Diseases of Iron Metabolism Flashcards
iron metabolism disorders
defect in hemoglobin synthesis due to a deficiency of iron or abnormal utilization of iron
microcytic hypochromic anemia
red cell disorders
types of iron metabolism disorders
microcytic hypochromic anemias
iron overload
types of microcytic hypochromic anemias
iron deficiency anemia
anemia of chronic disease
sideroblastic anemia
type of iron overload
hemochromatosis
causes of iron deficiency
insufficient dietary intake of iron
absorption is impaired
increased loss of iron through bleeding
causes of iron overload
absorption abnormally increases
individual receives multiple transfusions
individual receives iron injections
disturbances in heme & globin synthesis can cause
defective hb production
types of disturbances in heme synthesis
deficient iron
defective iron metabolism
defect in porphyrin synthesis
iron is found associated with or as
functional iron
transport
storage
types of functional iron
hemoglobin
myoglobin
type of transport iron
transferrin
types of storage iron
hemosiderin
ferritin
total iron concentration in the body
40-50 mg of iron/kg of body weight
iron homeostasis depends on balance of
absorption of iron
total body requirements
two forms of dietary iron
nonheme iron (ferric, fe3+) heme iron (ferrous, fe2+)
where is nonheme iron found
vegetables, whole grains
where is heme iron found
red meats
nonheme iron
ferric, fe3+
heme iron
ferrous, fe2+
how is nonheme iron different from heme iron
nonheme is not easily absorbed
gastric acid solubilizes the iron complex
reduces ferric iron to ferrous form
low pH allows transport of iron across the enterocyte membrane
where is ferrous iron form absorbed
through the mucosal cells (enterocytes) of the intestine
how is ferrous iron absorbed
fe2+ is oxidized to fe3+ for binding to transferrin
transferrin distributes to body tissues or for storage
absorption increased when erythropoiesis increased & iron stores depeleted
where is ferric iron form absorbed
enters through the blood stream
transferrin
plasma iron transport protein mediates iron exchange between tissues
what is transferrin made of
a single polypeptide
two homologous lobes
two atoms of ferric iron can bind to one transferrin molecule
what do the two atoms of ferric iron bound to one transferrin molecule do
maintains iron in soluble form
what does transferrin do
assists iron delivery to erythroblasts in bone marrow by plasma circulation
transferrin receptor 1 (TfR1)
expressed on virtually all cells
one molecule of transferrin binds to TfR1
transferrin/TfR1 complex
enters cell
iron is released
TfR1 available for recycling
iron not used for erythropoiesis
stored in the reticuloendothelial cells of BM, liver, spleen, as ferritin or hemosiderin
ferritin
major form of iron storage
stores up to 4500 molecules of Fe3+
primary storage compound for iron
readily available for erythropoiesis
ferritin stores what type of iron
nonheme - ferric, fe3+
hemosiderin
found in macrophages
aggregate of iron, carbohydrate, lipid, protein
iron from hemosiderin is released slowly - not readily available for cellular metabolism
BM macrophages contain hemosiderin if
iron stores are normal or high
stains with prussian blue
percent saturation in males & females in transferrin
20-50% males
15-50% females
total serum iron test
forces transferrin to let go of the iron
how many ferric irons can transferrin hold
2
total binding capacity
indirecty measures how much transferrin you have
transferrin is measured functionally as
TIBC - maximum amount of Fe able to be bound in serum
what is transferrin percent saturation
amount of transferrin complexed with iron - usually about 30%
the quality of storage iron accompanied by changes in serum iron & TIBC
when storage iron increases, serum iron increases, & TIBC decreases
when storage iron decreases or is absent, serum iron decreases, TIBC increases
transferrin saturation in IDA
<16%
transferrin saturation in iron overload or hemochromatosis
> 55%
unsaturated binding capacity test
approximates how many transferrin molecules are present by finding out how much iron can be bound
when leftover iron reacts with reagent to make a color, what is the relationship
darker the color, more was available
the less empty the slots were
total iron capacity
sum of the:
total serum + unsaturated iron binding capacity
approximates the amount of transferrin
transferrin saturation
~1/3 (33%) of transferrin is saturated with iron
indicator of amount of iron available for erythropoiesis
% transferrin saturation
serum iron / TIBC x 100
serum iron normal range
50 - 160 ug/dL
TIBC normal range
250 - 400 ug/dL
% saturation of transferrin
20 - 55%
in an iron deficient patient is there more or less transferrrin
more
total iron binding capacity increases in what type of patient
iron deficient patient
ferritin
much better measurement than serum iron & TIBC for assessment of iron stores
directly proportional to the amount of storage iron
acute phase reactant
what is the amount of serum ferritin in depletion of iron stores
<12 mcg/L
what is the amount of serum ferritin in iron overload
> 1000 mcg/L
low ferritin can be the first indicator of what
iron deficiency anemia
transferrin receptor - sTfR
inversely proportional to the amount of body iron
TfR synthesis increases in iron deficiency - only after iron stores are depleted
not affected by inflammation/infection
zinc protoporphyrin - ZPP
when iron not available for incorporation into the protoporphyrin ring to form Fe, zinc is incorporated forming ZPP
reflects iron supply over preceding weeks
CBC in IDA
