OXYGEN

DISSOCIATIO
N CURVE &
GAS
TRANSPORT
Benjamin Munyua
 • The Oxyhemoglobin
Dissociation curve shows
how blood carries oxygen
through the body.  
Introduction • It also shows the relationship
between SpO2 and PaO2 as
determined by hemoglobin's
affinity for oxygen.
Hemoglobin and 02 Transport
• hemoglobin is found
in RBC.
• Each hemoglobin Insert fig. 16.32
has 4 polypeptide
chains and 4 hemes.
• In the center of each
heme group is 1
atom of iron that
can combine with 1
molecule 02.
Hemoglobin

Oxyhemoglobin: Deoxyhemoglobin:
Normal heme contains iron in the reduced form Forms When oxyhemoglobin dissociates to
(Fe2+). release oxygen, the heme iron is still in the
Fe2+ bonds with oxygen. reduced form.
 Hemoglobin (continued)

• Methemoglobin:
• Has iron in the oxidized form (Fe3+).
• cannot bind with 02.
• Blood normally contains a small amount.
• Hemoglobin bound to CO2?
• Carboxyhemoglobin:
• The reduced heme is combined with carbon monoxide.
• The bond with carbon monoxide is 210 times stronger than the bond with
oxygen.
• Transport of 02 to tissues is impaired.
Hemoglobin (continued)

• Oxygen-carrying capacity of blood determined by its [hemoglobin].

• Anemia:
• [Hemoglobin] below normal.
• Polycythemia:
• [Hemoglobin] above normal.
• Hemoglobin production controlled by erythropoietin.
• Production stimulated by PC02 delivery to kidneys.

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Fick's law

• According to this law, a gas travels from areas of high pressure to areas of low
pressure.
• So, since room air has a partial pressure of oxygen (PaO2) of 160, and alveoli have a
PaO2 is 104, oxygen easily makes it's way through the air passages to the alveoli.
• Similarly, venous capillary blood has a PaO2 of 40, so oxygen easily diffuses across
the respiratory membrane to the capillary system.
• Capillary PaO2 now becomes 104, thus becoming part of the arterial circulation.
Affinity of Hemoglobin

• This is a protein present in red blood cells (erythrocytes).

• In the capillary system oxygen comes into contact with a reduced
hemoglobin, or a hemoglobin that has no oxygen molecule on it.
• This makes it so the hemoglobin has a high attraction, or high affinity,
for oxygen. Oxygen then binds with a hemoglobin
• The amount of oxygen bound to hemoglobin at any time is based on
the partial pressure of oxygen that it is exposed to.  
• Since freshly oxygenated capillary blood has a PaO2 of 104 under
normal conditions, reduced hemoglobin (hemoglobin that does not
have oxygen) has a high affinity for it.
Cont’d

