Iron and Anaemia Flashcards
Iron
− Haemoprotein, e.g. haem in haemoglobin in red blood cells (oxygen binds to Fe2+), myoglobin (a protein found in muscles)– haem is recycled for reuse again, as well as the amino acids in the haemoglobin
− Bound to a protein, e.g. transferrin, ferritin (storage – in a tin), haemosiderin (when it becomes excessive then the body will store it as this) - (transport of iron or storage of iron in the body) – TRANSFERRIN = TRANSPORT
2 main forms of iron:
- Ferric (Fe3+) - virtually insoluble
2. Ferrous (Fe2+) – soluble
total body count of iron:
2-5grams
Daily iron sources:
2 forms: non-haem and haem
- Haem is found in animal flesh and is well absorbed in humans – red meats
- Non-haem is less well absorbed but is more readily available to us – plant based diets
iron intake:
average western diet is 10-15mg
iron absorption:
- 5-10% (0.5-2mg) absorbed though upper small intestine (duodenum)
- Absorption adjusted to body needs – e.g. if you are going through a growth spurt, pregnant women who need more will be adjusted so more is absorbed
Iron transport and loss:
- Iron is converted from Fe3+ to Fe2+ by duodenal cytochrome b to be used by the body
- Inhibited absorption of iron by phytates (found in nuts – zinc, magnesium, iron), tannins (tea, wine) and tetracycline (an antibiotic)
- Lose small but steady amount, e.g. sweating, shedding skin cells of the mucosal lining of the GI tract, faeces
Daily iron cycle: Uptake and excretion of iron:
- Most of iron in body is in circulating haemoglobin
- Iron continuously circulates in plasma bound to transferrin
- Transferrin: delivers iron to tissues that have transferrin receptors – e.g. red blood cells in bone marrow incorporate it into haemoglobin
Stages of uptake and excretion:
- Absorbed through the gut by the enterocytes and into the gut by transferrin and delivered to wherever it is needed – erythroblasts (bone marrow to produce healthy red blood cells)
- Will also be delivered to tissues where it is needed, to help with the production
- Can be stored in the liver if necessary
- The haemoglobin is the main source of iron and will circulate for 120 days and will be broken down by the macrophages in the spleen and will go back into circulation and be reissued again
- The daily loss will be sided with the amount that is synthesised each day (same amount)
Molecular mechanism of iron absorption:
- Mainly in the duodenum
- Low gastric pH aids the reduction of ferric (3+) iron
- Ferrous iron is transported into the enterocyte by the divalent metal transporter (DMT)
- Stored as ferritin or transported across the basal membrane of cell into plasma: ferroportin (brings iron from the gut into the blood plasma)
- Levels of these proteins important for the rate at which iron can be absorbed:
(1) from the lumen into the cell
(2) from the enterocyte cell into the portal blood - transferrin only transports as Fe3+ to a cell that has a transferrin receptor
Transport of iron – transferrin receptor:
- Bound to a protein called transferrin in plasma
- Transferrin - able to transport iron to any cell that expresses on its surface a specific receptor called the transferrin receptor
1. single membrane spanning receptor
2. 2 subunits, each capable of binding a transferrin molecule.
3. 4 atoms of iron in total can be transferred into the cell each time transferrin binds it receptor and is internalised - Transferrin is recycled each time it transports iron to a cell.
- After binding to the receptor, the transferrin receptor complex is internalised.
- Iron is released and the receptor transferrin complex is recycled to the cell surface.
- Transferrin is released back into the plasma ready to go again – an efficient process that allows us to release transferrin and the receptor to allow more transport of iron to where it is needed
Soluble transferrin receptors (sTFr):
Shed from cells into plasma
Storage iron: FERRITIN
- water soluble
- Protein shell enclosing an iron core
- Serum ferritin level most valuable diagnostic indicator of iron status – how much iron an individual has in their body
- Easily measured by ELISA – immunoassay
Storage iron: Haemosiderin
− Water insoluble
− Derived from lysosomal digestion of ferritin aggregates
− Found in macrophages
− Increased in iron overload – detects this
− Pappenheimer bodies – aggregates of ferritin which you can find in cells – a stain (removed by spleen – makes cells unstable)
Iron loss:
- No specific excretory mechanism for iron – always recycled
- Daily loss:
- Continuous exfoliation of gut/skin epithelial cells (iron containing enzymes)
- Total amount of loss for healthy people in the developed world:
- ~ 1 mg a day for men
- 1.5–2 mg a day for women
- Steady loss means that people must continue to absorb iron – loss needs to balance with intake
- ?? Iron overload – transfusion patients are given iron-collating agents that collates all the excess
Iron requirements:
for growth
menstraul cycles
pregnancy
Defining anaemia:
- Low levels of haemoglobin in the blood
- in 1/3 population
Men less than 13g/dL
Women less than 12g/dL
Causes of anaemia:
- Decreased red cell production
- Increased destruction of red blood cells – haemolytic (in LECTURE 4), LESS INTAKE
- Blood loss (500ml blood contains 200-250mg iron) – menstrual cycle, haemophiliac or an accident
Signs and symptoms of anaemia:
- Pale
- Fatigue
- Dyspnoea – shortness of breath
- Palpitations – circulation becomes hyper-dynamic
- Headache – reduced blood flow to the brain
- Tinnitus – ringing in your ears
- Anorexia and bowel disturbance – haemorrhoids (blood in faeces)
Physiological response in anaemia:
- maintain adequate oxygenation of the body
- 2,3 DPG levels rise – ensure that oxygen is uploaded at tissues
- Cardiac output increases and circulation becomes hyperdynamic – rapid pulse & heart murmurs
