2. Learning Objectives:
Functions of Iron
Dietary sources and daily requirement
Metabolism of Iron: Absorption, storage and
excretion
Disorders of Iron metabolism: Iron deficiency,
Iron excess
3. Micronutrients: minerals required
in minute quantities, and are known
as trace elements or micronutrients
eg. Fe, I, Cu, Zn, Co, Mn , Mo, Cr, Se and F
Macronutrients: Some of these are required
in relatively large quantities, and are known as
principal elements or macronutrients. eg. Ca, P,
Mg,Na, K, Cl and S
4. • Iron
Total amount of iron in an adult human
being is 3-5 gm
Blood and blood-forming organs are the
largest reservoirs of iron in our body
But small amounts of iron are present in
nearly every tissue
6. TYPES OF THE IRON PRESENT IN THE
BODY
1.Essential ( or functional) iron
a.Hemeproteins
b.Cytochromes
c. Iron requiring enzymes
2. Storage iron
a.Ferritin
b.Haemosiderin
7. About 70% of the body iron is present in
haemoglobin and 5% in myoglobin, Ferritin and
haemosiderin, which are storage forms of iron,
contain about 20% of the body iron
Transferrin, an iron carrier protein present in
plasma, contains 0.1% of the body iron
The remaining iron is present in cytochromes and
enzymes
8. • Ferritin
• Ferritin is present in liver, spleen, bone marrow, brain,
kidneys, intestine, placenta etc
• It is one of the storage forms of iron
• The protein portion is known as apoferritin
• Apoferritin combines with iron to form ferritin
• The first step in the synthesis of ferritin is the
formation of apoferritin induced by the entry of ferrous
iron in the cell
9. • This is followed by oxidation of ferrous iron to the
ferric form
• Ferric iron forms ferric hydrophosphate micelles,
which enter the protein shell to form ferritin
• Apoferritin is made up of 24 identical subunits, each
having a molecular weight of 22,000 to 24,000
• The subunits are arranged at the vertices of a
pentagonal dodecahedron with a hollow space in
the centre
10. • Ferric hydrophosphate micelles are present in this
space
• When fully saturated, a molecule of ferritin
contains 5,000 atoms of iron, and has a molecular
weight of 900,000
11. • Haemosiderin
• Haemosiderin is a granular iron-rich protein
• It is insoluble in water unlike ferritin
• The exact structure of haemosiderin is not
known
• It has been shown that iron is first stored in the
body in the form of ferritin
12. • As the iron stores increase, the older ferritin
molecules are aggregated to form haemosiderin
• Some of the protein is degraded in this process
• Therefore, the percentage of iron in haemosiderin
is higher as compared to that in ferritin
• Normally, about two thirds of the stored iron is in
the form of ferritin and one third in the form of
haemosiderin
13. • Transferrin
• Transferrin is a carrier protein which transports iron in
circulation
• Free iron is toxic, and has a tendency to
precipitate
• These problems are overcome by combining iron with
transferrin
• Transferrin is a β1-globulin with a molecular
weight of about 90,000
• It is made up of two non-identical subunits
• One molecule of transferrin can transport two ferric atoms
14. • Transferrin carries iron to and from various tissues
through circulation
• There are specific receptors for transferrin on the cell
membranes of the cells requiring iron e.g. red cell
precursors
• Transferrin-iron complex attaches to these receptors
• This attachment produces a conformational
change in the transferrin molecule as a result of which the
iron is released
• The free transferrin molecules are then displaced from the
cell membrane by molecules carrying iron
15. • The concentration of transferrin in plasma is
200-400 mg/dl
• This amount of transferrin is capable of carrying
250-400 mg of iron per dl of plasma
• This is known as the total iron binding capacity of
plasma
16. • Normal plasma iron level is 50-175 μg/dl which
means that the iron binding capacity of plasma is
only about 30% saturated in healthy subjects
17. • Functions
• • Transport of oxygen
• • Oxidative reactions
• • Tissue respiration
19. Functions
• Oxygen Transport & Storage
– Hemoglobin
– Myoglobin
• Electron Transport & Energy Metabolism
– Cytochromes
– Fe-S proteins
• Substrate Oxidation & Reduction
– Iron dependent enzyme-
– Ribonucleotide reductase
– Amino acid oxidases
– Fatty acid desaturases
– Nitric oxide synthetase
– Peroxidases
• Regulation of intracellular iron
20. FUNCTIONS
Iron mainly exerts its function through the
compound in which it is present.
Hemoglobin and myoglobin are required for
the transport of O2 and CO2.
