7) Anemias of disordered iron metabolism & heme synthesis Flashcards
distribution of Fe in the body
- 70%…
- 25%…
- 4%…
- 1%…
- 70% in hemoglobin
- 25% as storage/serum iron
- 4% in myoglobin
- 1% in iron-containing enzymes
average adult total body iron
2.5-4 g
2/3 bound to heme
iron absorbed per day
about 1.5 mg
5% of daily need
iron needed to make 1 mL of RBCs
iron needed per day for new Hgb
0.5 mg
20 mg
3 processes that maintain iron homeostasis
- dietary iron
- recycling of iron from destroyed RBCs
- iron storage
5 phases of iron metabolism
- absorption
- transport
- storage
- loss
- utilization
cause increased Fe absorption
- decreased Fe stores
- erythropoiesis
- large amounts of Fe ingestion
special factors known to affect Fe absorption
- ascorbic acid and citric acid ↑ absorption
- gastric juices ↑ absorption
- phosphates, phytates, tannates ↓ absorption
2 forms of dietary Fe
- heme Fe —red meats and fish, ferrous form
- nonheme Fe —veggies and whole grains, ferric form
function of ferric reductase
reduces dietary ferric iron to ferrous iron, so it can be absorbed by intestinal mucosal cells
function of ferrooxidase
oxidizes ferrous iron in intestinal mucosal cell back to ferric iron, so it can bind to transferrin and be transported
transferrin binds ——– iron
ferric, 3+
serum iron measures…
transferrin-bound iron
iron measure affected by diurnal variation
serum iron
30% higher in morning
total iron binding capacity measures…
amount of iron bound if transferrin was fully saturated
normally, it is 1/3 saturated
TIBC equation
TIBC = UIBC + serum Fe
functional TIBC test
- excess Fe added to serum
- unbound Fe removed
- iron content of serum remeasured
% Fe saturation measures…
relates amount of iron present in the serum to amount of transferrin present (TIBC)
% sat = 100(serum Fe)/TIBC
normal = 33%
places ferritin can be stored
- mucosal cells
- BM
- spleen
- liver
- plasma
3 places transferrin can take Fe
- normoblasts (BM)
- liver, spleen
- other body cells
2 storage forms of iron
ferritin
hemosiderin
ferritin composition
ferric hydroxyphosphate
apoferritin
cannot be seen with usual iron stain
ferritin
amount of circulating ——– parallels concentration of storage Fe
ferritin
seen in unstained tissues as golden-brown granules
seen in Prussian blue stained tissues
hemosiderin
longer-term, larger capacity storage of Fe
hemosiderin
Fe deposits in the tissues, accumulates in macrophages in the RES
hemosiderosis
2 ways to accelerate Fe excretion
- chelating agents
- therapeutic phlebotomy
2 methods of transferring iron to developing RBCs
- transferrin-bound iron delivered to receptor sites
- Ropheocytosis: normoblasts encircle macrophages with iron (nursing red cells)
3 causes of IDA
- increased demand (birth through infancy, pregnancy)
- decreased absorption
- increased loss (donation, pregnancy, menstruation, GI bleeds)
3 stages of IDA
- Fe depletion
- Fe deficient erythropoiesis
- Fe deficiency anemia
events in stage 1 of IDA
- decrease in serum ferritin and hemosiderin
- increased mucosal absorption
- no anemic sx
events in stage 2 IDA
- TIBC increased
- % sat decreased to 15%
- serum iron decreased
- FEP increased
- normocytic, normochromic RBCs
events in stage 3 IDA
- Hgb, Hct, MCV decreased
- hypochromic microcytes appear
- RDW increased
- anemix sx (fatigue, dizziness, paresthesia, chelitis, pica)
chelitis
chapped lips
IDA sx
IDA may cause —— platelet ct because…
↑
increased CFU-EMk
more megakaryocytes
sideropenic state
low iron
no/few sideroblasts
if ———– is found in BM, IDA is excluded
if ———— are absent or decreased, it is suspected
hemosiderin
sideroblasts
first indicator of IDA
decreased serum ferritin
serum ferritin no longer correlates with stored iron if it is decreased below…
12 μg/L
not a good indicator of IDA, affected by many other things
transferrin levels
protoporphyrins found in IDA
FEP
zinc protoporphyrins
tx for dietary IDA
oral ferrous sulfate
it takes —– to correct 1/2 cases of IDA
3 weeks
autosomal recessive disorder affecting 1/200 Americans
most common form of Fe overload
hereditary hematochromatosis
in patients with HH, —— of Fe are absorbed daily
4 mg
HH generally manifests in…
males 50s-60s
Bronze diabetes
HH
body has adequate iron, but is unable to incorporate it into hemoglobin
sideroblastic anemia
classic sign of sideroblastic anemia
ringed sideroblasts
Fe accumulates in mitochondria of young RBCs, forms ring around nucleus
3 categories of sideroblastic anemia
- hereditary
- acquired
- idiopathic
hereditary SA population
young males
first 30 years of life
2 common causes of acquired SA
- lead poisoning
- alcohol abuse
coarse basophilic stippling
high FEP
lead poisoning
tx for lead poisoning
lead chelating agents
idiopathic SA is considered a… (2)
myelodysplastic syndrome (MDS)
refractory anemia with ringed sideroblasts (RARS)
idiopathic SA often ends in…
leukemia
micro/hypo anemia with ↓ retics
sideroblastic anemia
RS lyse before release into PB
increased RDW
pappenheimer bodies
high % sat transferrin
sideroblastic anemia
iron-laden non-nucleated RBCs
siderocytes
definitive direct test for assessing iron deposition and tissue damage in iron overload states
liver biopsy
