12-1: 1/4 - Disorders Of Iron Metabolism

Front 1

Iron is absorbed via ____ cells in the ______.

Back 1

Iron absorbed via mucosal cells in duodenum

Front 2

How much iron is stored in the body on average?

What is the daily requirement of iron?

Back 2

Average male has 4g of total body iron

Only needs 1 mg of iron per day

Note: no system in body for eliminating excess iron!

Front 3

Function of transferrin.

Effect of iron deficiency/excess on transferrin.

Back 3

Binds 2 molecules of Fe and delivers Fe to developing RBC.

Iron deficiency upregulates transferrin
Iron excess downregulates it

Front 4

Transferrin receptor:
Role
Location

Back 4

off loads iron bound to transferrin into RBC

Present on surface of RBC, tissue macs, and enterocytes

Front 5

Function of ferritin.

Effect of iron deficiency/excess on ferritin.

Back 5

Primary storage form of iron; partially soluble, can be measured in serum

Dec'd in Fe deficiency, inc'd in Fe overload

Front 6

Function of hemosiderin.

Back 6

Secondary storage protein

Totally insoluble; measured by Prussian blue stain

Front 7

Function of Divalent Metal Transporter (DMT)

Effect of iron deficiency/excess on DMT.

Back 7

Transports Fe across duodenal cell

Upregulated in Fe def; downregulated in Fe overload.

Front 8

Function of HFE Protein

Back 8

In conjunction with transferrin receptor, senses body Fe and up or downregulates DMT

Front 9

Function of ferroportin.

Back 9

Expressed in duodenal enterocytes; transports iron out of cell and onto transferrin

Facilitates iron release from macs

Front 10

Function of hepcidin.

Back 10

Produced in liver; role is negative regulator of iron absorption from duodenum.

Inhibits ferroportin. Blocks iron release from macs.

Front 11

Serum iron measures _____.

Effect of iron deficiency/excess on serum iron measures.

Back 11

Fe bound to transferrin

NL Range: 75-125

Dec'd with Fe def and anemia of chronic dz; inc in iron overload

Front 12

Total iron binding capacity measures _____.

Effect of iron deficiency/excess on total iron binding capacity.

Back 12

Fe bound transferrin + unbound transferrin

Inc'd w/iron def; dec'd with anemia

Front 13

Fe Saturation measures ________.

Back 13

Serum Fe/Total iron Binding Capacity; normal: 30%

Front 14

This molecule of iron is insoluble and can only be measured by BM stain.

Back 14

Hemosiderin

Front 15

This molecule is a direct measures iron stores.

Back 15

Ferritin

Front 16

Every ___ cc blood contains ____ mg of iron.

Back 16

Every 2 cc of blood contains 1 mg of iron.

Front 17

Iron deficiency anemia in men and non-menstruating women is considered _____ until proven otherwise.

Back 17

GI BLEEDING

Front 18

Koilonychia:
What is it?
Sign of?

Back 18

Spoon nails
Sign of iron deficiency anemia

Front 19

What would following tests be like in iron deficiency anemia?

MCV
Reitculocyte Count
Serum Iron
Total Iron Binding Capacity
Ferritin
Peripheral Blood Smear

Back 19

Low MCV, low MCH
Low retic count (BM can't respond)
Low serum iron
Inc'd Fe binding capacity (TIBC)
(Low transferrin saturation: serum Fe/TIBC)
Low ferritin in serum
Typical blood smear

Front 20

Iron replacement therapy:
Preferred route
Dose limiting toxicity
Best way to improve absorption

Back 20

Oral route preferred
Dose limiting toxicity is GI (constipation, cramping)
Asorbed best on empty stomach with orange juice (ascorbic acid enhances absorption)

Front 21

When is IV iron therapy indicated?

Back 21

Patients who are intolerant to oral prep or are malabsorbing.

Used when rapid replacement needed

During EPO admin in kidney failure

Front 22

What is the risk of IV iron therapy? Which drug poses greatest risk?

