CBS EXAM BOOKS

REVISION MODULE

DAY 4 Update 17

Updates taken from:

CRISP Physiology
2nd Edition
By S Krishna Kumar

TRANSPORT OF GASES Oxygen Transport Combined with

zz Once the oxygen diffuses from alveoli into the pulmonary capillaries, Hemoglobin
it is carried to the left heart and from there oxygen is transported in zz Once the oxygen enters pulmonary capillaries from alveoli, much of
blood to all other body regions combines with the oxygen carrier protein in RBCs called hemoglobin
zz Due to metabolism of oxygen by tissues, carbon dioxide is produced
and it is transported in blood to the lungs for expelling out of the Types of Hemoglobin
body.
Hemoglobin types Chains
Transport of Oxygen Hemoglobin A (Major adult Hb) α2β2
zz Oxygen is transported in blood in two forms. They are: Hemoglobin A2 (Minor adult Hb) α2δ2
 Dissolved form Hemoglobin F (Fetal hemoglobin) α2γ2
 Combined with hemoglobin

Oxygen Transport in Dissolved Form

zz According to Henry’s law, the amount of dissolved gas is proportional
to its partial pressure
zz For each mm Hg of Po2, there is 0.003 mL O2/100 mL of blood
zz We know that the normal arterial blood have PO2 of 100 mm Hg. So,
the amount of dissolved oxygen is 0.003 mL × 100 = 0.3 mL O2/100
mL of blood
Oxygen transported in dissolved form = 0.3 mL O2/100 mL of blood
 Structure of Hemoglobin (HbA)

C � Has four subunits – 2 α chains and 2 β chains

� Each subunit has a heme moiety
R � Heme is an iron-containing porphyrin
The iron is in ferrous iron (Fe2+)
I �

� Each molecule of Hb carries 4 molecules of O2

S � The globin units are tightly bound in
deoxyhemoglobin. This is called tense (T)
P �
configuration
Once the first molecule of oxygen binds, the globin
units are released and expose more oxygen binding
sites. This state is called relaxed (R) configuration

Oxygen Carrying Capacity of Hemoglobin  This is termed as cooperative binding kinetics and it is the
reason for the sigmoid nature of the curve.
zz Each gram of hemoglobin transport 1.34 mL of oxygen

Oxygen Carrying Capacity of Arterial Blood Loading Zone of the Curve

zz It refers to the upper flat part (plateau) of the curve
zz The hemoglobin concentration in normal blood is about
zz This is where loading of oxygen (association) happens in lung
15 g/dL.
zz At PO2 of 100 mm Hg, Hb is 97.5% saturated
zz Therefore, 1 dL of blood contains (1.34 mL × 15) 20.1 mL of
zz At PO2 of 60 mm Hg, Hb is still 90% saturated. “This is the
oxygen bound to hemoglobin. Such hemoglobin is termed fully
safety factor” where O2 carrying capacity of blood is not much
saturated or 100% saturated hemoglobin
affected if PO2 falls till 60 mm Hg
zz But in reality, hemoglobin is never 100% saturated because of
physiological shunts (venous admixtures). It is around 97%
saturated. Unloading zone of the curve
zz So, the arterial blood contains around 19.8 mL of O2 per dL zz It refers to the steep portion of the curve at PO2 below
out of which 0.29 mL in dissolved form and 19.5 mL bound to 60 mm Hg
hemoglobin zz This is where unloading of oxygen happens in tissues where
large amounts of oxygen can be liberated from the blood with
Oxygen Content in Venous Blood relatively minor fall of PO2
zz Remember, Hemoglobin is 75% saturated in venous blood and its
oxygen content is 15.2 mL/dL Shifts in O2–Hb dissociation curve
CHAPTER7  Respiratory Physiology

