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Haematology > Macrocytosis and macrocytic anaemia > Flashcards

Macrocytosis and macrocytic anaemia Flashcards

1
Q

What is macrocytic anaemia?

A

Anaemia in which the red cells have a larger than normal volume

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2
Q

What is used to measure cell size?

A

MCV - mean cellular volume

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3
Q

What do normal red cell precursors have that mature RBCs don’t, excluding reticulocytes?

A

A nucleus and are normally marrow based

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4
Q

What happens as erythroblasts develop?

A

They accumulate Hb, reduce in size and stop dividing (lost nucleus) once Hb content is optimal

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5
Q

What is a megaloblast?

A

An abnormally large nucleated red cell precursor with an immature nucleus

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6
Q

What characterises megaloblastic anaemias?

A

Predominant defects in DNA synthesis and nuclear maturation but RNA synthesis and Hb synthesis are preserved so the precursor cell is bigger with an immature nucleus i.e. a megaloblast

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7
Q

Once Hb level in the cell is optimal, the nucleus is extruded, leaving behind a bigger-than-normal red cell i.e. a macrocyte. This explains the megaloblastic part of megaloblastic anaemia but why are they actually anaemic?

A

There are too few macrocytes being produced, hence anaemia

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8
Q

What is the larger cell size in megaloblastic anaemia due to?

A

Not due to an increase in the size of the developing cell but a failure to become smaller

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9
Q

What are the main causes of megaloblastic anaemia?

A

B12 deficiency, folate deficiency

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10
Q

Why does lack of B12 or folate cause megaloblastic anaemia?

A

B12 and folate are essential co-factors for nuclear maturation. They enable chemical reactions for DNA synthesis and gene activity

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11
Q

Name the cycle that is important for nucleoside synthesis

A

Folate cycle

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12
Q

Name the cycle that is important for producing a methyl donor called S-adenosyl methionine

A

Methionine cycle - impact on DNA, RNA, proteins, lipids, folate intermediates

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13
Q

What can be used to measure B12 and folate deficiency?

A

Homocysteine

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14
Q

What foods provide vitamin B12?

A

Animal products - meat, fish, eggs

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15
Q

What protects vitamin B12 from digestion in the the stomach and duodenum respectively?

A

Haptocorrin and intrinsic factor

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16
Q

Where is vitamin B12 absorbed?

A

Terminal ileum

17
Q

Name some causes of vitamin B12 deficiency

A

Vegan diet, atrophic gastritis, PPIs, gastrectomy (stomach), coeliac disease, bacterial overgrowth (jejunum), resection, Crohn’s (duodenum)

18
Q

What is pernicious anaemia?

A

Autoimmune condition with resulting destruction of gastric parietal cells. Results in IF deficiency with B12 malabsorption and deficiency

19
Q

What is pernicious anaemia associated with?

A

Atrophic gastritis, autoimmune disorders e.g. hypothyroidism, vitiligo, Addison’s disease

20
Q

How is folate absorbed?

A

Dietary folates converted to monoglutamate, absorbed in jejunum

21
Q

Name some causes of folate deficiency

A

Dietary cause e.g. alcoholics, coeliac disease, crohn’s disease, haemolysis, pregnancy, malginancy, anticonvulsants

22
Q

What are the common clinical features of B12/folate deficiency?

A

Fatigue, weight loss, diarrhoea, infertility, glottitis, jaundice, developmental problems. Neurological problems with B12 deficiency - dorsal column abnormalities, neuropathy, dementia - subacute combined degeneration of the cord!!

23
Q

What is pancytopenia?

A

ALL cells are low

24
Q

How is megaloblastic anaemia diagnosed in the lab?

A
  • Low RBC count
  • Pancytopenia in some patients
  • Blood film shows macrovalocytes and hypersegmented neutrophils - normally 3-5 nuclear segments
  • Assay B12 and folate levels in serum
  • Check for auto-antibodies - anti-IF and anti-GPC
  • Bone marrow exam
25
Q

How is megaloblastic anaemia treated?

A

Treat the cause Vitamin B12 injections for life in pernicious anaemia Folic acid tablets If potentially life-threatening anaemia, transfuse red cells

26
Q

What are the causes of non-megaloblastic macrocytosis?

A

Alcohol, liver disease, hypothyroidism - these may not be associated with anaemia Marrow failure - myelodysplasia, myeloma, aplastic anaemia - associated with anaemia

27
Q

What is spurious/false macrocytosis?

A

The volume of the mature red cell is normal, but the MCV is measured as high

28
Q

What can cause spurious macrocytosis?

A

1) Reticulocytosis - rise in reticulocytes occurs as a marrow response to acute blood loss or red cell breakdown (haemolysis) Reticulocytes are bigger than mature RBCs and are analysed along with these for the MCV measurement 2) Cold agglutinins - clumps of agglutinated RBCs are registered as 1 giant cell

29
Q

What is the approach to finding the cause of macrocytic anaemia? (roughly)

A

See flow chart

Haematology (22 decks)

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