10. Vitamin B12 and folic acid deficiency Flashcards
(31 cards)
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
