Macrocytosis

Question 1

what is macrocytic anaemia

Answer 1

anaemia in which the red cells have a larger than normal volume

Question 2

how is ‘size’ expressed

Answer 2

Mean Corpuscular Volume (MCV) in femtolitres 1 femtolitre=10-15

Question 3

how is macrocytosis different to macrocytic anaemia

Answer 3

both have increased MCV but Hb is within normal range in macrocytosis but decreased in macrocytic anaemia

Question 4

what are the 2 main categories of macrocytosis

Answer 4

genuine (true) and spurious (false)

Question 5

what are the 2 types of genuine macrocytoiss

Answer 5

megaloblastic and non-megaloblastic

Question 6

what is an erythroblast/normoblast

Answer 6

a normal red cell precursor with a nucleus

Question 7

precursors of red cells usually originate from where

Answer 7

bone marrow

Question 8

describe the features of the developing erythroid cells in the marrow

Answer 8

accumulate Hb
reduce in size
stop dividing and lose nucleus (regulated by Hb content)

Question 9

what is the first step in erythropoiesis

Answer 9

pronormoblast

Question 10

describe the stages of development of a red blood cell

Answer 10

pronormoblast 
basophilic/early normoblst 
polychromatic/intermediate normoblast 
orthochromatic/late normoblast 
reticulocyte
mature red cell/erythrocyte

Question 11

do reticulocytes have a nucleus

Answer 11

no

Question 12

what is a megaloblast

Answer 12

an abnomrlaly large nucleated rec cell precursor with an immature nucleus

Question 13

how are megaloblastic anaemias characterised

Answer 13

predominant defects in DNA synthesis and nuclear maturation with relative preservation of RNA and haemoglobin synthesis

Question 14

what is the cellular consequence of this

Answer 14

cytoplasm has developed and is big enough to divde but the nucleus is still immature which leads to a bigger than normal red cell precursor

Question 15

what is the larger cell size in megablobalstic anaemia therefore due to

Answer 15

a failure to become smaller (cell doesn’t divide)

Question 16

what are the causes of megaloblastic anaemia

Answer 16

B12 deficiency, folate deficiency

others-drugs and rare inherited abnormalities

Question 17

why does B12 and folate deficiency cause megaloblastic anaemia

Answer 17

they are essential co-factors for nuclear maturation

they enable chemical reactions that provide enough nucleosides for DNA synthesis

Question 18

B12 is synthesised in what cycle

Answer 18

methionine cycel

Question 19

what does the methionine cycle produce which is important

Answer 19

s-adenosyl methionine which is a methyl donor to DNA, RNA, proteins, lipids, folate intermediated

Question 20

what does folate cycle produce

Answer 20

nucleoside synthesis (eg uridine to thymidine conversion)

Question 21

what is B12 combine with in stomach

Answer 21

intrinsic facotr

Question 22

where is B12 absorbed

Answer 22

distal ileum

Question 23

how long can the bodys store of B12 last for

Answer 23

2-4 years

Question 24

what is the daily requirement for B12

Answer 24

1-3 ug a day

Question 25

where is folate absorbed

Answer 25

duodenum and jejunum

Question 26

what are sources of folate

Answer 26

leafy veg, yeast, brown rice, chickpeas, nb destroyed by cooking

Question 27

what is the daily requirement for folate

Answer 27

100ugs/day

Question 28

what are the causes of folate deficiency

Answer 28

inadequate dietary intake is most common
malabsorption-coeliac disease, crohns disease
excess utilisation eg haemolysis, exfoliating dermatitis, pregnancy, malignancy, anticonvulsants

Question 29

what are the clinical features of B12/folate deficiency

Answer 29

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

Question 30

what are dietary folates converted to

Answer 30

monoglutamate

Question 31

what clinical feature is just due to B12 deficiency

Answer 31

neurological problems-posterior/dorsal column abnormalities, neuropathy, dementia, psychiatric problems

Question 32

what is pernicious anaemia

Answer 32

autoimmune condition with resulting destruction of the gastic parietal cells

Question 33

what is pernicious anaemia associated with

Answer 33

atrophic gastits, other autoimmune diseases eg hypothyroid, vitiligo, addisons disease

Question 34

how is pernicious anaemia diagnosed

Answer 34

macrocytic anaemia
pancytopaenia in some patients
blood film shows macrovalocytes in hypersegmented neutrophils (normally 3-5 nuclear segents)
also -assay B12 and folate levels in serum but low levels may not indicate deficiency and normal may not indicate normalcy
check for auto-antibodies (anti-gastric-parietal cell (GPC) and anti-intrinsic factor (IF)

Question 35

how is megaloblastic anaemia treated

Answer 35

treat the cause where possible
vitamin B12 injections for life in pernicious anaemia
folic acid tables (5mg per day orally)
only trandfuse red cells if life threatening anaemia

Question 36

what are the causes of non-megaloblastic macrocytosis

Answer 36

alcohol, liver disease, hypothyroidism (may not be associated with anaemia due to red cell membrane changes)
marrow failure-associated with anaemia-myelodysplasia, myeloma, anaplastic anaemia

Question 37

what is spurious macrocytosis

Answer 37

the size of the mature red cell is normal but the MCV is high

Question 38

what are the causes of spurios macrocytosis

Answer 38

increase in reticulocyte numbers as a marrow response to acute blood loss or red cell breakdown (hameolysis)
cold agglutins-clumps of agglutinate red cells as registered as 1 giant cell

Question 39

why can patients with pernicious anaemia appear mildly jaundice

Answer 39

intramedullary haemolysis
red cells die prematurely in the marrow, haemoglobin and lactate dehydrogenase LDH are released from dead cells, haemo converted to bilirubin

Question 40

what can complicate sever megaloblastic anaemia

Answer 40

pancytopenia