Dr. D.

Nandini
Learning Objectives
Describe the functions and metabolism of sodium,
potassium and chloride.
Describe homeostasis and clinical conditions related to
plasma level alterations of sodium, potassium and chloride

Describe the functions and metabolism of calcium,

phosphorus and magnesium
Describe homeostasis and clinical conditions related to
plasma level alterations of calcium, phosphorus and
magnesium
Describe the functions and metabolism of
trace elements chromium, cobalt, copper,
fluoride, iodine, iron, manganese,
molybdenum, selenium, and zinc
Describe homeostasis and clinical
conditions related to plasma level
alterations of trace elements
 Classification of minerals
• Macro minerals ( principle elements)
• The macro minerals are required in excess of 100 mg/day.
•
 Microminerals
• The microminerals or trace elements are required in amounts less
than 100 mg/day.
 Iron (Fe)
A normal adult possesses 3–5 gm of iron.
This small amount is used again and again in
the body.
Iron is called a one way substance.
• It is trace element.
• Iron is known as a
one-way
substance because
• It's absorbed in the
small intestine and
remains in the body,
rather than being easily
excreted.
• The body maintains iron
balance through
absorption, rather than
elimination.
Dietary sources
Dietary food sources
 The best sources of food iron include liver, meat, egg yolk,
green leafy vegetables, whole grains and cereals.
 There are two types of food iron:
• In animal foods, iron is often attached to proteins called heme
proteins and referred to as heme iron and is found in meat,
poultry and fish.
• Jaggery is good source .

• In plant foods, iron is not attached to heme proteins and is

classified as non-heme iron, found in green leafy vegetables.
Recommended dietary allowance per day
 Adult men and post menopausal
women: 10 mg
 Premenopausal women: 15–20 mg
 Pregnant women: 30–60 mg.
Women require greater amount than men
due to the physiological loss during
menstruation.
Functions:
• Iron is required for Synthesis of heme compound like
hemoglobin, myo­globin, cytochromes, catalase and
peroxidase. Thus iron helps mainly in the transport,
storage and utilization of oxygen.

• Major role of iron in humans is to carry oxygen to tissue

and carbon dooxide to lungs as haemoglobin.

• as a component of cytochrome and iron sulphar protein it

plays important role in ETC.
• Cytochrome p450

• detoxification of xenobiotics
• Catalase in RBC antioxidant role

• Lysosomal peroxidase phagocytosis

Absorption
 The normal intake of iron is about 10–20 mg/day.
 Normally, about 5–10% of dietary iron is absorbed.
 Non-heme iron bound to organic acids or proteins is
absorbed in the ferrous (Fe2+) state into the mucosal
cell .
 Heme of food is absorbed as such by the intestinal
mucosal cells. It is subsequently broken down and iron
is released.
Absorption of Iron in Three Phases

About 1-2 mg of iron enters the body daily

from dietary absorption.
Iron absorption takes place in 3 steps –
luminal phase,
mucosal cellular phase
 basolateral phase (release into the portal
blood stream).
Luminal Phase of Iron Absorption-GIT-
lumen
• Only ferrous (and not ferric) form of iron is absorbed.
• The trivalent ferric iron present in the food is
converted into bivalent ferrous iron by duodenal
ferric reductase.
• Ferrous iron in the intestinal lumen binds to mucosal
brush border protein, called divalent metal
transporter-1 (DMT-1).
 (Therefore, all other divalent ions,
including calcium, copper and lead will
competitively inhibit the iron absorption).

 The bound iron is then transported into the

mucosal cell.
• fe3+
Ferric Reductase
• fe2+

• Binding mucosal brush border protein( DMT-1)

Mucosal cell
 Mucosal Cellular Phase- mucosal cell
 iron is binding to apoferritin and temporarily stored in the
cell as ferritin or transported across the mucosal cell
depending on body iron status.

If there is anemia, the iron is further absorbed into the

bloodstream.
If body stores are saturated with iron, any iron accumulated
in the mucosal cell is lost when the cell is desquamated.

Thus the fraction of iron absorbed is decided by the iron

status. When iron is in excess, absorption is reduced; this is
the basis of "mucosal block".
Mucosal block Theory
Major regulation of body iron pool is at the level of absorption.

When iron stores in the body are depleted, absorption is

enhanced.
 When an adequate quantity of iron is stored, absorption is
decreased.
 This is referred to as the mucosal block of absorption of iron.

