Macrocytosis and Macrocytic Anaemia

Question 1

what is macrocytic anaemia

Answer 1

low levels of RBCs of a high volume

Question 2

how is RBC size measured

Answer 2

Mean cell volume

Question 3

causes of macrocytosis

Answer 3

genuine/true

• megaloblastic
• non-megaloblastic

Question 4

how do red cells develop

Answer 4

start with large cell
gains Hb
looses nucleus
shrinks

Question 5

stages of erythropoiesis

Answer 5

pronormoblast 
early normoblast 
intermediate normoblast 
late normoblast 
reticulocyte 
mature red cell

Question 6

what is megaloblastic anaemia

Answer 6

RBC come from megaloblasts

an abnormally large nucleated red cell precursor with an immature nucleus

Question 7

how are megaloblastic anaemias characterised

Answer 7

lack of red cells due to defects in DNA synthesis and nuclear maturation

RNA, cytoplasm and haemoglobin synthesis preserved so the precursor cell is v big

Question 8

what happens to megaloblasts after they have got all the Hb they need

Answer 8

nucleus is extruded leaving behind a bigger than normal red cell

overall fewer macrocytes than normal RBCs hence anaemia

Question 9

what happens after a megaloblast looses its nucleus

Answer 9

megaloblast becomes a macrocyte - large RBC

due to failure of them to get smaller at the right time

Question 10

causes of megaloblastic anaemia

Answer 10

B12 deficiency 
Folate deficiency 
Others 
-drugs 
-rare inherited abnormalities

Question 11

why do B12 and folate deficiency impact RBC production

Answer 11

they are important in DNA synthesis and nuclear maturation

also causes nervous system problems due to DNA modification and gene activity

Question 12

where is B12 in the diet

Answer 12

meat
eggs

(cobalamine = B12)

Question 13

physiology of B12 absorption

Answer 13

released from meat in stomach
binds to haptocorrin protein

causes release of intrinsic factor from parietal cells

pancreatic secretions into the small intestine causes PH to get more alkaline so B12 and haptocorrin release each other

THEN B12 is free to bind to the Intrinsic Factor (IF)

goes through the whole intestinal system as B12IF

in the ilial epithelium in the distal gut the B12 is released from IF and absorbed

binds to protein called transcobalamin into the blood

Question 14

where are iron, calcium and B12 absorbed

Answer 14

iron and calcium in proximal gut

B12 in distal gut

Question 15

causes of B12 deficiency anaemia

Answer 15

Diet
Stomach problems 
-pernicious anaemia 
-atrophic gastritis 
-PPIs, H2 receptor antagonists 
-Gastrectomy/bypass 

small bowel problems 
-jejunum 
  bacterial overgrowth 
  coeliac disease 
-duodenum 
 resection 
 crohns disease 

distal bowel problems
-inherited receptor deficiency
absorbed in the ilium

Question 16

what is pernicious anaemia

Answer 16

autoimmune destruction of gastric parietal cells, preventing the release of IF leading to B12 deficient anaemia

Question 17

where is folate absorbed

Answer 17

duodenum and jejunum

dietry folate is converted to monoglutamate

Question 18

where do you get folate from

Answer 18

liver
leafy veg
fortified cereals

Question 19

where do you get B12 from

Answer 19

animal products

Question 20

how long are the body stored from B12 and folate

Answer 20

B12 - 2-4 years

Folate - 4 months

Question 21

causes of folate deficiency

Answer 21

dietary causes 
malabsorption (coeliac, crohn's)
excess utilisation 
-haemolysis 
-exfoliating dermatitis 
-pregnancy 
-malignancy 

drugs
-anticonvulsants

Question 22

clinical features common to both B12 and folate deficiency

Answer 22

anaemia 
weight loss 
diarrhoea 
infertility 
sore tongue 
jaundice 
developmental problems

Question 23

clinical features of B12 deficiency

Answer 23

Neurological problems

• posterior column abnormalities
• neuropathy
• dementia
• psychiatric manifestations

Question 24

what are the blood film features of B12 deficiency

Answer 24

large oval shaped RBCs (macrovalocytes)

Hypersegmentated neutrophils (number of nuclear segments increases from 3-5 to much more)

Question 25

what other lab signs point to B12 deficiency

Answer 25

macrocytic anaemia

pancytopenia (all cells are low)

Question 26

investigations for B12 deficiency

Answer 26

assay B12 and folate serum levels

check for autoantibodies (anti-intrinsic factor and anti-gastric parietal cell)

Question 27

Treatment of megaloblastic anemia

Answer 27

treat cause

vitamin B12 injections for life in pernicious anaemia

folic acid tablets orally

one if potentially life threatening - transfuse red cells

Question 28

what are non-megaloblastic causes of genuine macrocytosis

Answer 28

alcohol (macrocytosis in the absence of anaemia)
liver disease
hypothyroidism
marrow failure - always associated with anaemia
-myelodysplasia
-myeloma
-anaplastic anaemia

Question 29

what is false macrocytosis

Answer 29

volume of MCV is normal but tests read it as being raised

Question 30

causes of false macrocytosis

Answer 30

an increase in reticulocyte numbers as a marrow response to acute blood loss
-because reticulocytes are larger in tests it looks like RBCs are larger

Cold-agglutinins

• abnormal proteins only active at room temp not body temp
• cause clumping of red cells and confuses the machine giving v high MCV values which aren’t possible

Question 31

why do people with pernicious anaemia appear mildly jaundice

Answer 31

red cells die prematurely in the marrow

intramedullary haemolysis - so the bilirubin is just released

this can also occur in B12 and folate deficiency?