24: Iron Metabolism - Schmidt Flashcards
low serum iron low hemoglobin *small erythrocytes low hematocrit high total iron binding capacity
dx: iron deficiency anemia
also observe SOB, dizziness, and a sore tongue
pallor and tachycardia
tx: oral iron supplements
small erythrocytes …
not enough iron
iron deficiency anemia
no free Fe________ is allowed
Fe2+/3+
Fe3+ is associated with ROS and useless
iron needs to be controlled at all times, but is very useful for binding oxygen and transferring electrons
ROS production by iron and copper
O2 + Fe2+ —> Fe3+ and O2- (ROS)
H2O2 + Fe2+ —> Fe3+ and HO and HO- (ROS)
about ______ mg/day of iron in normal diet
10-20
plants (Fe3+ not really usable) and animals (heme-bound) contain iron
how is iron excreted?
there is no mechanism of iron excretion - we are built to conserve it
iron should be bound to prtn all the time
also have sloughing off of iron-containing cells in the intestine and kidney
intravascular hemolysis –>
hemoglobin in urine
“active iron” (3)
hemogloin
myogloin
cytochromes
80% of iron
“inactive iron” (1)
ferritin
20% of iorn
transport of active iron
transferrin
degenerated, long-term storage =
hemosiderin
how does iron in the diet get to be in the plasma?
enterocytes
how does iron get from the plasma to the RBC?
erythroid precursors
how does iron get to be in a phagocyte from RBC?
mononuclear phagocytes
where would you find ferritin?
liver iron
phagocyte iron
where would you find heme?
RBC iron
diet iron
where would you find transferrin?
iron in plasma
draw out pattern on slide 9
fluxes of iron
function DMT1
takes in metals with a 2+ charge
function cytochrome B
changes Fe3+ to Fe2+
how does heme enter the enterocyte?
heme transporter (efficient 25% makes it in)
storage of Fe2+ and heme in the enterocytes
ferritin
function ferroportin 1
moves iron into the body from the enterocyte
function hephaestin
Fe2+ to Fe3+
need to be in 3+ form for transport in the body, travels bound to transferrin
iron export is inhibited by _______
hepcidin
peptide produced by liver
under stress infection, released to limit iron available (microbes need it to reproduce)
cells that need iron use ….
transferrin receptor and endocytosis
H+ ions pumped in (acidified)
DMT1 shuttles iron (Fe2+) out of endosome into the cell
determines how active a cell is in iron uptake
number of transferrin receptor on cell membrane
inside the cell iron binds to…
ferritin
high concentrations in liver, spleen, and bone marrow
ferritin particles slowly denature to…
hemosiderin granules
sign of iron overload
hemosiderin granules
life of RBC ends in…
splenic macrophages
macrophages take up the iron; hemolytic disorder leads to accumulation of ferritin and hemosiderin in macrophages
low hepcidin =
high uptake
iron uptake in body is regulated by …
release of iron from enterocytes
mutations in HFE cause …
low hepcidin expression and iron overload
hereditary hemochromatosis
how does iron regulatory prtn work?
low iron - binds and blocks
high iron - Fe2+ binds instead and translation of iron related gene continues
regulated on translational level with iron response element within gene
measures unoccupied transferrin
TIBC total iron binding capacity
higher the TIBC, the lower the iron stores
measure occupied transferrin
transferrin saturation
higher the saturation, higher the iron stores
best measure for body iron stores ***
serum ferritin
fraction of ferritin present in serum
lower the iron stores, the _____ the protoporphyrin
higher
protoporphyrin is iron-free precursor of heme
stages of iron deficiency developing into anemia (3)
- iron depletion - serum ferritin falls
- deficient eryhtropoiessi - hemoglobin still normal, but protoporphyrin levels up, transferrin saturation falls
- iron deficiency anemia - hypochromic (low hemoglobin), microcytosis
3 causes of iron overload
blood transfusions (iron accumulates in macrophages)
slow erythropoiesis (renal failure)
hereditary hemochromatosis (10% ppl carriers)
what would you look for in iron overload (2)
high transferrin saturation
hemosiderin deposits
