This document discusses iron, an essential trace mineral. It notes that iron is needed in small amounts but is critical for biochemical functions. The document covers where iron is stored and transported in the body, how its absorption is regulated, factors that influence absorption, dietary sources, and clinical conditions related to iron deficiency and overload. It provides details on iron metabolism, functions, normal ranges, deficiency states, causes and treatment of iron deficiency anemia.

1. 1
Minerals and its Metabolism
(Minor/Trace Minerals)
By
Akanksha Dubey

2.  Micro minerals or Trace elements are present in body in small
amount (Micrograms to milligrams) but are required for
biochemical functions
 The Trace Minerals are needed in much smaller amounts less
than 100 mg/day but are essential component of normal diet.
 They are: Iron, Iodine, Zinc, Copper, Manganese,
Chromium, Cobalt, Selenium, Molybdenum, Fluorine

4. Iron is the most essential trace element in the body
Inspite of the fact Iron is 4th most available and
abundant mineral in earth crust, iron deficiency is one
of the most common and prevalent nutritional
deficiency in India
Total body iron content is 3 to 5 gm; 75% of which is
in blood, the rest is in liver, bone marrow and muscles.

5. Iron is present in almost all cells.
There are two broad categories of Iron present in body:
a) Essential/functional Iron (Haem proteins/Enzymes and
Cytochromes)
b) Storage Iron (Ferritin/Haemosiderin)
Iron is k/a One Way Substance because this 3-5 gms is
used again and again and very little amount is excreted.

6. Normal iron kinetics.

7. Iron is not like other substance (Vitamins or other
minerals) which are being excreted
Blood contains 14.5 g of Hb per 100 ml. About 75%
of total iron is in Hemoglobin, and 5% is in
Myoglobin and 15% in Ferritin.

8.  Daily allowance of iron for an adult Indian is 20 mg,
out of which only 1-2 mg is absorbed.
 In Western countries, requirement is less (15 mg/day)
 Children between 13-15 (growing age) years need 20-
30 mg/ day.

9. Pregnant women need 40 mg/day. Transfer of iron
and calcium from mother to foetus occurs mainly in
the last trimester of pregnancy. Therefore, during this
period mother's food should contain surplus
quantities of iron and calcium.

10. In the first 3 months of life, iron intake is negligible
because milk is a poor source of iron. During this time,
child is dependent on the iron reserve received from
mother during pregnancy.
 Premenopausal women: 15 to 20 mg/day
Women require greater amount than man due to
physiological blood loss during menstruation.
2 ml of blood loss per day doubles the Iron requirement

11. Dietary food sources:
There are two types of food sources for Iron
a) Non- Haem Sources: Iron associated without
porphyrin is found in green leafy vegetables, cereals
and beans and this is not absorbed as such.
b) Haem- Iron: Iron associated with porphyrin is found
in meat and fishes which is readily absorbed.

12. Sources of Iron
i. Leafy vegetables are good sources. Pulses and cereals
contain lesser quantity of iron. 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.

13. ii. Liver and meat
iii. Jaggery is a good source of iron.
iv. Cooking in iron utensils will improve the iron
content of the diet.
v. Milk is a very poor source of iron, containing less
than 0.1 mg/100 ml.

14. Absorption
The normal intake of Iron is about 10-20 mg/day. Iron is
absorbed by upper part of duodenum.
Haem of food is absorbed directly from intestine and non
haem iron(inorganic iron) is absorbed in ferrous state
(Fe2+) in the mucosal cell.
The gastric acid HCL and organic acids in the diet
convert organic ferric compound of diet into free ferric
ions.

15. The free ferric ions are reduced with ascorbic acid and
glutathione of food to more soluble ferrous form which
is more readily absorbed than ferric ions.
After being converted to Ferrous form, Iron is either
stored in the form of ferritin in the mucosal cells or
transported across the mucosal cell to the plasma with
the help of Transferrin (Iron binding protein)

16. Factors Influencing Absorption of Iron
. Absorption is increased in Iron deficiency and
decreased in Iron overloading.
The following factors affect this absorption of iron:
i. Only Fe++ (ferrous) form (reduced form) is
absorbed. Fe+++ (ferric) form is not absorbed.
ii. Ferric ions are reduced with the help of gastric HCl,
ascorbic acid, cysteine and -SH groups of proteins.

17. Therefore, these will favour iron absorption.
About 50-75 mg of ascorbic acid per day will be
sufficient for normal iron absorption.
Rate of Erythropoiesis: when rate of RBC formation
is increased the iron absorption will be increased
irrespective of Iron storage.

