Week 1- macrocytic anaemia Flashcards

1
Q

What is macrocytosis?

A

Macro= big
Cytosis= excess of
Basically means big cells

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2
Q

What is macrocytic anaemia then?

A

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

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3
Q

How can size be measured/expressed?

A

MCV- mean corpuscular (cellular) volume. Units used are fentolitres.

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4
Q

Case 1
Hb- 100 Normal range- 130-180
RBC- 3.42 Normal range- 4.5-6.0
MCV- 115 Normal range- 80-100

A

Haemoglobin is low.
Red blood cells are low
MCV is high. This means the cells have increased in size, however red blood cells are low and Hb is low. This means macrocytic anaemia.

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5
Q

Case 2

Hb- 170 Normal range- 130-180
RBC- 5.44 Normal range- 4.5-6.0
MCV- 105 Normal range- 80-100

A

This person has macrocytosis because the cells are enlarged but they are not anaemic.

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6
Q

What is a RBC often compared to to determine whether it is microcytic or macrocytic?

A

Often compared to a nucleus of a small lymphocyte.
Smaller= microcytic
Larger= macrocytic

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7
Q

What can the causes of macrocytosis be categorised into?

A

Genuine (true)

  • megaloblastic
  • non megaloblastic

Spurious (false)

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8
Q

What does megaloblastic mean?

A

First of all- define normal
Erythroblast/normoblast are the normal red cell precursors with a nucleus. Red cell precursors tend to have a nucleus (excluding reticulocytes) and are marrow based.
A megaloblast is an abnormally large red cell precursor with an immature nucleus (ITS NOT NORMAL).

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9
Q

Which stage of development of RBC’s is there no Hb content in the RBC?

A

Pronormoblast (erythroblasts).

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10
Q

When does haemoglobin start appearing in RBC’s in their development?

A

At the early normoblast stage. (This is different to the pronormoblast stage).

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11
Q

What is a megablastic cell?

A

An abnormally large nucleated red cell precursor with an immature nucleus.

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12
Q

What are megablastic anaemias characterised by?

A

A defect in DNA synthesis of a cell meaning the nucleus maturation is delayed relative to that of the cytoplasm. This results in a bigger than normal cell.

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13
Q

Do any erythroblasts survive as megaloblasts?

A

A few survive. Generally apoptosis occurs but in the few that survive, the nucleus is ejected but the cell is larger than normal (the cell doesn’t get bigger, it just fails to get smaller). However, overall there are fewer of these cells leading to the overall anaemia.

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14
Q

Why do erythroblasts change in colour as they develop?

A

Go from blue to red as the haemoglobin is forming.

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15
Q

What are the causes of megaloblastic anaemia?

A

B12 deficiency
Folate deficiency
Others- drug, rare inherited abnormalities.

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16
Q

Why does lack of B12 and folate cause megaloblastic anaemia?

A

They are essential co-factors for nuclear maturation. They enable chemical reactions that provide enough nucleosides (nucleotide without the phosphate group) for DNA synthesis.

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17
Q

Which two biochemical cycles do B12 and folate mediate?

A

Methionine and folate cycle

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18
Q

What is the folate cycle important for?

A

Nucleoside synthesis (uridine to thiamine conversion)

19
Q

What does the methionine cycle do?

A

Produces s-adenosyl methionine, a methyl donor. This has potential impacts on DNA, RNA, proteins, lipids, folate intermediates.

20
Q

Are vitamin B12 and folate cycles linked?

A

YES.

21
Q

How does B12 get into the body?

A

Found in the diet only (eggs and meats for example).

22
Q

What is B12 also known as?

A

Cobalamins

23
Q

How does the body absorb vitamin B12?

A

Vitamin B12 is released by the acidic pH of the stomach.

Once it is free’d, the B12 binds to haptocorrin until it reaches the duodenum where it becomes bound to intrinsic factor (synthesised by the parietal cells of the gastric mucosa).

The pancreas produces enzymes making the conditions alkaline for B12 and intrinsic factor to bind and be absorbed. It attaches to cubulin receptors and is absorbed in the terminal ileum.

Once absorbed, it disconnects from intrinsic factor and enters the circulation bound to another protein.

24
Q

In which situations do people get vitamin B12 deficiencies?

