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Cardiopulmonary I > Iron Absorption and Metabolism - White > Flashcards

Iron Absorption and Metabolism - White Flashcards

1
Q

Fe

A

Important role in ETC and oxygen transport

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2
Q

Fe under aerobic conditions

A

Readily exchanges electrons

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3
Q

Total body iron

A

3-5g

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4
Q

How much iron is in RBCs?

A

2.7g

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5
Q

How many mg per day to support Hb production?

A

25mg

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6
Q

The iron cycle

A

Like a gang

Blood in, blood letting out

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7
Q

Why is iron chelated to proteins or other molecules?

A

Maintain solubility

Limit toxicity

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8
Q

Stored iron

A

Ferritin
Hemosiderin
Excess iron stored in liver, lungs and pancreas

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9
Q

Ferritin

A

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

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10
Q

Hemosiderin

A

Granules of ferritin

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11
Q

Excess iron mainly stored by

A

Liver
Lungs
Pancreas

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12
Q

Can iron freely diffuse across membranes?

A

No, need transport mechanisms

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13
Q

4 iron transporters

A

Ferrireductase
DMT1
Hephaestin
Ferroportin

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14
Q

Fe overloading

A

If iron absorption is high

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15
Q

Fe deficiency

A

If iron absorption is low

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16
Q

Dietary iron is in what form?

A

Ferric form Fe3+

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17
Q

Dcytb

A 
Duodenal cytochrome-like b
Reduces ferric (Fe3+) to ferrous (Fe2+)
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18
Q

DMT1

A

Iron uptake channel

On apical surface of the enterocyte in the microvilli region

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19
Q

Ferroportin

A

Iron door

Requires hephaestin

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20
Q

Hephaestin

A

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

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21
Q

Transferrin

A 
Carries ferric (Fe3+, non-toxic form) to the bone marrow
Found in sla - sex linked anemia
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22
Q

How is iron content in the body regulated?

A

Hepcidin - modulates Fe absorption

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23
Q

TfR

A

Transferrin-receptor mediated endocytosis

Erythroid precursors have 800,000 TfR molecules per cell

24
Q

hbd

A

Hemoglobin deficit

Docking protein

25
Q

Kiss and Run hypothesis

A

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

26
Q

Steap3

A

Ferrireductase that reduces Ferric to Ferrous Fe2+

27
Q

Aspirin abuse results in

A

iron deficiency

28
Q

Iron Deficiency

A

Hypochromic microcytic anemia

Tx: dietary iron supplement

29
Q

Hereditary hemochromatosis

A

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

30
Q

Conditional iron overloading

A

Repeated blood transfusions

eg. sickle cell anemia

31
Q

Genetic definition of hereditary hemochromatosis

A

Mutations HFE gene

Cys 282 –> Tyr

32
Q

HH

A

Hereditary hemochromatosis

33
Q

HH clinical presentation

A

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

34
Q

HH Lab tests

A

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

35
Q

HFE protein

A

Binds to transferrin receptor

Cys 282 Tyr (C282Y) mutation causes HH

36
Q

What genetic mutation causes HH?

A

Cys 282 Tyr (C282Y)

37
Q

HH treatment

A

Blood letting 1/wk for 80 weeks then monthly

ExJade

38
Q

ExJade

A

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

39
Q

Hepcidin

A

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

40
Q

Hepcidin if iron is replete

A

Expression of hepcidin is up and ferroportin levels down

41
Q

Hepcidin if iron is depleted

A

Hepcidin expression down and ferroportin levels up

42
Q

Hfe mutated

A

Cannot bind to TfR2

Cannot turn on hepcidin expression

43
Q

Hfe and signal transduction

A

Works through Smad signaling transduction

44
Q

2nd pathway for Hfe

A

BMP (bone morphogenic protein)

Affected in juvenile HH

45
Q

BMP6

A

Plays biggest role in BMP signaling

Induced by increased dietary iron and increased iron stores

46
Q

Juvenile hemochromatosis

A

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

47
Q

HJV protein

A

Enhances activity of BMPR

Results in increase in hepcidin

48
Q

Severe hepcidin deficiency

A

Juvenile HH

Severe iron overload

49
Q

Less hepcidin

A

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

50
Q

2nd type of juvenile hemochromatosis

A

HAMP gene is mutated

Hepcidin not binding to ferroportin leads to severe juvenile hemochromatosis

51
Q

Sickle cell anemia

A

Blood transfusions to prevent stroke

52
Q

B-thalassemis

A

No B-globin synthesis

Treatment is blood transfusions - this is what ultimately kills them (iron overload)

53
Q

Tranfusion-dependent non-hemochromatosis iron overloading

A

Sickle cell anemia

B-thalassemia

54
Q

Tmprss6

A

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

55
Q

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

A

Hereditary hemochromatosis

Cardiopulmonary I (34 decks)

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