Macrocytic Anaemias Flashcards
What is another name for vitamin B12?
Cobalamin
State some functions of vitamin B12
Used for the synthesis of myelin in the nervous system
Assists in DNA synthesis (cell division).
Involved in metabolism of all cells in the body especially those with a high turn over like RBC’s
How can a vitamin B12 deficiency be measured clinically? Name the main disadvantage of this method
An increased serum methylmalonic acid (MMA) level.
Not all with the a reduction have a B12 deficiency
What is the function of Methionine synthase?
It is an enzyme which used B12 to transfer a methyl group from 5-methyltetrahydrofolate to homocysteine, thereby generating tetrahydrofolate (THF) and methionine.
What is the function of tetrahydrofolate (THF)? What is the consequence of a deficiency?
methylene tetrahydrofolate is used in the synthesis of thymidine monophosphate which is needed in DNA synthesis
so reduced availability of THF results in ineffective production of cells with rapid turnover, in particular red blood cells
State 2 sources of tetrahydrofolate (THF)
Vitamin B12 and folate
If someone is vitamin B12 deficient they may not always present with the effects of reduced DNA synthesis but they will still present with reduced myelin synthesis, why?
B12 deficiency can be resolved if sufficient dietary folate is present. However the reduced myelin synthesis seen with B12 deficiency is NOT cured by folate.
What type of vitamin is Folate?
Vitamin B9
In which foods will you find vitamin B12 and folate respectively?
Vitamin B 12- Meat, eggs, cheese (animal protein)
Folate- Liver, greens, yeast, nuts, grains
Can vitamin B12 and folate be destroyed by cooking?
B12- No
Folate- Yes- boiling or deep frying. No in stir frys
For how long is vitamin B12 and folate stored?
vitamin B12 - 1000µg 3 years
Folate- 4 months
Where is in the body is vitamin B12 and folate absorbed?
Vitamin B12- Bound to intrinsic factor- ileum
Folate- duodenum & jejunum
How does a deficiency in vitamin B12 and folate lead to anaemia
- DNA synthesis is impaired
- Cells fail to divide
- Red cells are enlarged
- Increased rate of red cell destruction
- Anaemia presents
Describe how Vitamin B 12 is absorbed
- It is bound to a protein in food. It is released from the food via proteases in the saliva and then binds to haptocorrin.
- When released B12 binds to intrinsic factor in the stomach which is produced by the parietal cells of the gastric mucosa
- The intrinsic factor-B12 complex binds to receptors on the ileum epithelial cells. And is absorbed into the portal blood.
- In the blood it binds to transcobalamin which delivers it to the bone marrow and liver
How is Pernicious anaemia often caused?
A B12 deficiency caused by the absence or reduction of intrinsic factor or parietal cells due to Autoantibody against parietal cells and intrinsic factor (IF). Gastric atrophy occurs with decreased acid and intrinsic factor production.
The lamina propria is infiltrated with plasma cells and lymphoid cells
Name 2 substances produced by the parietal cells
Hydrochloric acid and intrinsic factor
What separates the ilium from the cecum (first part of colon)?
ileocecal valve (ICV) at the ileo-cecal junction
How would vitamin B12 and folate present in a blood test?
Low Hb
High MCV
Low WBC and platelets
How would vitamin B12 and folate present in a blood film?
Oval macrocytic RBC’s & Hypersegmented neutrophils
How would vitamin B12 and folate present in a biochemistry test?
High lactate dehydrogenase
High bilirubin
What are the main causes of B12 deficiency?
- Nutritional
- Malabsorption
gastric- Pernicious anaemia
Surgical gastrectomy
intestinal- Crohn’s disease
3.
What is crohn’s disease?
inflammatory bowel disease that may affect any part of the gastrointestinal tract
(cause unknown)
body’s immune system attacks the gastrointestinal tract
What type of condition is Pernicious anaemia? Which categories in the population are most affected?
An Autoimmune disorder
females more affected by males
- Associated with other autoimmune conditions- thyroid and addison’s.
Associated with fair hair, blue eyes, blood group A
What are the clinical features of Pernicious anaemia?
Insidious (gradual onset but fatal if untreated)
Anaemia
Glossitis (inflammation of tongue)
Mild jaundice
Neurological Symptoms- Peripheral neuropathy Damage to Sensory and Motor tracts Dementia Optic atrophy
What is the treatment for Pernicious anaemia?
intramuscular B12 every 3 months for life
What would a blood film show for Pernicious anaemia?
Macrocytic anaemia, Hypersegmented neutrophils
What are some causes for folate deficiency?
Nutritional- old age, poverty, alcoholism
Malabsorption- Coeliac, Crohn’s
Excess utilization- (pregnancy, lactation, heamolytic anaemias, psoriasis)
What type of anaemia is caused by vitamin B 12 and folate deficiency?
macrocytic Megaloblastic anaemia
Out side of itamin B 12 and folate deficiency what else can cause macrocytic Megaloblastic anaemia?
Drugs-
Methotrexate
Zidovudine (AZT)
Metformin
How does metformin caused Megaloblastic anaemia?
Reduces the absorption of metformin?
What can cause Macrocytic non megaloblastic anaemia?
- Alcohol use
- Liver disease is
- Myelodysplasia
When folate is absorbed, what is it converted to? When it enters the blood what does it bind to?
Converted to Methyl tetrahydrofolate
Bound to albumin
How long does it take for a nutritional deficiency in B12 take to manifest?
2 years
for B12 stores to be exhausted
How to diagnose pernicious anemia
Look for- antibodies to parietal cells (90%) and intrinsic factor (50%)
Describe a congenital cause of Pernicious Anaemia?
Congenital lack of IF presents at 2 years of age
List 5 neurological symptoms of B12 deficiency
- Paresthesia- impaired joint position sense
- Falling over while walking