18. Other minerals Calcium, copper, lead and
phosphates will inhibit iron absorption. One atom of
lead will inhibit absorption of 1000 atoms of iron. A
glass of milk, which contains calcium will
appreciably reduce iron absorption.

19.  Interfering substances: Iron absorption is decreased
by phytic acid (in cereals) and oxalic acid (in leafy
vegetables) by forming insoluble iron salts.
 An average Indian diet contains more than 20 mg of
iron. But the phytates and oxalates in the diet reduce
the absorption, and only about 1 mg of iron is
absorbed.
In Western diet, even though iron content is about 10
mg, about 2 mg is absorbed.

20. Duodenum and jejunum are the sites of absorption. Iron metabolism is unique
because homeostasis is maintained by regulation at the level of absorption and not
by excretion.
When iron stores in the body are depleted, absorption is enhanced. When adequate
quantity of iron is stored, absorption is decreased. This is referred to as mucosal
block of regulation of absorption of iron. Only ferrous (and not ferric) form of iron
is absorbed.
Ferrous iron in the intestinal lumen binds to mucosal cell protein, called divalent
metal transporter-1 (DMT-1). The bound iron is then transported into the mucosal
cell.
Inside the mucosal cell, the ferric iron is formed and is complexed with apoferritin
to form ferritin.
Mucosal Block Theory

22. 1.Mucosal regulation: Absorption of iron needs divalent metal ion transporter
and ferroportin.
2.Hepcidin decreases surface expression of the ferroportin, which is responsible
for moving iron across cell membranes.
3.Stores regulation: As body iron stores fall, the mucosa is signalled to increase
absorption.
4.Erythropoietic regulation: In response to anemia, the erythroid cells will
signal the mucosa to increase iron absorption. There is reciprocal relationship
between synthesis of ferritin and transferrin receptor (TfR). Thus, when iron
levels are high, ferritin is synthesized to store iron. At the same time, there is no
requirement for further uptake of iron, so the TfR is not synthesized.
Regulation of Absorption by Four Mechanisms

23. Iron Transport in Blood and Uptake by Cells
 The ferrous form in mucosal cells of GIT is converted to Ferric
form by Ferroxidase enzyme. This ferric combines with
Apoferritin to from Ferritin (Temporary storage form of Iron)
For further transfer in plasma or storage Ferric form in above
state is converted to Ferrous form by Ferroreductase and this
travels to plasma.
In plasma this ferrous form is converted to Ferric form by
Ferroxidase II or Ceruloplasmin. This ferrous form combines with
Apotransferrin to form Transferrin.

25. Transferrin:
also k/a Siderophilin
It is a glycoprotein with the molecular weight of 90,000
Each Transferrin molecule can combines to 2 atoms of
Ferric ions.
The major function of Transferrin is to transport Fe to
RE system so that Fe(Hb) can be incorporated in RBC’s
Normal plasma level of Transferrin is 250 mg/100 ml
which can bind to 400 mg of Iron.

26. This is k/a Total Iron Binding Capacity of plasma.
 In iron deficiency, this level is increased.
Transferrin receptors (TfR) are present on most of the
body cells, especially on cells which synthesize heme.

27. Storage of Iron: Iron is stored as Ferritin or Hemosiderin
Ferritin
 Iron is stored in Liver, spleen and bone marrow in the form of
Ferritin (The ferritin has a molecular weight of about 440 kilo
Daltons. It has 24 subunits. It can take up to 4,000 iron atoms per
molecule. Ferritin contains about 23% iron)
 In mucosal cell ferritin is temporary storage of Iron
 Apoferritin is protein content of Ferritin
 A molecule of Apoferritin (Molecular Weight 5 Lac) can combines
with 4000 atoms of Iron.

28. Normal plasma contains very little ferritin.
Ferritin in plasma is elevated in iron overload. Thus
ferritin level in blood is an index of body iron stores.
When iron levels are high, ferritin is synthesized to
store the iron

29. Hemosiderin
Another storage form of Iron.
Hemosiderin accumulates in spleen and liver when
supply of Iron is in excess than demand
It is insoluble as compared to ferritin and release of iron
is very slow
It is formed by partial deproteinization of ferritin by
lysosomes

30. Iron is one way substance:
Iron metabolism operates in closed system. It is very
efficiently Utilized and reutilized by the body
Iron loses from the body is very minimal around
<1 mg/day which may be in hair, bile, sweat.
Iron is not at all excreted into urine.
Iron entry in the body is controlled at absorption level
depending upon the body needs.

