Diffusion , Exchange & Transport Of O2 & Co2

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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. 09/19/09

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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

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•

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. 09/19/09

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

Total pr. of atmospheric air at sea level – 760 mm Hg

•

21% of O₂ of 760 = 160 mm Hg = Po₂ 09/19/09

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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. 09/19/09

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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

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Gas O₂

Solubility coefficients 0.024

CO₂

0.57

CO

0.018

N₂

0.012

He

0.008 09/19/09

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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

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

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. 09/19/09

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 ii. iii. iv. v. vi. vii.

Rate of gas diffusion in fluids depends on: Pr. difference Solubility of gas in fluid Cross-sectional area of fluid Diffusion distance Molecular weight of gas Temperature of gas 09/19/09

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Factors affecting diffusion rate of gases 09/19/09

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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. 09/19/09

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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. 09/19/09

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Respiratory unit 09/19/09

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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. 09/19/09

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 Different

layers of respiratory membranes :

•

Capillary endothelium

•

Capillary basement membrane

•

Interstitial space

•

Epithelial basement membrane

•

Alveolar epithelium

•

Surfactant layer 09/19/09

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Layers of respiratory 09/19/09

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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. 09/19/09

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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. 09/19/09

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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. 09/19/09

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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. 09/19/09

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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

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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 ventilationperfusion 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 09/19/09

Pco₂ = 0 mmHg 31



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. 09/19/09

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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.

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

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.

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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. 09/19/09

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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 09/19/09

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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.

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

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 combination with plasma haemoglobin (97%)

in dissolved state in (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 09/19/09

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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 09/19/09

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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. 09/19/09

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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 . 09/19/09

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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 09/19/09

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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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

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. 09/19/09

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 Exercising  Several

muscle releases more CO₂.

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. 09/19/09

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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.

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

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%. 09/19/09

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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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

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, 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

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 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 09/19/09

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