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MEH > 4.2. Iron Metabolism And Microcytic Anaemias > Flashcards

4.2. Iron Metabolism And Microcytic Anaemias Flashcards

1
Q

What are signs on microcytic anaemia?

A

Reduced rate of haemoglobin synthesis

Erythrocytes are smaller than usual

Hypochromic cells

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2
Q

What 5 things are likely to cause microcytic anaemias?

A

TAILS

Thalassaemia
Anaemia of chronic disease
Iron deficinecy
Lead poisoning 
Sideroblastic anaemia
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3
Q

What is iron required for in the body?

A

Oxygen carriers (myoglobin and haemoglobin)

Co-factor in many enzymes ( Cytochromes (oxidative phosphorylation), Krebs cycle enzymes, Cytochrome P450 enzymes (detoxification), Catalase)

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4
Q

Why is it important that iron is regulated?

A

Free iron is toxic to cells.

Body has to mechanism for excreting iron so must control how much we absorb.

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5
Q

What oxidation states can iron be found in?

A

Fe2+ = ferrous iron/haem iron

Fe3+ = ferric iron

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6
Q

Wha type of iron can the body absorb?

A

ferrous iron Fe2+

Ferric iron Fe3+ must be reduced to ferric iron Fe2+ before it can be absorbed in the diet.

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7
Q

How much iron is required daily in our diet?

A

10-15 mg per day

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8
Q

Where is ferrous iron absorbed?

A

Duodenum and jejunum (proximal intestines)

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9
Q

What are good sources of haem iron?

A 
Liver
Kidney
Beef steak
Duck
Chicken
Pork chop
Tuna
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10
Q

What are good sources of non haem iron?

A 
Fortified cereals
Raisins
Beans
Figs
Barley
Oats
Rise
Potatoes
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11
Q

What is hepcidin?

A

A protein produced in the liver. Function is to inhibit the action of ferroportin (ferrous iron transporter in the gut) reducing the amount of iron we absorb from our diet.

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12
Q

What is ferroportin?

A

A ferrous iron transporter on the basolateral surface of enterocyte of the duodenum and jejunum. It transports ferrous iron out of the enterocytes into the blood.

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13
Q

How is ferrous iron transported into enterocytes?

A
  1. Can be absorbed directly into enterocytes from stomach chyme across the apical surface
  2. Ferrous iron can be transported across the membrane with DMT1 transporter.
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14
Q

How is ferric iron absorbed?

A

Ferric ferric iron cannot be absorbed, and must be transformed into ferrous iron. Reductase enzyme on the apical surface transforms the ferric iron to ferric iron using vitamin c.

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15
Q

What is transferrin?

A

A transporter that carries iron around the body. By converting ferrous iron to ferric iron.

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16
Q

What is the function of hephaestin?

A

Hephaestin is an enzyme on the absolute rail surface of enterocytes. It transforms ferrous iron to ferric iron, allowing for iron to be transported by transferrin.

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17
Q

What factors inhibit the absorption of iron?

A

Tannins (in tea)
Phytates (pulses)
Fibre
Antacids (gaviscon)

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18
Q

What factors have a positive influence on the absorption of iron?

A

Vitamin C
Citrate
(Electron donors that allow ferric iron to become ferrous iron for absorption)

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19
Q

What is functional iron?

A

Iron that is currently in use and being transported around the body.
Examples are haemoglobin, myoglobin, enzymes and transported iron.

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20
Q

What is stored iron?

A

Iron that is not currently in use but has been absorbed and stored in the body.

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21
Q

What two molecules can iron be stored as?

A

Ferritin

Haemosiderin

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22
Q

What is ferritin?

A

A soluble iron storage molecule within enterocytes. Stores iron as ferric iron.

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23
Q

Describe the structure of ferritin

A

Globular protein complex with hollow core. Pores allow iron to enter and be released.

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24
Q

What is haemosiderin?

A

An insoluble iron storage molecule. Accumulates in macrophages, particularly in liver, spleen and marrow.

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25
Q

Describe the structure of haemosiderin

A

Insoluble aggregates of clumped ferritin particles, denatured protein & lipid.

