Gas Diffusion and Gas Exchange

function of respiratory system

to supply the tissues with oxygen to satisfy their metabolic demands

to eliminate CO2 generated as a consequence of metabolic activity

how is O2 transferred from alveolar gas into the pulmonary capillary bed?

via diffusion

overview of oxygen transport

carried around the body and delivered to the tissues, where it diffuses out of the systemic capillary blood into cells

COs travels in opposite direction

respiratory exchange ratio, R

ratio of CO2 production to O2 consumption, which at rest is approximately 0.80

also referred to as the respiratory quotient (RQ)

dependent on caloric intake and varies between 0.7 (fatty acid metabolism) and 1 (carbohydrate metabolism), normally assumed to be 0.8

general gas law

PV = nRT

P= pressure (mmHg)

V= volume (L)

n= moles (mol)

R= gas constant

T= temperature (K)

BTPS

body temperature (37 C or 310K), ambient pressure, and gas saturated with water vapor

in gas phase, this is used

STPD

standard temperature (0C or 273K), standard pressure (760mmHg), and dry gas

used in liquid phase (dissolved in blood)

To convert gas volume at BTPS to gas volume at STPD:

multiply the volume by (273/310) x ((Pb-47)/760)

Pb= barometric pressure, 47 mmHg is water vapor pressure at 37C

simplifies to 0.826

boyle’s law equation

P1V1=P2V2

dalton’s law equation

dry gas: Px= Pb x F

humidified gas: Px= (Pb - PH2O) x F

Px= partial pressure of gas (mmHg); Pb= barometric pressure (mmHg)

PH2O= water vapor pressure at 37C (47mmHg); F= fractional concentration of gas (no units)

boyle’s law description

at a given temp. the product of pressure multiplied by volume for a gas is constant

when volume decreases pressure must increase

when volume increases pressure must decrease

dalton’s law description

in a mixture of non-reacting gases, the total pressure exerted is the sum of each of the partial pressures of the individual gases

pressure of each individual gas is the partial pressure P, P is the total pressure x fractional content of dry gas

% O2 at barometric pressure (760mmHg)

21%

% N2 at barometric pressure (760mmHg)

79%

% CO2 at barometric pressure (760mmHg)

0%

why do we use partial pressures of gases not just concentrations?

concentration of a gas in a liquid is proportional to its concentration and its solubility—so if a liquid is exposed to 2 gases with the same partial pressure, concentrations will differ depending on their solubilities

ambient air

a gas mixture composed of N2 and O2 plus minute amounts of CO2, argon, and inert gases

In terms of gas fractions (F), the sum of all the individual gas fractions

must equal 1

FN2 + FO2 = Fargon + Fother gases = 1

The sum of all partial pressures (in mmHg) must equal

the total pressure

sum at barometric pressure at sea level approx 760 mmHg

partial pressure of a gas (Pgas) is equal to

the fraction of that gas in the gas mixture (Fgas) multiplied by the ambient (barometric) pressure

Pgas= Fgas x Pb

As a consequence of gas exchange, FO2 (therefore partial pressure)

decreases in the alveolus while the FCO2 increases

N2 and argon are inert, so no change

FH2O no change (gas remains fully saturated)

alveolar gas equation

describes PO2 in the alveolus

PAO2= PIO2 - (PACO2/R)

or PAO2= (Pb - PH2O) x FIO2 - (PACO2/R)

R= respiratory quotient

what is the level of alveolar PO2 (PAO2) determined by?

a balance between rate of removal of O2 by the blood (determined by the metabolic demands of the tissue) and the rate of replenishment of O2 by alveolar ventilation

If alveolar ventilation was low, what happens to PAO2 and PACO2?

falls, rises

How can we obtain the relationship between the fall in PO2 and the rise in PCO2 that occurs with changes in decreased ventilation (and vice versa)?

from the alveolar gas equation if we know the composition of inspired gas and the RQ

henry’s law description

deals with gases dissolved in solution (e.g. blood)

the amount of dissolved gas in a liquid is proportional to its partial pressure above the liquid

to calculate a gas conc in the liquid phase, the partial pressure in the gas phase is first converted to the partial pressure in the liquid phase

second, partial pressure in liquid is converted to concentration in liquid

at equilibrium, the partial pressure of gas in the liquid phase equals the partial pressure of the gas in the gas phase

henry’s law equation

Cx = Px x solubility

Cx= concentration of dissolved gas (ml gas/100 ml blood)

