
Dr. Basim Al-Ka'abi
Blood Physiology
Third Lecture
1
Lecture Name: The Hemoglobin and Iron
Lecturer Name: Dr. Basim A. Al-Ka'abi
Department: Medical Physiology
Stage: First Stage Medical Students
Lecture Objectives:
By the end of this lecture the students should be able to know the following:
Definition and function of hemoglobin.
The structure of hemoglobin and its constituents.
Synthesis, catabolism and reaction of hemoglobin.
Iron and its various stages of metabolism.
References:
Barrett, K et al. (2018). Ganong's Review of Medical Physiology. Twenty-
sixth edition. USA.
Guyton, A and Hall, J (2015). Text Book of Medical Physiology.
Thirteenth edition. Philadelphia, USA.

Dr. Basim Al-Ka'abi
Blood Physiology
Third Lecture
2
The hemoglobin
-Hemoglobin is the iron-containing pigment of the red blood cells that
function to carry oxygen from the lungs to the tissues.
-It is synthesized in the bone marrow by nucleated precursors of the
erythrocytes, since approximately 65% of Hb synthesis occurs during the
nucleated stages of RBC maturation and 35% occurs during the
reticulocytes stage.
-Hemoglobin is the main constituent of RBCs, which comprises 95% of
the RBC’s dry weight.
-Normal blood has about 16 g/dl of Hb in adult men and about 14 g/dl in
adult women.
Hemoglobin structure
-It is a globular molecule made up of four subunits, each subunit contains
a heme conjugated to a polypeptide (globin).
Heme structure
-Heme is an iron-containing porphyrin, and the porphyrin contains four
pyrrole-like rings linked by four methane bridges in an alternating double
bond ring system.
Globin structure
-The globin is consisted of two pairs of polypeptides, one pair containing
one type of polypeptide and the second pair contain another type.
-Normal adult human Hb (HbA) consists of two alpha chains and two beta
chains, thus HbA is designated as α
2
β
2
.
-Not all the Hb in the blood of normal adults is HbA. About 2.5% of the
Hb is HbA
2
, in which beta chains are replaced by delta chains (α
2
δ
2
).

Dr. Basim Al-Ka'abi
Blood Physiology
Third Lecture
3
-While the blood of the fetus normally contains fetal Hb (HbF) which is
normally replaced by adult Hb soon after birth. It is consisted of two alpha
chains and two gamma chains (α
2
γ
2
).
-Normal adult RBC contains 92-95% HbA, 2-3% HbA
2
and 1-2% HbF.
Hemoglobin synthesis
-Normal hemoglobin production is dependent on three processes
1. Adequate iron delivery and supply.
2. Adequate synthesis of protoporphyrins (the precursor of heme).
3. Adequate globin synthesis.
The globin synthesis
-Globin chain synthesis occurs on RBC-specific cytoplasmic ribosomes,
which are initiated from the inheritance of various structural genes. Each
gene results in the formation of a specific polypeptide chain.
-The RBC contains four alpha genes, two beta genes, two delta genes and
four gamma genes.
-The resulting gene products formed are called alpha, beta, delta and
gamma chains.
-All normal adult Hb are formed as tetramers consisting of two alpha
chains plus two non-alpha globin chains.
Catabolism of hemoglobin
-When old RBCs are destroyed in the reticulo-endothelial system, the Hb
is first split into globin and heme.
-The heme ring is opened to give a straight chain of four pyrrole nuclei,
that is the substrate from which bile pigments are formed.
-The iron from the heme is re-used for Hb synthesis.
-The globin is either recycled, destroyed or metabolized in the liver.

Dr. Basim Al-Ka'abi
Blood Physiology
Third Lecture
4
Reaction of hemoglobin
-Hemoglobin binds oxygen to form oxyhemoglobin, and the O
2
is attached
to the ferrous iron (Fe
+2
) in the heme.
-The affinity of Hb for O
2
is affected by pH, temperature and the
concentration of the 2,3 diphosphoglycerate (2,3 DPG), since 2,3 DPG
compete with O
2
for binding to Hb.
-When blood is exposed to various drugs and other oxidizing agents, the
Fe
+2
is converted to ferric atom (Fe
+3
) forming met-hemoglobin or sulf-
hemoglobin. These abnormal forms of Hb are unable to transport oxygen.
-Carbon monoxide (CO) reacts with Hb to form carboxy hemoglobin. The
affinity of Hb for CO is 30 times much greater than its affinity for O
2
.
Iron metabolism
-Iron metabolism involves absorption, transport, utilization, storage and
excretion.
-The tissues of a 70 kg adult male contain between 3-4 g of iron, which is
distributed in various compartments.
-Seventy percent of the iron in the body is in Hb, 3% in myoglobin and the
remainder is in ferritin.
-Normal plasma iron level is about 130 µg/dl in men and 110 µg/dl in
women.
Absorption
-Iron is absorbed in all parts of the small intestine, but absorbed almost
entirely in the upper part of the small intestine, mainly in the duodenum.
-In general, an acidic condition or low pH favors iron absorption, whereas
neutral and alkaline pH decrease iron absorption.
-The best sources of dietary iron are liver, red meat, egg yolk and dried
fruits.

Dr. Basim Al-Ka'abi
Blood Physiology
Third Lecture
5
Transport
-Iron is absorbed from the intestinal tract or is released by hemoglobin
catabolism.
-Iron is transported from the mucosal cells to the blood in the ferrous state,
where it is converted to the ferric state by serum ferroxidases.
-It is then incorporated into specific iron transport protein, the transferrin,
that one molecule of transferrin can bind two molecules of ferric iron.
-Transferrin releases iron to erythroblasts and reticulocytes by attachment
to specific receptors on the cell membrane which is then followed by the
reduction of the ferric iron to the ferrous iron again.
Utilization
-Iron within the cell is found in the mitochondria.
-The mitochondrial iron is incorporated rapidly into protoporphyrin to
form heme.
Storage
-Iron is stored in the tissues in two forms: as a soluble form called ferritin
and as an insoluble form called hemosiderin.
-Ferritin is found in all tissues and in high concentration in liver, spleen
and bone marrow.
-About 70% of the storage iron is present as ferritin and the remainder as
hemosiderin.
Requirement
-The average daily loss of iron in urine, feces and sweat is 1-2 mg and
although the normal diet contains about 15 mg of iron, only 1-2 mg are
absorbed, since the average quantity of iron derived from the diet each day
must at least equal that lost from the body.

Dr. Basim Al-Ka'abi
Blood Physiology
Third Lecture
6
-In menstruating women, the average blood loss is 60-80 ml/month,
representing approximately 30-40 mg of iron lost per month; an additional
1 to 1.5 mg of iron daily is therefore needed to maintain iron balance.
-Pregnancy creates an iron requirement of about 700 mg (fetus, placenta,
blood loss and lactation), so during pregnancy, iron absorption increases
up to 20%.