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 To learn about basic physics of diffusion.

 To understand the mechanisms involved in
exchange of respiratory gases.
 To also learn about the transport of
respiratory gases and the pressure
changes responsible for the whole
process.
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 Random molecular motions in both

directions through the respiratory

membrane & adjacent fluids .

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 For
diffusion to occur , source of energy
provided by kinetic energy of molecules
themselves.
 Net diffusion – effect of concentration
gradient i.e. net diffusion
of a
gas occurs from high
conc.
area to low conc. area of
09/19/09 4
• Pressure caused by constt. impact of
moving molecules against a surface.
• Pressure proportional to conc. of gas
molecules.
• Rate of diffusion of each gas proportional
to pr. caused by each alone c/a partial
pressure of that gas.
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 Total pr. of atmospheric air at sea level
–

760 mm
Hg

• 21% of O₂ of 760 = 160 mm Hg = Po₂

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 Factors determining pr. Of a gas
dissolved in fluid :
ii. Conc. Of gas
iii. Solubility coefficient of gas.

• Some gas molecules more attracted

towards water than others (CO₂) which
become dissolved easily without
building up excess pressure.
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• Whereas some molecules are repelled

by water , pressure builds up even

when fewer molecules are dissolved.

 Henry’s law :

partial pr. = conc. Of dissolved

gas/
09/19/09 8
 Gas Solubility
coefficients
O₂ 0.024

CO₂ 0.57

CO 0.018

N₂ 0.012

He 0.008
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 When partial pr. of a gas is > in alveoli
than pulmonary blood (O₂) , gas diffuses
out of the alveoli into pulmonary blood .

 If partial pr. of a gas is > in dissolved

phase in pulmonary blood (CO₂) , gas
diffuses out of pulmonary blood into the
09/19/09 10
 Pressure that the water molecules exert to
escape from surface of water is c/a
vapour pressure of water.
• It depends on temperature of water .
• At normal body temperature (37⁰C)
vapour pr. is 47mm Hg.

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 Rate of gas diffusion in fluids depends
on:
ii. Pr. difference
iii. Solubility of gas in fluid
iv. Cross-sectional area of fluid
v. Diffusion distance
vi. Molecular weight of gas
vii. Temperature of gas
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Factors affecting diffusion rate of
gases 09/19/09 13
D = ∆P * A * S / d * √MW

since temperature remains almost

constant in the body , it need not be
considered.
 Importance of humidification :

as the total pressure of gases

in alveoli cannot rise above 760 mm
Hg , water vapour dilutes all the
inspired gases. 09/19/09 14
09/19/09 15
 It is controlled by :

• Rate of O₂ absorption in blood.

• Rate of entry of new O₂ into lungs by
ventilatory process.

NOTE : extremely marked increase in

alveolar ventilation cannot increase Po₂
above 149mm Hg as long as person is
breathing atmospheric air as this is the
max. Po₂ in humidified air at this
pressure.
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 Alveolar Pco₂ rises in direct proportion

to the rate of co₂ excretion.

 Alveolar Pco₂ decreases inversely in

proportion to alveolar ventilation.

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09/19/09 18
Respiratory unit
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 Alveolar gases are in close proximity
with the blood of capillaries so gas
exchange between alveolar air &
pulmonary blood occurs through
membranes of all terminal portions of
the lungs not only alveoli.

These membranes are collectively

known as respiratory membranes.

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 Differentlayers of respiratory
membranes :
• Capillary endothelium
• Capillary basement membrane
• Interstitial space
• Epithelial basement membrane
• Alveolar epithelium
• Surfactant layer

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Layers of respiratory
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 Thickness of the membrane

increases occasionally due to edema

in the interstitium or some pulmonary
diseases may also cause fibrosis of
lungs leading to increased thickness
of some portions of the membrane.
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 Surface area of the membranes
can be greatly decreased in case of
removal of lung
Also in case of emphysema , there is
dissolution & destruction of many
alveolar walls.
 Diffusion coefficient
rate of diffusion is almost same as
that in water.
 Pressure difference
between partial pr. of gas in alveoli &
pulmonary capillary blood.
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 Defined as : volume of a gas that will
diffuse through the membrane each
minute for a pressure difference of 1
mm Hg .
 Diffusing capacity for O₂
• Under normal resting conditions it is
about 21ml/min./mmHg.
• Mean O₂ pr. difference across
respiratory membrane is 11mm Hg.
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 11* 21 = 230 ml of O₂ diffuses
through the respiratory
membrane each
minute.
Or this is the rate at which resting body
uses O₂.
 During strenuous exercise

diffusing capacity of O₂ increases upto

a max. of 65 ml/min./mmHg , this
happens due to :
 opening up of number of previously
dormant capillaries or extra dilatation
of already open capillaries.
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 Better match in the ventilation –
perfusion ratio.

