10. Vitamin B12 and folic acid deficiency Flashcards
What are haematinics?
- Vitamins and minerals required for normal erythropoiesis
* Iron, B12 and folate
What is vitamin B12 and folate generally required for?
B12
• DNA synthesis
• Integrity of the nervous system - CNS and PNS
Folate
• DNA synthesis
• Homocysteine metabolism
How does B12 and folate contribute to DNA synthesis?
• Deoxyuridine => deoxythymidine
- addition of methyl group
- this methylation requires the conversion of folate to different forms
- one of these steps also requires B12 (cofactor)
• Deoxythymidine = thymidine
What are the clinical features of B12/folate deficiency?
- All rapidly dividing cells affected
- Worse effects in bone marrow, epithelial surfaces of the GIT, gonads and embryogenesis
- Anaemia - weakness, shortness of breath
- Glossitis, angular cheilosis
- Weight loss, change of bowel habit
- Sterility may occur
What types of anaemia can B12/folate deficiency result in?
- Macrocytic - high MCV, large and macrocytic cells
* Megaloblastic - morphological change in red cell precursors within bone marrow
What are the causes of macrocytic anaemia?
- Vitamin B12/folate deficiency
- Liver disease or alcohol
- Hypothyroidism
- Drugs e.g. azathioprine (immunosuppressant)
- Haematological disorders e.g. reticulocytosis
How does the nucleus and cytoplasm of a red cell change during maturation?
- Nucleus gets smaller - until pyknotic (irreversible condensation of chromatin)
- Cytoplasm gets more pink due to haemoglobin
What happens during maturation in megaloblastic anaemia?
- DNA not produced normally
- Asynchronous maturation of the nucleus and cytoplasm
- Cells with blue cytoplasm and no nucleus, or pink cells with a nucleus
What can be observed in the peripheral blood in megaloblastic anaemia?
- Anisocytosis (red cells of unequal size)
- Large red cells
- Hypersegmented neutrophils
- Giant metamyelocytes
Where can folate be found in the diet and where is folate deficiency seen?
- Found in fresh or frozen leafy vegetables
- Can be destroyed by overcooking/canning/processing
- Deficiency can be caused by decreased intake: ignorance, poverty, apathy
- Deficiency often seen in the elderly and alcoholics
When does an increased demand in folate tend to occur (physiological and pathological)?
- Physiological - pregnancy, adolescence, premature babies
* Pathological - malignancy, erythroderma, haemolytic anaemias
How can you diagnose folate deficiency in the lab?
- Full blood count and blood film
* Serum folate levels in blood
How can you assess the cause of folate deficiency?
- Take a history: diet, alcohol, illness
* Examination: skin disease, alcoholic liver disease
What are the consequences of folate deficiency?
- Megaloblastic, macrocytic anaemia
- Neural tube defects in developing foetus
- Increased risk of thrombosis (in association with variant enzymes involved in homocysteine metabolism)
What neural tube defects can folate deficiency lead to in pregnancy and how can this be avoided?
- Spina bifida and anencephaly
* Take 0.4mg folic acid prior to conception and for the first 12 weeks of pregnancy
What is the link with homocysteine, folate/B12 and thrombosis?
- Step in folate pathway that involves B12, in which homocysteine => methionine
- Both essential amino acids
- Homocysteine is toxic
- Very high homocysteine levels are associated with atherosclerosis and premature vascular disease
What are mildly elevated levels of homocysteine associated with?
- Cardiovascular disease (definite)
- Arterial thrombosis
- Venous thrombosis
What are the neurological consequences of B12 deficiency?
- Bilateral peripheral neuropathy
- Subacute combine degeneration (SCD) of the spinal cord (posterior and pyramidal tracts)
- Optic atrophy
- Dementia
What type of history can you expect from a patient with B12 deficiency?
- Paraesthesiae
- Muscle weakness
- Difficulty walking
- Visual impairment
- Psychiatric disturbance
What motor neurone signs can you see in someone with B12 deficiency?
- Upper and lower motor neurone signs
- Reflexes may be absent (peripheral neuropathy)
- Upgoing plantar response (Babinski’s sign) - upper motor neurone lesion sign
What are the causes of B12 deficiency?
• Poor absorption (most common) • Reduced dietary intake - stores last 3-4 years - B12 found in all animal produce - vegans at risk • Infections (can consume B12) - abnormal bacterial flora - H. Pylori - fish tapework • Drugs
What are the 2 methods of B12 absorption?
1) In duodenum, slow and inefficient (1%), direct absorption across intestinal wall
2) B12 combines with intrinsic factor (made by parietal cells of stomach). B12-IF binds to ileal receptors (most absorption)
Excess B12 excreted in urine when stores are saturated
What 3 things does B12 absorption require?
- Intact stomach
- Functioning small intestine
- Intrinsic factor
What is pernicious anaemia?
- Autoimmune condition
- Severe lack of intrinsic factor
- Leads to B12 deficiency
- Peak age is 60 years
- Associated with family history
- Men have slightly decreased life expectancy due to increased risk of stomach cancer
When should you look out for GI malignancy in someone with B12 deficiency?
If they develop iron deficiency
Which antibodies should you look out for in pernicious anaemia?
- Intrinsic factor antibodies
- Parietal cell antibodies (90% of adults with PA, 16% normal female over 60yrs)
Antibodies are not enough to make a diagnosis
Which drugs are associated with low B12?
- Metformin
- Proton pump inhibitors
- Oral contraceptive pill
What tests can you do to identify the cause of B12 deficiency?
- Check for antibodies to IF, parietal cells and coeliac disease
- Breath test for bacterial overgrowth
- Check stool for H. Pylori
- Test for Giardia
What is the Schilling test?
- Treat the deficiency first - replenish B12 stores using injection and capsules
- Ask patient to drink radioactive B12
- Measure excretion in urine
- Normally there should be B12 present
- No B12 - suggests it cannot be absorbed or B12 hasn’t been corrected prior to the test
What are the new tests for B12 deficiency?
- Plasma homocysteine (high in B12 and folate deficiency)
- Serume Methylmalonic acid levels (expensive)
- Holotransconbalamin levels (immunoassay - measures active B12)
What is the treatment for B12 deficiency?
- Injections of B12 (1000μg IM)
- 3 times a week for 2 weeks
- Once every 3 months thereafter
- More often if patient has neurological involvement
