Macrocytosis & Macrocytic anaemia Flashcards

1
Q

1 femtoliter is equal to how many lites?

A

10^-15 L

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1
Q

What is macrocytic anaemia?

A

Anaemia in which RBCs have a larger than normal volume

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2
Q

How is blood size expressed?

A

MCV - Mean corpuscular (cellular) volume

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3
Q

How do modern analysers measure MCV?

A

Use light scatter properties of red cells to measure MCV

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4
Q

Which of the following is the most likely explanation for the results?
A. iron deficiency
B. B12 deficiency
C. Aplastic anaemia
D. Acute myeloid leukemia

A

B12 deficiency - important cause of microcytic anaemia (with megaloblastosis)

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5
Q

Which of the following is likely to explain the abnormal result?
A. Iron deficiency
B. B12 deficiency
C. Life style
D. Acute myeloid leukemia

A

Life-style
- Alcohol excess can cause changes in the red cell membrane to result in macrocytosis and is often not associated with anaemia

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6
Q

Which of the following is the most likely explanation for the results?
A. Iron deficiency
B. B12 deficiency
C. Pregnancy
D. Folate deficiency

A

Pregnancy
- Can be associated with low B12 levels even if this does not reflect B12 deficiency

This is because the functional B12 levels remain normal but levels of nun-functional B12, called haptocorrin, fall. We do not measure these components separately and hence the total B12 (reflecting the greater contribution of haptocorrin to the measurement) is low

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7
Q

What are genuine (true) causes of macrocytosis?

A

Megaloblastic
Non-megaloblastic

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8
Q

What does megaloblastic mean?

A

A larger than normal, nucleated red cell precursor (“mother cell”) with an immature nucleus

Based in bone marrow

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9
Q

Normal red cell precursors excluding what have a nucleus and are usually marrow based?

A

Normal red cell precursors (except reticulocyte) have a nucleus (erythroblasts or normoblasts) and are usually marrow based

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10
Q

As normoblasts develop, they?

A

Accumulate Hb
Reduce in cell and nuclear size as the nucleus matures
Stop dividing and lose nucleus (Hb content triggers this)

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11
Q

Where in erythropoiesis does enucleation happen?

A
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12
Q

What is the difference between these two?

A
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13
Q

What happens in megaloblastic anaemia?

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

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14
Q

In the surviving cells of megaloblastic anaemia, what happens?

A

Cytoplasmic development and Hb accumulation occur normally in surviving cells (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

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15
Q

Why are red cells bigger and why is there anaemia?

A
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16
Q

Megaloblastic anaemia is characterised by?

A

Larger precursor cells with an immature nucleus leading to macrocytic anaemia

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17
Q

What are causes of megaloblastic anaemia?

A

B12 deficiency
Folate deficiency
Others - drugs, rare inherited abnormalities

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18
Q

Why are B12 and folate important?

A

Essential co-factors in linked biochemical reactions regulating:
- DNA synthesis and nuclear maturation (e.g. blood cell effect), DNA modification, gene activity (e.g. nervous system)

B12 deficiency may also affect lipid synthesis, impacting on myelin (protective sheath around nerve fibres)

19
Q

Describe how B12 and folate are important in DNA synthesis

20
Q

How does B12 and folate get taken up in the GI system?

21
Q

What are GI causes of vitamin B12 deficiency?

22
Q

What is pernicious anaemia?

A

Autoimmune condition with destruction of gastric parietal cells -> intrinsic factor deficiency -> B12 malabsorption and deficiency

Associated with atrophic gastritis and personal or FH of other autoimmune disorders (e.g. hypothyroidism, vitiligo, Addison’s disease)

23
Q

Where is folate absorbed?

A

In jejunum (diffusion and actively)

24
Dietary folates converts to?
Monoglutamate
25
What are causes of folate deficiency?
Inadequate intake (dietary cause more likely than B12 due to lesser stores (e.g. alcoholic excess) Malabsorption - coeliac disease, Crohn's disease Excess utilisation - haemolytic, exfoliating dermatitis, pregnancy, malignancy Drugs - anticonvulsants
26
What is the source of B12 and folate?
B12- animal Folate - liver, leafy veg, fortified cereals
27
How long do body stores of folate and B12 last?
B12 - 2-4 years Folate - 4 months
28
Where is B12 absorbed?
Ileum
29
Where is folate absorbed?
Duodenum and jejunum
30
What is the daily requirement of B12?
1.5 micrograms/day
31
What is the daily requirement of folate?
200 micrograms / day
32
What are symptoms of B12 and folate deficiency?
Symptoms / signs of anaemia Weight loss, diarrhoea, infertility Sore tongue, jaundice Developmental problems
33
What symptom is more common with vitamin B12 deficiency?
?Myelin Neurological problems - dorsal / lateral column abnormalities, neuropathy, dementia, psychiatric manifestations
34
What neurological condition can occur due to B12 deficiency?
Subacute combined degeneration of the cord
35
What is seen on lab results of B12/folate deficiency?
Macrocytic anaemia (Red cell count is low) Pancytopenia (all cells low) in some patients Blood film shows macrovalocytes and "hypersegmented" neutrophils (normally 3-5 nuclear segments)
36
What auto antibodies should be investigated for in b12/folate deficiency?
Anti-gastric parietal cell Anti intrinsic factor
37
Why can b12 and folate levels test in serum be a flaw?
Low levels may not always indicate deficiency e.g. pregnancy and low B12 levels
38
What other tests exist for B12/folate deficiency?
Schilling's test (for B12 deficiency not in routine use anymore) Bone marrow examination (not usually required) Trial of therapy
39
How do we treat megaloblastic anaemia?
Treat cause where possible - e.g. diet/oral supplementation Vitamin B12 (hydroxycobalamin) injections for life in pernicious anaemia - higher dosing schedule if neurological features Folic acid (5mg per day) orally Only if potentially life-threatening anaemia, transfuse red cells extremely cautiously
40
What are causes of non-megaloblastic macrocytosis (red cell membrane changes)?
Alcohol Liver disease hypothyroidism (the above may not be associated with anaemia) Marrow failure (myelodysplasia, myeloma, aplastic anaemia) - associated with anaemia
41
What is spurious macrocytosis?
Volume of mature red cell is normal, but MCV is measured as high
42
Why does reticulocytosis occur?
An increase in reticulocyte numbers occurs as a marrow response to acute blood loss or red cell breakdown (haemolytic) Reticulocytes are bigger than mature red cells and are analysed along with these for MCV measurement
43
What approach can we use for macrocytic anaemia?
44
Why can patients with pernicious anaemia appear mildly jaundiced?
Due to intramedullary haemolytic Ineffective erythropoiesis: Red cells die prematurely in the marrow Haemoglobin and lactate dehydrogenase (LDH) are released from dead red cells Haemoglobin converted to bilirubin patients with megaloblastic anaemia may be mildly jaundiced since macrocytes are unable to pass through narrow openings easily and therefore break-down and fragment. The haemoglobin released from the broken down cells is converted to bilirubin to cause jaundice. The technical description of this phenomenon is ineffective erythropoiesis due to intramedullary haemolysis, meaning a break-down of cells within the bone marrow.
45
Pancytopenia can be a feature of?
A feature of B12 and folate deficiency because these co-factors can affect nuclear maturation in different lineages with increased apoptotic death of developing cells