Flashcards in Macrocytosis and Macrocytic Anaemias Deck (81)
What cell does macrocytosis refer to?
What is macrocytosis?
Anaemia in which the red cells have a larger than normal volume
What measurement assesses RBC size?
MCV – Mean Corpuscular (cellular) Volume
What is the units of MCV?
Femtolitres (1femtolitre = 10-15L).
What would the blood results be of a patient with macrocytic anaemia?
* Low Hb
* Low RCB's
* High MCV
What would the blood results be of a patient with macrocytosis (without the anaemia)?
* Normal Hb
* Normal RBC's
* High MCV
On a blood film, what is the size of RBC’s normally comparable to?
The nucleus of lymphocytes
If a RBC is smaller than the nucleus of a lymphocyte then it can be described as?
If a RBC is larger than the nucleus of a lymphocyte then it can be described as?
Outline what the causes of an apparent macrocytosis can be grouped into
1. True - megaloblastic or non-megaloblastic
2. Spurious (false)
What is an erythroblast/normoblast?
A normal red cell precursor with a nucleus
What is the basic structure of a mature red cell?
Flexible cell membrane surrounding soluble proteins and electrolytes
Do red cell precursors have a nucleus?
No – the reticulocyte doesn’t, but the other precursors do (erythroblasts)
Where are red cell precursors usually found?
What is a reticulocyte?
An immediate precursor of the red cell that has lost its nucleus, but still has a little bit of RNA in it
Outline 3 things that happen to erythroid cells in bone marrow as they develop.
* Accumulate Hb
* Reduce in size
* Stop dividing and lose nucleus (regulated by Hb content)
Describe megaloblastic development.
Involves the development of an abnormally large nucleated red cell precursor with an immature nucleus.
What are megaloblastic anaemias characterised by? (in terms of what is defective and what is preserved)
Predominant defects in DNA synthesis and nuclear maturation, with relative preservation of RNA and haemoglobin synthesis
What happens in more mature erythroblasts?
Division reduces and apoptosis increases
What happens in the few erythroblasts that survive as ‘megaloblasts’? What does this lead to? And why does this make a patient anaemic?
Cytoplasm development occurs normally and triggers enucleation
* this leads to a ‘bigger-than-normal’ red cell.
* the patient is anaemic because there are FEWER of these big red cells
What is the end result in enucleation?
Nucleus is more immature, and chromatin is less condensed
The larger cell size in megaloblastic anaemia is not due to an increase in the size of the developing cell but ....
A failure to become smaller
Suggest some causes of megaloblastic anaemia.
* B12 deficiency
* Folate deficiency
* Others – drugs, rare inherited abnormalities
Why does lack of B12 or folate cause megaloblastic anaemia?
B12 and folate are essential co-factors for nuclear maturation, enabling chemical reactions that provide enough nucleosides for DNA synthesis
B12 and folate biochemical reactions are interlinked Name 2 ‘cycles’ which these are involved in.
1. Methionine cycle
2. Folate cycle
What is the folate cycle important for? And what reaction does folic acid specifically catalyse?
Important for nucleoside synthesis
Conversion of uridine to thymidine in nucleoside synthesis (know for exams!!!)
What does the methionine cycle do?
Produces s-adenosyl methionine, a methyl donor (potential impact on DNA, RNA, proteins, lipids, folate intermediates)
What do B12 and folate both catalyse?
The conversion of homocysteine to methionine
What is the folate cycle important for?
The DNA cycle and nucleic acid synthesis