Folate, Vitamin B12, and Anaemia Flashcards
What is vitamin B12 needed for?
Nuclear maturation. (It is essential as a cofactor for DNA and cell metabolism)
Where is vitB12 absorbed?
ileum (requires intrinsic factor)
Where do we get vitB12 for?
animal products
What kind of anaemia is caused by vitB12 and folate deficiency?
macrocytic anaemia
What reactions need vitB12?
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)
Why is DNA methylation so important?
It is a part of the synthesis of new DNA
How much vitB12 do we need each day?
1 microgram
How much vitB12 does Western diet contain?
10 - 15 micrograms/day
How much vitB12 does the human body store?
2 - 4 micrograms in the liver and this is sufficient for 3 - 4 years without further supply
What does the long storage time mean?
Deficient intake may take years to manifest
How is vitB12 detatched from the carrier protein in the meat consumed?
The acidic environment of the stomach
What is vitB12 bound to before being absorbed?
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
Where is intrinsic factor produced?
Parietal cells of the gastric mucosa
Where is the vitB12-intrinsic factor complex absorbed?
At the ileum where there is cubulin/amnion protein
What does vitB12 bind to in the ileum?
cubulin/amnion receptor
What does vitB12 bind to after passing through the wall of the ileum? Why?
Transcobalamine (TcI and TcII) which transport vitB12 to the liver
Which Tc receptor can bind to receptors in organs?
TcII (this is where vitB12 is said to be active)
What happens to vitB12 attached to TcI?
It is inactive
What causes vitB12 deficiency?
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)
What is pernicious anaemia?
Autoimmune gastritis resulting in reduced intrinsic factor secretion.
Whenever someone has vitB12 deficiency they are automatically tested for autoimmune antibodies
Who’s most likely to have pernicious anaemia?
Females and elderly
Someone with family history of autoimmune diseases
How is vitB12 deficiency treated?
intravascular vitB12
How is vitB12 often diagnosed?
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
Why can neurological symptoms appear for vitB12 deficiency?
Axon synthesis involves vitB12
What are some symptoms/signs of vitB12 defciency?
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]
What does blood film of B12 deficiency anaemia show?
Hypersegmented neutrophils (more than 4/5 lobes of nucleus)
Oval macrocytes
How is B12 deficiency treated?
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)
What is the solubility of folate?
Water soluble
What type of vitamin B is folate?
vitamin B9
Where can vitamin B9 be eaten?
Liver
Green leafy vegetables
How much folate does normal diet contain?
200 - 250 micrograms (50% absorbed)
What is the daily adult requirement for folate?
100 micrograms
How long do body stores of folate last?
3 - 4 months
How much folate can the body store?
10 - 20 mgs
Where is folate absorbed?
In the upper GI tract
What is folate important for?
It is an assential coenzyme for the synthesis of thymidine monophosphate which is an important part of DNA synthesis.
What is folate reduced into?
tetrahydrofolate (THF)
What is folate important for production of?
Synthesis of purines, pyramidines, and metabolism of amino acids
How do vitB12 and folate interact?
When vitB12 converts homocystene into methionine it also converts 5-methyl TH4 into TH4.
Folate and vitB12 are important for each other’s metabolism
What causes folate deficiency?
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
What causes increased folate requirements?
Physiological: Pregnancy, lactation, and prematurity
Pathology: Haemolytic anaemia, inflammatory conditions, exfoliative dermatitis, Crohn disease
What are history and clinical features of folate deficiency?
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
How is folate replaced?
Folic acid 5mg per day for 4 months
Correct the anaemia
Decide whether ongoing folic acid is required
What type of embryological defects can be caused by folate deficiency?
Neural tube failure to close between 21 and 27 days post conception when most women are unaware of pregnancy.
What type of embryological malformations result from folate deficiency?
Anancephaly
Encephalocoele
Spina bifida
What does megaloblastic anaemia look like on blood film? (Haematology)
Macrocytic anaemia (oval) anaemia: MCV > 100 > 115fL
Hypersegmented neutrophils
Mild haemolysis
Increased bilirubin
Hypercellular BM
What are biochemical tests can be done to diagnose megaloblastic anaemia?
Reduced serum vitB12 or RBC folate
Intrinsic Factor or Parietal cell antibody assays can be used
What happens to RBC appearance as a result of megaloblastic anaemia?
Abnormal appearance of erythroblasts in the bone marrow.
Delayed development of nuclear chromatin giving an open “lacy” appearance
Defect in DNA synthesis
What causes megaloblastic anaemia?
Usually caused by deficiency of vitB12 or folate
What happens in the bone marrow of people with folate/vitB12 deficiency?
There is a dysynchrony between the nucleus development and the development of the RBC. This is due to deficient DNA synthesis.
What are other causes of megaloblastic anaemia?
Liver disease
Alcohol
Reticulocytosis (higher MCV response to anaemia)
Hypothyroidism
Myelodysplastic syndrome
What differentiates liver disease macrocytic anaemia from megalobasltic anaemia?
Target cells (cholestasis)
Acanthocytes / spur cells
What are acanthocytes?
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.
