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prePARed by

• One of the major events in
the process of ‘External

• The respiratory &

circulatory systems function
concurrently to transport O2
from lungs to the tissues &
CO2 in the reverse direction.

• Loading & Unloading of O2

& CO2 , not only occur
simultaneously but also
facilitate each other.
Gas movement
throughout the
respiratory system
• occurs predominantly via diffusion .
• A passive ,temp-dependent process
where there is net movement of gas
molecules from an area of higher partial
pressure to an area of lower partial
pressure & continues until an
equilibrium is reached.
• Similar whether occurring in a gaseous
or liquid phase & follows basic diffusion
To facilitate gas diffusion
The respiratory and circulatory systems
contain several unique anatomic and
physiological features:
• (1) large surface areas for gas exchange
(alveolar to capillary and capillary to tissue
membrane barriers) with short distances to
• (2) substantial partial pressure gradients &
• (3) gases with advantageous diffusion
from the lungs to the tissues
Acc. to differences in the partial pressure of
Oxygen (PO2) at various sites :
• Alveolar air PO2  104 mm of Hg
• Arterial blood PO2  95 mm of Hg
• Venous (or Pulmonary arterial) blood PO2  40
mm of Hg
• Tissue interstitial fluid PO2  40 mm of Hg
• Normal intracellular tissue PO2 avg. 23 mm Hg(an
arbitrary range of 5-40 mm Hg)
3 Major Steps
• A) Uptake of oxygen by
pulmonary blood
• B) Transport of oxygen in
the arterial blood
• C) Release of oxygen in
the tissues
of oxygen
•Along the pressure
gradient of 104-40 =
64 mm of Hg ,across
the respiratory
•oxygen readily
diffuses from the
alveoli into the blood.
B) Transport of oxygen
in the arterial blood:
• In 2 forms---
I. Dissolved form (1.5%)
II. Combined with Haemoglobin (98.5%)
• Normal O2 content (per 100ml blood)--
Arterial ~20 ml & Venous ~15 ml
So,~5ml of O2 is transported per 100ml of
blood from lungs to tissues.
• relatively insoluble in water.
• at the arterial PO2 value of 100 mm Hg,
100 ml of blood, contains only 0.3 ml of
dissolved O2 , expressed as ‘volumes%’ .
• measured clinically in an ABG-sample as
• product of the ‘oxygen solubility’(0.003
ml O2 /dl .Torr) & the oxygen
tension (Torr).
• Obeys Henry’s law---the amount
of gas dissolved will be directly
proportional to the partial
pressure of the gas .

• no limit to the amount of O2 that

can be carried in dissolved form,
provided the PO2 is sufficiently
increased---a distinct advantage .
• each molecule
consists of 4 non-
protein ‘haem’-groups
& 4 polypeptide chains
making up the ‘globin’-

• ‘Haem’ is an iron-
porphyrin compound,
where iron is present
in the ‘ferrous (Fe++ )’-
form & is the site of
More About Hb
• The ferrous O2 binding sites in Hb also bind
NO, & an additional NO binding site is
present on the beta chains. The affinity of
this 2nd site is increased by O2, so Hb binds
NO in the lungs and releases it in the
tissues, where it promotes vasodilation.
 functions of Hb:
• it facilitates O2 & CO2 transport;
• has an important role as a buffer ;
• it transports NO.
Oxygenation of Hb:
• most of the O2 quickly diffuses from
the plasma into the RBCs
• combines with Hb in a loose & readily
reversible manner---rapidly
• occupies the 6th coordination-position
of the iron atom & does not become
ionic oxygen .
• accompanied by a conformational
conversion in the Hb-molecule: deoxy-
hb(T) oxy-hb(R)
Reaction of Haem with Oxygen
(M, V, and P stand for the groups shown on the molecule on the left)
 One O2-molecule combines with the ‘(Fe )’- of each