zz This means that tissues remove about 4.6 mL of O2 (19.8 – 15.2) zz
from each dL of blood passing through them.
zz
Oxygen-Hemoglobin Dissociation Curve
zz Binding and release of oxygen from hemoglobin is assessed
using oxygen-hemoglobin dissociation curve (ODC) zz
zz The curve is sigmoid shaped because,
 Once the first molecule of oxygen binds with the first heme zz
in Hb, it increases the affinity for further oxygen binding
and making it lot easier. zz
 There is increasing affinity for oxygen binding so that
affinity for the fourth O2 molecule is the highest
Oxygen-hemoglobin dissociation curve can be shifted to left or
right by various factors
Means there is decreased affinity of oxygen to hemoglobin
leading to release of oxygen (unloading of oxygen)
Shift to right
Means a higher value of PO2 is required for hemoglobin to bind
a given amount of O2
Shift to right commonly occurs in tissues where unloading of
oxygen is very vital
If the oxyhemoglobin dissociation curve is shifted to the right,
the P50 increases

2
 leading to loading of oxygen
zz Shift to left commonly occurs in lungs where loading of oxygen
occurs
zz Left shift simply means that at same PO2, there is more uptake
of oxygen C
Causes of left shift of oxygen-hemoglobin dissociation R
curve
I
S
Oxygen-Hemoglobin Dissociation Curve of P
Fetal Hemoglobin
zz Fetal hemoglobin (HbF) causes left shift of oxygen dissociation
curve
zz Major reason for this left shift is:
“Two gamma chains present in HbF has less affinity for 2, 3-DPG
when compared to the beta (β) chains of HbA”
Right shift in O2–HB dissociation curve
zz HbF has more affinity for oxygen. For example, at a PO2 of
20 mm Hg, HbA is only 35% saturated but HbF is 70% saturated.
Remember!
Double Bohr Effect
Causes of right shift of Oxygen-hemoglobin
zz Double Bohr effect occurs at the fetal-maternal interface in
dissociation curve are:
placenta
zz Increase in PCO2
zz PaCO2 in the maternal blood is usually around 33 mm Hg and
zz Decrease in pH of blood (Acidosis)
the PaCO2 in fetal blood is around 55 mm Hg.
ƒƒ The decrease in O2 affinity of hemoglobin when zz Most of the CO2 and acids from fetal blood diffuses into the
pH of blood falls (PCO2 rises) is called the Bohr maternal blood
effect. This leads to release of oxygen at tissues zz Loss of CO2 makes the fetal blood more alkaline (left shift of
ƒƒ Bohr effect accounts for about 2% more release curve) and the increased CO2 in the maternal blood makes it
of oxygen at tissues more acidic (right shift of curve)
zz Increase in the temperature zz Fetus can bind oxygen released from mother with increased
zz Increase in 2,3-diphosphoglycerate (2,3-DPG)
affinity because of HbF
zz So, Bohr’s effect operates in one direction in materal blood and
ƒƒ 2,3-DPG is an intermediate product in
in other direction in fetal blood. This is called “Double Bohr’s
glycolysis
effect”
ƒƒ It binds with β chains of deoxyhemoglobin
causing more O2 to be released at tissues Oxygen Dissociation Curve of Myoglobin
ƒƒ Most important factors that decreases the
zz Myoglobin is the iron-containing pigment that stores oxygen
2,3-DPG concentration is
mainly present in skeletal muscle
 Acidosis (low PH) because acidosis inhibits
zz Each molecule of myoglobin can bind with only one molecule
glycolysis of oxygen
 Stored blood (acid citrated buffer used for
storage inhibits glycolysis)
Factors that increase 2,3-DPG concentration
are:
™™ Thyroid hormones
™™ Growth hormones
™™ Androgens
Theory

zz High altitude
zz During exercise

Shift to left
zz Means there is increased affinity of oxygen to hemoglobin 3
C Remember!
R Causes of left shift of oxygen-hemoglobin
dissociation curve are:
I 1. Decreased pCO2 of blood
2. Increased pH of blood (alkalosis)
S 3. Decreased temperature
P 4. Fetal hemoglobin
5. Methemoglobin (Iron in ferric form)

� The shape of oxygen dissociation curve of myoglobin is

rectangular hyperbola rather than sigmoid because there is
no cooperative binding kinetics involved
� Note that myoglobin binds with oxygen with increased
affinity leading to loading of oxygen (left shift)
� Myoglobin stores oxygen in skeletal muscle and releases it
during exercise when Po2 is low

