Folate, Vitamin B12, and Anaemia

Question 1

What is vitamin B12 needed for?

Answer 1

Nuclear maturation. (It is essential as a cofactor for DNA and cell metabolism)

Question 2

Where is vitB12 absorbed?

Answer 2

ileum (requires intrinsic factor)

Question 3

Where do we get vitB12 for?

Answer 3

animal products

Question 4

What kind of anaemia is caused by vitB12 and folate deficiency?

Answer 4

macrocytic anaemia

Question 5

What reactions need vitB12?

Answer 5

Conversion of homocysteine to methionine which is important for methylation of DNA, RNA and proteins

Convert Methylmalonyl CoA to Succinyl CoA (important for breakdown of fatty acids and production of energy)

Question 6

Why is DNA methylation so important?

Answer 6

It is a part of the synthesis of new DNA

Question 7

How much vitB12 do we need each day?

Answer 7

1 microgram

Question 8

How much vitB12 does Western diet contain?

Answer 8

10 - 15 micrograms/day

Question 9

How much vitB12 does the human body store?

Answer 9

2 - 4 micrograms in the liver and this is sufficient for 3 - 4 years without further supply

Question 10

What does the long storage time mean?

Answer 10

Deficient intake may take years to manifest

Question 11

How is vitB12 detatched from the carrier protein in the meat consumed?

Answer 11

The acidic environment of the stomach

Question 12

What is vitB12 bound to before being absorbed?

Answer 12

R-binder in the stomach then it passes into duodenum and pH change causes it’s release from R-binder

At duodenum intrinsic factor then binds to the vitB12

Question 13

Where is intrinsic factor produced?

Answer 13

Parietal cells of the gastric mucosa

Question 14

Where is the vitB12-intrinsic factor complex absorbed?

Answer 14

At the ileum where there is cubulin/amnion protein

Question 15

What does vitB12 bind to in the ileum?

Answer 15

cubulin/amnion receptor

Question 16

What does vitB12 bind to after passing through the wall of the ileum? Why?

Answer 16

Transcobalamine (TcI and TcII) which transport vitB12 to the liver

Question 17

Which Tc receptor can bind to receptors in organs?

Answer 17

TcII (this is where vitB12 is said to be active)

Question 18

What happens to vitB12 attached to TcI?

Answer 18

It is inactive

Question 19

What causes vitB12 deficiency?

Answer 19

Vegans: no animal products in diet

Infants born to B12-deficient mothers and breasfed

Malabsorption problems (gastric causes (gastrectomy), intestinal causes (defects of the ileum), or crohn’s disease, or bacterial overgrowth)

Question 20

What is pernicious anaemia?

Answer 20

Autoimmune gastritis resulting in reduced intrinsic factor secretion.

Whenever someone has vitB12 deficiency they are automatically tested for autoimmune antibodies

Question 21

Who’s most likely to have pernicious anaemia?

Answer 21

Females and elderly

Someone with family history of autoimmune diseases

Question 22

How is vitB12 deficiency treated?

Answer 22

intravascular vitB12

Question 23

How is vitB12 often diagnosed?

Answer 23

Often asymptomatic until a test is done specifically for it.

Blood film studies can show hypersegmented neutrophils leucopenia, macrocytes, and thrombocytopenia.

Active B12 can be tested whole transcobalamine assay

Question 24

Why can neurological symptoms appear for vitB12 deficiency?

Answer 24

Axon synthesis involves vitB12

Question 25

What are some symptoms/signs of vitB12 defciency?

Answer 25

If it is late anaemia can be gradual onset Jaundice (due to haemolysis) Neural and psychiatric disturbances (due to bad axon formation) [tingling of feet and difficulty walking or demyelination of spinal cord]

Question 26

What does blood film of B12 deficiency anaemia show?

Answer 26

Hypersegmented neutrophils (more than 4/5 lobes of nucleus) Oval macrocytes

Question 27

How is B12 deficiency treated?

Answer 27

1000 micrograms of hydroxocobalamin IM (3x a week for 2 weeks, then 1000 micrograms of hydroxocobalamin every 3 months for life unless deficiency is corrected) Large doses of oral vitamin B12 can be given (1 - 2 mgs daily but is less reliable than IM especially for pernicious anaemia)

Question 28

What is the solubility of folate?

