15 - Anaemia 2 Flashcards
What are B12 and folate needed for
DNA synthesis
convert homocysteine into methionine
Cells cannot divide - overlarge RBC
Another name for vitamin B12
cobalamin (water soluble)
What is the function of B12
Vital for myelin synthesis in the NS
Assists in DNA synthesis in every cell in the body
How is B12 measured
increase in serum methylmalonic acid
How does methionine synthase use B12
uses B12 to transfer a methyl group from 5-methyltetrahydrofolate to homocysteine
What does methionine synthase generate
tetrahydrofolate (THF) and methionine
What can prolonged B12 deficiency cause?
irreversible nervous system damage
What can slight deficiency of B12 cause?
fatigue, lethargy, depression, poor memory, breathlessness, pale skin
Where is B12 found?
Meat, eggs, animal protein – not destroyed by cooking
How much cobalamin do we need a day and how much do we store?
1ug/d
1000g - 3 year store
What is B12 bound to to be absorbed and where is it absorbed
Intrinsic Factor
Ileum
Is folate (Vitamin B9) water soluble
Yes -
Where is vitamin B9 found
Liver, greens, yeast but destroyed by cooking
How much folate do we require and how much do we store
150ug/d
Store enough for 4 months
Where is vitamin B9 absorbed?
duodenum and jejunum
What does the blood count of B12 and B9 deficiency look like
Reduced Hb - overlarge rbc cannot bend
Increased MVC
Decreased WBC and platelets - high turn over with DNA synthesis
What does a blood film look like with B12 or B9 deficiency?
Oval macrocytes and hyper segmented neutrophils (more than 4 lobes)
What is biochemistry like with B12 or B9 deficiency?
- Increase in lactate dehydrogenase (LDH)
- Increase in bilirubin – more haemolysis
What are the main causes of B12 deficiency
Poor diet
Malabsorption
Gastric – Pernicious Anaemia, Surgical gastrectomy
Intestinal – Illeal disease e.g Chrons
What is pernicious anaemia
B12 deficiency caused by the absence of intrinsic factor
Autoimmune disorder
What blood group is pernicious anaemia associated with?
Blood group A
What are the autoantibodies against in pernicious anaemia?
Gastric mucosa and IF
Apart from anaemia, what does pernicious anaemia lead to?
gastric atrophy, decrease in acid and decrease in IF secretion
Clinical features of pernicious anaemia
Insidious, anaemia, glossitis, jaundice, neurological symptoms (neuropathy, dementia, damage to sensory and motor tracts)
What is the treatment of pernicious anaemia?
Intramuscular B12 every 3 months for life
Why is intramuscular B12 given
Bc the B12 cannot be absorbed in the gut due to no IF workage
What are causes of folate deficiency
- Nutrition – old age, poverty, alcoholism
- Malabsorption – Coeliac, Chrons
- Excess utilisation – Pregnancy, lactation, haemolytic anaemias, psoriasis
- Others – anticonvulsants
Difference between folate deficiency and B12 deficiency
No neurological signs in folate deficiency
What is the treatment for folate deficiency?
Oral folic acid
What are the causes of haemolytic anaemia
Damaged membrane
Haemoglobin damage (SCD and thalassaemia)
Enzyme damage
What does G6PD do
G6PD prevents/reverses oxidation of Hb, membrane etc; prolongs lifetime of RBC.
Where is G6PD deficiency most common
Tropical africa
middle east
subtropical asia
Mediterranean
What is G6PD heritability
X-linked
How can a G6PD carrier show symptoms
Exposed to triggers
e.g foods such as fava beans
bacterial or viral infection
drugs e.g dapsone, cotrimoxazole, primaquine
Example of extra vascular haemolysis
SDC, Thalassaemia, o Antibody-induced haemolytic anaemia
o Rhesus mismatched transfusion
o Hereditary spherocytosis
What is hereditary spherocytosis
Membrane not forming double dimple
sphere shape and high fragility
- chronic haemolytic anaemia
What is the inheritance of hereditary spherocytosis?
Autosomal dominant
What are some causes of intravascular haemolysis?
ABO mismatched transfusion
Snake bites
Infections (Babesia, Clostridium)
What is the presentation of haemolytic anaemia?
Pallor and anaemia
Jaundice
Gallstones – urobilogen
Splenomegaly
What would lab investigations be to indicate increased red cell breakdown
↑ serum unconjugated bilirubin
↑ urinary urobilinogen
↑ lactate dehydrogenase
Heptaglobin goes down
What would lab investigations be to indicate increased red cell production
↑ reticulocytes in blood
↑ RBCs in marrow
What are the antibodies that are present in the blood and react with RBC membrane proteins in autoimmune haemolytic anaemia?
IgG
How can you prove there is antibody on a rbc?
Coombs test
- Take blood sample and wash and the cells will agglutinate with anti-human antibodies
What are causes of autoimmune haemolyic anaemia?
50% idiopathic
Secondary - drugs, penicillin, CT disease (Systemic lupus erythematosus)
Blood transfusion
