HEME- Lecture 5- Disorders of Iron Metabolism

Hb A chains

2 alpha 2 beta

Hb A percent

>95%

Hb A2 chains

2 alpha 2 delta

Hb A2 percent

1.5-3.7%

Hb F chains

2 alpha 2 gamma

Hb F percent (in adults)

<2%

how to calculate total iron concentration

40-50 mg/Kg body weight

functional compounds

myoglobin, myeloperoxidase, lactoferrin

transport compounds

transferrin

storage compounds

ferritin, hemosiderin

iron metabolism step 1

ferric iron comes into contact with duodenal cytochrome B (DcytB) on an enterocyte

iron metabolism step 2

duodenal cytochrome B (DcytB) reduces ferric iron to ferrous iron

iron metabolism step 3

divalent metal transporter 1 (DMT 1) takes the ferrous iron into the enterocyte

iron metabolism step 4- what two options does the iron now have

1) store as ferritin

2) move into the plasma via ferroportin 1

iron metabolism step 4.1- what happens to iron that is stored as ferritin

slough off with apoptosis

what does transferrin do

binds to ferrous iron in the plasma to bring to the bone marrow

what does hepcidin do (iron cycle specific)

inhibits function of ferroportin 1, preventing too much iron from being released into the bloodstream

how is hepcidin production triggered

released by hepatocytes when there is high amounts of iron and transferrin in the blood

what is apotransferrin

transferrin without iron on in

what does hephaestin do

converts ferrous iron to ferric iron

how much of daily iron intake actually absorbed?

5-10%

what is the primary storage form of iron

ferritin

what is the secondary storage form of iron

hemosiderin

what protein transports iron

transferrin

what state is iron often intaken

ferric

what state is iron absobed in

ferrous

what state is iron stored and transported in

ferric

what method is a noninvasive way to check iron stores in the liver

serum ferritin

why does this affect iron absorption: amount available from diet and recycling

early cell death decreases recycling

why does this affect iron absorption: condition of mucosal cells in the GI tract

1) reduced acidity, ferric iron cannot be reduced to be uptaken

2) damaged cells physically cannot pick it up

why does this affect iron absorption: condition of GI tract

parasites, toxins, intestinal motility, decrease in surface area

why does this affect iron absorption: rate of erythropoiesis

higher demand, not enough to go around no matter how much is being absorbed

why does this affect iron absorption: tissue iron stores

cannot transport if it does not exist!

why does this affect iron absorption: inflammation

release of cytokines that inhibit absorption or release of iron

why does this affect iron absorption: hemoglobin levels

cannot transport if it doesn’t exist

what organ commands iron homeostasis

liver

what does hepcidin do

regulates how much iron is absorbed and released into plasma from enterocytes, hepatocytes, and macrophages (binds to ferroportin)

what does HFE do

involved in hepcidin production pathway

what is HJV and what does it do

hemojuvelin, enhances hepcidin gene expression

how does EPO effect hepcidin

inhibit production

how does hypoxia effect hepcidin

increases EPO so inhibit production

how does high iron effect hepcidin

increase production

how does low iron effect hepcidin

decrease production

iron dietary sources

organ meat, wheat germ, brewer’s yeast, legumes, beef, fish, fowl, prunes, leafy green veggies, grains, breads, cereal

why must iron absorption and loss be equal

iron cannot be excreted

what groups have increased iron need

menstruators, pregnant persons, infants/children

laboratory tests to evaluate iron status

serum iron, serum ferritin, total iron binding capacity (TIBC), transferrin saturation, transferrin receptors (sTfRs), free erythrocyte protoporphyrin (FEP)

what does serum iron test for

total iron in serum

what does serum ferritin test for

ferritin in serum, acute phase reactant, one of the most sensitive indicators of iron stores

what does total iron binding capacity (TIBC) test for

availability of binding to trasferrin

TIBC when iron is increased

decreased

TIBC when iron is decreased

increased

what is transferrin saturation

(serum iron/TIBC) x 100

Transferrin receptors (sTfRs) when iron is increased

decreased

Transferrin receptors (sTfRs) when iron is decreased

increased

Free erythrocyte protoporphyrin (FEP) when ZPP is increased Fe is

decreased

symptoms of IDA

fatigue, pallor, vertigo, dyspnea, cold intolerance, lethargy, pica, chelitis, koilonychias

clinical indicators of IDA

decreased RBC count, hemoglobin, hematocrit, MCV, MCHC, serum irron, serum ferritin, and percent transferrin

increased TIBC and TfRs

first stage of IDA

iron depletion

second stage of IDA

iron deficient erythropoiesis

thrid stage of IDA

iron deficiency anemia

at what stage of IDA is the most notible sign only increase in RDW (red cell distribution width)

stage one

at what stage of IDA do symptoms start to appear

stage two

is anemia apparent on a CBC in stage two IDA?

no!

causes of IDA

dietary deficiency (rare in developed countries except in populations of growing individuals etc), blood loss, hemodialysis, malabsorption

treatment for IDA

treatment of underlying cause, dietary supplementation, blood transfusion ONLY if Hb is dangerously low

what does a retic count assess

bone marrow function

what does a RPI (reticulocyte production index) of <2 indicate

ineffective erythropoiesis