Transport of Carbon Dioxide

CHAPTER7  Respiratory Physiology

zz Carbon dioxide is transported in blood from tissues to the lungs

for exhaling it out of the body
zz CO2 is transported as:
 As bicarbonate form (70% - the major form of CO2
transport)
 As carbamino compound form bound with hemoglobin
(23%)
 In dissolved form (7%)

4 Carbon dioxide transport – as bicarbonate form

zz Bicarbonate form is the major form for CO2 transport (70%)  In lungs, chloride shift happen in opposite direction
zz After entering the blood, CO2 reacts with water to form carbonic leading to shrinkage of RBCs.
acid in RBCs
zz RBCs have abundant concentration of an enzyme carbonic Transport of Carbon Dioxide in Carbamino
zz
anhydrase
Carbonic anhydrase
form C
After entering the blood, CO2 combines with the amino group
 Catalyzes the rapid conversion of carbon dioxide and
water to bicarbonate and H+
zz
of hemoglobin proteins to form carbamino compounds R
zz This form transports around 23% of CO2


It is a metalloenzyme that contains zinc in its active site
The enzyme is also abundant in intercalated (I) cells of
I
Transport of Carbon Dioxide in Dissolved

kidney
It plays an important role in acid base balance form
S
zz H+ formed is buffered by hemoglobin and the bicarbonate
ion moves to plasma for an exchange of chloride ion. This
zz CO2 is 20 times more soluble than O2. P
zz So, the percentage of CO2 transport in dissolved form is more
phenomenon is called chloride shift
when compared to oxygen
zz Chloride Shift
zz 7% of CO2 is transported in dissolved form
 Also called as Hamburger phenomenon
zz Total CO2 content of arterial blood is 48 mL CO2/100 mL out of
 The channel responsible for chloride shift is called as anion
which 2.4 mL of CO2 is in dissolve form
exchanger 1 (AE 1). It is also called as Band 3 protein
zz Total CO2 content of venous blood is 52 mL CO2/100 mL out of
present in RBC membrane
which 2.7 mL of CO2 is in dissolve form
 HCO3– leaves the RBCs in exchange for Cl– (chloride
shift) and is transported to the lungs in the plasma
Carbon Dioxide Dissociation Curve
 Cl- ion is an osmotically active particle that drags water
along with it into the RBCs zz It is obtained by plotting Pco2 in X- axis and whole blood Co2
 Since RBCs take up water, it increases in size. This is the content in Y-axis
reason why hematocrit of venous blood is normally 3%
greater than that of arterial blood

Important points to be noted in CO2 dissociation curve are:

zz Normal arterial Pco2 is 40 mm Hg and venous Pco2 is
46 mm Hg
zz So, the normal operating range of this curve is between
40 and 46 mm Hg
zz The curve is linear and steep at the normal operating
range
zz Total CO2 content of arterial blood is 48 mL CO2/100
mL
zz Total CO2 content of venous blood is 52 mL CO2/100
mL
 In the normal operating range, note that CO2 content
changes by around 4 mL/dL (52–48)

Factors Affecting CO2 Dissociation Curve

zz Effect of Oxygen
 The carbon dioxide dissociation curve for whole blood is shifted to the right at greater levels of oxyhemoglobin (unloading of CO2)
 It is shifted to the left at greater levels of deoxyhemoglobin (loading of CO2)
 This effect is known as Haldane effect

Haldane Effect
Theory

zz This effect states that “when oxygen binds with hemoglobin, carbon dioxide is released at lungs and when oxygen is released from hemoglobin,
carbon dioxide is loaded at tissues”
zz This is simply because deoxygenated Hb in tissues is capable of loading more CO2
Haldane effect
zz At Po2 100 mm Hg and Pco2 45 mm Hg, CO2 content in blood changes from 48 ml/dl to 50 mL/dL
5
zz At Po2 40 mm Hg and Pco2 45 mm Hg, CO2 content in blood c