Lecture 4 RespiratoryPhysiology Ventilation & Gas Exchange

8/13/2019 Lecture 4 RespiratoryPhysiology Ventilation & Gas Exchange

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Ventilation and Gas ExchangeThomas E DeCoursey, Ph.D., Professor,

Department of Molecular Biophysics and Physiology

[email protected]

In respiratory physiology, ventilation is defined as the movement of gas into and out of alveoli.

The gas laws help us understand how atmospheric gases interact with the blood to get to thealveoli.

Resource Material: Berne & Ley, pp. !"#$!%

Lecture objectives'

(. )no* the appro+imate composition of the earths atmosphere.

-. List the factors affecting the diffusion of gases et*een aleoli and lood and those affecting the

concentration of gases dissoled in the lood.

!. Descrie the time course of diffusional e/uilirium of respiratory gases et*een aleolus andcapillary.

#. )no* the appro+imate alues of P0-and PC0-in air, trachea, aleoli, arterial lood, and mi+ed

enous lood.

1. Define the diffusing capacity of the lungs and list the factors that determine its alue.

. Descrie the magnitude and cause of the changes in aleolar P0-and PC0-during normal

reathing.

Terms:2entilationPartial pressure

Minute entilation

3leolar entilation

3leolar gas e/uationDiffusion arrier

4ic5s La* of DiffusionPartial pressure gradientDiffusional e/uilirium

Diffusing capacity of the lung
mailto:[email protected]:[email protected]


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The conductie one of the air*ays is considered dead s*ace, or space in *hich air e+ists ut 0-and C0-e+change *ith the lood does not occur. There are t*o main types of dead space'

natomic dead s*ace

o =egions incapale of 0-and C0-e+change *ith the loodo 2olume of the conducting air*ays

o G(1H ml in a normal person 72Din ml I ody *eight in pounds8

+h,siologic dead s*ace

o 3natomic J aleolar dead space 7aleoli that hae entilation *ithout lood flo*,

therefore, no gas e+change8

o 2olume of lungs that doesnt participate in gas e+change

o :n normal lungs, same as anatomic dead spaceo :n diseased lungs, may e larger than anatomic dead space

o 4unctional measurement

o Can e measured using the Bohr E/uation'

-

--

,

,,

COa

COECOa

T

D

P

PP

V

V =


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Do not memorize this! Kou *ill not need to calculate anything *ith the Bohr E/uation on the e+am.

>o*eer, you D0 need to understand *hy this e/uation *or5s This cartoon illustrates the concepts that

allo* the measurement of +h,siologic (ead -*ace. :nspired air has GH C0-*hereas aleolar air has P3,C0-#H torr. Therefore, if you measure the PC0-of a mi+ture of air from these t*o sources 7PE,C0-in the e/uation

aoe8, you can calculate *hat fraction *as in +h,siologic (ead -*ace. 4or e+ample, if PE,C0-< !H, then

of 2T *as in +h,siologic (ead -*ace, ecause N#H$!HO#H < H.-1. :n pulmonary disease, if there is aregion of the lung in *hich no gas e+change ta5es place, this *ill ehae ust li5e +h,siologic (ead -*ace.

:f, as is more li5ely, there is a region *here gas e+change occurs poorly, then this *ill increase +h,siologic(ead -*ace, as *ell.


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Table ./0 Total minute ventilation &VE) is not the same as e11ective2 or alveolar ventilation &V)0

f 2T VE


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III.2 Work of breathing

The *or5 done y the respiratory muscles in reathing can e enisioned from static and dynamic pressure$

olume cures.

6< 1orce distance I P 2.

To increase the lung olume from 2( to 2- 7$ig0 .78, *or5 must e done against elastic recoil of the lung.

This *or5 can e appro+imated as triangular area (, *hich starts from the static compliance cure. :n real

life, *hen *e reathe, the pressure and olume change continuously, *hich is a dynamic compliance cure

7slo*8. 6e still hae to do the same *or5 against elastic recoil, ut no* *e do additional *or5 against

air*ay resistance. This *or5 is sho*n as area -. :f *e reathe faster, this re/uires more *or5 against

air*ay resistance 7area !8 ecause *e are forcing the air to moe faster.

