5. Iron

Question 1

distribution of iron in the body

Answer 1

70% incorporated into haemoglobin as haem
4.9% in myoglobin, cytochromes and other enzymes as haem
0.1% bound to transferrin (transport protein) in plasma
25% stored in reticuloendothelial system bound into protein complexes, ferritin and haemosiderin (both storage proteins)

Question 2

storage of iron

Answer 2

so not reliant on just diet
ferritin - physiological storage of iron
haemosiderin is pathological, if we have too much iron stored in the body we see increased levels of haemosiderin
if stores are depleted, person is iron deficient

Question 3

two main forms of iron

Answer 3

Ferric (fe3+) : insoluble
Ferrous (Fe2+) : soluble
form depends on where we are getting the iron from and where we are transporting iron to
so form may change depending on where in body it is

Question 4

sources of iron from diet

Answer 4

Haem Iron is more accessible to us as Fe2+ : red meat, poultry, fish
Non haem iron is insoluble, need t convert Fe3+ to Fe2+ in body, this is limiting factor. spinach, leafy greens

Question 5

total body iron content of healthy adult

Answer 5

2-5g

Question 6

daily iron cycle: uptake and excretion

Answer 6

Gut absorbs 1mg of iron a day
we lose 1mg of iron a day in hair, skin, urine, faeces
4mg of iron in body in transferrin can be transported to bone marrow to produce Hb that’s incorporated in rbc which then circulate for 120 days and are broken down in spleen in reticular endothelial cells eg in lungs liver as have macrophages
iron withinhealthy rbc is recycled

Question 7

transferrin in iron cycle

Answer 7

delivers iron to tissues that have transferrin receptors eg liver hepatocytes, erythroblasts in bone marrow, tissues

Question 8

ineffective erythropoiesis in iron cycle

Answer 8

occurs if we lack a factor needed to produce rbc or if something is wrong w the bone marrow
if rbc identified as abnormal will be broken down prematurely by macrophages and the iron recycled

Question 9

iron intake and absorption

Answer 9

average western diet is 10-15mg iron daily
5-10%(0.5-2mg) is absorbed through the duodenum (upper small intestine)
absorption is adjusted to body needs
vitamin C increases absorption of iron

Question 10

iron is converting from Fe3+ to Fe2+ by what enzyme

Answer 10

duodenal cytochrome B

Question 11

iron inhibited by

Answer 11

phytates (spinach)
tannins (wine)
tetracycline (antibiotics)

Question 12

iron loss

Answer 12

we lose small but steady amount of iron eg sweating, shedding skin cells of the mucosal lining of the gi tract, faeces
iron loss is only a problem if the body has an increased iron demand

Question 13

iron absorption

Answer 13

mainly in the duodenum, gut lumen to enterocyte (apical cell) to storage in cell as ferritin or blood in transferrin if needed

Question 14

molecular mechanism of iron absorption

Answer 14

ferrous iron (fe2+) is transported into the enterocyte from the gut lumen by the divalent metal transporter (DMT1)
low gastric pH aids in reduction of ferric iron 
once incorporated into enterocyte cann then be stored as ferritin but if we need iron it is transported across the basal membrane into the plasma ie circulation by ferroportin
however to be transported in transferrin must be converted back into Fe3+ by hephaestin

Question 15

importance of protein levels in iron absorption

Answer 15

important for the rate at which iron can be absorbed

• from the lumen into the cell
• from the enterocyte into the portal blood

Question 16

transport of iron

Answer 16

bound to transferrin in plasma
transferrin- can transport iron to any cell that expresses a transferrin receptor on its surface
transferrin is recycled each time it transports iron to a cell
after binding to its receptor the resulting transferrin receptor complex is internalised
iron is released and the receptor transferrin complex is recycled to the cell surface
transferrin is released back in the plasma ready to go again

Question 17

transferrin receptor

Answer 17

• single membrane spanning receptor
• 2 subunits, each capable of binding a transferrin molecule
• 4 atoms of iron in total can be transferred into the cell each time transferrin binds its receptor and each internalised

Question 18

iron storage - ferritin

Answer 18

makes up 65% of iron storage  
water soluble
protein shell enclosing an iron core 
serum ferritin level is the most valuable diagnostic indicator of iron status 
easily measured by ELISA

Question 19

iron storage - haemosiderin

Answer 19

makes up 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)
increase in haemosiderin is pathological
increased iron intake when unable to store as ferritin becomes haemosiderin

