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RRY2HAEM > Vitamin B12 and Folate > Flashcards

Vitamin B12 and Folate Flashcards

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1
Q

What is vitamin B12?

A

Bacterial product that is ingested and stored in animals

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2
Q

What are good sources of B12?

A

Meat, salmon, cod, milk, cheese and eggs

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3
Q

Who suffers from vitamin B12 deficiency?

A

Vegans and due to malabsorption

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4
Q

What is the daily need for vitamin B12?

A

1.5-3 micrograms

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5
Q

What are the hepatic stores of vitamin B12 like?

A

2-5mg (lasts for several years)

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6
Q

What is vitamin B12 required for?

A

DNA synthesis

Integrity of nervous system

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7
Q

What is folic acid?

A

Thermoliable water soluble vitamin found in leafy green vegetablrs

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8
Q

What causes folic acid deficiency?

A

Dietary
Impaired absorption
Increased requirement

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9
Q

What is the requirement for folate?

A

400-600mcg

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10
Q

In terms of how quickly you run out, how does folate compare to vitamin B12?

A

Run out much quicker of folate

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11
Q

What is folic acid required for?

A

DNA synthesis

Homocysteine metabolism

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12
Q

What happens to B12 once it initially enters the stomach?

A

It binds to transcobalamin 1 (aka R protein)

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13
Q

What do the gastric parietal cells at the bottom of the stomach produce?

A

Intrinsic factor

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14
Q

What happens to B12 when it leaves the stomach and enters the duodenum?

A

Pancreatic enzymes displace it from transcobalamin and then free B12 binds to intrinsic factor

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15
Q

What happens to the B12-intrinsic factor complex after formation?

A

It travels all the way to the terminal ileum where there is a specific receptor that binds to the complex and allows it enter the cell

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16
Q

What happens after the B12-intrinsic factor complex enters the cell in the terminal ileum?

A

It enters the portal circulation

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17
Q

What happens after the B12-intrinsic factor complex enters the portal circulation?

A

The B12 binds to transcobalamin 2 making it active B12

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18
Q

What happens to folate when it enters the stomach?

A

It is hydrolysed to monoglutamates at acid pH then absorbed as pteroglutamates which can be methylated in the luminal cells to tetrahydrofolates

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19
Q

What is the link between folate and B12 in DNA synthesis?

A

Both needed for the synthesis of deoxythymidine (dTMP) which is a crucial building block in DNA synthesis

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20
Q

What is deoxythymidine made from?

A

Deoxyuridine

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21
Q

What happens to dietary folate during DNA synthesis?

A

It is converted to methyl tetrahydrofolate (Methyl-THF) as it’s absorbed into the luminal cells

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22
Q

What does B12 act as during DNA synthesis?

A

It acts as a cofactor for methionine synthetase for conversion of homocysteine to methionine

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23
Q

What does the formation of methionine release?

A

Methyl groups which go on to methylate building blocks of DNA

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24
Q

What are the clinical features of B12 and folate deficiency?