32. Excretion of Iron
i. Iron is a one-way element. That is, very little of it is
excreted. Although loss is thru Bile Faeces and
menstrual blood
ii. Any type of bleeding will cause loss of iron from the
body. Menstrual flow is the major cause for loss of iron
in women. Women up to menopause will lose iron at a
rate of about 1 mg/day. The loss in male is less than 0.5
mg/day.

33. iii. Almost no iron is excreted through urine. Faeces
contain unabsorbed iron(from mucosal cells) as
well as iron trapped in the intestinal cells.

34. Biochemical Functions:
 Iron mainly exerts its function through the compound in which it
is present.
 Hemoglobin in red blood cells transports oxygen and carbon
dioxide
 Myoglobin in muscle cells binds oxygen
 Electron transport chain as a component of cytochromes and Iron
sulfur protein
 Enzyme cofactor catalase of RBC

35. Normal Ranges:
a) Serum iron:
 Males 65--177 microgram/dL (11.6--31.7 micromole/L)
 Females 50--170 microgram/dL (9.0--30.4 micromole/L)
b) TIBC: 250--370 microgram/dL (45--66 micromole/L)
c) Serum ferritin :
 male 20--250 microgram/L
 Female: 15--150 microgram/L

36. Clinical Condition
Three stages of Iron deficiency are:
a) Iron storage depletion
b) Iron deficiency
c) Iron deficiency anaemia

37. Iron storage depletion
This phase is normally not recognizable by person and
does not elicit medical examination.
Serum ferritin is decreases in this stage and possibly
good indication for Iron deficiency
Non identified condition

38. Iron deficiency
In this phase iron stores are already exhausted.
Biochemically serum ferritin low and Transferrin
saturation low
Erythrocyte protoporhyrin level high (iron not
available for erythropoiesis)
Haemoglobin conc. falls to lowest limit of normal

39. Iron Deficiency Anaemia
 It is the most common nutritional deficiency disease
worldover. About 30% of world population is anaemic.
 All over India, this is about 70%.
85% of pregnant women suffer from anaemia.
In adults, anaemia results in impaired work capacity.

40. There are several factors which contribute to Iron
deficiency anaemia may be d/t inadequate
intake/defective absorption/ chronic blood loss
Strict vegans are more prone to Iron Def Anaemia
because the content of Iron in diet is low and inhibiting
agents are more.
Iron deficiency is characterized by Microcytic
Hypochromic anemia. Anemia is diagnosed when Hb
level is <10 g/dL and/or ferritin level is below 12 μg/dL.

41. Causes of iron deficiency are given below:
 Nutritional deficiency of iron
 Lack of absorption: Subtotal gastrectomy and
hypochlorhydria
 Hookworm infection
 Chronic blood loss: Haemorrhoids (piles), peptic ulcer,
menorrhagia.

42. Nephrosis: Transferrin are lost in urine, along with
loss of iron.
Lead poisoning: Iron absorption and hemoglobin
synthesis are reduced.

43. Clinical manifestations
i. When the level is lower than 10 gm, body cells lack
oxygen and patient becomes uninterested in surroundings
(apathy). Since iron is an important constituent of
cytochromes, their deficiency leads to derangement in
cellular respiration and all metabolic processes become
sluggish.

44. Very chronic iron deficiency anaemia will lead to
impaired attention, irritability, lowered memory and poor
scholastic performance.
Anaemia and apathy go hand in hand.
Prolonged iron deficiency causes atrophy of gastric
epithelium leading to Achlorhydria, which in turn causes
lesser absorption of iron.
Chronic iron deficiency is manifested as koilonychia or
“spoon nail”

45. Peripheral blood smear.
Iron deficiency manifests as
microcytic hypochromic
anemia.
Koilonychia or “spoon nail”
in chronic iron deficiency
anemia.

46. Laboratory Findings
Laboratory investigations generally used to diagnose
anaemia's are listed below:
 Serum iron level: It is depressed in iron deficiency,
acute and chronic infections.
 Total iron binding capacity (TIBC): It is elevated in
hypochromic anaemia's, acute hepatitis and
pregnancy.

47. Treatment of Iron Deficiency
Oral iron supplementation is the treatment of choice.
Iron tablets are usually given along with vitamin C, to
convert it into ferrous form, for easy absorption.
Unabsorbed iron may generate free radicals and so, it is
advisable to give vitamin E (to prevent free radical
generation) along with iron.

48. Iron Toxicity
 More than 50 mg of iron taken orally may cause nausea,
diarrhoea and abdominal pain.
Haemosiderosis, Haemochromatosis and Iron poisoning
are the conditions associated with Iron overload.