Question 20

iron loss

Answer 20

no specific excretory mechanism for iron
daily loss
- continuous exfoliation of gut/skin epithelial cells (iron containing enzymes)
-total amount of loss for healthy people in developed world is 1mg a day for men and 1.5-2mg a day for women(menstruation)
steady loss means people must continue to absorb iron
(women have greater need )

Question 21

how do we assess iron status

Answer 21

don’t need to remember numbers
normal iron stores
Serum ferritin (µg/L) : 200-300
Transferrin (g/L) : 1.7 - 3.4
Serum iron (µmol/L) : 10-30
Transferrin saturation (%) : >16
Iron deficiency anaemia
Serum ferritin (µg/L) : <20 decreased storage
Transferrin (g/L) : >3.4 increased transport
Serum iron (µmol/L) : <10 decreased conc
Transferrin saturation (%) : <16 decreased, not enough iron to saturate transferrin

Question 22

iron requirements

Answer 22

varies through life 
additional iron requirement:
- growth during childhood (0.5-1mg)
- menstrual periods (0.5-1mg) 
- pregnancy (3-4mg)
these are when youre more likely to suffer from iron deficiency as increased demand for iron

Question 23

anaemia

Answer 23

low level of haemoglobin in the blood
WHO criteria id less than 13g/dL in men and less than 12g/dL in women
Affects 1/3 of worlds population

Question 24

causes of anaemia

Answer 24

• decreased red blood cell production eg due to inadequate iron in diet
• increased destruction of red blood cells
• blood loss (500ml blood contains 200-250mg iron)
• in developing countries dietary deficiency and blood loss due to parasitic infections

Question 25

physiological response to anaemia

Answer 25

maintain adequate oxygenation of the body

• 2,3 DPG levels rise due to hypoxia, allows Hb to change its shape to tight form so more oxygen can be uploaded at the tissues
• cardiac output increases and circulation becomes hyperdynamic - rapid pulse and heart murmurs

Question 26

signs and symptoms of anaemia

Answer 26

pale
fatigue
dyspnoea
palpitations
headache (changes in circulation and inadequate oxygenation)
tinnitus (ringing in ears)
anorexia and bowel disturbance (poorer diet overall)

Question 27

iron deficiency

Answer 27

most common cause of anaemia worldwide
frequently due to another primary pathological state eg stomach cancer (anaemia is presenting feature)
- bleeding : most common cause of iron deficiency especially from the uterus or gi tract
one of the best understood anaemias

Question 28

clinical signs and symptoms of iron deficiency

Answer 28

• flattening and spooning of the nails into a concave shape (koilonychias)
• angular stomatitis : lesions at the corner of the mouth
• glossitis: inflammation and depapillation of the tongue
• reduction in Hb levels lead to mos recognisable features of anaemia such as pallor of skin and increased fatigue

Question 29

blood film of iron deficiency anaemia

Answer 29

anisocytosis and poikilocytosis
hypochromic cells
microcytic rbcs

Question 30

laboratory findings in iron deficiency anaemia

Answer 30

Hb conc decreases
microcytic rbc
mean cell volume MCV decreases <80fl
amount of iron in plasma falls
less iron available (increase in transferrin conc in plasma, but less saturated)
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 low

Question 31

treatment of iron deficiency anaemia

Answer 31

replace the lost iron
iron sulphate
- cheap
- contains 67mg or iron per 200mg tablet
Treatment is usually for at least 6 months (lifecycle of rbc, needs to give coverage for life cycle and then some)

Question 32

iron overload

Answer 32

no mechanism in the body for actively excreting iron

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

Question 33

main mechanisms of iron overload

Answer 33

increased iron absorption:
-hereditary haemochromatosis 
- chronic liver disease
- ineffective erythropoiesis 
Repeated blood transfusion 
- in conditions such as thalassaemia and aplastic anaemia 
- we need to give iron kelating supplements alongside to remove iron to a safe level
Increased iron intake eg by supplements

Question 34

hereditary haemochromomatosis

Answer 34

mechanism of iron overload
individual has inherited mutation within the gene that codes for one of the absorptive proteins and therefore you absorb more iron than you need

Question 35

aplastic anaemia

Answer 35

malignancy that affects all your blood cells, rnc wnc and platelets
treatment is bone marrow stem cell transplant

Question 36

disorders characterised by excessive iron sotage

Answer 36

hereditary (primary) haemochromatosis
- autosomal recessive condition
- excessive absorption of iron from the gi tract
- high incidence in those of northern European descent
treatment is venesection (remove some of the blood)
blood transfusion related
- occurs in transfusion dependent patients eg pyruvate kinase deficiency
Bantu Siderosis (south African tribe) due to methods of cooking