IRON METABOLISM

DR MODUPE OLAIYA
CONSULTANT HAEMATOLOGIST
SENIOR LECTURER
Ag HOD
OBJECTIVES
• Discuss the importance of iron in the body
• List the sites of iron distribution in the body
• State the minimum daily intake of iron required by men, women and
children
• State the site of iron absorption
• Describe the function of transferrin,transferrin receptor, hepcidin,
haemosiderin and ferritin
OBJECTIVES CONTD
• Describe the Diagram of the transport of iron from ingestion to
incorporation into heme
OUTLINE
• INTRODUCTION
• SOURCES OF IRON
• ABSORPTION
• TRANSPORTATION
• STORAGE
• IRON CYCLE
INTRODUCTION
• Iron in its ferrous and ferric states is essential for the life of all
organisms, both plants and animals. Iron is one of the most common
elements in the earth’s crust
SOURCES OF IRON
• Chief dietary sources are liver, kidney,egg yolk, green vegetables and
fruit. Milk particularly cow’s milk has low iron content.
• Considerable amount of iron can be obtained by cooking in iron
utensils.
• Haem iron present in the hb and myoglobin of meat is well absorbed
DISTRIBUTION
The total body iron of a normal adult is between 3-5g depending on the
sex and weight of the individual.
• It is greater in males than in females
ESTIMATED IRON REQM IN MG/DAY
S/N ITEMS Reqm for Menses Pregnancy Growth Total
Urine,sweat,
faeces
1 Men,Post 0.5- Nil Nil Nil 0.5-1.0
menopausal 1.0mg/day
women
2 Menstruating 0.5- 0.5-1.0 Nil Nil 1-2
Women 1.0mg/day mg/day mg/day
3 Pregnant 0.5-1mg/day Nil 1-2mg/day Nil 1.5-2.5
Women
4 Children 0.5mg/day 0.6 1.0
5 Girls aged 12- 0.5-1.0mg/ 0.5-1.0mg/ Nil 0.6 1-2.5
15yrs day day
IRON ABSORPTION
• The regulation of iron absorption is the primary mechanism by which
the body controls its iron content, as capacity to excrete iron is
extremely limited.
• The small intestine is highly sensitive to repletion or depletion of iron
stores and rapidly corrects imbalance by decreasing or increasing
absorption
IRON ABSORPTION
• Dietary intake contains 10-20mg of iron of which 10% or somewhat
less is absorbed.
• Absorption is greater in women than in men because of the greater
requirement due to menstrual loss and child-bearing
IRON ABSORPTION CONTD
• Absorption of non-haem iron in vegetables, fruit and cereals is
variable.
• Non-haem iron is released from food as ferric or ferrous ions by the
action of acid in the stomach and absorbed in the ferrous form
mainly.
• Ferric ions are soluble at low PH, but tend to polymerize and become
unavailable for absorption as the PH rises in the duodenum.
IRON ABSORPTION CONTD
• Ferrous ions are more soluble.
• Ascorbic acid facilitate absorption of iron.
• It reduces Ferric to ferrous ions, forms low mol.wt iron chelates that
remain soluble at the neutral PH of the gut.
• Absorption of iron is most efficient in the duodenum and proximal
jejunum
IRON ABSORPTION CONTD
• Non-haem iron attaches to surface glycoprotein receptors on the
brush border of the mucosal absorptive cells.
• After entry into the cells depending on body’s rqm, a portion is rapidly
transferred across the cell and to portal circulation for distribution to
tissue iron store. Most of the remaining iron in the mucosal cell
combines with apoferritin to form ferritin
IRON ABSORPTION CONTD
• Non-haem iron attaches to surface glycoprotein receptors on the
brush border of the mucosal absorptive cells.
• After entry into the cells depending on body’s rqm, a portion is rapidly
transferred across the cell and to portal circulation for distribution to
tissue iron store. Most of the remaining iron in the mucosal cell
combines with apoferritin to form ferritin
IRON DISTRIBUTION
• Hb iron constitutes approximately 60-70% of the total body iron.
• At the end of the lifespan of RBC, they are phagocytosed by cells of
Reticuloendothelial system (RES).
• Nearly all the iron derived from the breakdown of Hb is released into
the circulation bound to the iron-binding protein, transferrin and is re-
utilized by marrow erythroblasts for Hb synthesis
IRON DISTRIBUTION CONTD
S/N Amount of Iron in average adult Percentage of total Iron
1 Haemoglobin 65
2 Ferritin and Haemosiderin 30
3 Myoglobin 3.5
4 Haem Enzymes(eg. Cytochrome, Catalase, Peroxidase) 0.5
5 Transferrin-bound Iron 0.1
TISSUE IRON
• This can be subdivided into storage or available iron which is readily
mobilized for Hb synthesis OR non-available iron which is not
available for Hb synthesis.
• Amount of storage iron is estimated to be 1000-2000mg in a healthy
adult.
• Iron stores are gradually accumulated during childhood and
adolescence due to a slight excess of absorption over loss from the
body
STORAGE IRON
• Storage iron occurs in two forms: Ferritin and Haemosiderin.
• Ferritin is normally Predominant.
• In a normal person, storage iron is divided about equally between the
RES(Mainly in the spleen,liver and BM), Hepatic parenchymal cells
and skeletal muscles. Haemosiderin, the main storage form in
Reticuloendothelial cells
STORAGE IRON CONTD
• Is more stable and less readily mobilized for Hb formation than
Ferritin which predominates in hepatocytes.
• In states of iron overload, haemosiderin increases to a greater degree
than ferritin and become the dominant storage form.
NON-AVAILABLE TISSUE IRON
• This is made up predominantly of iron in muscle myoglobin and to a
less extent of iron in enzymes such as cytochromes, catalase and
peroxidase. Its amount is relatively constant
TRANSPORT (PLASMA) IRON
• 3-4mg of iron are present in the plasma where it is bound to
transferrin which is synthesized in the liver.
• Each molecule of transferrin binds one or two atoms of ferric iron.
• The function of transferrin is the transport of iron. It is the means by
which iron absorbed from the alimentary tract is transported to the
tissue stores.
TRANSPORT IRON CONTD
• From tissue stores to bone marrow erythroblasts and from one
storage site to another.
• Transferrin on reaching the marrow or storage site it attaches itself to
specific receptors(Transferrin receptor 1(TfR1) on cells and liberates
its ferric ions, which pass into the cell to be stored or utilized
• Plasma iron is continually being recycled with a turn over time of
about three hours
TRANSPORT IRON CONTD
• Total amount of transferrin in the plasma is about 8g. A similar
amount is in the extracellular fluid in equilibrium with plasma
transferrin.
• Transferrin is present in the serum in a concentration which enables it
to combine with 44-80μmol of iron per litre.
• This value is known as the total iron-binding capacity of the serum
• Total amount of transferrin in the plasma is about 8g. A similar
amount is in the extracellular fluid in equilibrium with plasma
transferrin.
• Transferrin is present in the serum in a concentration which enables it
to combine with 44-80μmol of iron per litre.
• This value is known as the total iron-binding capacity of the serum
TIBC