Px= partial pressure of gas (mmHg)

solubility= solubility of gas in blood (ml gas/100 ml blood/mmHg)

applied only to dissolved gas that is free in solution

fick’s law description

a solute will move from a region of high concentration to a region of low concentration down a concentration gradient

transfer of gases across cell membranes and capillary walls occurs by diffusion

fick’s law equation

Vx= (A x D x deltaP)/T

Vx= volume of gas transferred per unit time

A= surface area

D= diffusion coefficient of that gas

deltaP= partial pressure difference of the gas

T= thickness of the membrane

important parameters for efficient gas exchange in lungs

large driving force= partial pressure gradient, deltaP

large surface area

distance needs to be small

diffusion coefficient

D ∝ Sol/√MW

for CO2 is approx 20 times higher than for O2

CO2 elimination is not affected by

diffusion problems

what happens when mixed venous blood enters the capillary?

O2 is added to pulmonary capillary blood and CO2 is removed via diffusion across the alveolar/capillary barrier

what happens to remaining 2% of blood that doesn’t enter left atrium and pass through alveolar capillaries?

it is “shunted” from aorta through bronchial circulation—never enters gas exchange areas

venous admixture of blood

shunted blood combines with oxygenated blood

the total amount of gas transported across the alveolar-capillary barrier is limited by

diffusion and blood flow

partial pressure gradient is not maintained across alveolar-capillary barrier, so only way to increase amount of gas transported is

by increasing blood flow

fibrosis and oxygen diffusion

increases alveolar wall thickness, increasing barrier for diffusion

prevents equilibration

partial pressure gradient is maintained along entire capillary= now diffusion limited

effects exaggerated at high altitude—pulmonary capillary blood does not equilibrate by end of capillary resulting in even lower PaO2→impaired O2 delivery to tissues

barometric pressure reduced at high altitude, so

PAO2 also reduced

fick’s law simplified equation

Vgas- DL x (P1 - P2)
not possible to measure area and thickness in patient

diffusion capacity, DL

combines area, thickness, and diffusion properties of gas

measured diffusion barrier of the alveolar-capillary membrane

can be measured with CO since transfer of this gas is entirely governed by diffusion

diffusion capacity of CO

volume of CO transferred in millimeters per minute per mmHg of alveolar partial pressure

DL= VCO/(P1 - P2)

or DL= VCO/PACO because partial pressure of CO in capillary blood is so small we can ignore it

how is lung diffusion capacity usually measured?

by the single-breath test

single inspiration of CO (low concentration) made and the rate of CO disappearance from the alveolar gas is measured during a 10-second breath hold

analyze concentrations of CO in inspired versus expired air

helium also added to inspired gas to give a measurement for lung volume

normal range for DLCO at rest

20-30 mL/min/mmHg

increases 2-3 times this during exercise due to addition of extra capacity in the pulmonary capillaries

how does lung diffusing capacity change with emphysema?

decreases due to less surface area

how does lung diffusing capacity change with fibrosis?

decreases due to membrane thickness increasing

how does lung diffusing capacity change with anemia?

decreases due to less Hb in red blood cells

A - a gradient

describes the difference in PO2 between alveolar gas (PAO2) and systemic arterial blood (PaO2)

has there been equilibration of O2 between alveolar gas and pulmonary arterial blood (systemic arterial blood)?

ideally, should be as close to zero as possible, but sometimes increased, signifying a defect in O2 equilibration

A - a gradient equation

PIO2 - (PACO2/R) - PaO2

PIO2= inspired O2; R= respiratory quotient

causes of increased A-a gradient

diffusion defects, V/Q defects, shunts

diffusion defects and A-a gradient

e.g. fibrosis, pulmonary edema, increase diffusion distance or decrease surface area

O2 equilibration is impaired. supplemental O2 will raise PaO2 via PAO2, increasing driving force for diffusion

V/Q defects and A-a gradient

always cause hypoxemia

supplemental O2 helpful, it raises PO2 of low V/Q regions where blood flow is highest

shunts and A-a gradient

blood completely passes ventilated alveoli and cannot be oxygenated

supplemental O2 is of limited use as it only increases PO2 of non-shunted blood