Iron Absorption and Metabolism - White

Question 1

Fe

Answer 1

Important role in ETC and oxygen transport

Question 2

Fe under aerobic conditions

Answer 2

Readily exchanges electrons

Question 3

Total body iron

Answer 3

3-5g

Question 4

How much iron is in RBCs?

Answer 4

2.7g

Question 5

How many mg per day to support Hb production?

Answer 5

25mg

Question 6

The iron cycle

Answer 6

Like a gang

Blood in, blood letting out

Question 7

Why is iron chelated to proteins or other molecules?

Answer 7

Maintain solubility

Limit toxicity

Question 8

Stored iron

Answer 8

Ferritin
Hemosiderin
Excess iron stored in liver, lungs and pancreas

Question 9

Ferritin

Answer 9

Intracellular protein
Binds thousands of Fe3+ per molecule
Found in most cells

Question 10

Hemosiderin

Answer 10

Granules of ferritin

Question 11

Excess iron mainly stored by

Answer 11

Liver
Lungs
Pancreas

Question 12

Can iron freely diffuse across membranes?

Answer 12

No, need transport mechanisms

Question 13

4 iron transporters

Answer 13

Ferrireductase
DMT1
Hephaestin
Ferroportin

Question 14

Fe overloading

Answer 14

If iron absorption is high

Question 15

Fe deficiency

Answer 15

If iron absorption is low

Question 16

Dietary iron is in what form?

Answer 16

Ferric form Fe3+

Question 17

Dcytb

Answer 17

Duodenal cytochrome-like b
Reduces ferric (Fe3+) to ferrous (Fe2+)

Question 18

DMT1

Answer 18

Iron uptake channel

On apical surface of the enterocyte in the microvilli region

Question 19

Ferroportin

Answer 19

Iron door

Requires hephaestin

Question 20

Hephaestin

Answer 20

Changes ferrous to ferric so that transferrin can carry it to bone marrow

Question 21

Transferrin

Answer 21

Carries ferric (Fe3+, non-toxic form) to the bone marrow
Found in sla - sex linked anemia

Question 22

How is iron content in the body regulated?

Answer 22

Hepcidin - modulates Fe absorption

Question 23

TfR

Answer 23

Transferrin-receptor mediated endocytosis

Erythroid precursors have 800,000 TfR molecules per cell

Question 24

hbd

Answer 24

Hemoglobin deficit

Docking protein

Question 25

Kiss and Run hypothesis

Answer 25

Transfer of iron to mito Endosome docks transiently on mito and transpires iron directly NOT through a transport

Question 26

Steap3

Answer 26

Ferrireductase that reduces Ferric to Ferrous Fe2+

Question 27

Aspirin abuse results in

Answer 27

iron deficiency

Question 28

Iron Deficiency

Answer 28

Hypochromic microcytic anemia | Tx: dietary iron supplement

Question 29

Hereditary hemochromatosis

Answer 29

Genetic iron overloading Things go very wrong with iron transport system Sxs: cirrhosis, arthritis, endocrinopathy, skin pigmentation, cardiomyopathy 6th decade in life

Question 30

Conditional iron overloading

Answer 30

Repeated blood transfusions | eg. sickle cell anemia

Question 31

Genetic definition of hereditary hemochromatosis

Answer 31

Mutations HFE gene | Cys 282 --> Tyr

Question 32

HH

Answer 32

Hereditary hemochromatosis

Question 33

HH clinical presentation

Answer 33

Elevated total body iron WITH cell injury Liver, pancreas and heart are at risk Free iron is TOXIC

Question 34

HH Lab tests

Answer 34

Serum ferritin: > 400 ng/ml normal: 20-300 CT, MRI or histological exam of liver biopsy

Question 35

HFE protein

Answer 35

Binds to transferrin receptor | Cys 282 Tyr (C282Y) mutation causes HH

Question 36

What genetic mutation causes HH?

Answer 36

Cys 282 Tyr (C282Y)

Question 37

HH treatment

Answer 37

Blood letting 1/wk for 80 weeks then monthly | ExJade

Question 38

ExJade

Answer 38

Experimental tx HH Iron chelator Serious SE - nephrotic syndrome, death

Question 39

Hepcidin

Answer 39

Regulatory effect by binding to ferroportin - the iron door Ferroportin is receptor for hepcidin Hepcidin binds to ferroportin and causes internalization of ferroportin is destroyed by proteolysis

Question 40

Hepcidin if iron is replete

Answer 40

Expression of hepcidin is up and ferroportin levels down

Question 41

Hepcidin if iron is depleted

Answer 41

Hepcidin expression down and ferroportin levels up

Question 42

Hfe mutated

Answer 42

Cannot bind to TfR2 | Cannot turn on hepcidin expression

Question 43

Hfe and signal transduction

Answer 43

Works through Smad signaling transduction

Question 44

2nd pathway for Hfe

Answer 44

BMP (bone morphogenic protein) | Affected in juvenile HH

Question 45

BMP6

Answer 45

Plays biggest role in BMP signaling | Induced by increased dietary iron and increased iron stores

Question 46

Juvenile hemochromatosis

Answer 46

Iron overloading dz 2nd decade of life 1 type is mutation in HJV gene

Question 47

HJV protein

Answer 47

Enhances activity of BMPR | Results in increase in hepcidin

Question 48

Severe hepcidin deficiency

Answer 48

Juvenile HH | Severe iron overload

Question 49

Less hepcidin

Answer 49

Means more ferroportin and have increased ferroportin available for iron absorption Juvenile HH

Question 50

2nd type of juvenile hemochromatosis

Answer 50

HAMP gene is mutated | Hepcidin not binding to ferroportin leads to severe juvenile hemochromatosis

Question 51

Sickle cell anemia

Answer 51

Blood transfusions to prevent stroke

Question 52

B-thalassemis

Answer 52

No B-globin synthesis | Treatment is blood transfusions - this is what ultimately kills them (iron overload)

Question 53

Tranfusion-dependent non-hemochromatosis iron overloading

Answer 53

Sickle cell anemia | B-thalassemia

Question 54

Tmprss6

Answer 54

Mask mouse Microcytic, hypochromic anemia due to iron def HJV - less Smad activity - less hepcidin, more ferroportin

Question 55

Pt presents with excessive iron deposits in liver, serum ferritin is elevated and genetic test reveals homozygosity for C282Y. What is dx?

Answer 55

Hereditary hemochromatosis