49. Haemosiderosis: Iron excess is called Haemosiderosis.
Hemosiderin pigments are golden brown granules, seen
in spleen and liver without associated with any tissue
injury
It is initial state of Iron overload
Haemosiderosis occurs in persons receiving repeated
blood transfusions. Here the regulation at the level of
intestine is circumvented leading to iron overload.

50. Hemophilic children require blood transfusion every
3 months. If whole blood is given every time, by
about 20 years of age, the patient will develop
hemosiderosis.
This is the commonest cause for hemosiderosis in
India.

51. Haemochromatosis
Haemochromatosis is a clinical condition in which
excessive deposition of Iron in the form of hemosiderin
occurs and associated with Tissue injury.
The cause of Haemochromatosis may be genetic
(primary) or acquired(secondary)

52. Primary/Genetic Haemochromatosis
 It is also called hereditary Haemochromatosis.
The abnormal gene is located on the short arm of
chromosome no. 6.
 In these cases, unregulated increase in the intestinal
absorption of iron from normal diet. 4mg/day is
absorbed although normal is 1 mg/day
Iron is deposited in tissues Liver, spleen, pancreas and
skin.

53. After accumulation of many years excessive amount of
intracellular iron leads to tissue injury and ultimately
organ failure.
When total body iron is higher than 25-30 gm, (Normal
is 3-4 gm) Haemosiderosis is manifested.
 In the liver, Hemosiderin deposit leads to death of
cells and cirrhosis.

54. Secondary /Acquired Haemochromatosis
The main causes of Acquired Haemochromatosis are:
Chronic overload: occurs when diet contain excess of
absorbable iron.
Parenteral administration of iron or chronic blood
transfusion or blood disorders s/a thalessemia
Alcohol abuse d/t ethanol causes increase iron absorption

55. Clinical symptoms:
Liver cirrhosis
Pancreatic fibrosis
Bronze skin pigmentation
Arthritis(iron deposition in joints)
Cardiac arrhythmia
90% of affected cases are males, as females are are
protected because of menstruation and pregnancy

56.  Haemosiderosis some times accompany with
heaemochromatosis . Bronze coloration of skin, cirrhosis
of liver and Pancreatic cell death by pancreatic fibrosis
are the common manifestation of this disease.
The triad of Cirrhosis, Haemochromatosis and Diabetes
are referred to as Bronze Diabetes.

57. Bantu siderosis: Bantu tribe in Africa is prone to
hemosiderosis because the staple diet, corn, is low in
phosphate content and they cook their food in Iron pots
only. As phosphorus is low it will promote Iron
absorption leading to Siderosis

58. Iron poisoning
Acute overdose mainly occurring in children may cause
severe or fatal symptoms due to toxic effects of free iron
in plasma which may be life threatening.
Symptoms include
Nausea…..Vomiting……Abdominal pain….. Diarrhoea
……Haematemesis….and in advance cases liver damage
and coma

60. An adult human contains approx 100 to 150 mg of
copper.
Highest amount is present in Liver and Kidney. Foetal
liver contains 10 times higher copper than adult liver.
Significant amount is present in Cardiac and Skeletal
Muscle and in Bones.
It occurs as Erythrocuprein (RBC), Hepatocuprein (liver)
and Cerebrocuprein (in brain)

61. Dietary Food Sources:
Shellfish, Liver, Kidney, egg yolk, some legumes are
rich in copper. Milk is very poor in copper content
RDA: 2 to 3 mg/day

62. Absorption and Excretion
About 32 % of Dietary copper is absorbed from stomach
and small intestine. Phytates, Zinc, Cadmium, and high
amount of Vitamin C inhibit Cu absorption.
Absorbed copper is transported to Liver in the bound
form with Albumin and exported to peripheral tissues and
plasma in binding with Ceruloplasmin.
Excretion is mainly through bile. Urine does not contain
copper in normal circumstances.

63. Functions of Copper:
It is necessary for iron absorption and incorporation of
iron into haemoglobin (Ceruloplasmin). It promotes
oxidation of ferrous ion to ferric form, which is
incorporated into Transferrin. The copper atoms are
tightly bound with Ceruloplasmin.
 It is necessary for tyrosinase activity in melanin
synthesis

64.  The hydroxylation of Proline and Hydroxyproline
which are required for collagen cross linking requires
copper as a cofactor.
 It works as a cofactor of ALA synthase enzyme of
haem synthesis,
 Also required for formation of Myoglobin and
Cytochromes

65. Copper is the integral component of many
metalloenzymes.
Copper containing enzymes are ceruloplasmin
(Ferroxidase), cytochrome oxidase, cytochrome c,
tyrosinase, lysyl oxidase, ALA synthase, monoamine
oxidase, superoxide dismutase and phenol oxidase.
The major function of metalloenzyme is Oxidation-
Reduction.

