basic introduction

1. Oxygen Transport

2. MODES OF O2TRANSPORT
• Oxygen is transported from lungs to the tissues in two methods:
• physically dissolved in the plasma, and,
• in combination with hemoglobin (Hb) in the red cell.
• Approximately 98% of the oxygen is transported in combination
with hemoglobin and the remaining 2% in the physically
dissolved form.

3. In Physically Dissolved Form
• In the physically dissolved form in plasma, only about 2% of oxygen is
transported. The amount of physically dissolved oxygen in the blood can be
predicted from Henry’s law.
• Henry’s law states that the amount of gas that dissolves in a liquid at a given
temperature is proportional to the partial pressure of the gas.
• Thus, the quantity of dissolved oxygen in arterial blood is calculated from the
following equation:
• Dissolved O2 (ml/dl) = oxygen solubility  partial pressure of O2 in arterial
blood (PaO2).
• = 0.003 (ml /dl of blood per mm Hg)  95 mm Hg (normal PaO2 is 95 mm Hg)
• = 0.3 ml/dl of blood

4. • Thus, at PaO2 of 95 mm Hg, the dissolved O2 is 0.3 ml/dl.
That means, in a normal healthy adult, 0.3 ml of O2 is transported in
dissolved form in 100 ml of blood (Application Box 70.1).
• As cardiac output is 5 liters /min at rest, oxygen transported in dissolved
form at rest is about 15 ml/min.
• Therefore, oxygen transported in dissolved form alone is grossly
inadequate to meet the oxygen requirement of the body, which is about
250 ml/min at rest.

5. In Combination with Hemoglobin
• More than 98% of O2 is transported in combination with Hb.
• This becomes possible due to the binding affinity of hemoglobin for
oxygen.
• Hemoglobin that binds with oxygen is called oxyhemoglobin (HbO2) and
the hemoglobin that does not bind with O2 is called deoxyhemoglobin
(deoxy-Hb) or reduced-hemoglobin.
Oxyhemoglobin Formation
• The hemoglobin molecule is a protein made up of four subunits that are
bound together. Each subunit consists of a molecular group known as heme
and a polypeptide attached to the heme. The four polypeptides of a Hb
molecule are combinely known as globin.
• Each heme group contains one atom of iron (Fe++) to which oxygen binds

6. Structure of Hb molecule

7. • Since each iron atom can bind one molecule of oxygen, a single Hb
molecule can bind four molecules of oxygen.
• Hb binds with oxygen only when the iron is in ferrous (Fe++) state. The
Fe++ iron in Hb is oxidized to ferric (Fe+++) iron to form methemoglobin.
• Thus, methemoglobin can’t bind oxygen. Methemoglobin formation occurs
under the influence of various compounds like nitrites or sulfonamides.
Methemoglobin is also formed spontaneously.
• However, the enzyme methemoglobin reductase is present in red cell that
reduces methemoglobin to Hb. Therefore, normally only about 1.5% of total
Hb is methemoglobin.
• Deficiency of methemoglobin reductase (a genetic defect) increases the
methemoglobin concentration and decreases oxygen carrying capacity.
• Oxygen binds rapidly and reversibly to hemoglobin to form
oxyhemoglobin(HbO2): O2 + Hb  HbO2

8. • R & T STATES OF Hb:During this process of HbO2 formation, the heme remains in
ferrous state. Thus, this process is oxygenation, not oxidation. As there are four
subunits in Hb molecule, Hb reacts rapidly (in less than 0.01 s) with four molecules
of oxygen to form HbO8.
1. When oxygen is not bound with Hb (deoxyhemoglobin) the four subunits of Hb are
tightly bound with each other. This configuration of Hb is called Tense or T state. In
this T configuration, affinity of Hb for oxygen is less.
2. When, first oxygen molecule binds with Hb, the four subunits enter into the relaxed
or R state that exposes more oxygen binding sites. Therefore, in R configuration,
affinity of Hb for oxygen is greatly increased by 200 to 500 times.
3. When PO2 is very less, most of Hb molecules are in T state and have low oxygen
affinity.
4. When PO2 is very high, the Hb molecules are in R state and have high oxygen
affinity

9. Conversion of Hb molecule from T state to R state. As O2 is added, salt bridges are
successively broken and finally 2-3,BPG is expelled.
T (taught) conformation of deoxy-Hb is changed to relaxed (R) conformation of Oxy-Hb
5. Thus, the quantity of oxyhemoglobin formation is a function of partial
pressure of oxygen in the blood.
• In pulmonary capillaries, where PO2 is high, the reaction favours to form more
oxyhemoglobin, and in tissue capillaries, where PO2 is low, the reaction favours
formation of deoxyhemoglobin that helps oxygen to be unloaded from hemoglobin
and becomes available to the cells.

10. O2 Carrying Capacity of Hb
• Each gram of hemoglobin binds with 1.34 ml of oxygen. The maximum
amount of oxygen that can be carried by hemoglobin is called the oxygen
carrying capacity.
• In a healthy individual, the oxygen carrying capacity of arterial blood is about
20 ml of O2 per 100 ml of blood, considering the hemoglobin concentration
of 15 g% (1.34 ml  15 g = 20.1 ml O2/dl blood).
• OXYGEN CONTENTof Hb (HbO2 content) is the amount of oxygen actually
bound to hemoglobin, whereas OXYGEN CAPACITY of Hb (HbO2 capacity)
is the amount of oxygen that can potentially bind with Hb.
• The percentage saturation of hemoglobin with oxygen (SO2) is the ratio of
the quantity of oxygen actually bound (oxygen content) to the quantity that
can be potentially bound (oxygen capacity) multiplied by 100.

11. Oxygen-Hemoglobin Dissociation Curve:
• Oxygen-hemoglobin (Oxy-Hb) equilibrium curve (dissociation or
association curve) explains the relationship between partial pressure of
oxygen (PO2) in blood with oxygen saturation of Hb. Oxy-Hb equilibrium
curve is an S-shaped curve over the range of PO2 from 0 to 100 mm Hg
• The sigmoid shape of the curve results from hemoglobin affinity for oxygen
at various PO2 levels.
• As PO2 rises, the Hb saturation progressively increases.
• However, the saturation is not linear with increase in PO2 for which the
curve becomes sigmoid shaped.
• The S-shaped oxyhemoglobin equilibrium curve enables oxygen to saturate
hemoglobin under high partial pressures in the lungs and to give up large
amounts of oxygen with small changes in PO2 at the tissue level.