‘haem’-group. So, max four oxygen molecules can bind to

each Hb-molecule.
 Interaction & ‘Positive Co-operativity’
 the reaction proceeds in following four steps- 
• Hb4 + O2  Hb4O2
• Hb4O2 + O2  Hb4O4
• Hb4O4 +O2  Hb4O6
• Hb4O6 + O2  Hb4O8
*Some Related Concepts*
capacity :
• maximum amount of O2 that can be
combined with Hb .
• 1 gm of Hb can combine with avg.1.34 ml of
O2 (max.1.39 ml ,if in chemically pure form)
• as normal blood has about 15 gm of Hb/100
ml, the O2-carrying capacity is about 1.34 X
15,i.e. 20.1 ml O2 /100 ml= ~ “20 volumes%”
*Concepts Contd………
Oxygen-content of blood :
• Vol. of O2 contained per unit vol. of blood.
• Sum of the dissolved O2 (but is frequently ignored
d/t its’ small contribution) & Hb-bound O2 .
• Same unit as O2–carrying capacity.
• Decreases with anemia & conditions with
increased CO & CO2 .
*Concepts Contd………
Oxygen-saturation of haemoglobin

(SO2 ):
•  the amount of O2 bound to Hb relative to the
maximum amount of O2 that can bind with Hb. It
is expressed as a % .
• of systemic arterial blood with PO2 of 95 mm Hg
is about 97%
• of normal venous blood (returning from
peripheral tissues) with PO2 of 40 mm Hg is about
Curve(OHDC) :
• can also be expressed in terms of ‘volume %
of oxygen’, as shown by the far right scale.
• Shows that, as the PO2 increases , SO2 % also
increases. But the relation is sigmoid or S-
shaped (i.e.not linear), reflecting the change
of affinity of Hb for oxygen, with increased
binding of O2 to haem.
• Two distinct zones are recognized .
Curve(OHDC) :
(i) Loading or
• Upper Zone
flat (plateau) part ----above : Hg
P of 60mm

• Related to the O2-uptake in the lungs

• at a PO2 of 100 mm of Hg ,Hb is about 97.5 %
saturated & even if PO2 falls to about 60 mm of
Hg , Hb is still 90% saturated.
• provides a ‘margin of safety’ --ensures adequate O2
uptake by the pulmonary blood even when alveolar
PO2 is moderately decreased.
Curve(OHDC) :
(ii) Unloading or
Dissociation Zone:
• lower steep (almost linear) part.
• Related to the O2 –delivery to the tissues.
• Hb-saturation is significantly compromised when
PO2 progressively falls below 60 mm Hg.
• facilitates the O2 –delivery , keeping the PO2 in
the capillary blood relatively high .
Concept of P50 :
• The PO2 at which 50% of Hb is
• At sea level, in a normal adult
with 370C body temperature &
arterial blood PCO2 of 40 mmHg,
it is about 27 mm of Hg .
• Index of affinity for O2 –
inversely proportional.
P50 value is the most useful •Points on
point on the ODC for
specifying the curve’s ODC of HbA
position because it is on the
steepest part of the curve.
It is therefore the most
sensitive point for detecting
a shift of the curve &
allows comparison with the
position of other curves
under different conditions.
Other 2 imp. points:
•Arterial pointpO2 =100
mmHg with SaO2 = 97.5%
• Mixed venous pO2 =40
mmHg with SaO2 = 75%
•Factors that shift
the OHDC:
Bohr Effect
• Demonstrated by the danish physiologist Christian
Bohr (father of Neils Bohr & grandfather of Aage Bohr
—both got nobel prize in Physics)
• A shift of the OHDC to the right in response to
increases in blood CO2 and H+- ions(or decrease in pH)
 a significant effect by enhancing the release of O2
from the blood in the tissues & conversely enhancing
oxygenation of the blood in the lungs d/t exactly
opposite environment .
• Explains basic mech. of Hb-bound O2 –transport.
•At PO2 of 20 mm Hg, where
HBA is only 35%
saturated,HbF is ~60%
•Because affinity of gamma-
chains for 2,3-DPG is less
than beta-chains, HbF(P50 =
18 mm Hg) has more
affinity for O2 than HbA.
•Such property helps HbF to
take up adequate O2, inspite
of the fact that it is exposed
to rather low PO2 of the
maternal blood in placenta.
A haem-containing
oxygen binding protein
that is present in
skeletal muscle.acts as
‘temporary storehouse’
of O2 .