• Some oxygen molecules will remain in the plasma, although

a majority is picked up and transported by a hemoglobin
molecule.
• The normal percentage of hemoglobin carrying oxygen is
referred to as the oxygen saturation (SpO2), and a normal
value is generally considered to be in the 95-98%.  
• However, as you will soon see, 90% or greater can be
considered acceptable.
• Hemoglobin does not affect the partial pressure of oxygen,
and so the PaO2 of arterial blood remains 104.
Cont’d
• The accepted range of PaO2 is generally considered to be in
the 80-100 range.  
• When a cell uses up it's oxygen molecules, it has a PO2 that
ranges somewhere around 22-35. As the hemoglobin
approaches this cell with a lower PO2, it releases it's
hemoglobin.  
• The cell on this end is said to have a high affinity for oxygen.
The Oxyhemoglobin Dissociation Curve
• Venous blood has a PO2 of 40 and is generally referred to as PvO2.  
• As more oxygen molecules enter the capillary bloodstream, this
increases the PO2, and therefore increases reduced hemoglobin's
affinity for oxygen.  
• It is here where the capillary system converts from being part of the
unoxygenated venous system to the oxygenated arterial system.
• As the PO2 of capillary blood increases, more and more oxygen
molecules bind with hemoglobin until a majority of hemoglobin
becomes completely saturated.  
• A normal SpO2 value here is about 98%, or a range of 95-98%.  An
acceptable range is 90%.  The capillary then becomes part of the
arterial system, with its PO2 now being referred to as PaO2.
The
Oxyhemoglobi
n Dissociation
Curve
Cont’d
• So, the curve has an s-shape because, at lower PO2s, oxygen
binds to hemoglobin at a high rate, and this slows down as
hemoglobin become more saturated.
• At PO2s above 60 the curve is relatively flat, meaning that the
oxygen content of the blood will not change much with
subsequent increases in PO2.
• In other words, the only way to get more oxygen to tissues
would require adding more hemoglobin molecules to the blood,
which would require a blood transfusion.
• Or, another simpler method would be to add more oxygen to
the plasma by increasing the fraction of inspired oxygen
(FiO2).
4-5-6-7-8-9 Rule
• It is because of this curve that we can use SpO2 to estimate
PaO2.
PO2 40 = SpO2 70%
PO2 50 = SpO2 80%
PO2 60 = SpO2 90%
Shifting of the curve
• Certain conditions cause hemoglobin to release more oxygen
into the bloodstream, shifting the curve to the right;
• Certain conditions cause hemoglobin to pick up more oxygen
from the bloodstream, shifting the curve to the left.  
• Both of these conditions will have a direct affect on SpO2
and PaO2
Shift to the right
• The curve shifts to the right when hemoglobin has a decreased affinity
for oxygen, and has a "harder" time making the bond with oxygen.  
• This decreases hemoglobin's affinity for oxygen, causing it to un-bond
with hemoglobin and enter tissues.  
• Lower SpO2 for a given PO2
• Requires a higher PO2 to achieve the desired SpO2
• Hemoglobin more likely to dump oxygen into tissues (active muscles need
more oxygen)
• Anything that creates heat will move curve to right. Acidosis or low pH (heat)
• High CO2 causes Acidosis (heat)
• Exercise (heats up body)
• Increased 2.3 DPG
Shift to the left
The curve shifts to the left when hemoglobin has an increased affinity
for oxygen, and has an "easier" time making the bond with oxygen.  
• Higher SpO2 for a given PO2
• Hemoglobin is more likely to cling to O2 and not let go (activity is minimal)
• Think Cold. The colder your body, the slower activity will be.
• Hypothermia (cold tissues)
• Rest (minimal exertion)
• Hypocarbia
• CO2 poisoning
• Alkalotic (tissues cold)
• Decreased 2.3 DPG
• Fetal Hemoglobin (fetus needs less oxygen and can live off lower PO2s)
What is 2.3 DPG? 
• It's a substance in the blood that controls movement of oxygen from
the blood to tissues.
• 2,3-Bisphosphoglyceric acid
• An organic phosphate in red blood cells that alters the affinity of 
hemoglobin for oxygen.
• Blood cells stored in a blood bank lose 2,3-diphosphoglycerate, but
once they are infused, the substance is resynthesized or reactivated.
Effect of 2,3 DPG on 02 Transport