Mucosal cells absorb only about 1% of the dietary iron and the
unabsorbed iron is excreted in feces.
Basolateral Phase
During this third phase, ferrous iron is released
into the portal circulation by a basolateral iron
transporter called Ferroportin.

Ferroportin and DMT are inhibited by

hepcidin , a peptide secreted by liver when
body iron stores are adequate.
• Hypoxia
• Anemia or hemorrhage

Hepcidin

ferroportin
• Iron metabolism is unique because
homeostasis is maintained by regulation
at the level of absorption and not by
excretion.
• No other nutrient is regulated in this
manner.
• Iron is said to be a one-way element
because the body pool is mainly
regulated by absorption and utilization.
DMT – DIVALENT METAL
TRANSPORTER
HT- HEME TRANSPORTER
Factors affecting iron absorption
State of iron stores in the body
Rate of erythropoiesis
The contents of the diet
Nature of gastrointestinal secretions and
chemical state of iron
Transport and uptake of iron by cell

The transfer of iron from the storage ferritin (Fe3+ form) to plasma involves
reduction of Fe3+ to Fe2+ in the mucosal cell with the help of ferroreductase.
Fe2+ then enters the plasma where it is reoxidized to Fe3+ by a copper
protein, ceruloplasmin (ferroxidase).
Fe3+ is then incorporated into transferrin by combin­ing with apotransferrin.
Apotransferrin is a specific iron binding ­protein. Each apotransferrin can bind
with two Fe3+ ions.
• Transport form of iron is transferrin.
• Normal plasma level of transferrin is 250 mg/100 mL.
• In iron deficiency, this level is increased.
• One molecule of transferrin can transport 2 ferric
atoms.
• Total iron binding capacity (TIBC) in plasma is 400
μg/100 mL; this is provided by the transferrin. One-
third of this capacity is saturated with iron. In iron
deficiency anemia, TIBC is increased (transferrin level
is increased); but serum iron level is reduced.
Storage
Iron in plasma is taken up by cells and
either incorpo­rated into heme or stored as
ferritin or hemosiderin.
 Storage of iron occurs in most cells but
predominantly in cells of liver, spleen and
bone marrow.
Ferritin is the major iron storage compound
.
Excretion

• The regulation of homeostasis is done at the absorption

level.
• Women up to menopause will lose iron at a rate of about 1
mg/day. The loss in male is <0.5 mg/day.
• Almost no iron is excreted through urine. But is lost from
body via feces and menstrual blood.
• Iron excretion through feces is exogenous .
• All the cells in skin contain iron. The upper layers of skin
cells are constantly being lost, and this is another route for
iron loss from the body.
 Disorders of iron metabolism
Iron deficiency and iron overload are the
major disorders of
iron metabolism.
Causes of iron deficiency
Nutritional deficiency of iron.
Lack of absorption: Subtotal gastrectomy and
hypochlorhydria.
Hookworm infection: One hookworm will cause the loss of
about 0.3 mL of blood per day. Calculation shows that about
300 worms can produce a loss of 1% of total body iron per
day.
Repeated pregnancies: About 1 g of iron is lost from the
mother during one delivery.
Chronic blood loss: Hemorrhoids (piles),
menorrhagia.
Lead poisoning: Iron absorption and
hemoglobin synthesis are reduced. In turn, iron
deficiency causes more lead absorption.
Anaemia
• Iron deficiency is characterized by
microcytic hypochromic anaemia. Anaemia
is diagnosed when haemoglobin level is
<12 g/dL for women and
<13 g/dL for men and/or
ferritin level is below 12 μg/dL.
Clinical Manifestations
When the level is lower than 10 g, body cells lack
oxygen and patient becomes uninterested in
surroundings (apathy).
Prolonged iron deficiency causes atrophy of gastric
epithelium leading to achlorhydria, which in turn
causes lesser absorption of iron.
Very chronic iron deficiency anaemia will lead to
impaired attention, irritability, lowered memory and
poor scholastic performance.
Chronic iron deficiency is manifested as koilonychia
or “spoon nail”
Peripheral blood smear.
Iron deficiency manifests
as microcytic
hypochromic anemia.
Koilonychia or
“spoon nail” in
chronic iron
deficiency
anemia.
Clinical features of anaemia
Weakness, fatigue, dizzi­ness and
palpitation.
Nonspecific symptoms are nausea,
anorexia, constipation, and menstrual
irregularities.
Some individuals develop pica, a craving for
unnatural articles of food such as clay or
chalk.
Treatment

