Macrocytosis and Macrocytic Anaemia Flashcards
cytosis means…
an increase in numbers
macrocytic anaemia has what MCV, RBC and Hb level?
low Hb
high MCV
low RBC
macrocytosis has what MCV, RBC and Hb level?
high MCV
normal Hb
normal RBC
MCV over ___ is macrocytic
100fl
how can you tell whether a cell is macrocytic or not?
compare it to the nucleus of a lymphocyte on blood film
name the 2 TRUE causes of macrocytosis
megaloblastic
non-megaloblastic
red cell precursors tend to have a nucleus T or F
T, only exception is reticulocytes
when do precursor cells get Hb?
start to get Hb as a precursor
reduce in size
lose nucleus once Hb content optimal
when do red cells lose their nucleus?
when Hb content in the cell is optimal
how long is the life span of a reticulocyte before it becomes a red cell?
7 days
what is a megaloblast?
an abnormally large nucleated red cell precursor with an immature nucleus
cause of megaloblastic anaemias?
defects in DNA synthesis and nuclear maturation
what cell functions are preserved in megaloblastic anaemias?
RNA and Hb synthesis
what red cell precursors undergo apoptosis in megaloblastic anaemia?
erythroblasts
why is a megaloblast big?
cytoplasmic development and Hb occur as normal despite cellular defects so it fails to become smaller
why is there anaemia in megaloblastic anaemia?
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
causes of megaloblastic anaemia
B12 deficiency
folate deficiency
drugs
genetics
why are B12 and folate causes of MA?
essential cofactors for nuclear maturation by enabling reactions for DNA synthesis and gene activity
what process facilitates the switching on and off of genes?
methylation of DNA
folate cycle is important for what processes? what conversion in this cycle is most important?
nucleoside synthesis
uridine to thymidine
methionine cycle is important for?
produces a methyl donor group that helps with DNA methylation (switching on/off of genes)
what conversion interlinks the B12 and folate cycles? what relevance does this have?
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
what protein is released from the stomach when th
R binder protein
what happens to B12 in the GI tract? name the substances it binds to.
- 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
B12 is mainly in what foods?
meat/eggs
causes of B12 deficiency
vegan diet PPIs pernicious anaemia atrophic gastritis chronic pancreatitis malabsorption eg crohns excess utilisation eg haemolysis/pregnancy/malignancy anticonvulsants
define pernicious anaemia
autoimmune condition with destruction of gastric parietal cells resulting in B12 deficiency
Hx of hypothyroidism, vitiligo, atrophic gastritis with B12 deficiency..
pernicious anaemia
personal Hx of what conditions are associated with pernicious anaemia?
atrophic gastritis
autoimmune conditions eg hypothyroid, vitiligo, addisons
folic acid is absorbed where?
jejeunum
dietary folate is converted to what?
monoglutamate
food sources of folate?
liver
leafy veg
fortified cereal
B12 is absorbed in the ..
ileum
daily requirement of B12
1.5ug
daily requirement of folate
200ug
clinical features of B12/folate deficiency
anaemia signs weight loss diarrhoea infertility sore tongue jaundice developmental problems
what clinical feature is specific to B12 deficiency
neuro problems esp degeneration of spinal cord and DC abnormalities
B12/folate deficient patients get a __cytic anaemia
macro
pancytopaenia means…
all cells low
blood film of B12/folate deficiency
macrovalocytes (oval shaped macrocytes) and hypersegmented neutrophils
Ix B12/folate deficiency
FBC
blood film
assay B12/folate levels in serum - CAREFUL for false positives/negatives
autoantibodies
what autoantibodies are best for investigating B12/folate deficiency?
anti gastric parietal cell anaemia
anti-intrinsic factor
Tx megaloblastic anaemia
B12 (IM) and folate (PO) supplementation
transfuse red cells ONLY if life threatening
route of delivery of B12 supplement?
IM
non megaloblastic causes of macrocytic anaemia? what do they affect?
alcohol
liver disease
hypothyroidism
- affect membrane of the red cell, not nuclear maturation
marrow failure eg myeloma/myelodysplasia/aplastic anaemia
volume of the mature red cell is __ but the MCV is __ in non-megaloblastic macrocytosis
normal
high
causes of NMMA?
increase in reticulocytes in response to blood loss/haemolysis
cold-agglutinins cause red cells to clump
why can patients with pernicious anaemia appear jaundiced?
intramedullary haemolysis due to macrocytes dying in the marrow from being too big to get out of the capillaries
then converted to bilirubin
proximal bowel removal will cause __cytic anaemia; why is this?
microcytic
iron is absorbed in proximal gut
distal bowel removal will cause ___cytic anaemia; why is this?
macrocytic
B12 is absorbed in the distal gut
