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IMED2002 UWA > Folate, Vitamin B12, and Anaemia > Flashcards

Folate, Vitamin B12, and Anaemia Flashcards

1
Q

What is vitamin B12 needed for?

A

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

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2
Q

Where is vitB12 absorbed?

A

ileum (requires intrinsic factor)

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3
Q

Where do we get vitB12 for?

A

animal products

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4
Q

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

A

macrocytic anaemia

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5
Q

What reactions need vitB12?

A

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)

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6
Q

Why is DNA methylation so important?

A

It is a part of the synthesis of new DNA

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7
Q

How much vitB12 do we need each day?

A

1 microgram

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8
Q

How much vitB12 does Western diet contain?

A

10 - 15 micrograms/day

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9
Q

How much vitB12 does the human body store?

A

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

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10
Q

What does the long storage time mean?

A

Deficient intake may take years to manifest

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11
Q

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

A

The acidic environment of the stomach

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12
Q

What is vitB12 bound to before being absorbed?

A

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

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13
Q

Where is intrinsic factor produced?

A

Parietal cells of the gastric mucosa

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14
Q

Where is the vitB12-intrinsic factor complex absorbed?

A

At the ileum where there is cubulin/amnion protein

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15
Q

What does vitB12 bind to in the ileum?

A

cubulin/amnion receptor

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16
Q

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

A

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

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17
Q

Which Tc receptor can bind to receptors in organs?

A

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

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18
Q

What happens to vitB12 attached to TcI?

A

It is inactive

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19
Q

What causes vitB12 deficiency?

A

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)

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20
Q

What is pernicious anaemia?

A

Autoimmune gastritis resulting in reduced intrinsic factor secretion.

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

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21
Q

Who’s most likely to have pernicious anaemia?

A

Females and elderly

Someone with family history of autoimmune diseases

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22
Q

How is vitB12 deficiency treated?

A

intravascular vitB12

23
Q

How is vitB12 often diagnosed?

A

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

24
Q

Why can neurological symptoms appear for vitB12 deficiency?

A

Axon synthesis involves vitB12

25
Q

What are some symptoms/signs of vitB12 defciency?

A

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]

26
Q

What does blood film of B12 deficiency anaemia show?

A

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

Oval macrocytes

27
Q

How is B12 deficiency treated?

A

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)

28
Q

What is the solubility of folate?

A

Water soluble

29
Q

What type of vitamin B is folate?

A

vitamin B9

30
Q

Where can vitamin B9 be eaten?

A

Liver

Green leafy vegetables

31
Q

How much folate does normal diet contain?

A

200 - 250 micrograms (50% absorbed)

32
Q

What is the daily adult requirement for folate?

A

100 micrograms

33
Q

How long do body stores of folate last?

A

3 - 4 months

34
Q

How much folate can the body store?

A

10 - 20 mgs

35
Q

Where is folate absorbed?

A

In the upper GI tract

36
Q

What is folate important for?

A

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

37
Q

What is folate reduced into?

A

tetrahydrofolate (THF)

38
Q

What is folate important for production of?

A

Synthesis of purines, pyramidines, and metabolism of amino acids

39
Q

How do vitB12 and folate interact?

A

When vitB12 converts homocystene into methionine it also converts 5-methyl TH4 into TH4.

Folate and vitB12 are important for each other’s metabolism

40
Q

What causes folate deficiency?

A

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

41
Q

What causes increased folate requirements?

A

Physiological: Pregnancy, lactation, and prematurity

Pathology: Haemolytic anaemia, inflammatory conditions, exfoliative dermatitis, Crohn disease

42
Q

What are history and clinical features of folate deficiency?

A

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

43
Q

How is folate replaced?

A

Folic acid 5mg per day for 4 months

Correct the anaemia

Decide whether ongoing folic acid is required

44
Q

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

A

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

45
Q

What type of embryological malformations result from folate deficiency?

A

Anancephaly

Encephalocoele

Spina bifida

46
Q

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

A

Macrocytic anaemia (oval) anaemia: MCV > 100 > 115fL

Hypersegmented neutrophils

Mild haemolysis

Increased bilirubin

Hypercellular BM

47
Q

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

A

Reduced serum vitB12 or RBC folate

Intrinsic Factor or Parietal cell antibody assays can be used

48
Q

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

A

Abnormal appearance of erythroblasts in the bone marrow.

Delayed development of nuclear chromatin giving an open “lacy” appearance

Defect in DNA synthesis

49
Q

What causes megaloblastic anaemia?

A

Usually caused by deficiency of vitB12 or folate

50
Q

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

A

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

51
Q

What are other causes of megaloblastic anaemia?

A

Liver disease

Alcohol

Reticulocytosis (higher MCV response to anaemia)

Hypothyroidism

Myelodysplastic syndrome

52
Q

What differentiates liver disease macrocytic anaemia from megalobasltic anaemia?

A

Target cells (cholestasis)

Acanthocytes / spur cells

53
Q

What are acanthocytes?

A

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.

IMED2002 UWA (29 decks)

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