Iron Metabolism Flashcards by Iseoluwa Ojo

Iron

Transition metal

May be _____ or _____

2+ or 3+

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Ferrous(__+)
Ferric(__+)

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Ferrous(2+) “________”- ______an electron

Ferric(3+) “________”-_____an electron.

reduced; gained

oxidised; lost

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DIETARY SOURCES OF IRON

Non Haem:
•______________-___% bioavailability
-Absorption enhanced by ——- agents e.g. ascorbic acid(maintains Fe2+),hydroquinone, lactate, pyruvate, succinate, fructose, sorbitol, and cysteine
-Inhibited by ______,———-,_______

Cereals, legumes,vegetables

10; reducing

tannins ,phytates, and phosphates.

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DIETARY SOURCES OF IRON

Haem:
•
-_______
-_____% bioavailability -Haem is taken up intact.

meat, fish

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_______mg of iron enters the body each day and most of them enter ______

Most of the iron seen in the plasma is from ________________________

Each day, approximately ____ mg of iron is lost from the body

The remaining body iron is stored, primarily in _______

1 to 2

haemoglobin

continuous breakdown of haemoglobin in old red cells by RE macrophages

1 to 2

hepatocytes

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Iron functions

Oxygen carriers eg ________

Oxygen storage eg _______

Energy Production ________, _______

Other:

Liver detoxification (_________)

haemoglobin

Myoglobin

Cytochromes (oxidative phosphorylation); Krebs cycle enzymes

cytochrome p450

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IRON COMPARTMENTS

The concentration of Iron in adult human body is usually ___mg/kg in males and ___mg/kg in females.

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IRON COMPARTMENTS

_____ Iron compartments.

six

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IRON COMPARTMENTS

HAEMOGLOBIN
molecular weight ____ Da

____% iron by weight.
1ml packed RBC contains approximately 1mg iron
Total body amount is 2-2.5gm.
Lower in (males or females?) .

64500

0.34

Females

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IRON COMPARTMENTS

STORAGE IRON(FERRITIN)
Water (soluble or insoluble ?) protein –

Found in _______ cells of the body and tissue fluids.
Has an outer protein shell _____ and an _________________ core.
Can bind _________ atoms of Iron.

Soluble

apoferritin

iron- phosphate-hydroxide

4500-5000

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IRON COMPARTMENTS

MYOGLOBIN IRON
Structurally similar to _____ but ______.

Present in (small or large?) amounts in all __________ muscles.

Haemoglobin; monomeric

Small

skeletal and cardiac

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MYOGLOBIN IRON

__________ + ______________

Haem group +polypeptide chain of 150 amino acids.

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IRON COMPARTMENTS

LABILE POOL

Iron leaves plasma and is bound to ___________ , then incorporated into ____ or other structures, or refluxes into plasma

membrane or cytoplasmic proteins.

heme

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IRON COMPARTMENTS

TISSUE IRON
Heme proteins - ____,_______,______

Flavoproteins -__________, _______,_________

cytochromes, peroxidases, catalase

xanthine oxidase; dehydrogenases

cytochrome C reductase

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IRON COMPARTMENTS

TRANSPORT IRON

Contains ___mg of Iron and turns over ____ times per day.

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Smallest but most active compartment.is ???

Transport

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_______ and _______ transport Iron in plasma and milk respectively.

Transferrins and lactoferrins

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IRON ABSORPTION

Occurs in the ______
Taken up as ___ iron or _____ iron
1 – 2 mg iron are absorbed each day
Only ___% of dietary iron is absorbed

duodenum

ionic; haem

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Dietary iron is usually in excess

T/F

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Excess dietary iron is either ______, or __________ and shed into the gut

not absorbed

kept in enterocytes

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IRON ABSORPTION CONTINUED

_____- Reduction Fe+++ to Fe++

______- Transport into cell

______- Storage in cell

______- Oxidises Fe++ to Fe+++

_______- Transport out

DcytB

DMT1

Ferritin

Hephaestin

Ferroportin

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Non heme

2+ or 3+?

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Heme

2+ or 3+

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Which version is allowed into the enterocytes 2+ or 3+

Acidic PH hinders or favors iron absorption ?

Favors

Iron deficiency hinders or favors iron absorption ?

Favors

Pregnancy hinders or favors iron absorption ?

Favors

Hypoxia hinders or favors iron absorption ?

Favors

Iron overload hinders or favors iron absorption ?

Hinders

Phytates hinders or favors iron absorption ?

Hinders

HEPCIDIN _______ activity Hepatic ______ protein Master iron ______ hormone Inactivates ______ Stops iron __________, therefore Iron is lost in stool when gut cells shed Leads to ___eased gut iron absorption

Antimicrobial bacteriocidal regulatory ferroportin getting out of gut cells Decr

HEPCIDIN Increased production of Hepcidin is induced by inflammation via _____ Hepcidin synthesis and secretion are controlled by ___________,__________, and _________ Iron deficiency, hypoxia , and ineffective erythropoiesis.

interleukin 6. HFE, hemojeuvelin, and Transferrin receptor 2.

