Macrocytosis and macrocytic anaemia

Question 1

macrocytic anaemia

Answer 1

red cells have a larger than normal volume

Question 2

how is size expressed

Answer 2

MCV- mean corpuscular volume

expressed in units- femtolitres

Question 3

MCV

Answer 3

average size of a red blood cell

Question 4

reference ranges MCV

Answer 4

80-100fl - normal

> 100fl - macrocytic

Question 5

causes of genuine macrocytosis

Answer 5

Megaloblastic Anemia (Defective DNA Synthesis)
Vitamin B12 deficiency
Folate deficiency
Drug-induced (e.g., methotrexate, hydroxyurea, zidovudine)

Question 6

genuine macrocytosis

Answer 6

red blood cells are truly larger

Question 7

false macrocytosis

Answer 7

increase in MCV on lab tests that doesnt correspond to a true increase in rbc size

Question 8

causes of false macrocytosis

Answer 8

hypergylcaemia

leukocytosis

reticulocytosis

Question 9

megaloblastic

Answer 9

larger than normal nucleated red cell with an immature nucleus in the bone marrow

Question 10

megaloblastic anaemia characterisation

Answer 10

characterised by lack of red cells due to defect in dna synthesis and nuclear maturation in developing precursor cells in the marrow

due to this cell division is reduced and apoptosis increases

larger precursor cells with an immature nucleus leading to macrocytic anaemia

Question 11

what do b12 and folate help in the conversion of

Answer 11

uracil to thymine

Question 12

what reactions are b12 and folate co factors in

Answer 12

• DNA synthesis and nuclear maturation (e.g. blood cell effect)
• DNA modification and gene activity (e.g. nervous system)

Question 13

where is b12 absorbed

Answer 13

ileum

Question 14

where is folate absorbed

Answer 14

duodenum and jejenum

Question 15

metabolism of folate

Answer 15

dietary folates converted to monoglutamate

absorbed in jejunum

Question 16

metabolism of b12

Answer 16

• Vitamin B12 is liberated from protein complexes in food by gastric enzymes and then binds to a vitamin B12-binding protein (‘R’ binder)
• Vitamin B12 is released from the ‘R’ binder by pancreatic enzymes and then becomes bound to intrinsic factor
• Intrinsic factor is a glycoprotein secreted by gastric parietal cells; it combines with vitamin B12 and carries it to a specific receptor on the mucosa of the ileum
• Vitamin B12 enters the ileal cells and intrinsic factor remains in the lumen and is excreted
• Vitamin B12 is transported from the enterocytes to the bone marrow and other tissues by the glycoprotein transcobalamin II

Question 17

pernicious anaemia

Answer 17

autoimmune condition with resulting destruction of gastric parietal cells

Question 18

with does pernicious anaemia result in

Answer 18

intrinsic factor deficiency with b12 malabsorption and deficiency

Question 19

causes of folate deficieny

Answer 19

Inadequate intake
Dietary cause more likely than B12 due to lesser stores
Malabsorption
Coeliac disease, Crohn’s disease
Excess utilisation
Haemolysis
Exfoliating dermatitis
Pregnancy
Malignancy
Drugs
anticonvulsants

Question 20

clinical features of b12/ folate def

Answer 20

Symptoms/signs of anaemia
weight loss, diarrhoea, infertility
Sore tongue, jaundice
Developmental problems

Question 21

what deficiency can cause neurological problems

Answer 21

b12 def

irreversable damage

Question 22

lab diagnosis of b12/folate def

Answer 22

macrocytic anaemia- low red cell count

pancytopenia - all cells low

blood film shows macrovalocytes and hypersegmented neutrophils

Question 23

auto antibodies in b12/ folate def

Answer 23

anti gastric parietal cell - sensitive not specific

anti intrinsic fcator - specific not sensitive

Question 24

treatment of megaloblastic anaemia

Answer 24

diet/ oral supplementation

vit b12 injevtions for life in pernicous anaemia

folic acid tablets 5mg per day

Question 25

life threatening anaemia treatment

Answer 25

transfuse red cells

Question 26

causes of non megaloblastic macrocytosis

Answer 26

alcohol
liver disease
hypothyrodisim
marrow failure

Question 27

ineffective erythropoiesis points

Answer 27

Red cells die prematurely in the marrow

Haemoglobin and lactate dehydrogenase (LDH) are released from dead red cells

Haemoglobin converted to bilirubin

Question 28

can patients with pericious anaemia appear mildly jaundixed

Answer 28

yes due to intramedullary haemolysis