13. Anaemia 2 Flashcards
What is meant by macrocytic anaemia?
Oversized red blood cells
Erythrocytes are greater than 96 fl
What causes macrocytic anaemia and why?
Deficiency of B12 or deficiency of folate
These two compounds are required for DNA synthesis - i.e. synthesis of the methionine base required for DNA
SO without the B12/folate, cannot make DNA and hence, cannot make new cells - a lack of DNA synthesis impacts erythropoiesis
Why does a lack of DNA synthesis result in the production of larger cells?
Lack of DNA synthesis effects a part of the cell cycle in the bone marrow
Normal erythroblasts fail to divide and remain too big - i.e. a failure of mitosis
Hence overlarge erythrocytes are produced
Describe the compound B12
Water soluble
Found in milk, eggs, animal protein
Required by animals but not plants (hence why you have a B12 deficiency if you have a plant only diet)
Not destroyed by cooking
Stored in the body for up to three years - so even if you stop eating any, this will not have a massive impact on you for a while before you see any signs of deficiency
Absorbed in the ileum whilst bound to intrinsic factor
Describe the compound folate
Water soluble
Present in greens, yeast
Destroyed by cooking
Absorbed in the duodenum and jejunum
How do you tell apart a B12 deficiency from a folate deficiency?
You cannot tell them apart from each other
This is because they produce the same signs and symptoms as each other
How is B12 transported and absorbed in the body?
B12 is normally bound to proteins in the diet and is released from these proteins by stomach acids (PPIs may have an impact on this)
The B12 is then bound to a protein called intrinsic factor (B12 cannot be absorbed unless it is attached to IF)
The B12 is then carried in this IF complex to the ileum
IF and B12 complex is then absorbed by enterocytes at the surface of the ileum
Where is IF produced?
Produced by the parietal cells of the gastric mucosa
Why might someone have a B12 deficiency?
Lack of B12 in the diet
Lack of IF produced by parietal cells - cannot absorb B12
Damaged parietal cells
Malabsorption e.g. Chron’s disease
How will macrocytic anaemia show in a blood film?
Very large cells Hypersegmented neutrophils (usually have no more than three lobes in their structure)
How may macrocytic anaemia show in a blood test?
Increased levels of LDH due to damaged tissue
Increased levels of bilirubin due to increased levels of haemolysis
What is pernicious anaemia?
Describe this
Anaemia associated with lack of B12
Autoimmune disorder where the parietal cells are attacked via an autoantibody - antibody against gastric mucosa and IF
Unsure as to why this occurs
Greater in females than in males
Associated with fair hair, blue eyes and blood group A
Leads to gastric atrophy, reduced secretion of fluid and reduced IF secretion
What are the clinical features of pernicious anaemia?
Insidious - gradual onset but fatal if untreated (because it takes up a long time to use up all the reserves of B12)
Anaemia
Glossitis (inflammation of the tongue)
Mild jaundice
Neruological symptoms (because B12 is required by the nervous system - these are irreversible) e.g. peripheral neuropathy, damage to sensory and motor neurones, dementia, optic atrophy
What is the treatment for pernicious anaemia?
Intramuscular B12 every three months for life
What are the different causes of a folic acid deficiency?
Lack of folic acid in diet
Malabsorption
Excess utilisation e.g. pregnancy, lactation, psoriasis