Cytochromes and certain non heme proteins
are necessary for electron transport chain
and oxidative phosphorylation.
Iron is associated with effective
immunocompetence of the body.
21. • Transport of oxygen
• The most important function of iron is to transport
oxygen in the body in the form of haemoglobin
• A similar function is performed in muscles by
myoglobin
22. • Oxidative reactions
• As a component of the various oxidoreductase
enzymes mentioned earlier, iron plays a role in a
number of oxidative reactions
23. • Tissue respiration
• As a component of cytochromes in the respiratory
chain, iron is involved in tissue respiration
• It is the iron component of the cytochromes that
accepts and donates electrons
24. • Iron Balance
• Iron status depends upon the relative rates of iron
absorption and iron excretion
• Iron absorption is the major mechanism for
maintaining normal iron balance
25. • Iron metabolism is said to occur within a closed
system in the body i.e. there is hardly any exchange
of iron between man and his environment
• The iron present in the body is continuously
reutilised
• Only a minute amount of iron is lost everyday from
the body in the form of exfoliated cells
26. • The faecal iron loss in 0.4-0.5 mg a day
• The urinary iron loss is about 0.1 mg a day
• About 0.2-0.3 mg of iron is lost daily from the skin
along with the exfoliated cells
• Thus, the total iron loss is just under one mg a day
27. • In premenopausal women, there are two
additional routes of iron loss
• About 20-25 mg of iron is lost with menstrual blood
in each cycle
• This is equivalent to a daily loss of 0.7-0.8 mg of
iron
28. • During pregnancy, there is no menstrual loss but
the expectant mother has to provide iron to the
foetus
• This amounts to about 0.6 mg a day in the first
trimester, about 2.8 mg a day in the second
trimester, and about 4 mg a day in the third
trimester of pregnancy
29. • The iron losses are balanced by intestinal
absorption of iron
• The intestinal absorption is affected by body iron
stores, erythropoietic activity, degree of saturation
of plasma transferrin, the amount of dietary iron,
valency of ingested iron (Fe++ or Fe+++) and
presence of other substances in the food
30. • Absorption is more when body iron stores are low,
erythropoietic activity is increased, saturation of
plasma transferrin is low and iron is ingested in
ferrous form
• Presence of ascorbic acid, succinic acid, histidine
and cysteine in the food increases iron absorption
• Phytates and phosphates retard iron absorption
31. • Iron can be absorbed from all segments of the Small
intestine but presence and normal functioning of
stomach are also essential
• Patients with achlorhydria and those who have
undergone gastrectomy absorb less iron as
compared to normal persons
• Gastric enzymes and hydrochloric acid release iron
from iron-containing com-pounds and reduce ferric
iron to the ferrous form
32. • It is believed that ferritin content of mucosal cells of
the intestine regulates the absorption of iron
• These cells are formed in the crypts of Leiberkuhn
• They gradually reach the tip of the villi and are
shed off into the intestinal lumen
• Their average life-span is three days
33. • The function of ferritin in these cells is to blockthe
absorption of iron
• Those cells which are formed during a period of
iron overload are rich in ferritin
• These cells will absorb little iron during their
lifespan
• Moreover, when these are shed off, their iron
content will also be lost in faeces
34. • Conversely, the cells formed during a period of iron
deficiency are poor in ferritin
• These cells absorb more iron and transfer it into
the plasma
35. • Requirement
• Though the actual requirement of iron is very
small, much larger amounts have to be provided in
diet because only a small proportion of the dietary
iron is normally absorbed
36. • The daily requirement in different age groups is follows:
• Infants : 6-10 mg/day
• Children : 10 mg/day
• Adolescents : 12 mg/day
• Adult men and postmenopausal women : 10 mg/day
• Menstruating women: 20 mg/day
• Pregnant and lactating women : 40 mg/day
38. • A much greater proportion of iron can be
absorbed from animal foods than from vegetable
foods
• On a mixed diet, healthy subjects absorb
5-10% of the dietary iron
39. • Iron deficiency
• Iron deficiency is widespread both in poor and in
affluent countries
• Iron deficiency is the commonest cause of anaemia
throughout the world
