iron metabolism and disorders

1. IRONMETABOLISM
Presented by:
1. Hamza Sagheer(3078)
2. Muhammad Irfan( 3062)
3. Ghulam Baqir(3029)
4. Muhammad Sharaiz (3129)
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2.  Outline:
• Introduction
• Dietary iron
• Absorption of iron
• Transport of iron
• Iron storage in the body
• Blood iron
• Excretion of iron
• Laboratory diagnosis
• Iron Deficiency
• Iron overload
• Diseases related to Iron deficiency
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4.  Introduction:
 Iron:
• Is an essential element present mainly in heme of hemoglobin ,myoglobin,
cytochromes and in iron storage protein ferritin and hemosiderin.
• An adult human has 4 grams of iron in his body.
 Clinical importance:
• Iron deficiency in the body may lead to iron deficiency anemia (microcytic
hypochromic anemia)
• Over dose of iron may cause hemiosiderosis.
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5.  Dietary Iron:
Recommended dietary allowance(RDA):
Adult: 10 mg per day
Female below 50 years and during lactation:
increase up to 15mg per day .
Female during pregnancy increase up to 30 mg per
day.
Source of dietary iron:
Animal source: Liver ,spleen and meat
Plant source: molasses, dates, vegetables and whole
cereals.
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6.  Sources
The best sources of food iron include liver, meat,
egg yolk, green leafy vegetables, dates, whole
grains and cereals.
In a typical Indian diet, the major quantity of iron
is received from cereals because of the bulk
quantity taken, although they contain iron only in
moderate amounts.
Jaggery is a good source of iron.
Milk is a very poor source of iron, containing less
than 0.1 mg/100 ml.
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8.  Biochemical functions
Iron is a component of several functionally important molecules.
Iron is required for the synthesis of hemoglobin, myoglobin,
cytochromes, catalase and peroxidase.
Cytochromes & certain non-heme proteins are necessary for ETC
& oxidative phosporylation.
Peroxidase, the lysosomal enzyme is required for phogocytosis &
killing of bacteria.
Iron is also essential for the synthesis of non heme iron (NHI)
compounds like, succinate dehydrogenase, iron-sulfur proteins of
flavoproteins, NADH dehydrogenase.
Iron helps mainly in the transport, storage and utilization of oxygen.
Iron is associated with effective immuno- competence of body.
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10.  Absorption of iron:
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 Iron is called as one way substance,
because it is absorbed and excreted from
small intestine.
 Iron is absorbed from upper small intestine.
 Iron is absorbed in three forms:
(1) ferrous iron
(2) ferric iron
(3) heme iron.
 Iron is absorbed mainly in the ferrous form.

11.  Con,t….
Ferric ions are reduced with ascorbic acid & glutathione of
food to more soluble ferrous (Fe2+) form which is more
readily absorbed than Fe3
After taken up by the intestinal mucosa, iron is either
stored in the form of ferritin in the mucosal cells or
transported across the mucosal cells to the plasma in the
form of transferrin.
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13.  Factors affecting iron absorption
Factor favoring absorption:
Heme iron
Ferrous form fe2+
Acids(HCL vit,c)
Solubilizing agents
(sugar amino acid)
Iron deficiency
Increase erythropoiesis
Factor reducing absorption:
Inorganic iron
Ferric form fe3+
Alkalis; Antacid,
pancreatic secretion
Iron excess
Decrease erythropoiesis.
Infections
Tea
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14.  CON,T….
Achlorohydria:
 The deficiency of HCL results in impaired
conversion of ferric form of iron to ferrous form of
iron.
 Iron absorption is deceases in the presence of
gastrointestinal diseases.
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15.  Transport
Iron in the mucosal cells:
The iron (Fe2+) entering the mucosal cells by absorption is oxidized to
ferric form (Fe3+) by the enzyme ferroxidase (ferroxidase activity of
ceruloplasmin)
Major sources of iron in the plasma is from degraded erythrocytes.
Fe3+ combines with apoferritin to form ferritin, which the temporary storage
form of iron.
From the mucosal cells, iron may enter the blood stream.
Transport of iron in the plasma:
Iron enters plasma in ferrous state.
It is oxidized to ferric form by a copper containing protein, ceruloplasmin -
ferroxidase activity.
Ferric iron binds with a specific iron binding protein-transferrin or
siderophilin.
Transport form of iron is transferrin.
It is a glycoprotein, synthesized in liver.
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16.  Con,t…
Normal plasma level of transferrin is 250 mg/dl.
One molecule of transferrin can transport 2 ferric
atoms and the half-life of transferrin is 7- 10 days.
Serum iron and serum iron binding capacity:
Total iron binding capacity (TIBC) of transferrin is
250-450 µg/dl;
In iron deficiency anemia, serum iron level is
decreased and TIBC is increased.
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17.  Storage
Ferritin:
Iron is stored in liver, spleen & bone marrow in the form of ferritin.
In the mucosal cells, ferritin is the temporary storage form of iron.
