Macrocytosis and Macrocytic Anaemia Flashcards
What is macrocytosis?
Increased in rbc size
What is macrocytic anaemia?
Anaemia in which the rbcs have a larger volume than normal (MCV)
NOTE - macrocytosis and macrocytic anaemia are not the same
Units of MCV?
Mean Corpuscular Volume
Units are femtolitres (fL)
Results with a macrocytic anaemia?
*EXAMS*
Reduced Hb and RBC count = anaemia
Raised MCV = macrocytosis
Results with macrocytosis? *EXAMS*
Normal Hb and RBC count
MCV raised
2 broad classifications of macrocytosis causes?
Genuine (true) macrocytosis:
- Megaloblastic
- Non-megaloblastic
Spurious (false) macrocytosis
What is an erythroblast?
AKA normoblast
Normal rbc precursor, with a nucleus
NOTE - rbc precursors, except the reticulocyte, have a nucleus and are usually marrow-based
Changes in developing erythroid cells in the marrow?
Accumulate Hb
Reduced size
Stop dividing and lose nucleus (enucleation)
Structure of a mature rbc?
Membrane surrounding soluble proteins and electrolutes
NO NUCLEUS
Differences between a reticulocyte and a mature rbc/erythrocyte?
Reticulocyte is larger
Reticulocyte retains some RNA (blue tint)
What is a megaloblast?
Abnormally LARGE red cell precursor with an IMMATURE NUCLEUS
Characteristics of megaloblastic anaemias?
Predominant effects in DNA synthesis and nuclear maturation
WITH
Relative preservation of RNA and Hb synthesis
This results in the more mature erythroblasts having reduced division and increased apoptosis
A few erythroblasts survive as megaloblasts and have normal cytoplasmic development and enucleation; however, the rbc is larger than normal and there are fewer rbcs overall, i.e: patient has a macrocytic anaemia
NOTE - the bone marrow is full of megaoblasts in this type of anaemia
Why are the red cells bigger in a megaloblastic anaemia?
Megaloblasts are abnormally large precursors and, as less cell division occurs, the red cells FAIL TO GET SMALLER and thus are larger than normal
In fact, the rbcs are termed MACRO-OVALOCYTES (due to their large, oval shape)
Why is there anaemia in a megaloblastic anaemia?
The end result is a low number of rbcs, due to increased apoptosis
Causes of megaloblastic anaemia?
B12 deficiency
Folate deficiency
Others:
- Drugs
- Rare, inherited abnormalities, e.g: in enzymes assoc. with B12 and folate
Why does B12 or folate deficiency cause a megaloblastic anaemia?
B12 and folate are essential co-factors for nuclear maturation; they enable chemical reactions that provide enough nucleosides for DNA synthesis
Biochemical reactions of B12 and folate?
They are inter-linked:
- Methionine cycle - produces s-adenosyl methionine, a methyl donor that has a potential impact on DNA, RNA, proteins, lipids, folate intermediates
- Folate cycle - for nucleoside synthesis, e.g: uridine to thymidine conversion
What is homocysteine a marker of?
Homocysteine is converted to methionine as part of the methionine cycle, which is linked to the folate cycle
If homocysteine accumulates, indicates a B12 or folate deficiency
How is vitamin B12 absorbed?
Gastric parietal cells release intrinsic factor; this travels with B12 to the small bowel and the basic environment here allows them to bind and form a complex
Absorption occurs in the terminal ileum, into the bloodstream
Issues with B12 absorption at different sites?
Inadequate dietary intake is an unlikely cause
Stomach:
- Pernicious anaemia
- Atrophic gastritis
- Achlorohydria (PPIs, H2-receptor antagonists)
- Gastrectomy, bypass
Pancreas:
• Chronic pancreatitis (less basic pancreatic juices entering the small bowel)
Small bowel:
- Jejunum - coeliac disease (malabsorption), bacterial overgrowth (use B12)
- Duodenum - resection, Crohn’s disease
What is pernicious anaemia?
Autoimmune condition resulting in gastric parietal cell destruction; leads to intrinsic factor deficiency with B12 malabsorption and deficiency
Assoc. with atrophic gastritis and PMH or FH of other autoimmune disorders, e.g: Hypothyroidism, vitiligo, Addison’s disease
How is folate absorbed?
Dietary folates are converted to monoglutamate and absorbed in the jejunum
Compare the characteristics of folate and B12 diet and stores?
B12:
- Source - animal
- Body stores - 2-4 years
- Absorbed - ileum
- Daily requirement - 1-3 micrograms/day
Folate:
- Source - leafy vegetables, yeast; it is destroyed by cooking
- Body stores - 4 months
- Absorbed - duodenum and jejunum
- Daily requirement - 100 micrograms/day
Causes of folate deficiency?
Inadequate intake more likely with folate than with B12, as there are less stores of folate
Malabsorption:
- Coeliac disease
- Crohn’s disease
EXCESS UTILISATION:
- Haemolysis
- Exfoliating dermatitis
- Pregnancy
- Malignancy
Drugs, e.g: anti-convulsants
