Macrocytic anaemia be sub catagorised into?
- Megaloblastic anaemia (resulting from impaired DNA synthesis, preventing the cells from dividing normally. Rather than dividing, they grow into large, abnormal cells.)
or - A Normoblastic Macrocytic Anaemia.
What are some causes of a Megaloblastic anaemia?
B12 deficiency
Folate Deficiency
Others (drugs, Rare Inherited abnormalities)
What kind of Diet leads to a Vitamin B12 deficiency?
Low dietary intake via Veganism.
How does a B12 deficiency cause a megaloblastic anaemia?
Pernicious Anaemia:
- Autoimmune condition with resulting destruction of the Gastric Parietal cells.
- This results in an intrinsic factor deficiency with B12 malabsorption.
What condition is Pernicious anaemia often associated with?
Atrophic Gastritis.
How does a Folate deficiency occur?
- Inadequate intake (found in leafy green veg)
- Malabsorption
- Excess utilisation - haemolysis, exfoliating dermatitis, pregnancy, malignancy.
- Anticonvulsant drugs.
What is a Megaloblast?
An abnormally large nucleated red cell precursor with an immature nucleus.
Why do megaloblastic anaemias have a lack of red cells?
Due to predominant defects in DNA synthesis in developing precursor cells (megaloblasts) in the marrow.
What happens to the megaloblasts as a result of the defect in DNA synthesis?
Division of maturing megaloblasts is reduced and apoptosis is increased.
What happens when the Hb content of a megaloblast reaches optimum level?
The Nucleus is extruded, leaving behind a bigger than normal red cell i.e. a macrocyte.
What are B12 and folate essential for?
DNA synthesis and nuclear maturation (e.g. blood cell effect)
AND
DNA modification and gene activity (e.g. nervous system)
Where is Folate absorbed in the body?
Duodenum and Jejunum
Where is B12 absorbed in the body?
Ileum.
How long can folate stores last?
4 months
How long can B12 stores last?
2-4 yrs.
How is B12 released from Protein complexes in food (at the start of its metabolism)?
Vit B12 is liberated from protein complexes in food by gastric enzymes and then binds to a Vitamin B12-binding protein (R-Binder)
How does Vitamin B12 get released from the R binder?
By Pancreatic Enzymes
What does B12 become bound to after its been seperated from the R-Binder by pancreatic enzymes?
Intrinsic factor.
What is Intrinsic factor and where is it secreted from?
It is a Glycoprotein which is secreted from the gastric parietal cells.
Where does the Intrinsic factor take B12 once they have become bound?
to a specific receptor on the mucosa of the ileum.
What happens to B12 once it has been brought to the Receptors on the Ileum?
It enters the Ileal cells. (intrinsic factor remains in the lumen and is excreted)
How is Vitamin B12 transported from the enterocytes to the bone marrow?
By Glycoprotein transcoalbamin 2
How is Folate absorbed from dietary folate?
Dietary folate is converted to monoglutamate which is absorbed in the jejunum.
What neurological problems can present with B12 deficiency?
- Posterior / Dorsal column abnormalities.
- neuropathy
- Dementia
- Psychiatric manifestations.
What can be seen on the bloodfilm of patients with a Megaloblastic anaemia?
Macroovalocytes and “hyeprsegmented” neutrophils. (normally 3-5 nuclear segments)
What are Macroovalocytes?
Macroovalocytes are enlarged, oval-shaped erythrocytes (red blood cells)
What Autoantibodies can be checked for in a Megaloblastic anaemia?
- Anti Gastric-parietal cell (sensitive not specific)
- Anti intrinsic factor (Specific, not sensitive)
What is the management of a Megaloblastic anaemia?
Treat the underlying cause where possible.
Vitamin B12 injections for life in pernicious anaemia.
Folic acid tablets 5mg/day PO.
Red cell transfusions - only in potentially life-threatening anaemia.
What are some causes of a normoblastic macrocytosis?
- Alcohol
- Liver disease
- Hypothyroidism
- Marrow failure (will be assoc with anaemia)
(e.g. - Myelodysplasia, Myeloma, Anaplastic Anaemia)
What is Spurious Macrocytosis?
A macrocytosis where the volume of mature red cells is normal but the MCV has been measured as high.
What can cause a Spurious Macrocytosis?
- Reticulocytosis
- Cold-agglutinins (cause RBCs to clump at temperatures lower than core body Temp. making them appear as one giant cell.) - Make sure sample is warmed to 37 degrees.
