Macrocytosis and Macrocytic Anaemia

Question 1

cytosis means…

Answer 1

an increase in numbers

Question 2

macrocytic anaemia has what MCV, RBC and Hb level?

Answer 2

low Hb
high MCV
low RBC

Question 3

macrocytosis has what MCV, RBC and Hb level?

Answer 3

high MCV
normal Hb
normal RBC

Question 4

MCV over ___ is macrocytic

Answer 4

100fl

Question 5

how can you tell whether a cell is macrocytic or not?

Answer 5

compare it to the nucleus of a lymphocyte on blood film

Question 6

name the 2 TRUE causes of macrocytosis

Answer 6

megaloblastic

non-megaloblastic

Question 7

red cell precursors tend to have a nucleus T or F

Answer 7

T, only exception is reticulocytes

Question 8

when do precursor cells get Hb?

Answer 8

start to get Hb as a precursor
reduce in size
lose nucleus once Hb content optimal

Question 9

when do red cells lose their nucleus?

Answer 9

when Hb content in the cell is optimal

Question 10

how long is the life span of a reticulocyte before it becomes a red cell?

Answer 10

7 days

Question 11

what is a megaloblast?

Answer 11

an abnormally large nucleated red cell precursor with an immature nucleus

Question 12

cause of megaloblastic anaemias?

Answer 12

defects in DNA synthesis and nuclear maturation

Question 13

what cell functions are preserved in megaloblastic anaemias?

Answer 13

RNA and Hb synthesis

Question 14

what red cell precursors undergo apoptosis in megaloblastic anaemia?

Answer 14

erythroblasts

Question 15

why is a megaloblast big?

Answer 15

cytoplasmic development and Hb occur as normal despite cellular defects so it fails to become smaller

Question 16

why is there anaemia in megaloblastic anaemia?

Answer 16

lack of mature red cells from the presence of macrocytes induces erythropoetin to stimulate precursor cells to form again, but these undergo apoptosis so the total RBC level is low

Question 17

causes of megaloblastic anaemia

Answer 17

B12 deficiency
folate deficiency
drugs
genetics

Question 18

why are B12 and folate causes of MA?

Answer 18

essential cofactors for nuclear maturation by enabling reactions for DNA synthesis and gene activity

Question 19

what process facilitates the switching on and off of genes?

Answer 19

methylation of DNA

Question 20

folate cycle is important for what processes? what conversion in this cycle is most important?

Answer 20

nucleoside synthesis

uridine to thymidine

Question 21

methionine cycle is important for?

Answer 21

produces a methyl donor group that helps with DNA methylation (switching on/off of genes)

Question 22

what conversion interlinks the B12 and folate cycles? what relevance does this have?

Answer 22

homocysteine to methionine (B12 cycle needs a substance from the folate cycle to facilitate this)

if one system has a problem the other will too

Question 23

what protein is released from the stomach when th

Answer 23

R binder protein

Question 24

what happens to B12 in the GI tract? name the substances it binds to.

Answer 24

• B12 freed from food by stomach acid
• B12 binds to R binding protein
• intrinsic factor released from gastric parietal cells and travels along with B12 to duodenum
• pancreatic enzymes change pH of duodenum which frees B12 from RBP
• these combine and travel the length of the gut to be absorbed at the ileum

Question 25

B12 is mainly in what foods?

Answer 25

meat/eggs

Question 26

causes of B12 deficiency

Answer 26

``` vegan diet PPIs pernicious anaemia atrophic gastritis chronic pancreatitis malabsorption eg crohns excess utilisation eg haemolysis/pregnancy/malignancy anticonvulsants ```

Question 27

define pernicious anaemia

Answer 27

autoimmune condition with destruction of gastric parietal cells resulting in B12 deficiency

Question 28

Hx of hypothyroidism, vitiligo, atrophic gastritis with B12 deficiency..

Answer 28

pernicious anaemia

Question 29

personal Hx of what conditions are associated with pernicious anaemia?

Answer 29

atrophic gastritis | autoimmune conditions eg hypothyroid, vitiligo, addisons

Question 30

folic acid is absorbed where?

Answer 30

jejeunum

Question 31

dietary folate is converted to what?

Answer 31

monoglutamate

Question 32

food sources of folate?

Answer 32

liver leafy veg fortified cereal

Question 33

B12 is absorbed in the ..

Answer 33

ileum

Question 34

daily requirement of B12

Answer 34

1.5ug

Question 35

daily requirement of folate

Answer 35

200ug

Question 36

clinical features of B12/folate deficiency

Answer 36

``` anaemia signs weight loss diarrhoea infertility sore tongue jaundice developmental problems ```

Question 37

what clinical feature is specific to B12 deficiency

Answer 37

neuro problems esp degeneration of spinal cord and DC abnormalities

Question 38

B12/folate deficient patients get a __cytic anaemia

Answer 38

macro

Question 39

pancytopaenia means...

Answer 39

all cells low

Question 40

blood film of B12/folate deficiency

Answer 40

macrovalocytes (oval shaped macrocytes) and hypersegmented neutrophils

Question 41

Ix B12/folate deficiency

Answer 41

FBC blood film assay B12/folate levels in serum - CAREFUL for false positives/negatives autoantibodies

Question 42

what autoantibodies are best for investigating B12/folate deficiency?

Answer 42

anti gastric parietal cell anaemia | anti-intrinsic factor

Question 43

Tx megaloblastic anaemia

Answer 43

B12 (IM) and folate (PO) supplementation | transfuse red cells ONLY if life threatening

Question 44

route of delivery of B12 supplement?

Answer 44

IM

Question 45

non megaloblastic causes of macrocytic anaemia? what do they affect?

Answer 45

alcohol liver disease hypothyroidism - affect membrane of the red cell, not nuclear maturation marrow failure eg myeloma/myelodysplasia/aplastic anaemia

Question 46

volume of the mature red cell is __ but the MCV is __ in non-megaloblastic macrocytosis

Answer 46

normal | high

Question 47

causes of NMMA?

Answer 47

increase in reticulocytes in response to blood loss/haemolysis cold-agglutinins cause red cells to clump

Question 48

why can patients with pernicious anaemia appear jaundiced?

Answer 48

intramedullary haemolysis due to macrocytes dying in the marrow from being too big to get out of the capillaries then converted to bilirubin

Question 49

proximal bowel removal will cause __cytic anaemia; why is this?

Answer 49

microcytic | iron is absorbed in proximal gut

Question 50

distal bowel removal will cause ___cytic anaemia; why is this?

Answer 50

macrocytic | B12 is absorbed in the distal gut