66. Copper containing nonenzymatic proteins are
Hepatocuprein in liver (storage form) Cerebrocuprein
in brain, Hemocuprein in RBC and Erythrocuprein in
bone marrow

67. Out of whole blood copper content 95% is in RBC as
colorless Erythrocuprein.
In plasma Ceruloplasmin is an important copper
containing protein. Normal serum level of
Ceruloplasmin is 25-50 mg/dl.
Ceruloplasmin is a blue-coloured glycoprotein. It is
also called serum Ferroxidase.

68. Serum copper
10-22 micromole/L which is 90 % bound to
ceruloplasmin

69. Deficiency Manifestation:
Both children's and adult can develop symptomatic
deficiency.
Premature infants are more susceptible because
copper is stored in liver in third trimester of
pregnancy.

70. Signs of copper deficiency are:
Hypochromic anaemia
Osteoporosis : d/t impairment in copper dependent cross
linking of collagen in connective tissues.
Decreased pigmentation of skin d/t depressed tyrosinase
activity.
In later stages neurological abnormalities due to
depressed cyochrome oxidase activity.

71. Copper Deficiency Anemia: Copper is essential for the
formation of hemoglobin. Copper containing ceruloplasmin
helps in iron transport. Copper is an integral part of ALA
synthase, which is the key enzyme in heme synthesis. Copper
helps the uptake of iron by normoblasts. Copper deficiency is
manifested as anemia. RBC count is reduced; cell size is
small; but hemoglobin concentration is more or less normal.
Copper deficiency thus results in microcytic
normochromic anemia. If there is added iron deficiency,
hypochromic anemia results

72. Cardiovascular Diseases: Copper is a constituent of Lysyl
Oxidase. It oxidizes four lysine residues together to
form Desmosine which makes cross linkages in Elastin.
In copper deficiency, Elastin becomes abnormal, leading
to weakening of walls of major blood vessels. This
favours aneurysm (dilation or enlargement of aorta) and
fatal rupture of the wall of aorta.

73. Melanin: Copper is present in tyrosinase which is
necessary for melanin formation. Copper deficiency
thus leads to hypopigmentation and in extreme cases,
grey color of hair. The period of copper deficiency may
be marked on hair as alternate white patches;
sometimes called flag type of hair growth.
Low levels can cause brain dysfunction.

74. Inborn Error of Copper Metabolism
There are two Inborn Errors Of Copper Metabolism
Wilson’s disease
Menkes syndrome

75. Wilson's Disease
 It is a genetic disease(Autosomal recessive)
 The incidence of Wilson's disease is 1 in 30,000.
 Metabolic Defects: mainly Two defects:
The basic defect is in a gene encoding a copper binding ATPase in
cells (ATP7B gene in liver cells). This is required for normal
excretion of copper from liver cells into bile; in its absence,
copper is accumulated in cells, leading to copper deposition in
liver and later in brain(especially in lenticular nucleus). Hence this
condition is k/a Hepatolenticular Degenration

76.  Second defect is in incorporation of copper in apo-ceruloplasmin to
form ceruloplasmin.
 Clinical Features: total body retention of copper is increased particularly
in Brain, liver, kidney and cornea
Liver: causes hepatic cirrhosis
Brain: deposition in brain(especially in lenticular nucleus). Hence
this condition is k/a Hepatolenticular Degenration
Eye: Copper deposition in cornea leads to formation of clinical
finding that is Kayser-Fliescher ring (rusty brown pigmentation
around the iris)
Urinary copper excretion is high

78. Treatment:
 Administration of D- Penicillamine and BAL(British
Antilewisite), which helps in chelation and excretion of copper,
may help the affected persons.
 As zinc decreases copper absorption, zinc is sometimes used
therapeutically in Wilson's disease, to reduce copper load in the
body

79. Menke's Disease
Synonym: Kinky or Steel Hair Syndrome:
It is an X-linked defect.
It is a condition with genetic defect in absorption of
copper from the intestine.
Both copper and Ceruloplasmin and liver copper are
low

81. Symptoms:
Kinky/twisted and brittle hairs due to loss copper
catalyzed disulfide linkages.
De-pigmentation of skin and hair
Seizures
Mental retardation
This affects the activity of copper dependent enzymes.

82. Copper Toxicity
Excess copper intake may lead to toxic manifestations.
Copper can oxidize proteins and lipids; it can enhance
production of free radicals.
Chronic toxicity is manifested as diarrhoea and blue-
green discoloration of saliva.
Copper poisoning may result in haemolysis,
hemoglobinuria, and renal failure.