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Haematology > Macrocytic Anaemia > Flashcards

Macrocytic Anaemia Flashcards

1
Q

what is macrocytic anaemia?

A

red cells have a larger than normal volume

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2
Q

what is false macrocytic anaemia?

A

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

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3
Q

what are the two classifications of macrocytic anameia?

A

o Megaloblastic

o Non-megaloblastic

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4
Q

what are the causes megaloblastic anaemia?

A

B12 Deficiency
Folate Deficiency
Others – drugs, rare inherited abnormalities

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5
Q

what are the causes of non-megaloblastic anaemia?

A

Alcohol
Liver Disease
Hypothyroidism Marrow Failure – myelodysplasia, myeloma, aplastic anaemia

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6
Q

what are the blood count features of macrocytic anaemia?

A

Hb (low), RBC (low), MCV (high)

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7
Q

what are the blood count features of macrocytosis?

A

Hb (normal), RBC (normal), MCV (high)

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8
Q

what are the features of macrocytic anaemia on blood film?

A

o >100fl

o Macrocytic red blood cells greater in size than nucleus of Lymphocyte

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9
Q

what are the causes of normocytic anaemia?

A
  1. Acute blood loss
  2. Anaemia of chronic disease (or ↓MCV)
  3. Bone marrow failure
  4. Renal failure
  5. Hypothyroidism (or ↑MCV)
  6. Haemolysis (or ↑MCV)
  7. Pregnancy
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10
Q

what are the causes of megaloblastic anaemia?

A

B12/ Folate deficiency

– Drugs (hydroxycarbamide/ hydroxyurea

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11
Q

what are the causes of Vit B12 deficiency anaemia?

A

Diet - vegan

Impaired absorption: Pernicious anaemia, Gastrectomy, illeal disease/resection, coeliac disease.

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12
Q

what are the causes of pernicious anaemia?

A

Autoimmune condition where there is atrophy of the gastric mucosa, with failure of Intrinsic Factor (and acid production)→ B12↓ absorption.

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13
Q

what are the causes of folate deficiency anaemia?

A

Poor Intake - old age, poverty, alcohol excess, anorexia
Malabsorption - coeliac, tropical sprue
Excess utilization
– pregnancy, lacatation, prematurity, chronic haemolytic anaemia, malignant and inflammatory diseases, dialysis

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14
Q

what are the clinical features of megaloblastic anaemia?

A

Usually asymptomatic

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15
Q

what are the clinical features of vit B12 deficiency anaemia?

A

Peripheral neuropathy – dorsal column degen.

Rarely – dementia

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16
Q

what are the general clinical features of pernicious anaemia?

A

Glossitis, Angular stomatitis, Mild jaundice, weakness + tiredness, Dysponea, Diarrhoea, grey hair, Mild Splenomegaly, Fever

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17
Q

what are the clinical features of folate deficiency anaemia?

A

Anaemia

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18
Q

what is the management of Vit B12 deficiency anaemia?

A

Treat cause

IM B12 injections

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19
Q

what is the management of pernicious anaemia?

A

IM Hydroxocobalamin

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20
Q

what is the management of folate deficiency anaemia?

A

– Tx of underlying conditon.

– Oral folic acid 5mg daily for 4 months

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21
Q

what is the pathophysiology of megaloblastic anaemia?

A

delayed nuclear maturation relative to that of the cytoplasm.

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22
Q

what are the neurological clinical features of pernicious anaemia?

A

Polyneuropathy– weakness, ataxia, paraplegia

Optic atrophy – dementia, visual disturbances.

23
Q

what are the features on blood film of megaloblastic anaemia?

A

hypersegmented polymorphs (B12 ↓),

24
Q

what is the characteristic feature of pernicious anaemia?

A

Parietal cell antibodies 90%

IF antibodies 50%.

25
Q

what are the blood test features in pernicious anaemia?

A 
– Hb ↓
– WCC + Platelets ↓
– Serum B12 ↓ < 50ng
– Red cell folate ↓
– Serum Bilirubin ↑
26
Q

what are the blood tests features for folate deficiency anaemia?