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26
Q

How is ferric iron taken up by cells?

A

Receptor-mediated endocytosis

Fe3+ bound transferrin binds transferrin receptor and enters the cytosol receptor-mediated endocytosis.

once ferric iron is released, receptor is recycle back to the membrane

27
Q

What is the cytosol?

A

the aqueous component of the cytoplasm of a cell, within which various organelles and particles are suspended.

28
Q

What happens to ferric iron once it enters cells bound to transferrin?

A
  1. Fe3+ within endosome released by acidic microenvironment and reduced to Fe2+.
  2. The Fe2+ transported to the cytosol via DMT1.
  3. Once in the cytosol, Fe2+ can be stored in ferritin, exported by
    ferroportin (FPN1), or taken up by mitochondria for use in
    cytochrome enzymes.
29
Q

How much iron is in the body?

A

3350mg

30
Q

Why do we recycle iron from senescent red blood cells?

A

As only small fraction of total daily iron requirement gained from the diet (20%).
Need to recycle iron to meet requirement (80% of daily requirement is obtained from senescent RBC)

31
Q

How are old defective red blood cells broken down?

A

Engulfed by macrophages (phagocytosis). Mainly by splenic macrophages and Kupffer cells of liver.
Macrophages catabolise haem released from red blood cells.

Amino acids reused and Iron exported to blood (transferrin) or
returned to storage pool as ferritin in macrophage.

32
Q

What factors affect the regulation of iron absorption?

A

dietary factors
body iron stores
erythropoiesis
Dietary iron levels sensed by enterocytes

33
Q

What control mechanisms regulate iron absorption?

A

Regulation of transporters e.g. ferroportin
Regulation of receptors e.g. transferrin receptor &
HFE protein (interacts with transferrin receptor)
Hepcidin and cytokines
Crosstalk between the epithelial cells and other cells
like macrophages

34
Q

What is hepsidin?

A

A negative regulator of iron absorption. Produced in the liver.
Hepscidin induces degradation of ferroportin, an iron transporter allowing iron to move from enterocytes into the blood. Therefore iron levels deplete as it can not be absorbed. Also affects ferritin stores.

35
Q

What factors affect the synthesis of hepsidin?

A

Iron overload increases the synthesis of hepsidin

High erythropoietic activity decreases the synthesis of hepsidin.

36
Q

What causes anaemia of chronic disease?

A

When an inflammatory condition (rheumatoid arthritis, chronic infection, malignancy) caused cytokines (IL6) to be released by immune cells, these cytokines can inhibit iron absorption, resulting in anaemia.

37
Q

What effects can cytokines such as interleukin 6 have on iron absorption?

A
  1. Inhibition of erythropoiesis in marrow
  2. Inhibition of erythropoietin produced by the kidneys.
  3. Increased production of hepcidin by liver, which inhibits ferroportin transporter
38
Q

How is the plasma iron pool replenished?

A
  1. Erythrocyte destruction my macrophages, mainly in the spleen
  2. Dietary iron absorption
  3. Iron stores mainly in liver
39
Q

What depletes plasma iron stores?

A
  1. Erythrocyte production in bone marrow
  2. Loss of iron (menstration, blood loss, sweat, pregnancy)
  3. Iron stores, mainly in liver
40
Q

What is iron deficiency?

A

A clinical sign, not a diagnosis.

41
Q

What causes a patient to be iron deficient?

A

Insufficient iron in diet e.g. Vegan & vegetarian diets

Malabsorption of iron e.g. Vegan & vegetarian diets

Bleeding e.g. Menstruation, gastric bleeding due to chronic NSAID usage

Increased requirement e.g. Pregnancy, rapid growth

Anaemia of chronic disease e.g. Inflammatory bowel disease

42
Q

Why are iron requirements for females higher than males?

A

From puberty to menopause (19 - 50) females iron requirement is likely to be higher than males due to menstration.

43
Q

What are signs and symptoms of anaemia?

A 
Tiredness 
Pallor 
Reduced exercise tolerance (due to reduced
oxygen carrying capacity) 
Cardiac – angina, palpitations, development of
heart failure 
Increased respiratory rate 
Headache, dizziness, light-headedness
Pica 
Cold hands and feet
Epithelial changes
44
Q

What is pica?