• Anemia:
• RBCs total blood [hemoglobin] falls, each RBC
produces greater amount of 2,3 DPG.
• Since RBCs lack both nuclei and mitochondria,
produce ATP through anaerobic metabolism raising
the levels of 2.3 DPG.
• Fetal hemoglobin (hemoglobin f):
• Has 2 g-chains in place of the b-chains.
• Hemoglobin f cannot bind to 2,3 DPG.
• Has a higher affinity for 02.
Increasing 2.3 DPG
• This is your bodies way of responding to lack of oxygen.  
• It lowers hemoglobin's affinity for oxygen, causing hemoglobin to
release oxygen into the bloodstream for tissues to use.   
• This moves the curve to the right.
• The following conditions cause the body to increase production of 2.3
DPG:
• Anemia (it may take 24 hours after transfusion to replenish supply, and return
curve to normal)
• Chronic Obstructive Pulmonary Disease (COPD)
• Cystic Fibrosis
• Congenital heart diseases
• Anything that increases metabolism (HEAT), such as acidosis, exercise, fever,
etc.
Decreasing 2.3 DPG
• This results from lack of DPG enzymes to make 2.3 DPG.
• The body responds by increasing red blood cells (RBCs) that are weak
and burst easy.
• This moves the curve to the left.
• When this happens your body will increase 2.3 DPG production to try
to move it back to normal.
• The following conditions cause this:
• Erythrocytosis
• Anemia
• Large blood transfusion
 Sickle-cell anemia:
• Hemoglobin S differs in that valine is
substituted for glutamic acid on position 6
of the b chains.
Inherited • Makes the RBCs less flexible and more
fragile.
Defects in
Hemoglobin
Thalassemia:
Structure and • Decreased synthesis of a or b chains,
Function increased synthesis of g chains.
GAS TRANSPORT.
TRANSPORT OF GASES IN BLOOD
Oxygen Transport
•  Molecular oxygen is carried in blood in two ways:
bound to hemoglobin within red blood cells and
dissolved in plasma.
• Oxygen is poorly soluble in water, so only about 1.5% of
the oxygen transported is carried in the dissolved form.
• 98.5% of the oxygen ferried from the lungs to the
tissues is carried in a loose chemical combination with
hemoglobin.
• Hemoglobin (Hb) is composed of four polypeptide
chains, each bound to an iron-containing heme group.
Cont.
• Because the iron atoms bind oxygen, each
hemoglobin molecule can combine with four
molecules of O2, and oxygen loading is rapid and
reversible.
•  The hemoglobin-oxygen combination, called
oxyhemoglobin , HbO2.
• Hemoglobin that has released oxygen is called
reduced hemoglobin, or deoxyhemoglobin, HHb.
Cont..
•  After the first O2 molecule binds to iron, the Hb molecule
changes shape.
• As a result, it more readily takes up two more O 2
molecules, and uptake of the fourth is even more
easier/facilitated.
• When all four heme groups are bound to O2, a
hemoglobin molecule is said to be fully saturated.
• When one, two, or three oxygen molecules are bound,
hemoglobin is partially saturated.
• Unloading of one oxygen molecule enhances the
unloading of the next, and so on.
 Cont…
• The rate at which Hb reversibly binds or releases O2 is regulated
by:
 PO2,
 Temperature,
 Blood pH,
 PCO2, and
 Blood concentration of an organic chemical called DPG.
1. Influence of PO2 on Hemoglobin Saturation.
• Because the affinity of hemoglobin for O2 changes with O2
binding , the relationship between the degree of hemoglobin
saturation and the PO2 of blood is not linear. This S-shaped O2
dissociation curve has a steep slope for PO2 values between 10
and 50 mm Hg and then flattens out (plateaus) between 70 and
100 mm Hg.
• Temperature, blood pH, PCO2, and the amount of
BPG in the blood all influence hemoglobin
saturation at a given PO2.
• BPG (2,3-bisphosphoglycerate), which binds
reversibly with hemoglobin, is produced by red
blood cells (RBCs) as they break down glucose by
the anaerobic process called glycolysis.
• All of these factors influence Hb saturation by
modifying hemoglobin’s structure, and thereby its
affinity for O2.
• An increase in temperature, PCO2, H+ content of the blood, or BPG
levels in blood decreases Hb’s affinity for O2 and causes the oxygen-
hemoglobin dissociation curve to shift to the right ( releasing O2 at
tissue).
• This enhances oxygen unloading from the blood.
• a decrease in any of these factors increases hemoglobin’s affinity for
oxygen and shifts the dissociation curve to the left ( at the lungs).
• As cells metabolize glucose and use O2, they release CO2, which
increases the PCO2 and H+ levels in the capillary blood. Both declining
blood pH (acidosis) and increasing PCO2 weaken the Hb-O2 bond, a
phenomenon called the Bohr effect.
• As a result, oxygen unloading is enhanced where it is most
needed.
• Additionally, heat is a by-product of metabolic activity, and
active tissues are usually warmer than less active ones.
• A rise in temperature affects hemoglobin’s affinity for O2 both
directly and indirectly (via its influence on RBC metabolism and
BPG synthesis).
• Collectively, these factors see to it that Hb unloads much more
O2 in the vicinity of hard-working tissue cells.
 Carbon Dioxide Transport
• Normally active body cells produce about 200 ml of CO2 each minute—
exactly the amount excreted by the lungs.
• Blood transports CO2 from the tissue cells to the lungs in three forms:
1.  Dissolved in plasma    (7–10%). The smallest amount of CO2 is transported
simply dissolved in plasma.