Comparison with
•Rectangular Hyperbola
•Takes up O2 at lower
PO2 , much readily.
•Does not show Bohr’s
•Hb-affinity of CO is ~200
times than that of O2
•P50 value of CO= only 0.5
mm Hg
•CO binds with Hb at the
same site (as of O2 ) .
•Interferes with O2 –
transport by decreasing
functional Hb-conc.
•in the presence of CO as a
modifying factor, OHDC
Shifts to left as binding of
CO causes a conformational
change in the Hb causing
increased affinity for O2 by
the other subunits.
•O2 diffuses rapidly first from the
peripheral capillary blood to the ISF
along a PG of 95-40=55 mm Hg &
then from the ISF into the tissue-cells
along approx. PG of 40-23= 17 mm
•Tissue Po2 is determined by a
balance b/w (i)rate of O2 -transport to
the tissues by the blood & (ii) rate at
which the O2 is used by the tissues.
• Only 1- 3 mm Hg of PO2 is normally
required for the oxidative chemical
processes in the cell. So this low
intracellular PO2 is more than
adequate and provides a large safety
From tissues to the lungs.
Acc. to the differences in PCO2 at
various sites:
• Intracellular PCO2  46 mm Hg
• Interstitial Fluid PCO2  45 mm Hg
• Arterial blood(at the tissue
capillaries)PCO2  40 mm Hg
• Venous blood PCO2  45 mm Hg
Alveolar Air P  40 mm Hg
3 major
• A) Uptake of CO2 by the
• B) Transport of CO2 in the
• C) Release of CO2 in the
A) Uptake of CO2 by the blood:
•from the cells rapidly
diffuse to ISF even if the PG
is only 46-45=1 mm Hg
•From the ISF, diffuse into
the capillary blood(which
flows in the systemic
venous system)along a PG
of 45-40=5 mm Hg.
•Diffusivity of CO2 is ~20
times higher than O2 .
B) Transport of CO2 in the
In 3 forms—
• I) Dissolved form (7%)
• II) As Carbamino compounds (23%)
• III) As Bicarbonate (70%)
Normal CO2 content (per 100 ml blood)--
• Venous ~ 52 ml & Arterial ~ 48 ml
So, ~4ml of CO2 is transported per 100ml of
blood from tissue cells to lungs .
• Obeys Henry’s law.
• Venous blood(at PCO2 =45mm Hg)
& Arterial blood(at PCO2 = 40 mm
Hg) contain respectively 2.7 vol %
& 2.4 vol % of CO2 in dissolved
Only 0.3 ml of CO2 is transported
• After entering the blood, some CO combines with the
(-NH2) of proteins to form ‘carbamino-compounds’
In the Plasma: combines with plasma-proteins—
CO2 + Pr.NH2  Pr.NH.COOH (relatively insignificant)

In the RBC: with Hb, form carbamino-Hb—

CO2 + Hb.NH2  Hb.NH.COOH
 A loose,reversible binding—competed by 2,3-DPG
 Much slower reaction than that of CO2 & water.
• From plasma most CO2 enters RBCs ,where in the presence of CA, reacts
rapidly (within a very small fraction of a sec): H2O + CO2  H2CO3

• H2CO3 dissociates  H + HCO3

+ -

• HCO 3
diffuse out into the plasma & transported as Sod.bicarbonate
• H are buffered by deoxygenated Hb(weaker acid than oxygenated Hb)

• To maintain electrical neutrality,Cl ions diffuse into the RBCs to replace


HCO3- --- “Chloride Shift”.