• Oral iron supplementation is the treatment of

choice. 100 mg of iron + 500 μg of folic acid are
given to pregnant women, while 20 mg of iron +
100 μg folic acid to children.
• Iron tablets are usually given along with vitamin
C, to convert it into ferrous form, for easy
absorption.
• Administration of iron-zinc combinations are
beneficial to correct deficiency of both.
• There are different pharmaceutical preparations.
Ferrous sulfate is the first choice, as it is easily
absorbed and has maximum bioavailability.
• If that is not tolerated, ferrous fumarate or
ferrous gluconate may be tried.
• If that is also not tolerated, then iron
polymaltose or iron bisglycinate may be tried.
 Iron toxicity
Hemosiderosis
Iron excess is called hemosiderosis. It occurs in persons
receiving repeated blood transfusions. So, the regulation at the level of
intestine is circumvented leading to iron overload.
Primary Hemosiderosis
It is also called hereditary hemochromatosis.
Iron absorption is increased and transferrin level in serum is elevated.
Excess iron deposits are seen.
Bantu Siderosis
Bantu tribe in Africa is prone to hemosiderosis because they consume
home brewed beer in large quantities made in iron pot.
Hemosiderosis, continued
Hemochromatosis
 total body iron is >25–30 g,
In the liver, hemosiderin deposit leads to death of
cells and cirrhosis.
Pancreatic cell death leads to diabetes.
Deposits under the skin cause yellow-brown
discoloration, which is called hemochromatosis.
The triad of cirrhosis, hemochromatosis and diabetes
are referred to as bronze diabetes.
Treatment of Hemosiderosis

Repeated phlebotomy every week, till serum iron,

and ferritin reach near normal levels.
Desferroxamine, a chelating agent, forms an iron
chelate with Fe+++ to form ferroxamine which is
excreted in urine.
Case :1
• A young 26 year old pregnant female from low
socioeconomic status came to OPD with chief
complaints of tiredness, lethargy and difficulty in
breathing. She also complained of palpitation. On
examination she was pale had fissures at corners of
mouth. lab data showed Hb: 7g/dl
• Serum ferritin: 12microgram/L
• Peripheral smear showed the presence of microcytic
hypochromic anemia.
Questions:
• 1. what is the probable diagnosis? Justify
• Key factors in case scenario: 26 year old,
( reproductive age), pregnant female, low
socioeconomic status, tiredness, lethargy, difficulty in
breathing, palpitation.

• Key factors in examination: cheilosis, low blood Hb,

low serum ferritin, microcytic hypochromic anemia.
• 2. Explain biochemical basis of the disorder?
• Lack of iron ,leading to less production of hemoglobin is the
cause of iron deficiency anaemia. leading to symptoms like
breathlessness, tiredness and lethargy.
• Her age depicts that she is menstruating female and there is
menstrual blood loss every month.
• She is pregnant, so her iron requirement is more as compared
to non pregnant lady.
• She belongs to low socio economic status and her diet might
be compromised.
• Q.3 what are the characteristic clinical features
of the disorder.
• Tiredness
• Lethargy
• Difficulty in breathing
• Palpitation
• Koilonychia( spooning of the finger nails)
• Cheilosis is due to advanced tissue iron
deficiency.
Koilonychi
a
• What investigation are required to diagnose the
condition?
1. CBC
2. Sr. ferritin levels( decreased level observed in anaemic patient)
3. Peripheral smear shows microcytic hypochromic anaemia.
4. Plasma transferrin levels will be raised ( NRR: 200-360mg/dl)
5. Total iron binding capacity( TIBC): IT IS AN INDIRECT MEASURE OF
CIRCULATING TRANSFERRIN.
( NRR 300- 360 μg/dl ).
• Treatment:
• Iron rich food
• Ferrous ascorbate/ ferrous sulphate along
with vitamin C
• Transfussion for immediate intervention
 Case 2
• A 65 year old diabetic , non alcoholic male presented to OPD with complain
of rashes all over body. on examination ,yellow brown pigmentation was seen
all over the skin, more so on the back, liver biopsy showed the sign of
cirrhosis. This presentation is typically seen in tribal population of AFRICA.
• Key features of case?
• What is this condition called??
• Which micronutrient is responsible for such
presentation??
• Which organ get affected in this disorder?
• Treatment ?
• Plebotomy and desferroxamine