A

– Red cell folate ↓

– Serum folate ↓

27
Q

what doe the red blood cells look like in megaloblastic anaemia?

A

abnormally large nucleated red cell precursor with an immature nucleus (primitive)

28
Q

what normally happens to erythroblast DNA?

A

stop diving and lose nucleus once Hb content is optimal

29
Q

what is the main mechanism of megaloblastic anameia?

A

defects in DNA synthesis and nuclear maturation but RNA and haemoglobin synthesis are preserved.
Proerythroblasts expand but in maturing erythroblasts, division is reduced and apoptosis increases.

30
Q

what is the the process of megaloblastic cell formation?

A
  • Cytoplasmic development and haemoglobin accumulation occur normally, and so the precursor cell is bigger with an immature nucleus, i.e. a ‘megaloblast’.
  • Once haemoglobin level in the cell is optimal, the nucleus is extruded, leaving behind a bigger-than-normal red cell
31
Q

what are the roles of B12 and folate?

A

Enable chemical reactions for
 DNA synthesis
 Gene activity

32
Q

what is the role of the folate cycle?

A

nucleoside
synthesis (eg uridine to thymidine
conversion).

33
Q

what is the role of the methionine cycle?

A

producing
a methyl donor called ‘S-adenosyl
methionine’ (impact on DNA, RNA, proteins,
lipids, folate intermediates)

34
Q

what is the role of R protein?

A

Binds to B12 for transport

35
Q

what cells release intrinsic factor?

A

gastric cells in response to food

36
Q

what is the role of intrinsic factor?

A

Acid in stomach frees B12 which binds to intrinsic factor

bound form travels to terminal bowel to be absorbed

37
Q

what are the sources of B12?

A

animal

38
Q

what are the sources of folate?

A

liver, leafy veg, fortified cereals

39
Q

how long does the body store B12?

A

2-4 years

40
Q

how long does the body store Folate?

A

4 months

41
Q

where is B12 absorbed?

A

ileum

42
Q

where is folate absorbed?

A

duodenum and jejunum

43
Q

what is the daily requirement of B12?

A

1.5micrograms/day

44
Q

what is the daily requirement of folate?

A

200micrograms/day

45
Q

what are the causes of megaloblastic anaemia?

A

B12 Deficiency
Folate Deficiency
Others – drugs, rare inherited abnormalities

46
Q

what is the consequence of both vitB12 and folate deficiney?

A

microcytic anaemia (cancel each other out)

47
Q

what are the causes of B12 deficiency?

A

Diet – vegans
Pancreas - Chronic pancreatitis
Stomach – PA, Atrophic gastritis, PPIs/H2-receptor antganoists, Gastrectomy/Bypass
Small Bowel - Jejunum: bacterial overgrowth, coeliac disease - Duodenum: resection, crohns disease
Cubulin Receptors – inherited deficiency
Pernicious Anaemia

48
Q

what are the causes of folate deficiency?

A

Inadequate intake -
Malabsorption - Coeliac disease, Crohn’s disease
Excess utilisation – Haemolysis, Exfoliating dermatitis, Pregnancy, Malignancy, Drugs, anticonvulsants

49
Q

what are the clinical features of megaloblastic anaemia?

A

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

50
Q

what symptoms are specific to vit B12 deficiency?

A

Neurological problems** – posterior/dorsal column abnormalities, neuropathy, dementia, psychiatric manifestations

51
Q

how is megaloblastic anaemia diagnosed?

A 
FBC
Blood film
B12 and folate levels
Autoantibodies
Schillings test
Bone Marrow Exam
52
Q

what will FBC in megaloblastic anaemia show?

A

low red cells

Sometimes pancytopenia

53
Q

What will the blood film in megaloblastic anaemia show?

A

macrovalocytes and hypersegmented neutrophils (3-5 nuclear segments)

54
Q

what is the management of megaloblastic anaemia?

A

Treat cause
Vitamin B12 (hydroxycobalamin) injections for life in pernicious anaemia
Folic acid tablets (5mg per day) orally

Haematology (13 decks)

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