Iron Flashcards

1
Q

Which forms of iron exist in the body? which form is needed for oxygen transport? why is iron held in a prophyrin ring?

A

Fe2+ - ferrous = binds oxygen and is more easily absorbed
Fe3+ - ferric

Held in a porphyrin ring because it is toxic and generates free radicals

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2
Q

How is iron stored?

A

it is stored in RBCs within haemoglobin

it is stored in the liver (mainly) and in macrophages carried by ferritin

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3
Q

How is circulating iron carried?

A

it is bound to transferrin (protein with 2 binding sites for iron atoms) which transfers it from donor tissues (macrophages/intestinal cells/hepatocytes) to the bone marrow macrophages (and tissues expressing transferrin receptors) which ‘feeds’ it to RBC precursors

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4
Q

What tests are used to assess:

  • functional iron
  • transported iron
  • storage iron
A

Functional iron - Hb

Transported iron - serum iron, transferrin, transferrin saturation (% saturation of transferrin measures iron supply)

Storage iron:

  • ferritin (if this is too high = iron storage disorder, if this is too low = iron deficiency) = good test for iron deficiency
  • Tissue biopsy (bone marrow for iron deficiency and liver for iron overload in hepatocytes)
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5
Q

what could cause transferrin % saturation to be low? what could cause it to be high? why does this mean it is a bad measure for iron deficiency?

A

Low - anaemia of chronic disease/iron deficiency

high - genetic haemochromotosis

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6
Q

What combination of test results confirms an iron deficiency?

A
  • microcytic, hypochromic anaemia

- low ferritin

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7
Q

What are the three general reasons for iron deficiency?

A

Malabsorption
Low intake
Increased loss

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8
Q

What two causes are there for malabsorption of iron?

A
  • coeliac as need large S/A to absorb iron

- Achlordia as need acid to absorb iron

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9
Q

What is the difference between relative and absolute low intake of iron?

A

Relative - pregnancy/women/children

Absolute - e.g. vegetarians

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10
Q

What 5 ways could a patient be losing iron?

A
  • Haemorrhage
  • Haematuria
  • Menorrhagia
  • GI (could be occult): tumours/ulcers/NSAIDs/parasitic infection
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11
Q

What is occult GI blood loss?

A

loss of 5-10ml per day, this is 4-5g of iron and max. iron absorption is 4-5mg.

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12
Q

Describe iron absorption from the gut

A
  1. iron enters body
  2. DMT-1 transports Fe2+ from duodenum to duodenal cell (Fe3+ is converted to Fe2+ by enzymes on duodenal cell surface)
  3. Ferroportin then transports Fe2+ from duodenal cell to blood. (this is downreg. By hepcidin)
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13
Q

What are the three factors that regulate iron absorption?

A

Systemic factors - hepcidin:
-produced in the liver in response to load and inflammation
=iron can not get out of duodenal enterocytes or macrophages

Intraluminal factors:
- solubility of inorganic iron: reduction of ferric to ferrous

Mucosal factors:

  • ferroportin
  • DMT1
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14
Q

What are the four disorders of iron metabolism?

A

1 - iron deficiency
2 - iron malutilisation (inflammation/chronic disease hepcidin is released from liver)
3 - primary iron overload causing iron deposition in organs/tissues (hereditary haemochromotosis)
4 - secondary iron overload:
Sources - repeated red blood cell transfusions, excessive iron absorption
Disorders - massive ineffective erythropoeisis (thalassaemia/sideroblastic anaemias), refractory hypoplastic anaemias (red cell aplasia/myelodisplasia)

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15
Q

Hereditary haemochromatosis:

  • when does it present?
  • clinical features 6
A
  • presentation at middle age or later
  • cardiomyopathy
  • diabetes
  • cirrhosis
  • arthritis/joint pain
  • weakness/fatigue
  • impotence
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16
Q

What genetic mutation is most commonly found in hereditary haemochromatosis?

A

mutations in the HFE gene

-most likely causes a reduction in hepcidin synthesis

17
Q

What tests are used to diagnose heriditary haemochromatosis? what is the definitive test?

A

1: high transferrin saturation >50% sustained on repeat fasting sample
2: serum ferritin >300mg/l in men or >200m/l in pre-menopausal women
3: liver MRI = definitive

18
Q

How is heriditary haemochromatosis managed?

A

1st do weekly phlebotomy of 450-500mls until iron stores normal (serum ferritin <20nanog/l)

then monthly phlebotomy to keep serum ferritin <50nanog/l

19
Q

What is the role of family screening in hereditary haemochromatosis?

A
  • 1st degree relatives = 1/4 risk
  • if HFE phenotype and iron status = screen

because the disease is asymptomatic until irreversable organ failure = NEED TO SCREEN AND TREAT

20
Q

What is the treatment for secondary iron overload?

A

-iron chelating agents: desferrioxamine SC/IV, new oral agents (deferiprone/deferasirox)