Lecture 5 - Iron, IDA, anaemia, and iron overload

Question 1

Where is iron located in the body?

Answer 1

Haemoglobin - ~65%
Myoglobin - ~10%
Enzymes - ~5%
Ferritin, haemosiderin - ~20%
Transferrin - ~0.1/0.2%

Question 2

Myoglobin

Answer 2

Muscle stuff (google)

Question 3

Difference between active and depot iron

Answer 3

Active - in use but unavailable to the body

Depot - available to the body

Question 4

Difference between ferric and ferrous iron

Answer 4

Ferric iron (Fe³⁺) is virtually insoluble

Ferrous iron (Fe²⁺) is soluble

Question 5

Daily iron cycle

Answer 5

• Iron is absorbed (~1mg/day) and is taken in by transferrin
• Transferrin can then either store the iron in tissues (enzymes/myoglobin) or the liver (hepatocytes) or transfer the iron to erythroblasts for haemoglobin production
• After ineffective erythropoiesis or RBC breakdown, the iron is then transferred back into transferrin and it can be removed from the body through the hair, skin, urine, or faeces (~1mg/day)

Question 6

Duodenal cytochrome b: what is it and what does it do?

Answer 6

Converts iron from the inactive form (Fe³⁺) into the active form (Fe²⁺)

Question 7

What inhibits iron absorption

Answer 7

Phytates, tannins, and tetracycline

Tea, antibiotics

Question 8

Iron absorption molecular mechanism

Answer 8

Occurs mainly in the duodenum - low gastric pH aids the reduction of ferric iron.

The divalent metal transporter (DMT) transports ferrous iron into the enterocyte.

Stored as ferritin or transported across the basal membrane of the cell into plasma - ferroportin

Hepcidin, the gating structure that decides where the iron is moved to, has different levels which are affected by external stimuli which helps it send iron where it is most needed

Question 9

Transferrin

Answer 9

Transfers iron, can hold two irons at once, is recycled after use

Question 10

Ferritin

Answer 10

• 65% of iron storage
• water soluble
• Protein shell enclosing an iron core
• Serum ferritin level most valuable diagnostic indicator of iron status
• Easily measured by ELISA

Question 11

Haemosiderin

Answer 11

• 35% of iron storage
• Water insoluble
• Derived from lysosomal digestion of ferritin aggregates
• Found in macrophages
• Increased in iron overload
• Pappenheimer bodies
  (removed by spleen)

Question 12

Iron requirements

Answer 12

Additional iron requirement:
* Growth during childhood (0.5-1mg)
* Menstrual periods (0.5-1mg)
* Pregnancy (3-4mg)

Question 13

Normal iron stores of serum ferritin, transferrin, serum iron, and transferrin saturation

Answer 13

20-300 ug/L
1.7-3.4 g/L
10-30 umol/L
>16 %

Question 14

IDA stores of serum ferritin, transferrin, serum iron, and transferrin saturation

Answer 14

<20 ug/L
>3.4 g/L
<10 umol/L
<16 %

Question 15

Anaemia

Answer 15

Low level of haemoglobin level in the blood: less than 13g/dL in men and less than 12g/dL in women

Affects 1/3 of the world’s population

Question 16

What are the main causes of anaemia?

Answer 16

Decreased red cell production ()
Increased red blood cell production ()
Blood loss
Dietary deficiency

Not actual causes, but the reasons for them causing anaemia is the reason - ie less RBCs produced due to a vitamin issue

Question 17

Physiological response to anaemia

Answer 17

2,3 DPG (? google) levels rise to ensure oxygen is …

Cardiac output increases (circulation becomes hyperdynamic (rapid pulse and heart murmurs))

Question 18

Signs and symptoms

Answer 18

Pale
Fatigue
Dyspnea
Palpitations
Headache
Tinnitus
Anorexia
Bowel disturbance

Question 19

IDA: what is it and what are the signs and symptoms

Answer 19

Iron deficiency anaemia

Angular stomatitis (lesions at the corner of the mouth)
Koilonychias (flattening/spooning of the nails)
Glossitis (inflammation and depapillation of the tongue)
The pallor of skin and increased fatigue (less haemoglobin)

Question 20

Iron deficiency anaemia: how is it diagnosed and what typically are the findings?

Answer 20

A blood film test

• Haemoglobin concentration decreases
• Microcytic red blood cells - mean Cell Volume (MCV) < 80fl
• Less iron available and less saturated - amount of iron in the plasma falls and a rise in the amount of transferrin in the plasma
• Increase in amount of transferrin receptor shed into the plasma
  (important as this does not occur with chronic disease or thalassaemia)
• Serum ferritin level is very low

Question 21

IDA treatment

Answer 21

Replace the lost iron:

Iron sulphate - cheap, contains 67mg of iron per 200mg tablet

Usually taken for at least 6 months

Question 22

Iron overload

Answer 22

No mechanism in the body for actively excreting iron

Accumulation can result in serious damage to organs particularly the heart, liver and endocrine organs

Main mechanisms of iron overload include:

Increased iron absorption:

hereditary hemochromatosis - hepcidin issues,

Chronic liver disease

Repeated blood transfusion:

in conditions such as thalassaemia and aplastic anaemia

Increased iron intake-how?

Question 23

Excessive iron storage disorders

Answer 23

Hereditary (primary) haemochromatosis

Autosomal recessive condition

Excessive absorption of iron from the GI tract

Northern European descent: high incidence

Treatment: venesection