$igure .70:t ta5es more *or5 to reathe faster.

The total *or5 is the sum of oth components of *or5'

-tatic 8om*liance 8urve

o Elastic *or5 7*or5 against elastic recoil of the lungs and chest *all8

(,namic 8om*liance 8urves

o

6or5 against air*ay resistance =a*


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$igure .90 0+ygen consumption y respiratory muscles reflects the *or5 they do.

How much wor do those respiratory muscles do anyway" 6e reathe all of the time. $ig0 .9sho*s the

rate of total ody 0- consumption in resting suects during oluntary hyperentilation. :ncreasing the

minute entilation rate, VE,increases the *or5 done. 6or5 is measured as the rate of 0-consumption y

the respiratory muscles.

Normal Individual:3 normal person sitting /uietly consumes aout -1H ml of 0-per minute, *hich is the aseline for this

graph. 3t the resting VEG1 litersmin, the respiratory muscles comprise a ery small fraction 7($-S8 of the

total metaolic 0-demand. 6hen you e+ercise igorously, VEincreases enormously, and the *or5 that it

ta5es to sustain this high VEalso increases.

Em*h,sema

9o* consider the poor geeer *ith emphysema. >is lungs are so shot that it ta5es a tremendous amount of

*or5 ust to reathe. Moderate e+ercise 7*al5ing up a flight of stairs8 increases the *or5 done y the

respiratory muscles 7i#e#their 0-consumption plotted in $ig0 .98 to that used y a normal person running amarathon. 6ith strenuous e+ercise, this patient may use all of the 0-ta5en in ust to po*er his respiratory

muscles. This is oiously a losing strategy.


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The follo*ing tale 7Table .8 descries ho* the *or5 of reathing aries *ith reathing pattern. 3s *e

go through it, try to predict ho* *or5 *ould ary depending on the conditions'

t constant alveolar ventilation

Decreasing the reathing fre/uency *ould hae *hat effect on 2T 7a answers $elow8

o :ncreased 2T*ould lead to increased anatomic dead space ecause air*ays are stretched

*ider and hae more air 7as you moe up the tale, you see this8

t lo3 1re;uenc,

6or5 against *hat force is higher 7$ answers $elow8.

o The lungs hae to otain a high 2Tat lo* fre/uency, so they hae to stretch eyond the high

compliance region of the P$2 cure, the flatter part of the cure 7rememer8. This therefore

re/uires more *or5.

t high 1re;uenc,

6or5 against *hat force is higher 7c answers $elow8

o 6or5 against =a*increases at highfecause the respiratory muscles must contract harder to

force the air in and out of the lungs at a higher rate 7they must generate a higher pressure

gradient to ma5e the air moe faster8. 3t high fturulence starts to ecome significant,*hich increases *or5 ecause turulent air flo* is less efficient.

%nswers' 7a8 re/uire an increased 2T78 elastic recoil 7c8 =a*

Bottom line' Lo* fre/uencyhigh VTmore *or5

Bottom line' >igh fre/uencyhigh turulenceincreased contractionmore *or5

Table .


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$igure .


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EM+=>-EM &obstructive disease):

3ir*ay resistance increases 7duringe+piration8 due to dynamic compression

of the air*ays

Elastic recoil is decreased 7*hich lo*ers

the pressure inside air*ays s. normal8

Breathing less fre/uently may e more

efficient

$I4R!-I- &restrictive disease):

:ncreased elastic recoil

harder toinflate lungs

Total *or5 increases, ecause higherfmeans greater V

Eis needed to achiee

the same V3

Most efficient *ay to reathe' increasef, reduce 2

T

$ig0 .