41. • Deficiency can be caused by inadequate intake of
iron especially when the requirement is high e.g. in
infancy, adolescence and pregnancy
• Malabsorption resulting from steatorrhoea, coeliac
disease, gastrectomy etc can also cause iron
deficiency
• Persistent blood loss, e.g. from genital
tract,gastrointestinal tract, hookworm infestation
etc, can also result in iron deficiency
42. • When iron deficiency develops, the earliest
change is a depletion of body iron stores
• Other changes follow progressively
• Plasma transferrin saturation is decreased
• Plasma iron is decreased
43. • A microcytic, hypochromic anaemia develops
• Poikilocytosis becomes evident
• Hemoglobin level falls
• Severe and prolonged deficiency leads to tissue
changes e.g. koilonychia, angular stomatitis, glossitis,
pharyngeal and oesophageal webs, atrophic gastritis,
partial villus atrophy etc
44. • Iron overload
• Iron overload is much less common than iron
deficiency
• Two types of iron overload syndromes are
known:
• When excessive iron is deposited in
reticuloendothelial cells without tissue damage, it is
known as haemosiderosis
45. • This occurs when excessive amounts of iron
enter the body through the parenteral route
• Repeated blood transfusions given to patients with
thalassaemia and sideroblastic anaemia may lead to
deposition of iron in reticuloendothelial cells
46. • When excess iron enters the body through the
alimentary route, it gets deposited in parenchymal
cells and causes tissue damage
• This condition is known as haemo-chromatosis
• It may be primary or secondary
• Primary (genetic) haemochromatosis is far more
common
47. • The gene responsible for this and the protein
encoded by it have not been identified
• The genetic defect leads to excessive intestinal
absorption of iron
• Excess iron is deposited in liver, heart, pancreas
and other endocrine glands, skin etc
48. • Hepatomegaly, cardiomegaly, congestive heart
failure, hypogonadism, diabetes mellitus and
bronze-coloured pigmentation of skin are the
usual clinical abnormalities
• The condition is also known as bronzed diabetes
49. • Serum iron, ferritin and per cent saturation of iron-
binding capacity are increased in haemo-
chromatosis
• Phlebotomy and iron-chelating agents e.g.
desferrioxamine are used to remove excess iron
50. • Secondary haemochromatosis may occur in
alcoholic liver disease in which iron deposition is
usually confined to hepatic tissue
• South African Bantus are known to develop
haemochromatosis due to excessive ingestion of
iron present in an alcoholic beverage brewed in
iron vessels
51. EVENTS IN INTESTINAl MUCOSAL CELL
• In the mucosal cell cytoplasm, there is a
carrier called intracellular iron carrier (I.I.C.).
• Fe++ iron is oxidized again in mucosal cell to
Fe+++ form by ceruloplasmin.
• IIC delivers a fixed amount of iron to
mitochondria.
• It also transfers certain amount of iron Fe+++
to apoferritin, which synthesized by
mucosal cell.
52. IRON ABSORPTION
• Mainly, stomach & duodenum
• In normal people, about 10 % of dietary iron
is usually absorbed.
• Iron is mostly found in the foods in ferric form.
• Iron in the ferrous form is soluble and readily
absorbed.
• Garnick proposed a “Mucosal block theory”
for iron absorption.
53.
54. IRON ABSORPTION & TRANSPORT
Mucosal Cell of
GIT
Apoferritin
Ferritin (Fe+++)
Fe+++ Fred
Fe++
Ferroxidase
Fe++
Plasma
Apotransferritin
Transferritin
(Fe+++)
Fe+++
Ceruloplasmin
Fe++
Tissues
Liver
Ferritin
Hemosiderin
Bone
marrow (Hb)
Muscle (Mb)
Other tissues
(Cyts & NHI)
Lumen of
GIT
Food Fe
Hcl
Fe+++
Vit C
Fe++
55.
56. FACTORS AFFECTING Fe ABSORPTION
• Acidity, ascorbic acid and cysteine promote
iron absorption.
• In iron deficiency anemia, iron absorption is
increased to 2-10 times that of normal.
• Small peptides and amino acids favor iron
uptake.
• Phytate and oxalate interfere with iron
absorption.
57. TOTAL IRON BINDING CAPACITY (TIBC)
• Each transferrin molecule can bind with two
atoms of ferric ion (Fe+++).
• The plasma transferrin ( concentration 250
mg/ dl) can bind with 400 mg of iron / dl
plasma. This is known as TIBC.
58. CLINICAL ASPECT
A. Iron deficiency: Three stages
1) Iron storage depletion
2) Iron deficiency
3) Iron deficiency anaemia
B. Iron overload:
1) Haemochromatosis
2) Haemosiderosis
59. Riddles
1. The requirement of iron in diet is about 10
times the bodies normal requirements. Why is
this so?
2. What are the common probable condition
that increase physiological demands for dietary
iron?
