Anaemia: Biochemistry Flashcards
how can iron status be tested?
functional iron= Hb
transported iron= serum transferrin
storage= serum ferritin
what is normal transferrin saturation?
20-50%
define holotransferrin
iron bound to tranferrin
what is apotransferrin?
unbound transferrin
what is transferrin?
a protein with two binding sites for iron atoms
function of transferrin
transports from donor tissues to tissues expressing transferrin receptors
donor tissues
macrophages
intestinal cells
hepatocytes
what tissues express transferrin receptors?
erythroid marrow
when is saturation of transferrin reduced?
iron deficiency
anaemia of chronic disease
when is saturation of transferrin increased?
haemochromatosis
what does ferritin store?
4000 ferric ions (Fe3+)
what is ferritin?
large intracellular protein that is spherical
why are tiny amounts of ferritin present in the serum?
reflects ferritin synthesis in response to iron status of host
what does serum ferritin also act as?
acute phase protein
what causes serum ferritin to increase (acute phase protein)
infection
malignancy
liver injury
two forms of iron
ferric (Fe3+)
ferrous (Fe2+)
is there a mechanism for iron excretion?
no
what enhances absorption of iron?
dedicated haem iron transporter
ascorbic acid (reduces iron to Fe2+)
alcohol
what inhibits iron absorption (food examples)?
tannins (tea)
phytates (cereals, bran, nuts, seeds)
calcium (dairy products)
mechanisms of iron absorption
duodenal cytochrome B
DMT-1
ferroportin
role of duodenal cytochrome B
reduces Fe3+ to Fe2+
role of DMT-1
transports ferrous iron into duodenal enterocyte
role of ferroportin
facilitates iron export from enterocytes and passed to transferrin
what regulates iron absorption?
hepcidin
what produces hepcidin?
liver
what causes hepcidin to be produced?
increased iron load
inflammation
action of hepcidin
binds to ferroportin causing its degradation so iron is trapped in duodenal cells and macrophages
what causes hepcidin levels to decrease?
iron deficiency
consequences of iron deficiency
low ferritin
low MCV
microcytic anaemia
epithelial changes (skin, koilonychia and angular cheilitis)
causes of iron deficiency
diet insufficiency
losing too much blood
not absorbing enough
causes of diet insufficiency of iron intake
vegetarian diets
causes of blood loss
menorrhagia GI tumours occult ulcer NSAIDs haematuria
causes of lack of absorption
Coeliac’s
achlorhydria (vitamin C needed to absorb iron)
describe the macrophage iron block in inflammation
ferritin synthesis increased
increased hepcidin reducing iron release
decrease iron for erythroblasts
what is the macrophage iron block for?
protective mechanism as microorganisms like iron
what are B12 and folate?
co-factors in maturation of blood cells and nervous system
where is B12 found?
animal food products
digestion of B12
acid in the stomach allows it to bind to intrinsic factor from gastric parietal cells
alkaline environment activates it
travels to jejunum/ileum before entering bloodstream
where are dietary folates found?
plant foods
absorption of folates
converted to monoglutamate and absorbed in jejunum
causes of B12 and folate deficiency
alcoholics Coeliac's Crohn's haemolysis pregnancy malignancy anticonvulsants
body stores of B12
2-4 years
body stores of folate
4 months
daily requirements of B12 and folate
B12= 1.5ug/day folate= 200ug/day