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III.3 Partial Pressures

Daltons La* 7E/. 18 states that the total *ressuree+erted y a mi+ture of gases is e;ual to the sum o1

the *ressuresthat *ould e e+erted y each of the gases if it alone *ere present and occupied the total

olume. :n other *ords, if you hae a mi+ture of gases, each indiidual gas acts li5e the other gases are

not around. The concept of partial pressureis important here ecause it applies to gases dissoled in

li/uids 7e#g., lood8 as *ell as in gas phase. 3s youll see in the rest of this syllaus, almost eerything isaout gas pressures Partial pressures are ery useful in the respiratory system, ecause gases al*ays

diffuse do*n their partial pressure gradient.

3t e&uili$rium, gas dissoles into the li/uid at the same rate that dissoled gas eaporates 7leaes the

li/uid8. :f a li/uid and a gas are at e;uilibrium, then the *artial *ressures o1 all gases in

the li;uid are e;ual to their *artial *ressures in the air 7Pgasin li/uid < Pgasin air8. This

is the definition of partial pressure.

Comining 3ogadros hypothesis *ith Daltons La*, *e can see that the pressure e+erted y a gas 7in

the gas phase8 is directly proportional to its fractional concentration 74gas8'

+gas" $gas# +total

E+ample' P0-< H.-( QH torr < (H torr

E+ample' P9-< H.Q" QH torr < 1%! torr

6e use QH torr for Ptotalecause that is the arometric pressure at sea leel.

Table .?0 Most o1 the air 3e breathe is N.2 but .@A o1 the air is !.0

Table 29


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Things to note'

(. Please rememer thatpartial pressureis N!T e;uivalent to content. The partial pressure of a

gas dissoled in a li/uid is indeed an indication of the amount of gas there is. But the amount of

gas dissoled in a li/uid also depends on the soluility of the gas in that li/uid. >enrys La*states this mathematically' the amount of gas that dissoles 7Cgas8 depends on oth partial pressure

and soluility.

=enr,Bs La3: 8gas" gas +gas &e;0 @/)

Cgas< gas concentration

gas< soluility of gas in li/uid 7see Table %C8

Pgas< partial pressure of the gas

Table 30


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I (igress2 but

This will )OT $e on the e*am +,E%--./ $ut some people are naturally curious a$out things +if not you

then your ids will $e/#

The de* point that *eather forecasters li5e to tal5 aout is the temperature at *hich the amient

P>-0

*ould saturate the air. :f the temperature *ere #HCand the relatie humidity *ere Q-S, P

>-0

*ould e H.Q- 11.! torr < !%." torr 7refer to $ig0 .78. The temperature at *hich that much *ater

*ould saturate the air 7the de* point8 is !#C. :f the temperature drops elo* the de* point,

*ater apor *ill e deposited as de*.

Vloal *arming

$igure %%03erage Vloal Temperature from years (1HH$-HHH.

$igure %/0Caron Dio+ide Concentration in the 3tmosphere.

The smooth line data 7e.g. (1HH$("1H8 *as

attained y sampling the temperature atarious depths in the earths surface. The

noisy lines 7e.g. ("1H$-HHH8 sho* mean

surface air temperature measured directly.0er the past 1HH years, the aerage

temperature at the surface of the earth has

increased (C due to anthropogenic causes

7urning fossil fuels, deforestation, and

greenhouse gas production8.

This figure sho*s the correlation et*een the

earths temperature and the amount of C0- andmethane 7greenhouse gases8 in the atmosphere.

The time scale coers (H,HHH years. Boine

flatus and eructation account for -HS of gloalmethane emissions.


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III.% &iffusion

III070@ (i11usion La3s

To understand the rate at *hich gas diffuses from air into lood, or ice ersa, *e use 4ic5s La* ofDiffusion.

