Macrocytic Anaemia

Question 1

What are the two types of macrocytic anaemia?

Answer 1

genuine or spurious/false

Question 2

What is a megaloblast?

Answer 2

abnormally large RBC precursor with a nucleus

Question 3

How do megaloblasts arise?

Answer 3

lack of RBCs due to defects in DNA synthesis and nuclear maturation - RNA and haemaglobin synthesis are preserved
this means higher levels of EPO = which affects proeryhtroblasts the most
therefore division is reduced and apoptosis increases

Question 4

What causes megaloblastic anaemia?

Answer 4

B12 deficiency
folate deficiency
drugs that interfere with nuclear or DNA synthesis
rare inherited abnormalities

Question 5

When does a megaloblast turn into a macrocyte?

Answer 5

when the Hb level is correct - the nucleus is removed

Question 6

What is the role of B12 and folate?

Answer 6

DNA synthesis and nuclear maturation

DNA modification and gene activity

Question 7

Where does B12 come from?

Answer 7

meat and eggs

Question 8

How is B12 absorbed?

Answer 8

binds to haptocorin in the stomach
gastric parietal cells release intrinsic factor
in the proximal small bowel pancreatic secretions change the pH to alkaline so haptocorin and B12 dissociate
IF and B12 bind
in the distal small bowel IF and B12 bind to cubulin receptors and are absorbed

Question 9

Where are iron and calcium absorbed?

Answer 9

proximal gut

Question 10

Where is B12 absorbed?

Answer 10

distal gut

Question 11

What is pernicious anaemia?

Answer 11

autoimmune condition against the parietal cells of the stomach so they cannot produce IF and B12 then isnt absorbed

Question 12

What is pernicious anaemia associated with?

Answer 12

atrophic gastritis

family/personal history of autoimmune disorders - hypothyroidism, addisons and vitiligo

Question 13

How is folate absorbed?

Answer 13

converted to mono glutamate

absorbed in jejunum

Question 14

How long do B12 stored last for before they will show problems?

Answer 14

2-4 years

Question 15

How long do folate stores last for before they show problems?

Answer 15

4 months

Question 16

What causes a folate deficiency?

Answer 16

inadequate intake
malabsorption - coeliac, crohns
excess utilsation - haemolysis, exfoliating dermatitis, pregnancy, malignancy
drugs - anticonvulsants

Question 17

What are the clinical features of B12/folate deficiency?

Answer 17

symptoms/signs of anaemia 
weight loss, diarrhoea, infertility
sore tongue
jaundice
developmental problems

Question 18

What clinical feature is specific to B12 deficiency?

Answer 18

neurological problems - dorsal colim abnormalities, neuropathy, demetia, pyschiatric manifestations

Question 19

What does blood film show in B12/folate deficiency?

Answer 19

macroovalocytes and hypersegmented neutrophils (3-5 nuclear segments)

Question 20

How is megaloblastic anaemia treated?

Answer 20

treat cause - dietry

folic acid 5mg a day

Question 21

How is Pernicious anaemia treated?

Answer 21

IM B12 injections for life

Question 22

What can cause non megaloblastic genuine anaemia?

Answer 22

alcohol
liver disease
hypothyroidism
marrow failure - myeloma, myelodysplasia, anaplastic anaemia

Question 23

What is false macrocytosis?

Answer 23

volume of the mature red cell is normal but MCV is measured as high

Question 24

What causes false macrocytosis?

Answer 24

reticulocytosis

cold agglutinations

Question 25

What is reticulocytosis?

Answer 25

happens when there is an acute blood loss or red cell breakdown so increase in reticulocyte formation reticulocytes are bigger than mature red cells but are still analysed alongside them for MCV measurement

Question 26

What is cold agglutinations?

Answer 26

proteins that are activated at room temperature cause clumping of RBCs when in the machine - so machine thinks its one big cell

Question 27

What can normochromatic normocytic anaemia be due to?

Answer 27

marrow failure and infiltration renal impairment chronic disease - damaged kidneys dont produce EPO hypometabolic