Iron

Metabolism

John Santangelo
Extravascular Pathway for RBC Destruction
ferrous (Fe+2) is
more readily
absorbed in the
small intestine
than the ferric (Fe Phagocytosis & Lysis
+3) form, which is
not very soluble.
Hemoglobin

Bilirubin Haem Globin

Fe2+
Amino Acids

Excreted
Recycled
 The History of Iron

• The importance of dietary iron has been recognized for

centuries.

• In 4000 BC the Persian physician, Melampus, gave iron

supplements to sailors to make up for the iron lost from
bleeding wounds.

• In the 17th century, chlorosis was treated with iron.

• It wasn’t until 1932 that the value of iron therapy was
proven.
 Iron Exists in several oxidation states.

• There are 2 forms of iron:

Heme; animal
Non-heme; plants

• In the human body and food, iron exists in

Ferric (Fe+3) and ferrous (Fe+2) forms.

• Heme contains the iron bound to the porphyrin ring,

called a metalloporphyrin.
 ferrous (Fe+2) is more readily
absorbed in the small intestine
than the ferric (Fe +3) form, which
is not very soluble.
 Iron in human body

Total iron in human body ~3.8 g (men),

~2.3 g (women);

Iron is localized mostly in cells;

1-2 mg are taken up from food (10 % absorption);

1-2 mg are released with skin and gut tissues.
􀃆 Fe metabolism is conservative;

Transferrin is the major Fe binder in blood plasma.

Most ferritin is found in hypatocytes (liver), spleen,
bone marrow;
 Storage and Excretion

Storage
Iron is delivered by transferrin to the liver, bone marrow and spleen.
Primary storage form of iron is Ferritin in cells and tissues.

Secondary storage form of iron is Hemosiderin (protein).

Stored more in the liver, then bone marrow and spleen.

Excretion
Not needed iron as ferritin it is excreted with the mucosal cells that are
shed off into the lumen of GI tract every 2-3 days.
Most iron is lost from the GI Tract,, then skin, kidney.
Small amount lost in urine.
During menstrual cycle lost iron accounts for 17.5mg per cycle.

Every mL of Blood contains 0.5 mg iron.

 Functions of Iron

Cofactor for enzymes

Heme dependent enzymes used in:-
-Oxygen transport and storage
-Electron transport, energy metabolism and detoxification of drugs
-Antioxidant
-Defense mechanism by binding free iron to ensure bacteria does not
use it to grow – fight infection.
-DNA synthesis and cell replication -as amino acid metabolism.
-Thyroid hormone production
Non heme dependent enzymes used in:-
-Neurotransmitters, and pro-oxidant functions
-Regulation of intracellular iron by levels of transferrin receptors
present
 Interactions
Vitamin C- Improves iron absorption. Ascorbic acid forms a
chelate with nonheme iron, which remains soluble in the small
intestine therefore increasing intestinal absorption of non heme
iron.
Vit. C rich foods should be eaten at the same meal as iron source.

Vitamin A- Deficiency in vitamin A may intensify iron deficiency

anemia.
Low plasma retinol concentrations are associated with decreased
iron.
Combination of Vit. A and iron, together, seems to improve anemia
Copper- Required for iron transport to the bone marrow for RBC
production.
Zinc- Iron and zinc supplements taken together without food can
inhibit the absorption of Zinc.

Solution: Don’t take supplemental iron on a empty stomach.

 Interactions

Calcium- Decreases the absorption of iron when consumed

together.
Solution: Avoid consuming calcium rich foods at the same time
of a meal containing iron.
Coffee and Tea- Decreases iron absorption by 60% ! Tannins
(polyphenols) bind to iron affecting iron availability.
Solution: Do not consume coffee/tea at the time of meal
containing iron or just after.
Phytates- Interferes with iron absorption. Phytates bind
minerals such as iron, forming a complex that is insoluble and
therefore poorly absorbed,
(Found in maize, whole grains, legumes, spinich).