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 Usually we assume , all alveoli are equally

ventilated & equal blood is flowing through all

alveolar capillaries.

But that’s not the case , practically in normal people

to some extent & also in many lung diseases if

the alveoli is well
ventilated adequate 09/19/09 28
Or there may be normal ventilation &

blood flow but both are going to

different parts of the lung.

This concept is termed as ventilation-

perfusion ratio.

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 Va / Q = 0
When Va = 0 ; Q = present

 Va / Q = ∞
When Va = present ; Q = 0

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 Po₂ & Pco₂ when Va / Q = 0
Po₂ & Pco₂ in alveoli = Po₂ & Pco₂ in venous
blood .
• As air in alveoli comes in equilibrium with
venous blood passing through the capillaries.
Po₂ = 40 mmHg Pco₂ = 45 mmHg
 Po₂ & Pco₂ when Va / Q = ∞
Po₂ & Pco₂ in alveoli = that of inspired humidified
air.
Po₂ = 149 mmHg Pco₂ = 0 mmHg
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 Po₂ & Pco₂ when Va /Q = normal
Po₂ = 104 mmHg Pco₂ = 40
mmHg

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 When Va / Q < normal
• Inadequate ventilation to completely
oxygenate the blood passing through
the capillaries , some part of venous
blood does not get oxygenated c/a
shunted blood .
• Also some blood flows through
bronchial vessels rather than capillaries
(about 2% of the CO)is also shunted
blood .
• Total amount of shunted blood / min. is
c/a physiologic shunt.
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 When Va / Q > normal
• Ventilation is more but the blood flow
through the capillaries is reduced , hence
ventilation in such alveoli is wasted .
• Also ventilation of anatomical dead space
areas of respiratory passages is wasted .
• Sum of these two wasted ventilations is
c/a physiologic dead space.

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 Abnormal Va / Q in upper & lower lobes of
a normal lung.
• In normal upright posture , in upper lobes
Va > Q which causes moderate amount of
dead space.
• In lower lobes Va < Q , causing
physiologic shunt .
• During exercise , Q in upper lobes & Va in
lower lobes improves to get a better Va /
Q ratio. 09/19/09 35
 Va / Q in COPD
• For eg. Smokers , develop bronchial
obstruction followed by air trapping &
eventually emphysema leading to
destruction of alveolar walls.
• 2 abnormalities seen henceforth :
iv. Va/Q = 0 in alveoli below obstructed
bronchioles.
v. Areas of lung with destructed alveolar
walls most ventilation is wasted due to
inadequate blood flow.09/19/09 36
09/19/09 37
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• Po₂ in alveoli = 104mm Hg
• Po₂ of blood entering pulmonary capillary
at arterial end = 40mm Hg
• O₂ diffuses from alveoli to pulmonary
capillaries.
• Po₂ of blood rises almost to that of alveoli
by the time blood has covered ⅓ of the
distance through capillary.
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 During strenuous exercise :
• Body requires 20 times the normal O₂
• Duration that blood remains in capillaries
is reduced to half due to increase CO. So,

Diffusing capacity of O₂ increases to 3

times normal due to :
• Increased capillary surface area
• Nearly ideal Va/Q in upper part of lungs
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• Blood normally stays 3 times than
required in the capillaries .

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 98% of blood enters left atrium from
lungs ,

2% passes directly to the bronchial

circulation & is shunted past the gas
exchange area in lungs. Po₂ of this blood
is equal to that of venous blood
(40mmHg) & it supplies deeper tissues of
the lungs. 09/19/09 42
 This 2% blood combines with
oxygenated blood in pulmonary veins ,
c/a venous admixture which causes the
Po₂ of the blood pumped into the aorta
to fall to 95 mm Hg.

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 NOTE : CO₂ can diffuse 20 times as
rapidly as O₂ hence pressure difference
required to cause CO₂ diffusion is far
less than that required for O₂.
• For eg. Intracellular Pco2 – 46mmHg
• Interstitial Pco2 – 45mmHg

Pressure differential is merely a 1 mmHg.

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 Increased blood flow , decreased Pco₂
in tissues & vice versa.
 Increased metabolic rate , increased
tissue Pco₂
 Decreased metabolic rate , decreased
tissue Pco₂ .

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 in chemical in dissolved
combination with state in
plasma
haemoglobin (97%) (3%)

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 O₂ molecule combines loosely with heme
protein of hemoglobin.
• High Po₂ – O₂ binds with hemoglobin
• Low Po₂ – O₂ released from hemoglobin

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Combination & release of O₂ from Hb
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 It is the curve plotted between
percentage saturation of hemoglobin v/s
gas pressure of O₂

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Oxy – hemoglobin dissociation curve
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• Normally 15gms Hb / 100ml blood is
present.
• 1gm Hb can bind with 1.34ml of O2 so,
15 * 1.34 = 20.1
• Hb in 100ml of blood can combine with
20ml of O2 exactly when the blood is fully
saturated .
• This is expressed as 20 volumes percent.