Answer 28

Water soluble

Question 29

What type of vitamin B is folate?

Answer 29

vitamin B9

Question 30

Where can vitamin B9 be eaten?

Answer 30

Liver Green leafy vegetables

Question 31

How much folate does normal diet contain?

Answer 31

200 - 250 micrograms (50% absorbed)

Question 32

What is the daily adult requirement for folate?

Answer 32

100 micrograms

Question 33

How long do body stores of folate last?

Answer 33

3 - 4 months

Question 34

How much folate can the body store?

Answer 34

10 - 20 mgs

Question 35

Where is folate absorbed?

Answer 35

In the upper GI tract

Question 36

What is folate important for?

Answer 36

It is an assential coenzyme for the synthesis of thymidine monophosphate which is an important part of DNA synthesis.

Question 37

What is folate reduced into?

Answer 37

tetrahydrofolate (THF)

Question 38

What is folate important for production of?

Answer 38

Synthesis of purines, pyramidines, and metabolism of amino acids

Question 39

How do vitB12 and folate interact?

Answer 39

When vitB12 converts homocystene into methionine it also converts 5-methyl TH4 into TH4. Folate and vitB12 are important for each other's metabolism

Question 40

What causes folate deficiency?

Answer 40

Reduced folate intake Poor absorption Increased folate requirements Excess folate loss (dialysis due to it being protein bound) Drugs such as anticonvulsants Others include alcoholism

Question 41

What causes increased folate requirements?

Answer 41

Physiological: Pregnancy, lactation, and prematurity Pathology: Haemolytic anaemia, inflammatory conditions, exfoliative dermatitis, Crohn disease

Question 42

What are history and clinical features of folate deficiency?

Answer 42

Diet, drugs, and alcohol described Gradual onset of anemia described Mild jaundice (ineffective haemopoiesis) Lab investigations show low serum folate, low red cell folate, or normal/low serum vitB12

Question 43

How is folate replaced?

Answer 43

Folic acid 5mg per day for 4 months Correct the anaemia Decide whether ongoing folic acid is required

Question 44

What type of embryological defects can be caused by folate deficiency?

Answer 44

Neural tube failure to close between 21 and 27 days post conception when most women are unaware of pregnancy.

Question 45

What type of embryological malformations result from folate deficiency?

Answer 45

Anancephaly Encephalocoele Spina bifida

Question 46

What does megaloblastic anaemia look like on blood film? (Haematology)

Answer 46

Macrocytic anaemia (oval) anaemia: MCV > 100 > 115fL Hypersegmented neutrophils Mild haemolysis Increased bilirubin Hypercellular BM

Question 47

What are biochemical tests can be done to diagnose megaloblastic anaemia?

Answer 47

Reduced serum vitB12 or RBC folate Intrinsic Factor or Parietal cell antibody assays can be used

Question 48

What happens to RBC appearance as a result of megaloblastic anaemia?

Answer 48

Abnormal appearance of erythroblasts in the bone marrow. Delayed development of nuclear chromatin giving an open "lacy" appearance Defect in DNA synthesis

Question 49

What causes megaloblastic anaemia?

Answer 49

Usually caused by deficiency of vitB12 or folate

Question 50

What happens in the bone marrow of people with folate/vitB12 deficiency?

Answer 50

There is a dysynchrony between the nucleus development and the development of the RBC. This is due to deficient DNA synthesis.

Question 51

What are other causes of megaloblastic anaemia?

Answer 51

Liver disease Alcohol Reticulocytosis (higher MCV response to anaemia) Hypothyroidism Myelodysplastic syndrome

Question 52

What differentiates liver disease macrocytic anaemia from megalobasltic anaemia?

Answer 52

Target cells (cholestasis) Acanthocytes / spur cells

Question 53

What are acanthocytes?

Answer 53

Acanthocyte (from the Greek word ἄκανθα acantha, meaning 'thorn'), in biology and medicine, refers to a form of red blood cell that has a spiked cell membrane, due to abnormal thorny projections.