Macrocytic anaemia Flashcards
What is the function of iron?
Creates haemoglobin
What is MCV?
Size of the red blood cells
What are the three categories of anaemia?
Microcytic (low MCV)
Normocytic (normal MCV)
Macrocytic (large MCV)
There are 3 As and 2 Hs for normocytic anaemia
A – Acute blood loss
A – Anaemia of chronic disease
A – Aplastic anaemia
H – Haemolytic anaemia
H – Hypothyroidism
Macrocytic anaemia can be _________ or _________
Macrocytic anaemia can be megaloblastic or normoblastic
Megaloblastic anaemia results from..
Impaired DNA synthesis, preventing the cells from dividing normally. Rather than dividing, they grow into large, abnormal cells
Megaloblastic anaemia is caused by..
Vitamin B12 deficiency
Folate deficiency
Secondary to methotrexate,anti-convulsants and sulphonylureas
Normoblastic macrocytic anaemia is caused by..
Alcohol
Reticulocytosis
Hypothyroidism
Liver disease
Cytotoxics, azathioprine
Myelodysplasia
Pregnancy
What causes Reticulocytosis?
Rapid turnover of red blood cells - haemolytic anaemia or blood loss
Symptoms specific to iron deficiency anaemia include..
Pica
Hair loss
What does the following clinical signs show?
Specific causes of anaemia
Also: atrophic glossitis, brittle hair and nails, jaundice, bone deformities, oedema, hypertension and excoriations
Ix for anaemia
FBC, reticulocyte count, blood film, renal profile
LFT, ferritin, B12 and folate
A ____________ and ____________ are indicated for unexplained iron deficiency anaemia to exclude gastrointestinal cancer as a source of bleeding
A colonoscopy and oesophagogastroduodenoscopy (OGD) are indicated for unexplained iron deficiency anaemia to exclude gastrointestinal cancer as a source of bleeding
A _____________ is indicated for unexplained anaemia or possible malignancy (e.g., leukaemia or myeloma)
Bone marrow biopsy
Modern analysers use the _____________ properties of red cells to measure the MCV
Light scatter
What are the causes of
macrocytosis?
Megaloblastic
Non-megaloblastic
Define Megaloblastic
A larger than normal, nucleated red cell precursor (‘mother cell’), with an immature nucleus
What happens in megaloblastic anaemia?
Lack of red cells due to predominant defects in DNA synthesis and nuclear maturation in developing precursor cells in the marrow
Cell division is reduced and apoptosis increases
In surviving cells, Hb accumulation occur normally so precursor cell is bigger with an immature nucleus, i.e. a ‘megaloblast’
Once Hb level is optimal, the nucleus is removed, leaving behind a bigger-than-normal red cell, i.e. a ‘macrocyte’
Causes of megaloblastic anaemia
B12 deficiency
Folate deficiency
Drugs and rare inherited abnormalities
Why are B12 and folate important?
Regulates:
DNA synthesis and nuclear maturation - (e.g. blood cell effect)
DNA modification, gene activity – (e.g. nervous system)
B12 deficiency may also affect lipid synthesis, impacting on..
Myelin (protective sheath around nerve fibres)
What is pernicious anaemia?
Autoimmune disorder affecting the gastric mucosa that results in vitamin B12 deficiency
Causes of pernicious anaemia
B12 deficiency
Atrophic gastritis (e.g. secondary to H. pylori infection), gastrectomy, malnutrition (e.g. alcoholism)
Explain the pathophysiology of pernicious anaemia
Antibodies to intrinsic factor +/- gastric parietal cells, blocking the binding site
Reduced acid production and atrophic gastritis
Reduced intrinsic factor production → reduced vitamin B12 absorption
Vitamin B12 is important in..
Production of blood cells and the myelination of nerves → megaloblastic anaemia and neuropathy
Risk factors of pernicious anaemia
Middle to old aged females
Autoimmune disorders: thyroid disease, type 1 diabetes mellitus, Addison’s, rheumatoid and vitiligo
A blood group
Mild jaundice
Glossitis (sore tongue)
Pins and needles’, numbness. Typically symmetrical and affects the legs more than the arms
Memory loss, poor concentration, confusion, depression, irritabiltiy
Pernicious anaemia
Ix for pernicious anaemia
FBC
Vit B12 and folate
Antibodies
FBC checked in pernicious anaemia
Macrocytic anaemia: macrocytosis may be absent in around of 30% of patients
Hypersegmented polymorphs
Low WCC and platelets
Vit B12 and folate in pernicious anaemia
Level of >200 nh/L is generally considered normal
Antibodies checked in pernicious anaemia
Anti intrinsic factor: sensitivity is only 50% but specific for pernicious anaemia (95-100%)
Anti gastric parietal cell: 90% but low specificity so often not useful clinically
Mx for pernicious anaemia
Vitamin B12 replacement IM
If no neuro sx: 3 injections per week for 2 weeks followed by 3 monthly
If neuro sx: alternate days till improvement, then every 2 months
Folic acid supplementation
Complications of pernicious anaemia
Increased risk of gastric cancer
Where is folate absorbed?
Jejunum (diffusion and actively)
Causes of folate deficiency
Inadequate intake - alcoholic excess
Malabsorption - coeliac disease, Crohn’s disease
Haemolysis, exfoliating dermatitis, pregnancy, malignancy
Anticonvulsants
Where is B12 absorbed?
Ileum
B12 sources
Animal
Folate sources
Liver, leafy veg, fortified cereals
Folate is absorbed in..
Jejunum
Iron is absorbed in…
Duodenum/proximal jejunum
B12 is absorbed in..
Ileum
Megaloblasts vs Macrocytes
Megaloblasts are large nucleated RBC precursors with noncondensed chromatin due to impaired DNA synthesis
Macrocytes are enlarged RBCs
Pregnancy can be associated with low B12 levels, even if this does NOT reflect B12 deficiency. Why is that?
Functional B12 levels (25% of the B12 complex) remain normal, but levels of non-functional B12, called haptocorrin (75% of the B12 complex) fall. We do not measure these components separately and hence the total B12 (reflecting the greater contribution of haptocorrin to the measurement) is low
Causes of B12 deficiency include..
Gasterctomy/bariatric surgery
Terminal ileal disease (crohns, rarely TB)
Ileal resection
A vegan diet as B12
Bacterial overgrowth, acid suppression with a PP, coeliac
The iron within enterocytes can either be stored as _______, or transferred into the bloodstream via the protein _______. Once in the blood, iron is bound to the transport protein _______
The iron within enterocytes can either be stored as ferritin, or transferred into the bloodstream via the protein ferroportin. Once in the blood, iron is bound to the transport protein transferrin
Some iron is taken up by _________ in the reticuloendothelial system as a storage pool
Macrophages