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 In 97% saturated arterial blood 19.4ml
O2 is bound with Hb / 100ml of blood.
 On passing through tissue capillaries it
is reduced to 14.4ml.
 Thus , normally 5ml of O2 is
transported from lungs to tissues /
100ml of blood. 09/19/09 52
 During heavy exercise , muscle cells use
O₂ at a rapid rate causing interstitial
tissue Po₂ to fall to 15mmHg , at this
pressure only 4.4ml of O₂ is bound to Hb/
100ml blood. So,
19.4-14.4 = 15ml of O2 is
actually delivered to tissues / 100ml blood
which is 3 times the normal.
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 Also CO in trained athletes can
increase upto 6-7 times the normal ,
multiplying it with the 3 fold increase in
O₂ delivered gives a 20 fold increase in
O₂ transport to tissues .

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 Percentage of blood that gives up its O₂
while passing through tissue
capillaries.
• Its normal value is 25%
• During strenuous exercise 75-85%

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• For normal 5ml of O₂ to be released /
100ml of blood , tissue Po₂ must fall to
40mmHg.
• If tissue Po₂ rises above this, Hb would not
be released at the tissues.
• Conversely , small fall in Po₂ causes extra
amount of O₂ to be released at the
tissues as during heavy exercise .
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 Shift to right :
• increased H⁺
• increased CO₂
• increased temperature
• increased DPG
 Shift to left
• decreased H⁺
• decreased CO2
• decreased temperature
• decreased DPG
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09/19/09 58
09/19/09 59
 blood passes through lungs , CO₂
diffuses
from blood to alveoli

decreased blood Pco₂

decreased H⁺ due to decreased carbonic
acid

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 blood reaches tissue capillaries,
CO₂ enters blood from tissues & curve
shifts to the right

this displaces O₂ from Hb &

delivers
O₂ to the tissues

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09/19/09 62
 Normal DPG keeps the curve slightly to
the right always.

Hypoxic conditions lasting for more than

a few hours , DPG in blood increases
shifting the curve more to the right

due to this O₂ is released to the tissues

at a pressure 10mmHg higher than
without increase in DPG.
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 Exercising muscle releases more CO₂.
 Several acids produced by the muscle
increases the H⁺ concentration.
 Temperature of the working muscle is
raised by 2-3⁰ C.

All these factors shift the curve towards the

right during exercise.
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 Effect of intracellular Po₂
• Enzyme system of cells function well even
when the cellular Po₂ is > 1mmHg , so O₂
is no longer a limiting factor.
• Main limiting factor is ADP conc.
• Under normal conditions , rate of O₂ usage
is controlled by rate of energy expenditure
within the cell. 09/19/09 65
 Effect of diffusion distance
• Greater diffusion distance cellular Po₂
may fall below 1mmHg
• In such conditions rate of O₂ usage
becomes diffusion limited & not
determined by ADP conc.

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 Effect of blood flow
• Low rate of blood flow through the
tissues,

Cellular Po₂ may fall below 1mmHg

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o At normal arterial Po2 (95mmHg) 0.29ml
of O2 is dissolved / 100ml blood.
o At Po2 < 40mmHg (in tissues) 0.12ml of
O2 remains dissolved / 100ml of blood.
therefore , 0.17ml of O2 is
transported in dissolved state.
o During strenuous exercise , dissolved O2
decreases to about 1.5%.
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Dissolved in form of in
combination
State(7%) bicarbonate with
Hb(30%)
ions(70%)

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 In dissolved state
• At 45mmHg – 2.7ml/dl CO₂
• At 40mmHg – 2.4ml/dl CO₂

therefore 0.3ml of CO₂ / 100ml

of blood is transported in dissolved
state.

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 In form of bicarbonate ions

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09/19/09 73
 Combination with Hb
• CO₂ reacts with amine radicals of Hb to
form carbaminohemoglobin –
reversible

reaction , loose
bond

CO₂ easily released

at

alveoli.
09/19/09 74
09/19/09 75
 Binding of O₂ with Hb tends to displace
CO₂ from blood . This is because ,
combination of O₂ with Hb in lungs makes
Hb more acidic so,
Acidic Hb has less tendency to combine
with CO₂ & displaces CO₂ present in
carbamino form from blood.
Due to increased acidity of Hb , increased
release of H⁺ , increased binding with
HCO⁻₃ to form carbonic acid which
dissociates into
CO₂ + H₂O & CO₂ released to alveoli.
09/19/09 76
 Ratio of CO₂ output to O₂ uptake.
• Exclusive use of carbohydrates in diet R =
1
• Exclusive use of fats in diet R = 0.7
• For normal healthy diet containing
balanced proportion of all nutrients R =
0.82
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