Solution: Avoid consumption of phytates with the iron

containing meal.
utilization utilization

Dietary iron Bone marrow

1-2 mg/day 300 mg

Myoglobin Plasma transferrin

Erythrocyte
300 mg 3 mg
1800 mg

Liver Slough mucosal cell Spleen

1-2 mg/day 600 mg
1000 mg
 Iron absorption
Promote absorption Ferrous Fe++
-Fructose Fe+++ More readily

absorbed
-Vitamin C HCl
Fe ++
-Heme iron
Inhibit absorption
-Amino acid
Fe++ -Phosphate
-Phytate
Fe++ ferritin -Tannin
-Soil clay

Fe+++ - transferrin
 Common diseases

Iron deficiency
Iron overload
Anaemia of chronic disease
Vegetarian groups

Iron Functions

Oxygen carriers
Haemoglobin

Oxygen storage
Myoglobin
 Iron Toxicity

Iron can damage tissues (Haemachromatosis)

Catalyzes the conversion of hydrogen peroxide to free-radical
ions
Free-radicals can attack:
cellular membranes
Proteins
DNA

Iron excess possibly related to cancers, cardiac toxicity and

other factors
 Iron distribution

35 – 45 mg / kg iron in adult male body

Total approx 4 g
Red cell mass as haemoglobin - 50%
Muscles as myoglobin – 7%
Storage as ferritin - 30%
Bone marrow (7%)
Reticulo-endothelial cells (7%)
Liver (25%)
Other Haem proteins - 5%
Cytochromes, myoglobin, others
In Serum - 0.1%
 Iron Transport in Blood

Red cells
As haemoglobin

Plasma
Bound to Transferrin
Carries iron between body locations
eg between gut, liver, bone marrow, macrophages
Iron taken up into cells by transferrin receptors
 The serum contains about 0.1% of body iron
Over 95% of iron in serum bound to transferrin
Serum iron is a routine blood test
Measures all serum iron (not in red cells)

Low levels:
Iron deficiency
Other: Random variation; acute or chronic inflammation;
pre-menstrual.

High levels:
Iron Overload
Other: Random variation, OCP, pregnancy, recent iron
ingestion.
 Ferritin

A routine blood test – reflects iron stores

Low serum levels

Indicate Iron deficiency (high specificity)

High serum levels

Iron overload
Other - Ferritin may be increased in serum by:
Tissue release (hepatitis, leukaemia, lymphoma)
Acute phase response (tissue damage, infection, cancer)
Interpretation
Low levels always indicate Fe deficiency.
 Iron Loss
Physiological
Cell loss: gut, desquamation
Menstruation (1mg/day)
Pregnancy, lactation

Pathological
Bleeding
Gut, menorrhagia, surgery, gross haematuria
Iron Absorption Regulation

Increased
Low dietary iron
Low body iron stores
Increased red cell production
Low haemoglobin
Low blood oxygen content

Decreased
Systemic inflammation
 Iron Deficiency

Laboratory changes:
Low iron (poor specificity)
Low ferritin (excellent specificity)
Elevated Transferrin (TIBC)
Low transferrin saturation
Hypochromic, microcytic Anaemia
 Causes of Iron deficiency

Increased demand for iron

Infancy and adolescence
Pregnancy and lactation

Iron loss
Bleeding

Decreased iron intake or absorption

Hepciden
In physiologic conditions
Menstruation

In pathologic conditions
Surgery,
Haemoglobinuria,
haemoptysis
Gastrointestinal tract pathology

In therapeutic procedures
Phlebotomy

In blood donation
Iron Deficiency—Decreased Iron Intake or Absorption

Vegetarians or malnutrition (low-cost diet)

Malabsorption syndromes

Sprue, Ulcérative colitis, and Crohn’s disease

After gastric and intestinal surgery

Intestinal parasitosis

Helicobacter pylori infection

Autoimmune atrophic gastritis

 Iron Deficiency
Clinical Manifestations

Fatigue
Decreased exercise tolerance
Tachycardia
Dermatologic manifestations
Decreased intellectual performance
Dysphagia
Depression, increased incidence of infections
Restless legs syndrome
Symptoms of anemia

