Haem 10 - Vitamin B12 and folic acid deficiency Flashcards
What is vitamin B 12 and folate used for?
Required for DNA synthesis: They both are needed for the production of deoxythymidine which is required for DNA synthesis. Deoxyuridine –> deoxythymidine
Absence leads to severe anaemia which can be fatal
What is B12 required for?
1) DNA synthesis
2) Integrity of the nervous system
What is folic acid required for?
1) DNA synthesis
2) Homocysteine metabolism to methionine.
- Very high levels of homocysteine is associated with atherosclerosis and premature vascular disease.
- Mildly elevated levels of homocysteine are associated with:
cardiovascular disease DEFINITELY
arterial thrombosis PROBABLY
venous thrombosis POSSIBLY
What are the clinical features of vitamin B12 and folate deficiency?
ALL RAPIDLY DIVIDING CELLS ARE AFFECTED
- Bone marrow
- Epithelial surfaces of mouth and gut
- Gonads
- embryos
Anaemia: weak, tired, short of breath Jaundice Glossitis and angular cheilosis Weight loss, change of bowel habit Sterility
Describe the anaemia associated with B12 or folate deficiency?
Macrocytic anaemia
Megaloblastic anaemia
Raised MCV with deficiency of B12 and folate deficiency
Define macrocytic anaemia
Average red cell size is above the normal range
Caused by:
- Vitamin B12/folate deficiency
- Liver disease or alcohol
- Hypothyroid
- Drugs e.g. azathioprine (immune suppressive drug)
- Haematological disorders: Myelodysplasia, aplastic anemia, Reticulocytosis e.g. chronic haemolytic anemia
Define megaloblastic?
Describes a morphological change in the red cell precursors within the bone marrow - this must be a folate and vitamin B12 deficiency since they affect DNA synthesis.
What is the normal red cell maturation?
1) Erythroblast
2) Normoblast
3) Reticulocyte
4) Circulating RBC Erythrocyte
Define megaloblastic anaemia?
Defined by asynchronous maturation of the nucleus and cytoplasm in the erythroid series.
Maturing red cells seen in the bone marrow.
It is only caused by B12 and folate deficiencies.
Describe the peripheral blood in a patient with megaloblastic anaemia?
Anisocytosis
Large red cells
Hypersegmented neutrophils - think B12/folate deficiency
Giant metamyelocytes
What tests would you do if someone had a macrocytosis?
B12
Folate
Liver function
Thyroid function
Where can you get dietary folate?
Fresh leafy vegetables
Destroyed by overcooking/canning/processing
You get decreased folate with - IGNORANCE POVERTY APATHY Elderly - alcoholics
What situations would you get increased demands for folate?
There aren't massive stores of folate PHYSIOLOGICAL - Pregnancy - Adolescence - Premature babies
PATHOLOGICAL
- Malignancy: turn over of extra cells can lead to extra folate required e.g haemolytic anaemia
- Erythoderma: high turn over of skin cells
- Haemolytic anaemias
Define pernicious anaemia?
Pernicious anemia is a form of megaloblastic anemia that happens when a person’s body is unable to absorb vitamin B12 from their gastrointestinal tract.
It is an autoimmune condition associated with severe lack of intrinsic factor. Males have a decreased life expectancy = stomach cancer
What is the laboratory diagnosis of folate deficiency?
FBC and film
Folate levels in the blood
How do you assess the cause of decreased folate?
EASY – history (diet/alcohol/illness)
EXAMINATION – skin disease/ alcoholic liver diseaseq
What are the consequences of folate acid deficiency?
1) Megaloblastic, macrocytic anemia
2) Neural tube defects in developing fetus: Spina bifida, anencephaly. ALL PREGNANT WOMEN TAKE FOLIC ACID 0.4MG PRIOR TO CONCEPTION AND FOR FIRST 12 WEEKS
3) Increased risk of thrombosis in association with variant enzymes involved in homocysteine metabolism
What are the consequences of B12 deficiency?
Neurological problems: affect central and peripheral nerves.
- Bilateral peripheral neuropathy
- Subacute combined degeneration of the cord
- Posterior and pyramidal tracts of the spinal cord
- Optic atrophy
- dementia
What may a history of B12 deficiency be like?
Paraesthesiae Muscle weakness Difficult walking Visual impairment Psychiatric disturbance
Examination:
Absent reflexes and up going plantar reflex (babinski response)
What are the causes of B12 deficiency?
POOR ABSORPTION
Reduced dietary intake
- Stores are large and last for 3-4 years
- Animal produce
- Vegans are at risk
Infections/infestations
- Abnormal bacterial flora (stagnant loops)
- Tropical sprue
- Fish tapeworm
Where does normal B12 absorption occur?
small intestine – B12 is then stored – when stores are saturated excess B12 is excreted in the urine
2 methods of absorption
Method 1 - Slow and inefficient (1%)
- duodenum
Method 2 = most absorption this way. SMALL BOWEL
- B12 must combine with intrinsic factor
- Intrinsic factor is made in the stomach
(parietal cells)
- B12-IF complex binds to ileal receptors
THREE THINGS ARE ESSENTIAL
Intact Stomach
Intrinsic factor
Functioning small intestine
What can cause an impaired B12 absorption?
1) Reduction in intrinsic factor
a) post gastrectomy
b) gastric atrophy
c) antibodies to intrinsic factor or parietal cells
2) Diseases of small bowel (terminal ileum)
a) Crohns - inflammatory disorder of the bowel which can affect the small bowel.
b) Coeliac disease - autoimmune affecting absorption in small bowel.
c) surgical resection In
Describe a test for pernicious anaemia?
Test for antibodies
Intrinsic factor antibodies
- Occasionally found in other conditions
Parietal cell antibodies
- 90% adults with PA
- 16% normal females over age of 60
- Increased in relative of patients with PA
Describe antibodies in PA?
LISTEN TO LECTURE FOR THIS BIT
