Iron health and disease Flashcards
functions of iron
oxygen transport in Hb
electron transport in mitochondria
Iron is a safe element, true or false
FALSE
it is dangerous
why is iron dangerous and what needs to be done as a result
due to production of free radicals and oxidative stress
iron needs to be transported and stored safely
how is iron excreted
it is not
there is no mechanism for this
where is the majority of iron found in the body
in Hb (haem)
why do macrophages have an iron store
because they take up aged RBCs which contain iron
how can iron loss occur
physiological bleeding
shedding of skin cells, enterocytes
where does iron absorption occur
duodenum - proximal gut
which dietary factors increase iron absorption
haem iron transporter - haem iron
ascorbic acid
alcohol
which absorbs easier, haem or non-haem iron
haem iron due to presence of haem iron transporter
which dietary factors decrease iron absorption
tannins in tea
phytates - nuts, cereal, seeds
calcium
Where is Duodenal Cytochrome B enzyme found
What is its function
luminal surface of gut wall
reduces Fe3+ to Fe2+
what is the function of DMT-1
transports Fe2+ into duodenal enterocyte
what is the function of ferroportin
exports iron out of the enterocyte and passes it onto transferrin
what is hepcidin
major negative feedback regulator of iron absorption
where is hepcidin produced
in the liver in response to ^ iron or inflammation
how does hepcidin work
binds to ferroportin and degrades it meaning iron is trapped in duodenal enterocytes and macrophages
It cannot get to the rest of the body
Hepcidin levels are high/low in iron deficiency
low
in order to bind to transferrin, iron must be oxidised/reduced
oxidised - in the Fe3+ state
How can you assess iron status
functional iron
transported iron
storage iron
how do you measure functional iron
Hb concentration
how do you measure transported iron
% saturation of transferrin with iron
how do you measure storage iron
serum ferritin
what is transferrin
protein containing 2 binding sites for iron
to make Fe3+ safer
what is the role of transferrin
transports Fe3+ from donor tissue (macrophages, liver, intestines) to cells expressing transferrin receptor eg erythroid marrow
what do cells expressing transferrin receptors do
internalise transferrin/Fe3+ complex, use iron and release transferrin back out
holotransferrin has bound/unbound iron
bound iron
what is the normal % transferrin saturation
20-50%
in iron overload, what is % transferrin saturation like
elevated
in iron deficiency, what is % transferrin saturation like
reduced
What is ferritin
intracellular spherical protein that stores Fe3+
what is serum ferritin a marker of
indirect marker of storage iron
serum ferritin is also an acute phase protein, true or false
TRUE
what is a cause of low ferritin
iron deficiency
what are causes of high ferritin
iron overload
infection
malignancy
inflammation
What are disorders of iron metabolism
iron deficiency
iron malutilisation
iron overload
how is iron deficiency confirmed
low Hb
low ferritin
what is the most important thing to do in iron deficiency anaemia
identify a cause
what is a cause of iron malutilisation
anaemia of chronic disease
what is the pathophysiology of anaemia of chronic disease
upregulated ferritin levels therefore increase in storage iron even though normal iron is the same
hepcidin levels increase which destroy ferroportin and so iron is unable to leave the cells to get to the rest of the body
what are the findings in anaemia of chronic disease
high ferritin
low % transferrin saturation
what are the categories of iron overload
primary
secondary
define iron overload
> 5g
example of primary iron overload
hereditary haemochromatosis
AR
pathophysiology of haemochromatosis
mutation in HFE gene which decreases hepcidin levels
this means there is more iron absorption over a gradual period of time which can result in end organ damage
what tests are done for haemochromatosis
genetics
transferrin saturation - high
ferritin - high
symptoms of haemochromatosis
arthralgia fatigue cardiomyopathy liver disease DM
management of haemochromatosis
weekly venesection to exhaust ferritin stores <20
then keep levels under 50
why is haemochromatosis problematic
because you can be asymptomatic and disease is irreversible
what are secondary causes of iron overload
repeated red cell transfusions
thalassaemias
sideroblastic anaemia
refracory hypoplastic anaemia
management of secondary iron overload
iron chelating drugs
