Vitamin B12 and Folate Deficiency Flashcards
What is vitamin B12 required for?
- DNA synthesis
- Integrity of the immune system
What is folate required for?
DNA synthesis
- To get from dUMP -> dTMP (in DNA synthesis), you need a methyl group which is provided indirectly by dietary folate
Homocystine metabolism
What are the clinical features of B12 and folate deficiency?
- All rapidly dividing cells are affected (such as RBCs) – i.e. bone marrow, epithelial surfaces of gut, gonads, embryos
clinical features of B12 and folate deficiency will be broad:
- Anaemia – weak, tired, short of breath
- Jaundice – due to breakdown of RBCs
- Glossitis (inflammation of the tongue) and angular cheilosis (red swollen patches at corner of mouth)
- Weight loss and change of bowel habit – as affects rapidly dividing cells of the gut
- Sterility – affects rapidly dividing sperm cells
What can cause macrocytic anaemia?
- B12/folate deficiency
- liver disease
- hypothyroidism
- drugs (e.g. azathioprine)
- haematological disorders (e.g. myelodysplasia, aplastic anaemia and reticulocytosis)
What is megaloblastic anaemia?
a morphological change in RBC precursors within the bone marrow
Normal RBC maturation:
erythroblast -> normoblast (early, intermediate and late) -> reticulocyte -> RBC
- reticulocyte loses nucleus
- The colour changes quite a lot:
Basophilic (blue) -> polychromatic -> RBC pink
Megaloblastic anaemia – asynchronous maturation of the nucleus and cytoplasm in the erythroid series
- Nucleus seen in a pink RBC (shouldn’t have nucleus)
- Maturing red cells seen in the bone marrow.
*** Peripheral blood will appear: > Anisocytosis – variation in size of RBCs > Large RBCs > Hypersegmented neutrophils > Giant metamyelocytes.
What tests would you do if someone has a macrocytosis?
Blood test – folate, iron and B12 tests
Thyroid function test
Reticulocyte count and blood film
What are possible underlying clinical disorders of someone who has a hypersegmented neutrophil?
- Megaloblastic anaemia – B12 deficiency
- Megaloblastic anaemia – folate deficiency
What are causes of folate deficency?
Decreased intake
- people may also be folate deficient if they are alcoholics or in the elderly (as they may not make enough effort to eat folate)
Increased demand
- PHYSIOLOGICAL (pregnancy, adolescence and premature babies)
- PATHOLOGICAL (malignancy, erythroderma, haemolytic anaemias)
What is the laboratory diagnosis of folate deficiency?
Laboratory diagnosis comes about with: FBC, blood film and the folate blood levels
Assessment including: history and examination (skin disease etc.)
What are consequences of folate deficiency?
- Megaloblastic, macrocytic anaemia
- Neural tube defects in developing foetuses – spina bifida, anencephaly
- Increased risk of thrombosis in association with variant enzymes involved in homocysteine metabolism - if homocysteine levels build up, there is increased risk of atherosclerosis and premature vascular disease
- Mildly elevated levels of homocysteine are still associated with CVD, arterial/venous thrombosis
What are the consequences of B12 deficiency?
- Neurological problems – bilateral peripheral neuropathy, subacute combined degeneration of cord (can cause paralysis), optic atrophy and dementia - Subacute combined degeneration of the cord -> paralysis
- Paraesthesia (pins and needles)
- Muscle weakness
- Difficult walking
- Visual impairment
- Psychiatric disturbance
What would you find on examination of B12 deficiency?
Absent reflexes and upgoing plantar responses – combination of UPPER and LOWER motor neuron signs
What causes B12 deficiency?
- Poor absorption – there is a complex method of absorption that can go wrong in many ways
- Method 1 – 1% - slow and inefficient (1% of all B12) absorption through the duodenum
- Method 2 – 99% - B12 combines with intrinsic factor and this binds to ileum receptors in the ileum
* So 3 things are essential – intact stomach, IF and a functioning small intestine - Reduced dietary intake – difficult for this as stores are large and are found in all animal produce
- Infections/infestations – abnormal bacterial flora, tropical sprue and fish tapeworm
What can cause impaired B12 absorption?
Reduction in intrinsic factor:
- Post gastrectomy
- Gastric atrophy
- Pernicious anaemia – autoimmune condition associated with a severe lack of intrinsic factor
> Males have a decreased life expectancy as they can get cancer of the stomach
> There is either a presence of: IF-antibodies (occasionally found in other conditions) or parietal cell antibodies (90% in adults with PA but also in 16% of NORMAL females over 60)
Diseases of the small bowel (and terminal ileum):
- Crohn’s
- Coeliac disease
- Surgical resection
Infections/infestations:
H. pylori, giardia, fish tapeworm, bacterial overgrowth
Drugs:
metformin, PPIs (e.g. omeprazole), oral contraceptive pill
How do you diagnose the cause of B12 deficiency?
in patients with low B12 therefore, we can measure;
- Antibodies to parietal cells and IF
- Antibodies for coeliac disease
- Breath test for bacterial overgrowth
- Stool test for H. pylori and a test for giardia
- Schilling test