2.  Chemically bound to hemoglobin    (just over 20%). In this form, CO2 is

carried in the RBCs as carbaminohemoglobin. CO2+Hb=HbCO2.
• This reaction is rapid and does not require a catalyst.
 Cont.
• Carbon dioxide binds directly to the amino acids of globin (and not to the
heme).
• Carbon dioxide transport in RBCs does not compete with the
oxyhemoglobin transport mechanism.
•  CO2 loading and unloading to and from Hb are directly influenced by the
PCO2 and the degree of Hb oxygenation.
• Carbon dioxide rapidly dissociates from hemoglobin in the lungs, where
the PCO2 of alveolar air is lower than that in blood.
• Carbon dioxide is loaded in the tissues, where the PCO2 is higher than that in
the blood.
• Deoxygenated hemoglobin combines more readily with carbon dioxide
than does oxygenated hemoglobin
 Cont..
3.  As bicarbonate ion in plasma    (about 70%).
• Most carbon dioxide molecules entering the plasma quickly enter the
RBCs, where most of the reactions that prepare carbon dioxide for transport
as bicarbonate ions (HCO3–) in plasma occur.
• When CO2 diffuses into the RBCs, it combines with water, forming
carbonic acid (H2CO3).
• H2CO3 is unstable and quickly dissociates into hydrogen ions and
bicarbonate ions.
•  Although this reaction also occurs in plasma, it is thousands of times faster
in RBCs because they (and not plasma) contain carbonic anhydrase , an
enzyme that reversibly catalyzes the conversion of carbon dioxide and water
to carbonic acid.
• Hydrogen ions released during the reaction (as well as CO 2 itself) bind to
Hb, triggering the Bohr effect; thus, O2 release is enhanced by CO2 loading.
• Because of the, the liberated H+ is buffered effect of Hb
•  Once generated, HCO3– moves quickly from the RBCs into the plasma, where
it is carried to the lungs.
• To counterbalance the rapid outrush of these anions from the RBCs, chloride
ions (Cl–) move from the plasma into the RBCs.
• This ion exchange process, called the chloride shift, occurs via facilitated
diffusion through an RBC membrane protein.
•  In the lungs, the process is reversed. As blood moves through the pulmonary
capillaries, its PCO2 declines from 45 mm Hg to 40 mm Hg.
• For this to occur, CO2 must first be freed from its “bicarbonate housing.”
HCO3– reenters the RBCs (and Cl– moves into the plasma) and binds with H+ to
form carbonic acid, which is then split by carbonic anhydrase to release CO 2
and water.
• This CO2, along with that released from hemoglobin and from solution in
plasma, then diffuses along its partial pressure gradient from the blood into the
alveoli.
• The amount of carbon dioxide transported in blood is markedly affected by the
degree of oxygenation of the blood.
• The lower the PO2 and the lower the extent of Hb saturation with oxygen, the more
CO2 that can be carried in the blood.
• This phenomenon, called the Haldane effect, reflects the greater ability of reduced
hemoglobin to form carbaminohemoglobin and to buffer H+ by combining with it.
• As CO2 enters the systemic bloodstream, it causes more oxygen to dissociate from
Hb (Bohr effect), which allows more CO2 to combine with Hb and more HCO3– to
be formed (Haldane effect).  
•  In the pulmonary circulation, the situation is reversed—uptake of O 2 facilitates
release of CO2.
• As Hb becomes saturated with O2, the H+ released combines with HCO3–, helping
to unload CO2 from the pulmonary blood.
• The Haldane effect encourages CO2 exchange in both the tissues and lungs.
Carbon Dioxide Transport

Insert fig. 16.38

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 Influence of CO2 on Blood pH
• Typically, the H+ released during carbonic acid dissociation is buffered by
Hb or other proteins within the RBCs or in plasma.
• The HCO3– generated in the red blood cells diffuses into the plasma,
where it acts as the alkaline reserve part of the blood’s carbonic acid–
bicarbonate buffer system.
• The carbonic acid–bicarbonate buffer system is very important in
resisting shifts in blood pH.
• For example, if the hydrogen ion concentration in blood begins to rise,
excess H+ is removed by combining with HCO3– to form carbonic acid (a
weak acid that dissociates very little at either physiological or acidic pH).
• If H+ concentration drops below desirable levels in blood, carbonic acid
dissociates, releasing hydrogen ions and lowering the pH again.
•   Changes in respiratory rate or depth can produce dramatic changes in
blood pH by altering the amount of carbonic acid in the blood.
• Slow, shallow breathing allows CO2 to accumulate in the blood. As a
result, carbonic acid levels increase and blood pH drops.
• rapid, deep breathing quickly flushes CO2 out of the blood, reducing
carbonic acid levels and increasing blood pH.
• Thus, respiratory ventilation can provide a fast-acting system to adjust
blood pH (and PCO2)
• Respiratory adjustments play a major role in the acid-base balance of the
blood.
Effect of Bicarbonate on Blood pH

Insert fig. 16.40

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 Acclimatization to High Altitude

• Adjustments in respiratory function when moving to an area

with higher altitude:
• Changes in ventilation:
• Hypoxic ventilatory response produces hyperventilation.
• Increases total minute volume.
• Increased tidal volume.
• Affinity of hemoglobin for 02:
• Action of 2,3-DPG decreases affinity of hemoglobin for 02 causing its release
at tissues.

• Increased hemoglobin production:

• Kidneys secrete erythropoietin.