Back 22

Risk of anaphylaxis due to carbohydrate ligand (which is bound to ferric hydroxide core)

Iron dextran poses greatest risk

Ferric gluconate and iron sucrose pose minimal to no risk of anaphylaxis (because have gluconate and sucrose as ligands instead of carbohydrate)

Front 23

Anemia of Chronic Disease:
Disease associations
Pathophys

Back 23

Asocd w/chronic inflamm states or chronic infections, e.g., TB, rheumatoidd arthritis

Pathophys:
Inflamm releaces IL-6 from macs-->liver makes hepcidin
Hepcidin binds ferroportin to block release of iron from macs and limiting Fe absorption in duodenum
Thus, iron sequestered in tissue macs and poorly available for maturing RBCs

Front 24

Hepcidin:
Site of Synthesis
Role
Protein essential for its production
2 things that increase its production

Back 24

Synthesized by hepatocytes
Blocks release of Fe by enterocytes and macs by binding Ferroportin

Membrane Bound Hemojuvelin (HJV) essential for hepcidin production

Inc'd Fe stores stimulate hepcidin produciton
Inc'd IL-6 increases hepcidin production

Front 25

How does anemia of chronic disease differ from iron deficiency anemia LAB wise?

Back 25

Anemia is mild: Hgb 8-10
MCV NORMAL (or slightly low)
Low retic count
Normal RBC morphology
Low serum iron (similar to Fe def anemia), low transferrin (bc iron overloaded), inc'd ferritin (inc'd iron stores)
Inc'd BM iron

Front 26

What is hemochromatosis?

Back 26

Genetic disorder leading to inc'd absorption of iron from duodenum

Front 27

Why does excess iron pose a problem for the body (general)?

Back 27

body has no mechanism to dispose of unwanted iron; thus deposits in and damages multiple organs

Front 28

Missense mutation in C282Y is associated with __________.

Back 28

80% of cases of hereditary hemochromatosis

Front 29

Hereditary Hemochromatosis:
Crypt vs Liver Model

Back 29

Crypt: Abnormal HFE protein impairs iron sensing mech in crypt cell; cell perceived iron deficiency and upregulates DMT, releasing Fe from GI tract

Liver Model: abnormal HFE blocks hepcidin production and leads to unopposed ferroportin transport of iron into circuln

Likely both mechs involved

Front 30

Effect of hemochromatosis on:
Liver
Pancreas
Myocardium
Skin

Back 30

Liver: cirrhosis***
Pancreas: DM**
Myocardium: CHF* (EKG abnlts)
Skin: bronzing (bronze diabetes)***

Other: arthralgia, impotence, weakness and lethargy(***)

Front 31

Lab values of hemochromatosis.

Back 31

High serum iron
Transferrin low to normal (thus high transferrin saturation)
High serum ferritin

Liver biopsy was gold standard but largely replaced by genetic testing for abnl HFE gene

Front 32

Hemochromatosis:
Treatment

Back 32

Phlebotomize; may needs as many as 100 (every 1-2 weeks until ferritin is less than 50)

Front 33

Hemosiderin values in normal patient.

Back 33

2+

Front 34

Lab values in Fe deficiency anemia:
Serum Fe
Transferrin (TIBC)
Transferrin SAT (%)
Ferritin
Hemosiderin

Back 34

Serum Fe: Low
Transferrin (TIBC): High (it's a ratio, look it up)
Transferrin Sat: Low
Ferritin: Low
Hemosiderin: 0

Front 35

Lab values in anemia of chronic disease:
Serum Fe
Transferrin (TIBC)
Transferrin SAT (%)
Ferritin
Hemosiderin

Back 35

Serum Fe: Low
Transferrin (TIBC): Low (iron overload downregs)
Transferrin SAT (%): high or low
Ferritin: High
Hemosiderin: 4+

Front 36

Lab values in hemochromatosis:
Serum Fe
Transferrin (TIBC)
Transferrin SAT (%)
Ferritin
Hemosiderin

Back 36

Serum Fe: High
Transferrin (TIBC): Low
Transferrin SAT (%): High
Ferritin: High
Hemosiderin: 4+

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