Macrocytosis and macrocytic anaemia Flashcards
What is macrocytosis?
when red blood cells exceed 100 femolitres (1fl = 10^-15 L)
What is macrocytic anaemia?
What are causes of macrocytosis?
- Genuine (True)
- Megaloblastic
- Non-megaloblastic
*Megaloblastic refers to a larger than normal, nucleated red cell precursor, with an immature nucleus (contrast with normoblast)
- Spurious (false causes)
What are causes of MEGALOBLASTIC anaemia?
B12 or folate deficiency
On rare occasions could be drug-induced or genetic
What is the pathophysiology of megaloblastic anaemia?
Megaloblastic anaemias are characterised by a lack of red cells due to predominant defects in DNA synthesis and nuclear maturation in developing precursor cells in the marrow.
Due to these DNA defects, CELL DIVISION IS REDUCED and apoptosis increases.
In the surviving cells, cytoplasmic development and Hb accumulation occur normally (in preparation for division), and so the precursor cell is bigger with an immature nucleus, i.e. a ‘megaloblast’.
Once Hb level in the cell is optimal, the nucleus is removed, leaving behind a bigger-than-normal red cell, i.e. a ‘macrocyte’.
But overall, there are fewer macrocytes, and hence ANAEMIA.
Why are B12 or folate important?
They are cofactors in reactions involved in DNA synthesis and DNA modification, so are particular relevant in sustaining the normal functioning of high turnover cells (like enterocytes, hair cells and blood cells)
Two of the reactions are converting uracil to thymine (essential DNA building block), and converting homocysteine to methionine (act as methyl donor to modify gene expression)
Describe absorption of B12 and hence causes of its deficiency.
Meat and eggs are main sources of B12 –> Vegans might lack intake
Salivary glands secrete haptocorrin/R-proteins, and is bound with B12 under the acidic environment of stomach –> PPIs/H2-receptor antagonists/Gastrectomy or bypass would all render this problematic
Gastric parietal cells secrete intrinsic factors –> In pernicious anaemia, autoimmune antibodies result in destruction of gastric parietal cells, hence IF deficiency (associated with atrophic gastritis)
In duodenum, haptocorrins are digested by proteases secrete in pancreatic juice, and consequently IF bind to B12 –> chronic pancreatitis, coeliac (duodenum), Crohn’s (~all small intestine) can affect this
IF-B12 is absorbed in ileum via Cubam receptors
Where is folate absorbed?
jejunum
What are causes of folate deficiency?
What are clinical features of B12/folate deficiency?
Mild jaundice can be a presentation in macrocytic anaemia since there would be increased apoptosis due to formation of more faulty cells, hence more bilirubin produced
How to diagnose B12/folate deficiency?
- Macrocytic anaemia (high MCV, low RBC count)
- Macroovalocytes (big oval-shaped RBCs) and hypersegmented neutrophils (beyond 3-5 segments of nuclei)
Other tests are less robust
How to treat megaloblastic anaemia?
Treat the cause via diet/oral supplementation
B12 injections in pernicious anaemia
Folic acid tablets
What are other causes of macrocytosis?
Non-megaloblastic macrocytosis would be due to red cell membrane changes
Spurious: Due to faulty measurements