Ferritin contains about 23% iron.
Ferritin in plasma level is elevated in iron over load.
Ferritin level in blood is an index of body iron stores.
Ferritin is an acute phase reactant protein, elevated in inflammatory
diseases.
Hemosiderin:
It is another iron storage protein, which can hold about 35% of iron
by weight.
Hemosiderin accumulates when iron levels are increased.
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20.  Blood Iron:
In hemoglobin of RBCS:
Hemoglobin contains 3.4 mg iron per gram of hemoglobin is 15 mg/100 ml
in blood
Amount of iron in hemoglobin is 50mg/100 ml blood
In plasma:
Transferrin:
Iron is carried in blood by transferrin, which carries two atoms of fe3+
/molecules
Only about 30% of transferrin is saturated with iron (called total iron binding
capacity TIBC)
Synthesized in the liver
In iron deficiency anemia plasma iron is reduced while TIBC tends to
increase.
In liver disease both plasma iron and TIBC are decreased .
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21.  Continue:
Plasma ferritin:
 Ferritin in plasma (20 to 25 microgram per/L) it is a
good index of iron storage .
 Decrease in iron deficiency anemia and increased in
hemiosiderosis
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22.  Excretion of iron:
In feces (90 to 95%): Fecal iron is mainly unabsorbed iron .
In urine and sweat (5 to 10 %): Daily loss of iron I urine and
sweat is about 0.5 to 1 mg of iron
Menstruation and milk (5 to 10 %): About 15 to 30 % mg of
iron ( in the form of hemoglobin ) is lost in menstruation per
month (0.5 to 1 mg per day)
Lactation leads to loss of 0.5 to 1 mg of iron per day
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24. Laboratory assessment of iron status:
1) Plasma iron:
 Level fluctuate widely in healthy due to many factors( as
diurnal rhythm, menstruation ,oral contraceptive pills intake,
pregnancy ,etc.)
Measurement of plasma iron do not provide an adequate index
of iron status ,as In cases of iron deficiency anemia plasma iron
is reduced late when iron is entirely depleted from iron stores .
 In iron overdose plasma iron is elevated late when iron
stores are seriously overloaded with iron.
Plasma iron alters in cases not associated with changes in iron
stores:
As in acute infections or trauma in which plasma iron is rapidly
reduces to low level while iron store are not affected.
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25.  Continue:
2) Plasma ferritin:
Plasma ferritin is closely related to body iron store weather low normal or
high. (while plasma iron become abnormal only in presence of gross
normality's)
Low (or upper normal) plasma ferritin indicates depleted iron stores.
High plasma ferritin indicate iron overdose (hemiosiderosis).
3)Plasma transferrin and Total iron binding capacity (TIBC):
Transferrin level is reduced in chronic liver disease, acute infection and
neoplasm.
 Transference synthesis is increase in iron deficiency
Transference can be measure:
Directly
Indirectly : by total iron binding capacity (TIBC)
TIBC is the ability to transferrin to be iron30 to 40% of binding site of
transferrin are occupied by iron
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26.  Iron deficiency:
common single nutrient deficiency worldwide.
Cause of iron deficiency:
Deficient intake of iron: ingestion diet poor iron for a long time
Increased requirement of iron: as in pregnancy ,lactation and menstruation
Impaired of iron absorption: due to intestinal cause (malabsorption syndrome)
Excessive loss of iron: in cases of chronic bleeding( from (GIT) bleeding etc.
Laboratory and clinical manifestation:
 Low plasma ferritin
 increase transferrin
 then Low plasma iron
 Finally anemia is evident by LAB investigation (microcytic hypochromic anemia) and by
clinical manifestations.
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28.  Hemochromatosis(Iron overload )
Iron overload disorders are a group of
medical conditions that cause the body to
store excess iron. They include hereditary
hemochromatosis, a genetic condition in
which a person’s body absorbs too much
iron from foods and drinks
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29.  In a healthy body, when the stores of iron are sufficient,
the intestines reduce the absorption of this mineral from
food and drink to prevent its levels from rising too high
People with iron overload disorders absorb more iron than
usual from food or supplements. The body cannot excrete
the extra iron fast enough, so it continues to build up. The
body stores it in organ tissue, mainly in the liver, as well
as the heart and the pancreas.
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31.  Types
Primary hemochromatosis:
 A genetic mutation
Secondary hemochromatosis:
Blood transfusions, taking oral iron pills, some kinds of
anemia, such as thalassemia, or chronic liver disease,
such as chronic hepatitis C infection or alcohol-related
liver disease.
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32.  Symptoms
Tiredness or fatigue
Heart failure
Liver Cirrhosis
Abdominal pain
High blood sugar levels
Hyperpigmentation, or the skin turning a bronze
color.
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33.  Diagnosing hemochromatosis
Genetic Testing:
Mutation of HFE gene.
MRI
Liver Biopsy
SERUM Test:
Serum transferrin
Serum ferritin
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