Hepcidin deficiency targets the _____ and ______

Duodenum and spleen

Ferroportin ________ transmembrane segment protein

12 (or 10)

The only cellular iron exporter in vertebrates is _____

Ferroportin

Ferroportin Present in the _______,_______,_________, and _________

macrophages, duodenum, hepatocytes, and the placenta

Ferroportin The molecular target of ______ is ferroportin

hepcidin

Iron Transport in Blood Red cells As _______ Plasma – Bound to _______ – Carries iron between body locations – eg between gut, liver, bone marrow, macrophages

haemoglobin Transferrin

Iron taken up into cells by transferrin receptors T/F

ENDOCYTOSIS OF TRANSFERRIN _____ binds to ____ on RBC. _____ complex localize to ____-coated pits which invaginate to form _____. A _______ _____eases pH leading to iron release. ______ moves iron across endosomal membrane to cytoplasm. _________ are recycled to the cell surface for further use. In RBC most iron is incorporateed into ________ to make _____ (mitochondria).

Fe 2+Tf ; TfR1 Fe 2+Tf/TfR1; clathrin; endosomes proton pump; decreases DMT1 Apo-Tf& TfRl protoporphyrin; Heme

IRON IN THE ERYTHROBLAST Iron must be transported to ______ to be incorporated into heme or taken up by _______ within ______. Within the vesicle, the protein(_____; Nramp2) effects the release of Fe+++ into the cytosol, where it is taken up by mitochondria for heme synthesis.

mitochondria ferritin; siderosomes DMT-1

In the presence of increased iron: IRP detaches from ______ allowing more ______ to be synthetised. IRP detaches from ___, _______ synthesis.

ferritin mRNA ferritin TfR reducing

IRP= __________ IRE= _________

Iron Regulatory Proteins (IRP) Iron Responsive Elements (IRE)

IRON SCAVENGING •Breakdown of red cells in the circulation Free haemoglobin binds _____ -> taken up by liver Intravascular haemolysis Free haem binds ______ -> taken up by liver Haem passing through ______ is resorbed Three mechanisms to conserve iron in pathological situations

haptoglobins haemopexin kidney

Historically ________ is the disease we have evolved to avoid.

iron deficiency

ASSESSMENT OF IRON STATUS Serum Iron level (___________ level) TIBC : measurement of _________ % transferrin saturation = (______/_____ x 100)

Transferrin bound iron transferrin Serum iron/TIBC

_______________________ (TIBC)

Total iron binding capacity

Serum ferritin : Level correlates with body stores _________ assessment in bone marrow

Haemosiderin

Serum Iron The serum contains about ___% of body iron Over ___% of iron in serum is bound to transferrin

0.1; 95

Serum iron is a routine blood test T/F

Serum iron ______ rythym Meaning it is (lower or higher?) in the morning

Diurnal Lower

Serum iron Measures all serum iron and those in red cells T/F

F Measures all serum iron (not in red cells)

Serum iron Of limited use on its own Useful for interpretation of iron status only if _______– eg iron ______ Commonly combined with ________ to express ____________

grossly abnormal poisoning serum transferrin transferrin saturation

Serum Iron Measurement Serum iron is a routine blood test Low levels: – Iron deficiency – Other: Random variation; _____________; pre-______. High levels: – Iron Overload – Other: Random variation, OCP, _______, recent iron ingestion.

acute or chronic inflammation; menstrual pregnancy

Total Iron-Binding Capacity Is the _______________________

Amount of Iron that could be bound by transferrin and other minor iron-binding proteins.

Total Iron-Binding Capacity Typically __/3 of iron sites on transferrin are saturated. Ranges from 250 to 425μg/dl ___eases with serum transferrin

1 Incr

transferrin is a (positive or negative?) acute phase protein

Negative

Transferrin Saturation Percent of ______________ which are ______ Ranges from _____-____% Values <__% cannot support erythropoiesis Combines two factors to improve sensitivity

transferrin (TIBC) iron-binding sites filled with iron; 15-50 15

Transferrin Saturation Iron overload (High or Low?) iron plus (High or Low?) transferrin (High or Low?) saturation (________%)

High; low High; 50 – 100

Best serum marker of increased body iron is __________

Transferrin saturation

Transferrin saturation is Used in screening for iron overload T/F

Iron Storage - Ferritin Iron store in the ____ and nearly all other cells. Outer shell: ________, consists of 22 protein subunits ________________ core.

liver apoferritin Iron-phosphate-hydroxide

Iron Storage - Ferritin ___% iron by weight, binding up _____ atoms of iron per molecule. Small fraction found in circulation (contains less than 1% of serum iron). Stores iron and releases it in a controlled fashion.

