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Hematology > Iron and Heme > Flashcards

Iron and Heme Flashcards

1
Q

What is the form of iron found in veggies?

A

Fe 3+

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2
Q

Why can’t Fe be found in the free form in the circulation?

A

forms ROS

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3
Q

What are the two storage forms of Fe?

A

Ferritin

hemosiderin

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4
Q

The appearance of hemosiderin molecules in tissues is a sign of what?

A

Fe overload

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5
Q

What is the form of Fe found in the blood when it is being shuttled from the enterocytes?

A

Transferrin

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6
Q

Where does Fe go to be made into heme?

A

Erythroid precursors

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7
Q

Where is ferritin found (in what cells)?

A

Phagocytes

Hepatocytes

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8
Q

What are small erythrocytes indicative of?

A

Fe deficiency anemia

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9
Q

What are the two problems when Fe is oxidized in the body?

A

Fe 3+ is useless

superoxide is created

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10
Q

What is the most damaging ROS?

A

hydroxide radical

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11
Q

Why is meat a better source of Fe than plants?

A

In heme and Fe2+ form

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12
Q

How is Fe regulated?

A

Uptake (there is no loss through urine)

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13
Q

What are the only two ways in which you can lose Fe?

A

Sloughing off of enterocytes

Blood loss

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14
Q

What percent of the Fe in the body is active?

A

80%

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15
Q

What is the dynamic storage form of Fe?

A

Ferritin

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16
Q

What is the degenerated, long-term storage form of Fe?

A

Hemosiderin

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17
Q

What happens to the Fe in RBCs when the RBCs die?

A

Taken up by splenic macrophages, added to transferritin, and exchanged with the liver

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18
Q

What is the protein that transports Fe into enterocytes?

A

DMT1

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19
Q

What is the protein that takes up heme?

A

Heme carrier protein HCP1

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20
Q

How is non-heme iron (Fe3+) taken up into enterocytes?

A

First, reduced to Fe2+ by duodenal p4500. Then DMT1 takes it up

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21
Q

The uptake of Fe is not dependent on how much Fe the body has. How, then, do we not have a constant accumulation of Fe in the blood?

A

Enterocytes can keep the Fe, and it will be lost when the enterocytes are sloughed off

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22
Q

What is the protein channel on the blood side of the enterocytes that allows ferritin to travel out?

A

Ferroportin 1

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23
Q

What is the kep protein that regulates how much Fe is released into the blood? What organ produces this?

A

Hepcidin

Produced by the liver if there is too much Fe

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24
Q

How do cell signal that the need Fe?

A

Transferrin receptor upregulated.

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25
Q

How is Fe brought into cells?

A

Transferrin binds it, endocytosis, acidification, release

26
Q

What happens to Fe when it enter the circulation? What about when it enters a cell?

A

Turns to Fe3+ in the circulatuion

2+ in the cell

27
Q

What is the protein that acidifies the endosome that contain the tranferrin receptor?

A

ATPase

28
Q

What is the protein on the lysosome containing Fe, that allows for Fe to escape into the cell?

A

DMT1

29
Q

Inside the cell, Fe is stored as what?

A

Ferritin

30
Q

What are the three organs in the body where ferritin is held?

A

Liver
Spleen
Bone marrow

31
Q

Ferritin denature into what?

A

Hemosiderin

32
Q

Low hepcidin means Fe uptake is low or high?

A

high

33
Q

What is the basis for hemochromatosis?

A

mutations in HFE (Fe upstream regulator) resulting in low hepcidin

34
Q

What are the two physiologic consequences of hepcidin release?

A

Low release of Fe by enterocytes

Macrophages do not release Fe into the blood

35
Q

What is the part of the DNA that regulates Fe? How is this regulated?

A

Iron response element (IRE)

Iron regulatory proteins bind to the mRNA (that is always there) and prevent transcription.

36
Q

What are the three proteins that are encoded on the IRE?

A

Ferritin
delta-ALA synthase
Transferrin receptor

37
Q

What is the role of delta-ALA synthase?

A

Produces heme

38
Q

What is serum Fe used to test for?

A

Fe poisoning or overload

39
Q

What is total iron binding capacity used for?

A

Tests transferrin saturation, which is usually around 30%. Lower = anemia

40
Q

What complicates the total iron binding capacity values?

A

Hypoproteinemia

41
Q

What is the value of the serum ferritin?

A

Best measure of Fe body stores

42
Q

What is the value of red cell protoporphyrin?

A

Fe-free precursor of heme. Elevation = shortage of iron to complete heme synthesis

43
Q

What cytokine stmulates the production of hepcidin? Why?

A

IL-6–reduces Fe available to bacteria

44
Q

What is the first stage of Fe deficiency anemia?

A

Fe depletion

45
Q

What is the second stage of Fe deficiency anemia?

A

Deficient erythropoiesis with normal [Hb]

46
Q

What is the third and final stage of Fe deficiency anemia?

A

Hb production is inadequate, resulting in microcytic anemia

47
Q

What are two iatrogenic causes of Fe overload?

A

transfusion

Inappropraite parenteral nutrition

48
Q

Draw the heme synthesis pathway

A

Draw

49
Q

What enzyme is the reguatory point for heme synthesis? What is the regulator?

A

ALA synthase

Heme or Fe will inhibit it

50
Q

What intermediate of the heme synthesis pathway is susceptible to UV light?

A

UPG III

51
Q

Where is ALA synthase located?

A

Membrane of the mitochondria

52
Q

What is x-linked sideroblastic anemia?

A

Defective ALA synthase means not enough heme is produced

53
Q

What are diseases that involve defects in heme synthesis called?

A

Porphyrias

54
Q

What is the problem with how the heme synthesis is regulated, and porphyrias?

A

Since no heme is produced d/t porphyrias, ALA synthase is upregulated, generating more defective intermediates

55
Q

What is the most common presentation of a porphyria?

A

Abdominal pain

56
Q

What is the effect of EtOH consumption on porphyrias?

A

induces the synthesis of cytochrome p450s, which require heme

57
Q

What is acute intermittent porphyria? Symptoms?

A

Deficiency in porphobilinogen deaminase (PBG deaminase)

Dark red urine

58
Q

What is porphyria cutanea tarda? Symptoms?

A

Deficiency of uroporphyrinogen decarboxylase.

Fluorescent urine
Photosentivity of the skin

59
Q

What are the two enzymes that Pb affects in the heme synthesis pathway?

A

ALA synthase

Ferrochelatase

60
Q

Which is the photosensitive porphyria?

A

PCT since UPG III absorbs UV light

Hematology (32 decks)

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