A

unusual cravings for non-nutritive substances e.g. dirt, ice

45
Q

What epithelial changes do patients with anaemia experience?

A

Angular cheilitis
Glossitis
Koilonychia

46
Q

What are common FBC results in a patient with iron deficiency anaemia?

A

Decreased MCV, RBC, mean corpuscular haemoglobin concentration, serum ferritin, serum iron

Raised platelet count, white blood cell count

47
Q

How do RBC appear on a blood film in iron deficiency anaemia?

A

Microcyti
Hypochromic
Anisopoikilocytosis
Occasionally pencil cells and target cells

48
Q

Where can ferritin be found?

A

Cytosol of cells, mainly in the liver.

Ferritin is predominantly a cytosolic protein but small amounts are secreted into blood where it functions as an iron carrier.

49
Q

What is measured as a marker of iron status?

A

Plasma ferritin levels. Reduced plasma ferritin levels indicate iron deficiency, but normal or increase plasma ferritin levels does not exclude iron deficiency.

CHr (reticulocyte haemoglobin content) recommended by NICE to
test for functional iron deficiency. Reticulocyte haemoglobin content remains low during inflammatory responses.

50
Q

Why are plasma ferritin levels not always reliable in testing for iron deficiency?

A

Because ferritin levels can also increase considerably in cancer, infection, inflammation, liver disease, alcoholism

51
Q

What is the first line treatment for iron deficiency?

A

Dietary advice

Oral supplements

52
Q

Why is compliance with oral iron supplement treatment poor?

A

GI side effects

53
Q

What treatments for iron deficiency are considered if first line treatment isn’t effective?

A

Intramuscular iron injections
Intravenous iron
Blood transfusion

54
Q

Why is iron excess dangerous?

A

Excess iron can exceed binding capacity of transferrin This excess iron cannot be transported and is instead deposited in organs as haemosiderin.
Iron promotes free radical formation by Fenton reaction resulting in organ damage

55
Q

What is the Fenton reaction?

A

The process by which iron forms hydroxyl and hydroperoxyl free radicals.

56
Q

How do hydroxyl and hydroperoxyl radicals cause damage to cells?

A

Lipid peroxidation
Damage to proteins
Damage to DNA

57
Q

What 2 things can cause deposition of haemosiderin?

A

Transfusion associated haemosiderosis

Hereditary haemochromostosis

58
Q

What is transfusion associated haemosiderosis?

A

Repeated blood transfusions give gradual accumulation of iron (400ml blood = 200mg iron)
Problem with transfusion dependent anaemias such as thalassaemia & sickle cell anaemia
Iron chelating agents such as desferrioxamine can delay but
do not stop inevitable effects of iron overload

59
Q

Where does haemosiderin usually accumulate?

A

Liver, heart and endocrine organs.

60
Q

What conditions can be caused by haemosiderin deposition in organs?

A
  • Liver cirrhosis
  • Diabetes mellitus
  • Hypogonadism
  • Cardiomyopathy
  • Arthropathy
  • “Slate grey” colour of skin
61
Q

What is hereditary haemochromatosis?

A

Autosomal recessive disease caused by
mutation in HFE gene (on Chr 6). Mutated HFE cant bind to transferrin so the negative influence on iron uptake is lost and iron levels are high and too much enters cells. Iron accumulates in organs causing damage.

62
Q

What is the function of HFE protein?

A

The HFE protein has 2 functions:

  1. HFE protein normally interacts with transferrin receptor reducing its affinity for iron-bound transferrin. Resulting in cells absorbing less iron from blood.
  2. HFE also has negative influence on hepcidin production so, again, a negative influence on iron uptake is lost
63
Q

How is hereditary haemochromatosis treated?

A

With venesection.

64
Q

What are signs and symptoms of hereditary haemochromatosis?

A
  • Liver cirrhosis
  • Diabetes mellitus
  • Hypogonadism
  • Cardiomyopathy
  • Arthropathy
  • Increased skin pigmentation (bronze skin)

MEH (23 decks)

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