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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

that gas. 404/08/23

• 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.504/08/23

Total pr. of atmospheric air at sea level –

760 mm Hg

• 21% of O₂ of 760 = 160 mm Hg = Po₂

• 79% of N₂ of 760 = 600 mm Hg = PN₂

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Factors determining pr. Of a gas dissolved in fluid :

i. Conc. Of gasii. 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/

solubility coefficient

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Gas Solubility coefficients

O₂ 0.024

CO₂ 0.57

CO 0.018

N₂ 0.012

He 0.008904/08/23

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

alveoli. 1004/08/23

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:

i. Pr. differenceii. Solubility of gas in fluidiii. Cross-sectional area of fluidiv. Diffusion distancev. Molecular weight of gasvi. Temperature of gas

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Factors affecting diffusion rate of gases

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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.

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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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Respiratory unit1904/08/23

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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Different layers of respiratory membranes :

• Capillary endothelium

• Capillary basement membrane

• Interstitial space

• Epithelial basement membrane

• Alveolar epithelium

• Surfactant layer

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Layers of respiratory membrane

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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.2404/08/23

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.2504/08/23

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 blood Is not flowing

through it or vice versa.

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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 mmHg3104/08/23

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. 3504/08/23

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 :

i. Va/Q = 0 in alveoli below obstructed

bronchioles.

ii. Areas of lung with destructed alveolar

walls most ventilation is wasted due to

inadequate blood flow. 3604/08/23

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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.3904/08/23

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.4204/08/23

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.

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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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blood passes through lungs , CO₂ diffuses from blood to alveoli decreased blood Pco₂ decreased H⁺ due to decreased carbonic

acid

curve shifts upwards to the left

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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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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.04/08/23 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%.04/08/23 68

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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Combination with Hb

• CO₂ reacts with amine radicals of Hb to

form carbaminohemoglobin – reversible

reaction , loose bond

CO₂ easily released at

alveoli.

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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,

i. Acidic Hb has less tendency to combine with CO₂ & displaces CO₂ present in carbamino form from blood.

ii. 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.04/08/23 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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