Vitamin B12 And Folic Acid Deficiency Flashcards
What is vitamin B12 and what types of food is it commonly found in?
Cobalamin (vitamin B12) is a bacterial product that is ingested and stored by animals.
It is found in meat, cheese, salmon, cod, milk, eggs
How much B12 is needed every day and how much is found in hepatic stores?
1.5-3 mcg/day required
Store: 2-5 mg (will last several years)
What is Vitamin B12 needed for?
DNA synthesis
Integrity of the nervous system (involved in myelination)
Broadly speaking, what tends to cause Vitamin B12 deficiency?
Dietary deficiency (vegans) Decreased absorption
What is folic acid required for?
DNA synthesis
Homocysteine metabolism
What is the dietary requirement of folic acid?
400-600 mcg
You run out of folate much quicker than B12
Broadly speaking, what can cause folic acid deficiency?
- Dietary deficiency
- Increased demand for folate
- Impaired absorption
Deoxythymidine (dTMP) is a major building block of DNA synthesis. How is it produced?
It is produced by the methylation of deoxyuridine (dUMP)
For the methylation to take place, you need the release of methyl groups from methyl-tetrahydrofolate (derived from dietary folate) by the action of B12 as a cofactor accompanied by the conversion of homocysteine to methionine.
In what reaction is B12 a co-factor? State the enzyme.
The conversion of homocysteine to methionine
Enzyme = methionine synthetase
State some clinical features of B12 and folate deficiency.
- Anaemia (macrocytic and megaloblastic)
- Jaundice (due to ineffective erythropoiesis)
- Angular Cheilosis
- Glossitis
- Sterility
- Weight loss and change of bowel habit
State some causes of macrocytic anaemia.
- Vitamin B12/Folate deficiency
- Liver disease and alcoholism
- Hypothyroidism
- Drugs that interfere with DNA synthesis e.g. azathioprine
Haematological disorders:
- Myelodysplasia
- Aplastic anaemia (failure of blood cell production resulting in pancytopenia)
- Reticulocytosis (in response to haemolytic anaemia or bleeding)
Describe how the appearances of cells of the red cell lineage change as they mature.
They become smaller and their cytoplasm becomes pinker
Their nucleus starts off being quite diffuse (open chromatin) and it becomes more and more compact/pyknotic until it is spit out by the red cell => reticulocyte (young red blood cell with no nucleus)
Hence, what two things do you look at when determining the maturity of a red blood cell?
Chromatin – how open is it?
Colour of the cytoplasm – how blue is it?
What is meant by ‘megaloblastic changes’?
These are changes seen in the red blood cell precursors in the bone marrow.
Megaloblastic change is when there is asynchronous maturation of the nucleus and cytoplasm => immature, open nucleus with mature cytoplasm
What changes are seen in the peripheral blood in megaloblastic anaemia?
- Anisocytosis
- Large red cells
- Hypersegmented neutrophils
- Giant metamyelocytes (due to asynchronous maturation)
Give 3 tests that you would do if someone had a macrocytosis
B12/folate measurement
thyroid function test
liver function test
Reticulocyte count
Which groups are at particular risk of dietary folate deficiency?
Elderly, sick, eating disorders, alcoholics
What are the consequences of folate deficiency for DNA synthesis?
Folate deficiency means that you can’t methylate dUMP to dTMP, which affects DNA synthesis.
It also leads to the accumulation of homocysteine (it can’t be converted to methionine without folate)
What food is high in dietary folate? What is it destroyed by?
Fresh leafy vegetables
Destroyed by overcooking/canning/processing
State some physiological and pathological causes of increased folate demand (which if unaccounted for would cause a folate deficiency).
Physiological (times of increased growth)
- Pregnancy
- Adolescence
- Premature babies
Pathological (rapid cell turnover)
- Malignancy
- Erythroderma (whole body redness and eczema)
- Haemolytic anaemia
State some tests to identify folate deficiency.
- Full blood count
- Blood film
- Serum folate (useful as a screening test);
Shows diurnal variation
Affected by recent changes in diet - Red cell folate – useful as confirmatory test
What would you expect the serum folate and red cell folate of a patient with B12 deficiency to be and why?
Serum folate = high
Red cell folate = LOW
This is because B12 is required for the folate to enter the red blood cells
What are the three main consequences of folate deficiency?
- Megaloblastic anaemia
- Neural tube defects (e.g. spina bifida, anencephaly)
- Increased risk of venous thromboembolism in association with variant enzymes involved in homocysteine metabolism
How much folic acid should all pregnant women take?
0.4mg/day prior to conception and for the first 12 weeks