normocytic-normochromic cells are replaced by microcytic-hypochromic cells
RDW increased
what biochemical transports ferric in the blood stream
transferrin
what biochemical has ferrous iron and binds oxygen & CO2
hemoglobin
what biochemical is the best indicator of iron stores
ferritin
what biochemical is used for deposits of iron in tissues & cells
hemosiderin
prussian blue stains
iron
erythroblastic island
erythroid progenitors clustering around a central macrophage
iron can only enter cells that have a
transferrin receptor
free erythricyte protoporphyrin
a heme precursor
without iron, porphyrins will
build up “FEP” & complex with zinc to make ZPP
serum iron/TIBC x 100% =
transferrin saturation
the amount of transferrin can be estimated by the
total iron binding capacity
increased ZPP indicates that
the patient is deficient in iron, so zinc takes its place
most common anemia
iron deficiency aneia
etiology of IDA
diet & increased need
blood loss - GI bleeds & menstruation
malabsorption - celiac disease, gastric bypass, etc
stage 1 iron depletion
ferritin decreased
transferrin increased
total iron binding capacity increased
stage 2 iron deficient erythropoiesis
FEP & ZPP increased
H&H decreased with microcytes
TfRs increased
stage 3 iron deficient anemia
H&H mycrocytic hypochromic very low
clinical features of IDA
glossitis
koilonychias
chellitis
blue sclera
treatment for IDA
correction of primary disease
oral supplements
transfusion
the most common cause of hypochromic anemia is
iron deficiency anemia
anemia of chronic disease
common complication in inflammation/infection
principal pathogenesis is related to hepcidin
hepicidin
peptide hormone that is involved in iron absorption & recycling
block release of iron from cells
hepicidin’s expression is dependent upon
iron availability
IL-6 mediated inflammatory signaling
hepicidin is released by
the liver
hepicidin induces
iron sequestration & hypoferremia
hepicidin prevents
iron availability for RBC production
1-3 months after anemia of chronic disease hypothesis
activated immune system produces cytokines that reduce iron in the circulation
1-3 months after anemia of chronic disease characteristics
low serum iron, TIBC decreased, transferrin saturation decreased, ferritin is normal or increased (it’s an acute phase protein)
lower EPO; response to EPO is blunted
ACD blood smear characteristics
60-70% are normocytic, normochromic & rest are microcytic
retic count not appropriate for degree of anemia
bone marrow has increased stainable iron
FEW & ZPPincrease
differential diagnosis of IDA vs ACD is
measurement of plasma transferrin receptors
tratement of ACD
treat the disease
transfuse if needed
IDA characteristics hgb mcv iron TIBC ferrin rbc rdw sTfR
hgb - low mcv - low, <80 iron - low TIBC - high ferrin - low rbc - low rdw - high sTfR - high
ACD characteristics hgb mcv iron TIBC ferrin rbc rdw sTfR
hgb - low mcv - normal or <80 iron - low TIBC - low ferrin - normal or increased rbc - low rdw - normal to slight increase sTfR - normal
TfR is elevated in ___ but not in ___
IDA not in ACD
types of sideroblastic anemia
inherited
acquired
sideroblastic anemia
iron is incorporated into heme through a series of enzymatic steps
iron is abundant, but heme synthesis is poor
inherited sideroblastic anemia
iron incorporated into heme has a defect in one or more of the enzymes
inherited sideroblastic anemia is caused by
sex linked form
autosomal recessive form
acquired sideroblastic anemia
iron incorporated into heme blocks one or more of the steps
acquired sideroblastic anemia is caused by
drugs, chloraphenicol
lead poisoning
in sideroblastic anemia, prussian blue stain of marrow shows
ringed sideroblasts
ringed sideroblasts
normoblasts with iron deposits surrounding the nucleus, awaiting incorporation into heme
siderobastic anemia may be improved with
pyridoxing to stimulate heme synthesis
sideroblastic anemia characteristics hgb mcv iron TIBC ferrin rbc rdw sTfR
hgb - low mcv - normal iron - increased TIBC - decreased ferrin - increased rbc - decreased rdw - increased sTfR - normal or low
lead poisoning is what type of anemia
acquired sideroblastic anemia
lead poisoning
lead interferes with conversion of ALA to porphobilinogen & incorporation of iron into protoporphyrin IX
lead poisoning anemia may be
normochromic/normocytic or microcytic hypochromic
lead poisoning characteristics
retic count is high
basophilic stippling
ringed sideroblasts have iron deposits in the
mitochondria
defect in the conversion of d-ALA to porphobilinogen can lead to
sideroblastic anemia
basophilic stippling
representation of precipitation of rRNA
porphyria
enzyme block in porphyrin production
porphyrin precursors build up in tissue
excreted in urine & feces
porphyria causes
photosensitivity, motor dysfunction, mental disturbances
hemochromatosis
excess iron builds up in tissues
types of hemochromatosis
primary
secondary
primary hemochromatosis
hereditary hemochromatosis HFE mutation
secondary hemochromatosis
to RBC destruction & transfusion
hereditary hemochromatosis
caucasian genetics
HFE glycoprotein binds transferrin receptors to regulate their affinity for transferrin
common mutations in hereditary hemochromatosis
C282Y & H63D
hemochromatosis symptoms
joint pain
fatigue
iron ferritin, & transferrin are increased
hallmark of hemochromatosis
transferrin saturation
>50% = females
>60% = males
then HFE analysis
what is the most common mutation causing hereditary hemochromatosis
C282Y HFE
therapy for primary iron overload
therapeutic phlebotomy
therapy for secondary overload
therapeutic phlebotomy
desferrioxamine iron chelation therapy
