Megaloblastic Anaemia

Question 1

What are the two types of megaloblastic anaemia?

Answer 1

1. B12 deficiency
2. Folate deficiency

Question 2

Why may megaloblastic anaemia occur?

Answer 2

1. Inadequate intake
2. Increased requirements in the body
3. Impaired absorbance
4. Excess loss (renal dialysis - folate)
5. Impaired utilisation (drugs - folate)

Question 3

Where is folate stored in the body + duration?

Answer 3

Liver - 4 months

Question 4

Normal dietary intake of folate?

Answer 4

400μg/day
Minimal adult requirement: 200-250μg/day
High requirements during pregnancy

Question 5

How is folate lost from the body?

Answer 5

• Cells shedding from skin + intestinal epithelium
• Bile
• Saliva
• Sweat
• Urine

Question 6

Normal dietary intake of B12

Answer 6

7-30μg/day
Minimal adult requirement: 1-2μg/day

Question 7

How long can B12 be stored for?

Answer 7

2-4 years

Question 8

Role of B12

Answer 8

1. Trapping folate in DNA synthesis
   Stop miss-incorporation of DNA synthesis
2. Required for other conversions of coenzymes
   Can cause pathology if not converted
   If not converted = build up

Question 9

What’s the role of methylmalonic acid in B12 deficiency?

Answer 9

High amounts of MMA could bad a sign of B12 deficiency.
B12 deficiency = serum build up of MMA

MMA needs to be converted into methylmalonyl CoA. But if B12 not present, MMA cannot be converted thus causing a build up.

Question 10

What’s the role of homocysteine in B12 + folate deficiency?

Answer 10

It is an amino acid. B12 and folate breaks down this AA but similar to MMA mechanism, if B12 or folate not present, it cannot be broken down = build up which means there’s a vitamin deficiency

Question 11

Treatment for B12 + folate

Answer 11

1. Therapy - neurological, CNS/spinal cord damage due to B12 deficiency- irreversible
2. Small levels of B12 help trap folate
3. Folic acid given orally
   5mg daily for 4 months
   You will see improvement ends in reticulocytes (6-8 days) + normal Hb levels (60 days)
4. Hydroxocobalamin/cyanocobalamin
   Given intramuscular injection
   6 x 1000μg
   2-3 weeks
   Maintenance dose: 1000μg every 3 months
   Improvement will be seen after 2 days

Question 12

How is B12 absorbed?

Answer 12

In the duodenum + terminal ileum

Question 13

What is intrinsic factor?

Answer 13

They are released by parietal cells

Question 14

How is B12 transported in the blood + where is it stored?

Answer 14

Transcobalamin ll
Stored: Liver

Question 15

Red cell indices

Answer 15

Whole blood count - pancytopenia
Hb + RBC - decreased
MCV - increased
RDW - increased

Reticulocyte count - low
WBC - hyper segmented neutrophils, >5% have 6 or more lobes

Question 16

Blood smear

Answer 16

Forms a dimorphism blood film.
Aniocytosis - Oval macrocytes
Poikilocytosis
Schistocytes
Pancytopenia
Howell-Jolly bodies

Question 17

Other tests

Answer 17

Red cell indices
Blood films
Serum B12 - 200-850μg/day
Red cell folate - >120ng/ml
ELISA/Schillings test - pernicious anaemia
Intrinsic factor assay - gastric juice
Barium meal

Question 18

Bone marrow aspirate

Answer 18

Marrow smears are hyper cellular with erythroid hyperplasia
Myeloid:erythroid 1:5

1. Megakaryocytes change
   Decrease granulation
   Abnormal nuclear appearance
   Larger cells
2. Granulocytes larger
   Chromosomal abnormalities similar to erythronium precursors
   Metamyelocyte - giant with sausage shape nucleus
   Immature nucleus relative to mature cytoplasm
3. Erythroid precursors
   All large
   Each cell division = increased nuclear problems
   Red cell precursors delay development + begin to die in the marrow (life expectancy: 27-35 days instead of 120 days)

Question 19

Clinical presentation

Answer 19

• Weakness
• Sclera of eye
• Glossitis/sore tongue
• Nausea
• Constipation/diarrhoea
  Due to epithelial abnormalities
• Jaundice
  Spleen recognises large RBC + clears them from system. This causes increased bilirubin from increased RBC breakdown so causing splenomegaly
• Neurological problems
  Pins + needles or numbness
  Usually in B12 deficiency
  Demyelination of dorsal + lateral columns of spinal cord
  Personality changes
• Impaired development of foetal nervous system
  Causes neural tube defect - spina bifida
  Usually in pregnancy for folate deficiency
• Degradation of collagen, elastin, etc
  Elevated homocysteine due to folate deficiency = vascular occlusion + thrombosis

Question 20

Other causes of megaloblastic anaemia

Answer 20

Pernicious anaemia
This occurs when there’s a lack of intrinsic factor so causing reduced absorption of B12.
Age: 50 years old. Prevalence increase with age
Most common in white Northern European populations