Macrocytosis and Macrocytic anaemia Flashcards
Describe the difference between a macrocytosis and a macrocytic anaemia
Macrocytosis - cells are larger than normal but no anaemia
Macrocytic anaemia - MCV larger and RBC and Hb count low
What other cell on a blood film can be used as a reference point for the normal size of a mature RBC?
Nucleus of a small lymphocyte = same size as RBC
=> if RBCs are larger than this, suspect macrocytosis
What are the genuine causes of macrocytosis?
Megaloblastic
- nucleus is immature and stops as much cell division as would normally take place
=> cells end lineage larger than normal
=> macrocytosis with overall fewer macrocytes => anaemia
Non-Megaloblastic
- Alcohol/Liver disease
- Hypothyroidism
- Marrow failure (assoc. with anaemia unlike above)
e. g. Myelodysplasia, Myeloma, Aplastic anaemia
WHat can cause megaloblastic anaemias?
B12 deficiency
Folate deficiency
Others - Drugs, inherited abnormalities
Why are B12 and folate important in blood cell production?
For:
DNA synthesis / nuclear maturation
DNA modification and gene activity – (e.g. nervous system)
Explain the physiology of how B12 is absorbed in the body
- comes from meat/eggs/ meat products
- stomach acid causes B12 to dissociate from meat and bind to haptocorrin protein
- in response to food gastric parietal cells make Intrinsic Factor (IF)
- all 3 travel into duodenum and pancreatic secretions cause increase in pH (more alkaline)
- Haptocorrin dissociates from B12 allowing IF to bind
- this complex binds to receptors in distal small bowel
- B12 absorbed into bloodstream and attaches to transcobalamin
What problems can therefore cause patients to be deficient in B12?
STOMACH
- PPI/H2RA causes decreased stomach acid for dissociation of B12 from meat
- gastrectomy/bypass
- pernicious anaemia
GUT
- bacterial overgrowth
- crohns
- coeliac disease
- resection
PANCREAS
- chronic pancreatitis stops secretions being produced
What is pernicious anaemia?
Autoimmune condition (anti-IF, anti-GPC) - destruction of gastric parietal cells - intrinsic factor deficiency => B12 malabsorption and deficiency
Associated with other autoimmune disorders (eg. hypothyroidism, Addison’s)
Where in the small bowel are iron, B12 and folate each absorbed?
Iron - proximal small bowel
Folate - jejunum
B12 distal small bowel
How long do the body’s folate stores last in comparison to the B12 stores?
Folate 4 months
B12 - 2-4 years
=> if deficient, may take this long for symptoms to show
What can cause folate deficiency?
Inadequate intake in diet
- more likely in alcoholics as poor diet
Malabsorption
- Coeliac /Crohn’s
Excess utilisation
- Haemolysis
- Pregnancy
- Malignancy
Drugs
- anticonvulsants
- methotrexate
What symptoms are common in both B12 and folate deficiency?
- Symptoms/signs of anaemia
- weight loss, diarrhoea, infertility
- Sore tongue, jaundice
- Developmental problems
Neurological problems are more commonly associated with what anaemia causing deficiency?
B12
- causes dorsal column abnormalities, neuropathy, dementia, psychiatric manifestations
What would show up on a macrocytic anaemia blood film?
macrovalocytes and hypersegmented neutrophils (normally 3-5 nuclear segments, but more in this case)
some pts can be - Pancytopenic (all cells low)
How can you attempt to confirm a cause of macrocytic anaemia?
- serum B12 and folate levels
- autoantibody testing (anti-IF and anti-GPC)
