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MCD - Haematology > Vitamin B12 and folic acid deficiency > Flashcards

Vitamin B12 and folic acid deficiency Flashcards

1
Q

What role does vit B12 play in haematopoiesis and biochemical pathways?

A
  • Required for DNA synthesis and integrity of nervous system
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2
Q

What are the dietary sources of vitamin B12 and folic acid?

A

Vit B12: meat, salmon, cod, milk, cheese, eggs

Folic acid: leafy green vegetables

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3
Q

How is vitamin B12 absorbed?

A
  1. B12 binds to transcobalamin 1 in stomach
  2. Gastric parietal cells at bottom of stomach produce IF
  3. B12 displaced from transcobalamin 1 by pancreatic enzymes in duodenum
  4. Free B12 binds to IF
  5. B12-IF complex travels to terminal ileum
  6. B12-IF receptors bind to B12-IF complex and cells take in complex
  7. Complex enters portal circulation
  8. B12 binds to transcobalamin 2 in circulation = active B12
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4
Q

What are the causes of vitamin B12 deficiency?

A
  1. Reduced dietary intake
  2. Infections/infestations - abnormal bacterial flora, tropical sprue, fish tapeworm
  3. Malabsorption
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5
Q

What are the causes of folic acid deficiency?

A
  1. Dietary
  2. Malabsorption
  3. Increased requirement
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6
Q

What are the clinical features of folic acid and vit B12 deficiencies?

A 
Both:
Anaemia - macrocytic, megaloblastic - weak, tired, SOB
Jaundice - ineffective erythropoiesis
Glossitis
Angular cheilitis
Weight loss
Change of bowel habit
Sterility
B12:
Paraesthesiae
Muscle weakness (fatigue, lethargy)
Difficulty walking and loss of balance
Visual and memory impairment
Psychiatric disturbance
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7
Q

What are the haematological features of vit B12 and folic acid deficiencies?

A

Macrocytic anaemia:

  • Oval macrocytes
  • Hypogranular neutrophils and/or monocytosis
  • Reticulocytosis

Megaloblastic anaemia: in bone marrow

  • Hypersegmentation - >5% of neutrophils have >5 lobes
  • Fall in MCV due to red cell fragmentation/poikilocytosis
  • Dysplastic red cells
  • Fragments
  • Giant metamyelocytes
  • Open chromatin + maturing cytoplasm
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8
Q

How are folic acid and B12 deficiencies diagnosed?

A

Full blood count
Blood film
Blood folate level:
- Serum folate - useful as screening test, diurnal variation and affected by recent dietary changes
- Red cell folate - useful to confirm and more stable diagnostic test, not good for screening

High serum folate + low red cell folate = B12 deficiency

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9
Q

How are vit B12 and folic acid deficiencies managed?

A

Dietary changes

Give oral folate

B12 injections 3x/week for 2 weeks
Thereafter every 3 months
If neurological involvement, B12 injections alternate days until no further improvement for up to 3 weeks
Thereafter every 2 months

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10
Q

What role does folic acid play in haematopoiesis and biochemical pathways?

A

Required for DNA synthesis and homocysteine metabolism

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11
Q

How is folic acid absorbed?

A
  1. Folic acid (as folate polyglutamates) is hydrolysed to monoglutamates at acid pH
  2. Folates are absorbed as pteroglutamates which can be methylated in luminal cells to tetrahydrofolates
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12
Q

Explain the importance of folate and B12 in DNA synthesis

A

Both needed for deoxythymidine (dTMP) synthesis
dTMP = crucial building block in DNA synthesis
dTMP made from deoxyuridine

Dietary folate converted to methyl tetrahydrofolate (m-THF) in luminal cells
m-THF to THF occurs with B12 reaction as below

B12 acts as co-factor for methionine synthetase for conversion of homocysteine –> methionine
This reaction releases methyl groups that methylate DNA building blocks (necessary, w/o can’t make DNA)

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13
Q

What are some consequences of folic acid and B12 deficiencies?

A

B12:

  • Macrocytic and megaloblastic anaemia
  • Neurological problems due to demyelination - bilateral peripheral neuropathy, subacute combined degeneration of the cord, optic atrophy, dementia

Folic acid:

  • Megaloblastic anaemia
  • NTDs - spina bifida, anencephaly
  • Increased risk of venous thromboembolism
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14
Q

What 3 things are needed for normal B12 absorption?

A

Intact stomach
Intrinsic factor
Functioning SI

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15
Q

How can B12 absorption be impaired?

A
  1. Reduction in IF
  2. Diseases of small bowel (terminal ileum)
  3. Infections
  4. Drugs
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16
Q

What can cause a reduction in IF?

A 
Post gastrectomy
Gastric atrophy
ABs to IF or parietal cells
Pernicious anaemia
Age (peaks at 60)
FHx
17
Q

What kind of small bowel problems can impair B12 absorption?

A

Crohn’s disease
Coeliac disease
Surgical resection

18
Q

What infections can impair B12 absorption?

A

H. Pylori
Giardia
Fish tapeworm
Bacterial overgrowth

19
Q

What drugs can impair B12 absorption?

A

Metformin (diabetes, PCOS)
PPIs, e.g. omeprazole
Oral contraceptive pill

20
Q

What would you find on neurological examination of a B12 deficient patient?

A

Neurology (legs»arms)
Loss of vibration and procioception but with cutaneous sensation loss
Absent reflexes and upgoing plantar responses in legs
Upper AND lower motor neurone signs

21
Q

When is folate requirement increased?

A

Physiological (rapid increase in growth):
Pregnancy
Adolescence
Premature babies

Pathological (rapid cell turnover):
Malignancy
Erythroderma - whole body skin rash
Haemolytic anaemia - caused by SCD, hereditary elliptocytosis, AI haemolysis

22
Q

What are the causes of folate malabsorption?

A
  1. Combined w/iron deficiency in Coeliac disease
  2. Surgery or IBD (esp. Crohn’s) interferes w/normal absorption
  3. Drugs
    - Colestyramine, sulphasalazine, methotrexate
    - Trimethoprim can exacerbate pre-existing deficiency but no megaloblastic anaemia
    - Anticonvulsants, nitrofurantoin, possibly alcohol
23
Q

What are the consequences of dietary folate deficiency?

A

Decreased folate availability at cellular level –> inability to methylate nucleotides and affects DNA synthesis

Homocysteine accumulates bc can’t convert it to methionine w/o folate

24
Q

What are high homocysteine levels associated with?

A

Independently associated with atherosclerosis and premature vascular disease

25
Q

What are mildly elevated homocysteine levels associated with?

A

CVD definitely
Arterial thrombosis probably
Venous thrombosis possibly

26
Q

How long do B12 stores usually last?

A

Stores are large

3-4 years

MCD - Haematology (11 decks)

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