A

Pernicious anemia- autoimmune destruction of parietal cells with consequent impairment of intrinsic factor secretion.
Vegan diet- dont consume animal products which contain B12.
Food bound cobalamin malabsorption- the food doesn’t release the vitamin B12. This can be caused by atrophic gastritis, use of PPI’s,

25
Q

What is pernicious anaemia associated with?

A

Atrophic gastritis and other autoimmune conditions (hypothyroidism, vitiligo, Addisons disease).

26
Q

How is folate brought into the body?

A

Dietary folate is converted to monoglutamate. This is absorbed in the jejunem

27
Q

Name some dietary sources of folate? How is folate destroyed?

A

Leafy veg, yeast.

Destroyed via cooking.

28
Q

How much does the body store of folate? How long will this last?

A

Body has 4 months worth of folate.

29
Q

How much does the body store of vitamin B12? How long does this last?

A

Has 2-4 years.

30
Q

What is the daily intake of folate and vitamin B12?

A

Vitamin B12- 1-3 micrograms/day

Folate- 100micrograms/day

31
Q

what are the causes of folate deficiency?

A

Inadequate intake (dietary cause is more likely than vitamin B12 because of the smaller stored folate)
Malabsorption (coeliac disease, crohns disease)
Excess utilisation (haemolysis, exfoliating dermatitis, pregnancy, malignancy)
Drugs- anticonvulsants.

32
Q

What are the clinical features of B12/folate deficiency?

A

Symptoms/signs of anaemia
Weight loss, diarrhoea, infertility
Sore tongue, jaundice
Developmental problems

With vitamin B12 deficiency you are more likely to get neurological problems. Believed that B12 is involved in myelin synthesis.

33
Q

What is pancytopenia?

A

Anaemia (low red cells), thrombocytopenia (low platelets), and neutropenia (low neutrophils)

34
Q

What will the blood film show of patients with macrocytic anaemia?

A
Macrovalocytes (oval shaped, large red cells)
Hypersegmented neutrophils (normally nucleus split into 3-5 segments)
35
Q

How would you diagnose B12 or folate deficiency via lab tests?

A

Assay B12 and folate serum levels- however low levels may not mean deficiency and high levels may not mean normal
Check for auto-antibodies- (anti-gastric parietal cell and anti-intrinsic factor)

36
Q

How do you treat megaloblastic anaemia?

A

Treat the cause where possible.
Vitamin B12 injections for life in pernicious anaemia
Folic acid tablets- orally.
Only blood transfuse in life threatening situations.

37
Q

What are the non-megaloblastic causes of macrocytic anaemia?

A

Alcohol
Liver failure
Hypothyroidism
The above may not be associated with anaemia
Marrow failure- myelodysplagia, myeloma, aplastic anaemia- these are all associated with anaemia.

38
Q

What is spurious macrocytosis in regards to the Mcv?

A

The size of the mature red cell is normal but the MCV is high. It is generally a fault with the analyser.

39
Q

What causes spurious macrocytosis?

A

An increase in reticulocyte numbers as a marrow response (these are bigger than normal mature red cells) in response to acute blood loss or red cell breakdown (haemolysis)
Cold agglutins disease.

40
Q

What will be different about the investigation into spurious macrocytosis?

A

The cells will be polychromatic- as the reticulocytes still have the remnants of the RNA- they will be blue in colour.

41
Q

What is cold agglutins disease?

A

The immune system produces a protein causing the red cells to stick together (agglutinate) appearing as one large cell giving a false MCV reading.

42
Q

What is the structural approach to macrocytosis?

A

First look at the reticulocyte count. If this is increased- likely to be marrow response to haemorrhage or increased haemolysis.
If this is normal/decreased look at the blood film. Look for macrovalcytes and hyperhsegmented nuclei. If these are present check the serum B12 and folate levels.

43
Q

What is the structural approach to macrocytosis?

A

First look at the reticulocyte count. If this is increased- likely to be marrow response to haemorrhage or increased haemolysis.
If this is normal/decreased look at the blood film. Look for macrovalcytes and hyperhsegmented nuclei. If these are present check the serum B12 and folate levels.
If no macrovalcytes or hyperhsegmented nuclei are present- look for other conditions like liver disease, hyperthyroidism.

44
Q

Why can patients with pernicious anaemia appear jaundiced?

A

Intramedullary haemolyisis (breakdown of red cells immaturely)- causes bilirubin build up and therefore jaundice.