20; 4,500

Ferritin - Measurement – High serum levels Other - Ferritin may be increased in serum by: Tissue release (_____,______,______) Acute phase response (____,_____,_____) Interpretation

hepatitis, leukaemia, lymphoma tissue damage, infection, cancer

Things you need to know about Laboratory Testing for ferritin ________ most useful test Low serum ferritin is certain proof that _______ Normal serum ferritin does ____________ Certain conditions raise ferritin for _____________

Serum ferritin patient is iron deficient not always rule out iron deficiency reasons unrelated to iron status

Bone marrow aspiration Gives an idea of ___ iron as well as _____ Iron. _______ stain is used

RE; Erythroblast Pearl’s stain

Free unbound iron is toxic T/F

Unbound iron deposited in the heart can cause??

Restrictive cardiomyopathy

In meat, iron is in the ______ state In plants, iron is in the _______ state

Ferrous Ferric

Only ____ state of iron can be absorbed by the enterocytes

Ferrous

______ reduces the fe3+ from plants to Fe2+

Duodenum cytochrome B

Fe__ is transported by _________ into the enterocytes where it is _______ into ____ and stored as ______

2+ Divalent metal transporter(DMT-1) Oxidized Fe3+ Ferritin

______ oxidizes Fe2+ to Fe3+

Hephaestin

About ____% of iron is stored as hemoglobin in the marrow

3 stages of iron deficiency Anaemia Stage 1: _____ signs o Anaemia because the body _______ Stage 2: _____ signs of Anaemia and there is ineffective _______ Stage 3: _____ signs of anemia

No signs; uses the stored iron No signs; erythropoesis There are Signs

In severe iron deficiency Anaemia, there is _____cardia ______ loss Short _______

Tachy Hair Attention span

Total iron binding capacity If transporters are exhausted, TIBC is (High or low?) If transporters are free, TIBC is (High or low?)

Low High

In iron deficiency Anaemia, _____eased TIBC ____eased percentage saturation of iron transporters ____eased serum iron _____eased serum ferritin

Incr Decr Decr Decr

In Anaemia of chronic inflammation _____eased TIBC ____eased percentage saturation of iron transporters ____eased serum iron _____eased serum ferritin

Decr Decr Decr Incr

In iron deficiency and Anaemia of chronic inflammation combined, _____eased TIBC ____eased percentage saturation of iron transporters ____eased serum iron _____eased serum ferritin

Decr Decr Decr Decr

Iron overload It can be genetic( defective gene is _____ gene) or acquired

HFE( homeostatic iron regulator)

Defective HFT gene leads to Down regulation of the production of ______

Hepcidin

Other types pf primary hemachromatosis Type 2A- ______ defect Type 2B-________ defect Type 3-__________ defect Type 4-___________ defect

Hemojuvelin Hepcidin Transferrin receptor Ferroportin receptor

Glucose hinders iron absorption T/F

F It aids it

Iron requirement Amount that must be absorbed daily for hemoglobin synthesis by : Infants Children Young non pregnant women Pregnant women Men Post menopausal women

1 0.5 2 3 1 1

Iron requirement Minimal Amount of hemoglobin thgat should Be ingested daily by : Infants Children Young non pregnant women Pregnant women Men Post menopausal women

10 5 20 30 10 10

Iron is An essential element T/F

Iron content(mg) of ; total body iron(%) of Hemoglobin Storage iron Myoglobin iron Transport iron

2000; 67 1000;27 130; 3.5 3;0.08

Function of Ceruloplasmin in iron metabolism

Oxidises ferrous to ferric Iron in the plasma

LABORATORY MARKERS OF IRON STATUS IN SEVERAL DISEASE STATES In Malnutrition, everything is ______ In iron overdose , everything is _______ In Hemochromatosis everything is _______ In viral hepatitis , everything is _______ In acute liver disease, everything is _______ In sideroblastic Anaemia, everything is _______ In chronic Anaemia, everything is _______

Decreased Increased, except transferrin that is decreased Increased, except transferrin that is decreased Increased In viral hepatitis , everything is _______ Increased, except transferrin that is decreased Decreased , expert ferritin that is increased

Sideroblastic Anaemia has similar level of iron markers as _______ Viral hepatitis has similar level of iron markers as _______

Iron overdose Acute liver disease

Laboratory findings: Blood film: ____chromic ____cytic Picture. Occasional ____ cells. _____shaped ____cytes. _____ reticulocyte count.

Hypo; micro Target Pencil; poikilo Normal

Laboratory findings •Bone marrow iron: __________cellular. RBC precursors are ____eased in number. Iron stain_____tive.

Normal to hyper incr nega