Macrocytosis and Macrocytic Anaemia

Question 1

what is the MCV value in macrocytosis?

Answer 1

> 100

Question 2

what is a megaloblast?

Answer 2

abnormally large, nucleated red cell precursors

Question 3

macrocytosis can occur with or without anaemia - true or false?

Answer 3

true

Question 4

megaloblastic anaemias can be characterised into what two things?

Answer 4

megablastic

non megaloblastic

Question 5

how does macrocytosis occur?

Answer 5

cells become larger due to defective nuclear maturation and DNA synthesis during haematopoesis

this results in growth without division prior to nucleus extrusion (therefore, large cell size created by failure to become smaller opposed to cells becoming larger)

Question 6

what is megablastic anaemia?

Answer 6

large precursor cells with an immature nucleus leading to macrocytic anaemia

Question 7

due to their size, macrocytic cells are more prone to what?

Answer 7

early breakdown

Question 8

what are the different causes of macrocytosis?

Answer 8

megaloblastic macrocytic anaemia

non megaloblastic macrocytosis

Question 9

what are the different causes of megaloblastic macrocytic anaemia?

Answer 9

B12 and folate deficiency

drugs: cytotoxics

Question 10

a deficiency in either B12 or folate can impact the functioning of the other - true or false?

Answer 10

true

Question 11

where is B12 mainly sourced from?

Answer 11

animal foods

Question 12

where is B12 absorbed?

Answer 12

in the terminal ileum via binding to intrinsic factor

Question 13

is the body store of B12 small or large?

Answer 13

large - lasts 2-4 years

Question 14

where is folate mainly obtained from?

Answer 14

plant foods, especially leafy green vegetables

Question 15

where is folate absorbed?

Answer 15

duodenum

Question 16

is the body store of folate small or large?

Answer 16

much smaller than B12, meaning the body will become deficient in folate before B12

Question 17

what are dietary causes of B12 deficiency?

Answer 17

vegan diet
alcoholism
old age

Question 18

what conditions cause reduced absorption of B12 in the stomach?

Answer 18

pernicious anaemia
gastrectomy
PPI
anti histamine

Question 19

what conditions cause reduced absorption of B12 in the small intestine?

Answer 19

bacterial overgrowth
coeliac disease (affects terminal ileum)
chrons disease
bowel resection

Question 20

what conditions cause reduced absorption of B12 in the pancreas?

Answer 20

chronic pancreatitis

Question 21

what is pernicious anaemia?

Answer 21

autoimmune atrophic gastritis in which there is reduction in the production of HCL and intrinsic factor

Question 22

who is pernicious anaemia most commonly seen in?

Answer 22

women in their 40s with other autoimmune conditions (thyroid, addisons, vitiligo)

Question 23

what autoantibodies are seen in pernicious anaemia?

Answer 23

anti gastric parietal cell = sensitive but not specific

anti intrinsic factor = specific but not sensitive

Question 24

what is the treatment of pernicious anaemia?

Answer 24

B12 injections for life

Question 25

what are circumstances which cause low intake of folate?

Answer 25

poverty old age alcoholism

Question 26

what conditions cause malabsorption of folate leading to folate deficiency?

Answer 26

coeliac disease | tropical sprue

Question 27

what conditions cause increased demand of folate leading to folate deficiency?

Answer 27

``` pregnancy malignancy myelofibrosis exfoliating dermatitis haemolytic anaemia ```

Question 28

what drugs cause folate deficiency?

Answer 28

methotrexate trimethoprim alcohol anticonvulsants: phenytoin, valproate

Question 29

as well as the symptoms of anaemia, what else can be seen in megaloblastic macrocytic anaemia?

Answer 29

mouth: glossitis / angular stomatitis jaundice: due to chronic haemolysis psychiatric: irritability, depression neurological (more with B12): numbness, tingling, subacute degeneration of spinal cord weight loss, diarrhoea, infertility

Question 30

what is sub acute combined degeneration of spinal cord and how does it present?

Answer 30

insidious degeneration of corticospinal tract and dorsal columns presentation: parasthesia, ataxia, weakness (sensory symptoms tend to occur first?

Question 31

what is seen on investigation in megaloblastic macrocytic anaemia?

Answer 31

serum: low B12/folate FBC: low Hb, high MCV, reticulocytes bone marrow biopsy: megalolasts film: howel jolly bodies, macrovalocytes and hypersegmented neutrophils

Question 32

how is megaloblastic macrocytic anaemia treated?

Answer 32

identify and treat underlying cause folate deficiency = 5mg for 4 months B12 deficiency = B12 injections (initially on alternative days, then 3 monthly if appropriate) transfuse red cells only if life threatening

Question 33

why should folate not be given alone in megaloblastic macrocytic anaemia?

Answer 33

due to failing to provide B12, precipitating or worsening subacute combined degeneration of cord

Question 34

all the causes of non megaloblastic macrocytosis cause an increase in red cell size by what?

Answer 34

altering the red cell membrane

Question 35

what are the main causes of non megaloblastic macrocytosis?

Answer 35

alcohol pregnancy hypothyroidism liver disease (target cells on blood film) marrow failure (myelodysplasia, aplastic anaemia)

Question 36

what is the difference between marrow failure as a cause of non megaloblastic macrocytosis and the other causes eg alcohol?

Answer 36

marrow failure will always present with anaemia

Question 37

what is reticulocytosis?

Answer 37

increased amounts of circulating reticulocytes due to increased production of RBCs occurs as marrow response to acute blood loss or red cell breakdown (haemolysis)

Question 38

are reticulocytes bigger or smaller than mature RBCs?

Answer 38

bigger they are analysed along with these for MCV measurement

Question 39

in what conditions is reticulocytosis seen in?

Answer 39

haemolysis haemorrhage treatment of anaemia thalassemia (will cause reticulocytosis but not macrocytosis)

Question 40

other than reticulocytosis, what is another kind of spurious (fake) macrocytosis?

Answer 40

cold agglutinin disease