A 
Anaemia- macrocytic, megaloblastic
Weak, tired and short of breath
Jaundice
Ineffective erythropoiesis
Glossitis- red, raw tongue
Angular cheilosis- soreness in corner of mouth
Weight loss, change of bowel habit
Sterility
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25
What causes macrocytic anaemia?
``` Vitamin B12/folate deficiency Liver disease or alcohol Hypothyroidism Haematological disorders- myelodysplasia, reticulocytosis and aplastic anaemia Drugs that interfere with DNA synthesis Prolonged nitrous oxide anaesthesia ```
26
What is the difference between macrocytic anaemia caused by B12/folate deficiency and liver disease?
B12/folate- oval macrocytes | Liver- round macrocytes
27
What is myelodysplasia?
Group of disorders in which production of any one or all types of blood cells by the bone marrow is disrupted
28
What is aplastic anaemia characterised by?
Failure of blood cell production resulting in pancytopenia and reduced bone marrow cellularity
29
Name some drugs that interfere with DNA synthesis?
Azathioprine Zidovudine Hydroxycarbamide Methotrexate
30
What does the term megaloblastic describe?
Morphological change in red cell precursors within the bone marrow
31
What effects how blue or pink a reticulocyte is?
More blue= More DNA | More pink= More haemoglobin
32
What is the nucleus of a proerythroblast like?
It has a lot of space in it- this is chromatin which looks very open in the proerythroblast
33
As a proerythroblast becomes more mature, what happens?
It becomes tighter and just before red cell is about to spit out its nucleus, it appears very dark
34
To determine whether the cells in the lineage are normal, what do you have to look at?
Chromatin and how open it is | Colour of cytoplasm and how blue it is
35
What should a normal big precursor cell be like?
Open chromatin and blue cytoplasm
36
Why are big precursors not like this in megaloblastic anaemia?
There is asynchronous maturation of the nucleus and cytoplasm in the erythroid= Nucleus doesn't mature but cytoplasm does so you get immature open nuclear chromatin with normal mature haemoglobinisation of the cytoplasm- unable to synthesise DNA properly
37
Which people are at increased risk of decreased folate intake?
Elderly, sick, eating disorders and alcoholics
38
What does a decrease in folate lead to?
Inability to methylate nucleotides and affects DNA synthesis | Homocysteine will accumulate because it can't be converted to methionine without folate
39
What causes increased demand of folate?
Physiological: Pregnancy, adolescence and premature babies Pathological: Malignancy, erythroderma and haemolytic anaemia
40
In what condition does folate malabsorption and iron deficiency occur?
Coeliac disease
41
What happens in coeliac disease?
Sensitivity to gliadin in wheat leads to subtotal villous atrophy with crypt hyperplasia in the duodenum
42
What can be used to diagnose coeliac disease?
Anti-gliadin (transglutaminase) antibodies or duodenal biopsy
43
What interferes with normal absorption?
Surgery Inflammatory bowel disease Drugs
44
Where does Crohn's mainly affect and what does this lead to normally?
Terminal ileum so B12/folate deficiency
45
What tests would you use to establish folate deficiency?
``` FBC Blood film Blood folate level Serum folate- screening test Red cell folate- confirmatory test ```
46
What are the consequences of folate deficiency?
Megaloblastic anaemia Neural tube defects Increased risk of VT
47
What neural tube defects occur?
Spine- Spina bifida | Brain- Anencephaly
48
What are very high levels of homocysteine (caused by lack of folate) associated with?
Atherosclerosis | Premature vascular disease
49
What are mildly elevated homocysteine levels associated with?
Cardiovascular disease | Probably arterial and venous thrombosis
50
What can affect normal B12 deficiency?
Autoimmune- Pernicious anaemia Surgery- Partial/total gastrectomy, gastric bypass, resection of ileum Inflammatory disease- Crohn's disease, chronic pancreatitis, bacterial overgrowth and parasitic infection
51
What is pernicious anaemia?
Lack of intrinsic factor
52
What are the consequences of B12 deficiency?
Macrocytic and megaloblastic anaemia (reversible) Neurological problems due to demyelination Subacute combined degeneration of spinal cord Cognitive impairment due to loss of white matter in central nervous system Optic atrophy
53
What is the relationship between Hb level and neurology in B12 deficiency?
Inverse- higher Hb more likely to have neurological findings
54
In subacute combined degeneration of spinal cord, where is there demyelination?
Posterior and lateral columns- they are pale
55
What does subacute combined degeneration of the cord result in?
Loss of joint position sense and vibration sense
56
How would a patient with subacute combined degeneration of the cord present?
Wide based gait and sometimes pain
57
What are the symptoms of B12 deficiency?
``` Weak, tired, lethargic Symmetrical paraesthesiae/numbness Muscle weakness Difficulty walking and loss of balance Visual impairment Memory impairment Psychiatric disturbance ```
58
What are the signs of B12 deficiency?
Anaemia and jaundice- lemon-yellow tinge Neurology- loss of vibration and joint position sense but also cutaneous sensation lost and absent reflexes and up-going plantar responses in legs
59
What level of serum B12 is normal?
>180ng/l
60
How accurate is serum B12 levels as a test for B12 deficiency?
Not very- poor positive predictive value You can have healthy people with a low level Falsely high levels in B12 deficient patients due to high levels of antibodies interfering with commercial assays
61
Why is there a problem with measuring serum B12 levels?
You measure total B12 levels- bound to transcobalamin 1, 2 and 3
62
What tests are used to establish B12 deficiency?
Serum B12 Plasma homocysteine- easy and reliable (high with folate as well) Serum methylmalonic acid levels- expensive Holotranscobalamin levels (transcobalamin II)- automated immunoassay that measures active B12 rather than total
63
What was the Schilling test used to test?
B12 absorption
64
What is the schilling test?
Give B12 injection to replenish B12 stores then two B12 capsules orally (different radioisotopes): Capsule 1= B12 alone Capsule 2= B12 and intrinsic factor complex Then you collect urine for 24 hours after administration and measure presence and relative proportion of each isotope
65
What would you expect to find in the Schilling test in urine of a normal person, someone with pernicious anaemia and inflammatory disease of terminal ileum?
Normal- both isotopes excreted Pernicious anaemia- Only B12 isotope complexed with IF Inflammatory disease of terminal ileum- Neither isotope excreted
66
What is pernicious anaemia?
Autoimmune atrophic gastritis with loss of intrinsic factor
67
What does pernicious anaemia result in?
Macrocytic/megaloblastic anaemia +/- neurological damage
68
How do you diagnose pernicious anaemia?
You look at the auto-antibodies: Intrinsic factor antibodies- (occasionally found in other conditions) 40-60% of people with PA have them Parietal cell antibodies- 80-90% of people with PA Increased in relatives of patients with PA

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