• Fatigue
• Dizziness
• Headache
• Palpitation
• Dyspnoea
• Lethargy
• Disturbances in menstruation
• Impaired growth in infancy
Symptoms of iron deficiency

• Irritability
• Poor attention span
• Lack interest in surroundings
• Poor work performance
• Behavioural disturbances
• Pica
• Defective structure and function of epithelial tissue
– especially affected are the hair, the skin, the nails, the
tongue, the mouth, the hypopharynx and the stomach
• Increased frequency of infection
Pica

• The habitual ingestion of unusual

substances
– earth, clay (geophagia)
– laundry starch (amylophagia)
– ice (pagophagia)

• Usually is a manifestation of iron deficiency

and is relieved when the deficiency is
treated
 Iron Deficiency
Clinical Manifestations

Skin and conjuctival pallor

Koilonychia

Angular cheilosis

Burning tongue

Glossitis

Hair loss (alopecia areata)

 Iron Deficiency Anemia (IDA)

• Most common cause of anemia

• Microcytic hypochromic anemia
• MCV, MCH, MCHC are reduced
• blood film : small red cells (microcytic)
: pale red cells (hypochromic)
Microcytic Hypochromic
 Megaloblastic Anaemia
(Pernicious Anaemia)
Hypersegmented Neutrophils
and
Oval Macrocytes
 Koilonychia
Spoon shaped fingernail that occurs in
Iron deficiency anaemia
 Side effects of Iron Therapy

Oral iron - GI irritation

Black Stools - Diarrhoea
- Constipation

IV iron - anaphylactoid
- hypotension
- muscle cramp
 Iron Deficiency—Diagnosis
Microphotograph
of bone marrow
staining for iron.
Iron is stained
blue and it is
mainly in the
macrophages
(lower left)
 Iron requirements (RDA)
Category Age (years) RDA – Iron Females 11 – 14 15
(mg)
15 – 18 15
Infants 0 – 0.5 6
0.5 – 1 10
19 – 24 15

Children 1–3 10 25 – 50 15
4–6 10 51 + 10
7 – 10 10 Pregnant 30
Males 11 – 14 12 Lactating 1st 6 15
15 – 18 12 months
19 – 24 10 2nd 6 15
months
25 – 50 10
51 + 10
Laboratory findings (2)

• Iron metabolism tests

– serum iron concentration 

– total iron-binding capacity (TIBC) 
– saturation of transferrin 
– serum ferritin levels 
– sideroblasts 
 Response to treatment
• Less irritable & increased appetite within
24 hrs
• Bone marrow response by 48 hrs
• Increased reticulocyte count by 3rd day
• Increased Hb level by 2 months
• Body iron store repletion
 Hemochromatosis

Also known as accumulating disease.

This is a genetic disorder in which the
intestine is not able regulate iron absorption.

Result: iron absorption increases = build up

of excess iron = organ damage.

Most often seen in Caucasian males around

age 20
 Accumulation

Iron accumulation in tissues

causes damage/ failure to:
Liver
Heart
Pancreas
Skin
May generate free radicals which
can damage normal cells.
 Too much Iron
Haemochromotosis
Uncontrolled Iron absorption leads to Iron overload

Iron accumulates in: And causes:

1. Liver
1. Cirrhosis
2. Heart
2. Cardiomyopathy
3. Pancreas
3. Diabetes
4. Skin
4. Bronzing
5. Joints
5. Arthritis

It is Autosomal recessive
Autosomal recessive
An abnormal gene on one of the autosomal chromosomes (one
of the first 22 "non-sex" chromosomes) from each parent is
required to cause the disease.
People with only one abnormal gene in the gene pair are called
carriers, but since the gene is recessive they do not exhibit the
disease.
In other words, the normal gene of the pair can supply the
function of the gene so that the abnormal gene is described as
acting in a recessive manner.
BOTH parents must be carriers in order for a child to have
symptoms of the disease. A child who inherits the gene from
one parent will be a carrier.
 Iron
Iron study
study

1. Serum iron

2.Total iron binding capacity (TIBC)

3. %Transferrin saturation (% sat)

4. Ferritin
Normal

Iron Overload
 Iron
Overload
Haemochromatosis
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