Session 4- Iron Metabolism and microcytic anemias

Question 1

what is iron required for?

Answer 1

Required for:
• Oxygen carriers:
Haemoglobin in red cells
Myoglobin in myocytes

• Co-factor in many enzymes:
• Free iron potentially very toxic to cells

• Complex regulatory systems to ensure the safe
absorption, transportation & utilisation

• Body has no mechanism for excreting iron

Question 2

ferrous

Answer 2

Fe2+

Question 3

ferric

Answer 3

Fe3+

Question 4

what form is dietary iron in

Answer 4

haem iron and non-haem (mix of ferrous and feric)
Ferric iron must be reduced to
ferrous iron (Fe2+) before it can be absorbed from diet

Question 5

where does haem absorption occur

Answer 5

duodenum

upper jejenum

Question 6

dietary absorption of iron

Answer 6

Fe2+ transported via DMT1

Fe3+ reduced to Fe2+ by reductase then transported into cell via DMT1.

FE2+ move into blood via ferroportin this can be prevented by hepcidin from liver

Hephaestin converts Fe2+ Into Fe3+

Fe3+ transported around the body using trasnferrin

Question 7

negative influence on absorption of non-haem iron

Answer 7

• Tannins (in tea)
• Phytates (e.g. Chapattis, pulses)
• Fibre
these three can bind non-haem iron in the intestine. Reduces absorption

• Antacids (e.g. Gaviscon)

Question 8

positive influence on absorption of non-haem iron

Answer 8

Vitamin C & Citrate
• Prevent formation
of insoluble iron compounds
• Vit C also helps reduce ferric
to ferrous iron

Question 9

stored iron

Answer 9

Ferritin
• Globular protein complex with hollow core
• Pores allow iron to enter and be released.
soluble

Haemosiderin
• Aggregates of clumped ferritin particles,
denatured protein & lipid.
• Accumulates in macrophages,
particularly in liver, spleen and marrow.

insoluble

Question 10

cellular iron uptake

Answer 10

1) Fe3+ bound transferrin binds
transferrin receptor and enters
the cytosol receptor-mediated
endocytosis.
2) Fe3+ within endosome released
by acidic microenvironment and
reduced to Fe2+
.
3) The Fe2+ transported to the
cytosol via DMT1.
4) Once in the cytosol, Fe2+ can be
stored in ferritin, exported by
ferroportin (FPN1), or taken up
by mitochondria for use in
cytochrome enzymes

Question 11

iron recycling

Answer 11

• Most (>80%) of iron requirement met
from recycling damaged or
senescent red blood cells
• Old RBCs engulfed by macrophages
(phagocytosis)
• Mainly by splenic macrophages and
Kupffer cells of liver
• Macrophages catabolise haem
released from red blood cells
• Amino acids reused and Iron
exported to blood (transferrin) or
returned to storage pool as ferritin in
macrophage

Question 12

hepcidin: a negative regukar of iron absorption

Answer 12

• Hepcidin synthesis is increased
in iron overload.
• Decreased by high erythropoietic
activity

it induces internalisation and degradation of ferroportin

Question 13

anaemia of chronic disease

Answer 13

inflammatory condition

cytokines released by immune cells

increased production of Hepcidin by liver

inhibition of ferroportin

decreased iron release from reticuloendothelial system
decreased iron absorption in gut

plasma iron reduced

inhibition of erythropoesis

Question 14

causes of iron deficiency

Answer 14

Insufficient iron in diet
e.g. Vegan & vegetarian diets

Malabsorption of iron
e.g. Vegan & vegetarian diets

Bleeding
e.g. Menstruation, gastric bleeding
due to chronic NSAID usage

Increased requirement
e.g. Pregnancy, rapid growth

Anaemia of chronic disease
e.g. Inflammatory bowel disease

Question 15

iron deficiency signs and symptoms

Answer 15

• Tiredness
• Pallor
• Reduced exercise tolerance (due to reduced
oxygen carrying capacity)
• Cardiac – angina, palpitations, development of
heart failure
• Increased respiratory rate
• Headache, dizziness, light-headedness

Pica (unusual cravings for non-nutritive
substances e.g. dirt, ice)

Cold hands and feet

Epithelial changes

Question 16

testing for iron deficiency

Answer 16

plasma ferritin
reduced plasma ferritin
Chr (low reticulocyte Haemoglobin Content) remains low during inflammation

Question 17

treatment of iron deficiency

Answer 17

• Dietary advice
• Oral iron supplements
• Intramuscular iron injections
• Intravenous iron
• Blood transfusion if severe

Question 18

why is excess iron dangerous

Answer 18

• Excess iron can exceed
binding capacity of transferrin
• Excess iron deposited in
organs as haemosiderin
• Iron promotes free radical
formation & organ damage

Question 19

transfusion associated haemosiderosis

Answer 19

• Repeated blood transfusions
give gradual accumulation of
iron

• Problem with transfusion
dependent anaemias such as
thalassaemia & sickle cell
anaemia

• Iron chelating agents such as
desferrioxamine can delay but
do not stop inevitable effects of
iron overload

Question 20

heriditary haemochromatosis

Answer 20

autosomal recessive disease caused by mutation in HFE gene

HFE protein normally interacts with transferrin receptor reducing its affinity for iron-bound transferrin

HFE promotes hepcidin expression through activation of signalling pathways in liver

mutatted HFE therefore results in loss of negative influences on iron uptake and absorption

too much iron enters cells and accumulates in end organ damage

treat with venesection

Question 21

how does the body adapt to anaemia

Answer 21

increased 2,3 DPG production shifts oxygen dissociation curve to the right meaning that Hb gives up oxygen more readily in the tissues

the blood becomes more visous which reduces systemic vascular resistance which increases cardiac output

Question 22

Name two intracellular protein-iron complexes that are used to store iron.

Answer 22

Ferritin and haemosiderin

Question 23

Ferritin

Answer 23

Ferritin is a universal intracellular protein that stores iron and releases it in a controlled fashion. Ferritin is found in most tissues as a cytosolic protein, but small amounts are secreted into the serum where it functions as an iron carrier. A ferritin blood test is therefore a useful diagnistic.

Question 24

haemosiderin

Answer 24

aemosiderin is also an iron-storage complex and is only found within cells. Haemosiderin is complex of ferritin, denatured ferritin and other material. Unlike ferritin, the iron within deposits of haemosiderin is very poorly available.

Question 25

treatment of hereditary haemochromatosis

Answer 25

therapeutic phlebotomy to remove excess iron