1.04 Macrocytosis and macrocytic anaemia

Question 1

what is a femtolitre?

Answer 1

1 femtolitre = 10^-18 m&3

or 10^-15L

Question 2

macrocytosis

Answer 2

increased numbers of cells >100fL

Question 3

What are the ABCDEF of macrocytic anaemia causes?

Answer 3

alcoholism- liver disease
b12 deficiency 
compensatory reticulocytosis 
drugs- cytotoxic, AZT, dysplasia
endocrine- hypothyroidism
folate deficiency/fetus (pregnancy)

Question 4

megaloblastic

Answer 4

erythroblast/normoblast- normal red cell precursor with a nucleus

Question 5

megaloblast

Answer 5

an abnormally large nucleated red cell precursor

Question 6

megaloblastic anaemia

Answer 6

defects in dna synthesis and nuclear maturation

preservation of RNA and haemoglobin synthesis

Question 7

what happens in megaloblastic development of RBC?

Answer 7

cytoplasm development ahead of nuclear development; cell senses that it has enough haemoglobin and doesn’t need to divide anymore, but the cell is too big after enuclation

Question 8

what are the 4 main causes of megaloblastic anaemia?

Answer 8

b12 deficiency
folate deficiency
drugs
rare inherited abnormalities

Question 9

why do b12 and folate deficiencies cause megaloblastic anaemia?

Answer 9

these are essential cofactors for nuclear maturation. they enable chemical reaction that provide enough nucleosides for DNA synthesis.
in their absence, the nuclear maturation lags behind.

Question 10

which nucleoside is affected in the impaired DNA replication of b-12 defieicies?

Answer 10

slow uracil to thymine conversion

Question 11

where is b12 abnorbed?

Answer 11

terminal ileum

Question 12

causes of b12 deficiency

Answer 12

vegan diet
pernicious anaemia
gastrectomy- no IF
tropical sprue 
blind loop syndrome
fish tapeworm

Question 13

What is filate converted to?

Answer 13

monoglytamate

Question 14

Where is folate absorbed?

Answer 14

in jejunum, active and by diffusion

Question 15

Which has a smaller body store? b12 or folate?

Answer 15

folate- it would run out in 4 months.

there is also a greater daily requirement- 100 micrograms per day

Question 16

what are the causes of folate deficiency?

Answer 16

dietary insufficiency of leafy greens, yeasts, destroyed by cooking
malabsorption- coeliac, crohn’s
excess use: haemolysis, exfoliating dermatitis, pregnancy, malignancy
drugs- anticonvulsants

Question 17

B12/folate/or both deficient in: 
s/s of anaemia
weight loss, diarrhoea
sore tongue 
jaundice

Answer 17

common to both

Question 18

b12 deficiency s/s only:

Answer 18

neurological problems
posterior/dorsal column abnormalities
neuropathy
dementia
psychiatric manifestations 

myelin sheath

Question 19

what other autoimmune disorders are associated with pernicious anaemia?

Answer 19

atrophic gastritis
hypothyroidism
vitiligo
addisons disease

Question 20

what is the pathogenesis of atrophic gastritis in pernicious anaemia?

Answer 20

autoimmune attack by dendritic cells in stomach
they clear apoptotic parietalcells
they go to paragastric lypmh nodes to activate CD4+ cells that recognise the H+/K+ ATPase on gastric parietal cells

Question 21

lab diagnosis of macrocytic anaemia

Answer 21

macrocytic anaemia
somtimes pancytopaenia
macroovalocytes
hypersegmented neutrophils- (>3-5 nuclear segments)

b12 and folate levels in serum ( but low may not mean deficiency, and normal may not mean normal)
autoantibodies- anti-gastric parietal cell(more sensitive) and anti-intrinsic factor (more specific)

Question 22

Schilligs test

Answer 22

step 1- saturate cells with b12
step 2- give radiolabelled b12
step 3- measure b12 in urine

if high- the absorption mechanism is intact, and cells are refusing extra b-12
if low- there is no absorption of b12 in the gut, and thus impossible to get into urine

part 2
step 4- give oral intrinsic factor to see if more appears in urine. if yes there is insufficient intrinsic factor

part 3
repeat test after antibiotics because overgrowth can prevent b12-IF complex absorption

Question 23

mx of megaloblastic anaemia

Answer 23

tx cause
b12 injections for life in pernicious anaemia
folic acid tablets 5mg/day orally

in life-threatening anaemia- transfuse red cells

Question 24

causes of non-megaloblastic macrocytosis

Answer 24

may not be assocaited with anaemia (because due to cell membrane changes)
alcohol
liver disease
hypothyroidism

associated with anaemia:
-marrow failure- myelodysplasia, myeloma, asplastic anaemia

Question 25

what are the 2 causes of spurious macrocytosis?

Answer 25

reticulocytosis

cold agglutinins

Question 26

can perinicious anaemia patients appear mildly jaundiced?

Answer 26

yes

due to intramedullary haemolysis

Question 27

what occurs in ineffective erythropoiesis?

Answer 27

red cells die prematurely in bone marrow
haemoglobin and lactate dehydrogenase release from dead red cells
hb converted to bilirubin