Lecture 5 - Iron, IDA, anaemia, and iron overload Flashcards
Where is iron located in the body?
Haemoglobin - ~65%
Myoglobin - ~10%
Enzymes - ~5%
Ferritin, haemosiderin - ~20%
Transferrin - ~0.1/0.2%
Myoglobin
Muscle stuff (google)
Difference between active and depot iron
Active - in use but unavailable to the body
Depot - available to the body
Difference between ferric and ferrous iron
Ferric iron (Fe³⁺) is virtually insoluble
Ferrous iron (Fe²⁺) is soluble
Daily iron cycle
- 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)
Duodenal cytochrome b: what is it and what does it do?
Converts iron from the inactive form (Fe³⁺) into the active form (Fe²⁺)
What inhibits iron absorption
Phytates, tannins, and tetracycline
Tea, antibiotics
Iron absorption molecular mechanism
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
Transferrin
Transfers iron, can hold two irons at once, is recycled after use
Ferritin
- 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
Haemosiderin
- 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)
Iron requirements
Additional iron requirement:
* Growth during childhood (0.5-1mg)
* Menstrual periods (0.5-1mg)
* Pregnancy (3-4mg)
Normal iron stores of serum ferritin, transferrin, serum iron, and transferrin saturation
20-300 ug/L
1.7-3.4 g/L
10-30 umol/L
>16 %
IDA stores of serum ferritin, transferrin, serum iron, and transferrin saturation
<20 ug/L
>3.4 g/L
<10 umol/L
<16 %
Anaemia
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
What are the main causes of anaemia?
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
Physiological response to anaemia
2,3 DPG (? google) levels rise to ensure oxygen is …
Cardiac output increases (circulation becomes hyperdynamic (rapid pulse and heart murmurs))
Signs and symptoms
Pale
Fatigue
Dyspnea
Palpitations
Headache
Tinnitus
Anorexia
Bowel disturbance
IDA: what is it and what are the signs and symptoms
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)
Iron deficiency anaemia: how is it diagnosed and what typically are the findings?
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
IDA treatment
Replace the lost iron:
Iron sulphate - cheap, contains 67mg of iron per 200mg tablet
Usually taken for at least 6 months
Iron overload
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?
Excessive iron storage disorders
Hereditary (primary) haemochromatosis
Autosomal recessive condition
Excessive absorption of iron from the GI tract
Northern European descent: high incidence
Treatment: venesection
