Flashcards in 13. Anaemia 2 Deck (27):
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
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
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?
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)
Glossitis (inflammation of the tongue)
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
Excess utilisation e.g. pregnancy, lactation, psoriasis
What are the clinical features of folic acid deficiency?
Essentially the same as in pernicious anaemia but no neurological signs
How is folate deficiency treated?
Oral folic acid
What is meant by haemolytic anaemia?
Anaemia where there is a shortened RBC survival
Normal lifespan of erythrocyte is 120 days
If the lifespan is less than this then haemolysis is present
How will haemolysis present in a blood test and explain why
Increased levels of bilirubin - this is produced when the haem is removed from the erythrocyte - reduced cell life so haem is removed more frequently and hence greater levels of bilirubin is produced - leads to mild jaundice
Increased levels of LDH - due to the breaking open of the erythrocytes
How will haemolysis present on a blood film and why?
Presence of spherocytes - these may form due to a failure of proteins that hold the erythrocytes into their bioconcave shape
What other clinical feature may occur dude to haemolytic anaemia?
Increased levels of bilirubin can result in the production of gallstones - development of gallstones can be a sign of haemolytic anaemia
These can obstruct the bile duct
What can cause haemolysis?
Abnormalities of the RBC - of the membrane, Hb. or intracellular enzymes (required for glycolysis as there are no mitochondria)
Rhesus mismatch transfusion
What is hereditary spherocytosis?
Type of haemolytic anaemia
Genetic inability to produce relevant actin required to maintain the bioconcave disc shape of RBCs
This leads to premature breaking open of erythrocytes and haemolysis
What are the clinical presentations of haemolytic anaemia?
Splenomegaly (abnormal enlargement of the spleen)
What is a common RBC enzyme defect leading to haemolytic anaemia?
If you don't have this, then Hb. will be oxidised more rapidly and erythrocytes will be worn out earlier
What is autoimmune haemolytic anaemia?
This is where IgG antibodies attach to the antigens on erythrocytes and mark them for destruction
These erythrocytes are then removed by the spleen