• The percentage of the total binding protein

to which iron is attached is known as the
percentage saturation of the iron binding
protein.
• Calculation= Serum Iron
• TIBC
• Average normal value is about 33%
FERRITIN
• Serum ferritin are cleared by hepatocytes.
• Levels in children are high at birth but rapidly fall and are low from
6months to about 15 years of age
• Serum ferritin concentration in adults range between 15 and 300μg/l
FERRITIN CONTD
• Serum ferritin concentrations correlate well with tissue iron stores but
in special situations such as in infection and inflammation,
malignancy, the serum level may be greater than 15ug/l even when
marrow iron is absent.
• <12ug/l (Iron def.)
• >10,000(Iron Overload)
EXCRETION
• Body is unable to regulate its iron content effectively by excretion.
• Loss is constant and its independent of intake.
• Loss is through desquamation of epithelial cells from alimentary
canal, excretion from the urine, sweat, hair,nail. Iron from faeces is
almost entirely of unabsorbed iron in desquamated mucosa
HEPCIDIN
• Hepcidin is a polypetide produced in the liver.
• It is the major hormonal regulator of iron homeostasis. It acts as a
negative regulator of intestinal iron absorption and also suppresses
release from macrophages. Hepcidin acts by binding with ferroportin
receptor, causing degradation of ferroportin(transmembrane iron
exporter) and trapping iron I the intestinal cells
HEPCIDIN CONTD
• Hepcidin synthesis rises when when transferrin is carrying its
maximum capacity of iron( transferrin saturationnof more than 50% in
females or 60% in males) and diminishes when iron saturation is low