Summary of changes that occur in a RBC on addition of CO2 to blood.For each CO2
molecule that enters the RBC, there is an additional HCO3– or Cl– ion in the cell.
• by the presence of a special ‘bicarbonate-
chloride carrier protein’ in RBC membrane that
shuttles these two ions in opposite directions at
rapid velocities.
• As a result, the chloride content of venous RBCs
is greater than that of arterial RBCs, l/t osmotic
absorption of fluid into these RBCs-- ‘water shift’.
Fluid content is greater in Venous RBCs.
Size of venous RBCs are larger than arterial
Venous RBCs are more fragile than arterial RBCs.
Schematic Representation of uptake & transport of CO2 in blood from
peripheral tissues
 In comparison with typical
• total CO2 -content on Y-axis
•Nearly linear over the wider range
of PCO2
• Practically ,in the body PCO2 varies
within a narrow range (40-45 mm
Hg) in contrast to PO2 (40-100)
•So, this full range shown here is an
experimental theoretical

Factors affecting CDC:

• O2 – deoxy-Hb binds more CO2,
shifts CDC to left.aka ‘Haldane or
CDH Effect’.
•2,3-DPG – decrease carbamino-Hb
formation esp in deoxygenated
blood---shifts to right
•Body temp– increased temp cause
release of O2 from blood—left shift
•Deoxygenated Hb is capable of loading
more CO2 than oxygenated Hb. i.e.for Effect:
any given PCO2, the blood will hold more
CO2 when the PO2 has been diminished.
CDH effect depicts that:
• Blood reaching the tissues(PCO2 = 4o
mm Hg) is capable of drawing CO2 more
at PO2 =4o mm Hg,than at PO2 =100 mm
Hg left shift of CDC
•Blood reaching lungs (PcO2 =45 mm Hg)
is capable of releasing more CO2 at PO2
=100 mm Hg, than at PO2 = 40 mm Hg 
right shift of CDC

**The line AB is called ‘Physiological CDC’

C) Release of CO2 in the lungs:
Following changes occur in venous blood on reaching pulmonary capillaries:
Release of CO2 from carbamino-Hb into plasma:

O enters the capillary blood & in RBC, converts deoxy-Hb to oxy-Hb  released CO2
• 2
diffuse out.
Release of CO2 from bicarbonate into plasma:

Strong acidity of oxy-Hb HCO3- diffuse into RBCs to neutralize H+ form

H2CO3dissociates(in CA-presence)H2O + CO2 CO2 diffuse out.
Ingoing of HCO3- outgoing of Cl- to maintain electrical neutralityreversal of Cl- shift

to alveoli:
•All the dissolved &
released CO2 diffuses
into the alveoli along
a PG of 45-40=5 mm

•D/t constant
ventilation this CO2 is
then transported to
the atmosphere.
Schematic Representation of blood transport & release of CO2
in Lungs
Outline of summary of the Blood Gas Transport
Gas Content of
2 Special Related
Utilization Co-efficient: Respiratory Quotient:
• percentage of the ratio • Ratio of rate of CO2
of O2 consumption
rate(N=250 ml/min) &
O2 -delivery rate
00 ml) & rate of O2
(N=1000ml/min) in the consumption(N=5
tissue. ml/100 ml) per
Normal avg. UC =
250/1000 X 100% = 25  Normal avg. RQ =
4/5= 0.8
Till Death.........
Think before You Move…
Combination oxygen with
Hb is called ‘oxygenation’
but not oxidation.
Almost flat bottom portion of
the initial OHDC is a safety
measure, esp for persons with
Chronic lung disease.
Stored blood(esp with ACD as
anticoagulant) is not safe to be
transfused in a severely
hypoxic patient.
The high RBC count in
foetus is basically d/t
the characteristic ODC
of HbF.
The Hct value of venous
blood is about 3% higher
than that of arterial
Hypoxemia occur much
earlier than hypercapnia in
patients with ‘Diffusion-
defects of lungs’.
Hyperbaric oxygen is
therapeutically utilised
in CO poisoning.
The point on OHDC
representing PO2 = 60 mm
Hg & SO2 %=90, is called
the ‘ICU Point’.