E;uation @7. 4ic5Zs La* of Diffusion'

[gas< flu+ rate

7Cgas($ Cgas-8 < concentration gradient 7driing force for diffusion, ut only

*hen oth compartments are in the same phase Ngas or li/uidO8

Dgas< diffusion constant for the gas

3 < area aailale for e+change

d< path length for diffusion

6e can comine 4ic5s La* *ith >enryZs La* 78gas" gas# +gas8 to yield'

7P($ P-8 < gas partial pressure gradient

gas< soluility of gas in li/uid

Therefore, the rate of diffusion 7[gas8 is proportional to the area 738 aailale for diffusion. This e+plains

the enefits of the anatomical structure of the lungs, *here the ranching tree and the !HH million aleoli

result in an area 738 roughly the same surface area as a tennis court. :f your lungs *ere simply t*o

alloons filled *ith air 7li5e frog lungs8, they *ould each hae to e (- feet in diameter to proide the

same surface area for diffusion

The rate of diffusion is also proportional to the concentration gradient. This is referred to as the *artial

*ressure gradient*hen one tal5s aout gas diffusion. 3s you might rememer, diffusion al*ays occurs

D069 the partial pressure gradient 7meaning from high to lo* partial pressure8. :n the lungs, the large

partial pressure gradient is maintained y the residual gas at 4=C F a uffer of sorts, 5eeping P3,0-and

P3,C0-relatiely constant. 7This is ecause a normal 2Te+changes only a fraction of the air in the lungs.8

:n the tissues, diffusion also occurs according to 4ic5s La*. :f capillary lood has a lo* Pa,0-7normally

d

CC%D0

gasgasgas

gas

87 -( =

d

PP%D0

gasgasgasgas

gas

87 -( =


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regulated at (HH mm >g8, then o+ygen *ill not diffuse rapidly enough to the tissues 7lo* P0-8, and they

*ill ecome h,*oxic7more details later8.


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III070. (i11usional E;uilibrium7et*een aleolus and aleolar capillary8

3ll this diffusion happens /uic5ly, and normally there is plenty of time for lood gases to e/uilirate *ith

aleolar gases. :t ta5es aout C07 seconds for lood to enter the dense mesh*or5 of the aleolar

capillary ed, 1lo3*astthe aleolar surface, and exitthe capillary on its *ay to the heart and eentually

the tissues. 3maingly, ample diffusion ta5es place during this short period

111#2#3#a O*ygen E&uili$ration

0- diffuses through the airlood arrier, and then diffuses into a =BC, chemically inding to

hemogloin. 0nce it enters the red cell and inds to hemogloin, it no longer contriutes directly to the

partial pressure, thus maintaining the partial pressure gradient for further diffusion. More 0-molecules

/uic5ly enter and ind until the hemogloin reaches a steady$state leel of saturation.

$ig0 %9sho*s that after H.-1 seconds in a normal person, the lood P 0-has already fully e/uilirated *ith

the aleolar P0- Thus, in a normal indiidual, diffusion is rarely rate$limiting. >o*eer, if diffusion is

impaired 7anormal and grossly anormal lines in $ig0 %9, top panel8, as it is in edema 7e+cess fluidin aleolar air space8, full e/uiliration ta5es much longer than H.-1 seconds, if it occurs at all. 6hen the

aleolar P0-is anormally lo* 7$ig0 %9, ottom panel8, such as occurs at high altitudes, it ta5es longer for

the normal indiiduals lood gases to e/uilirate. This is ecause there is a decreased aleolar$capillary

gradient. The anormal indiidual does not eer e/uilirate *hen aleolar P0-is anormally lo*

$igure %9. 0-diffusion from aleolar air into capillary lood.


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>o* does e+ercise affect e/uiliration >eay e+ercise increases cardiac output y up to a factor of fie.

>o*eer, the length of time *hen the =BC is flo*ing through the aleolar capillary ed is F at most F

reduced to H.-1 seconds. 7This reflects recruitment and dilatation of pulmonary lood essels at high BP,

*hich *e *ill discuss later8. Een this is long enough for full e/uiliration. 9ote that there may e some

diffusion limitation if a normal person e+ercises at high altitude. :f an anormal patient tries to e+ercise

at high altitude, diffusion is significantly impaired.

111#4#3#a Car$on Dio*ide E&uili$ration

Caron dio+ide diffusion has a ery similar oerall time course to that of o+ygen diffusion. This seems

surprising, ecause the driing force F the partial pressure gradient is only G1 torr for C0 -, ut is GH torrfor 0-. The diffusion coefficient for C0-is not ery different, Q%S that of 0-7ecause C0-is a larger

molecule8. >o*eer, 4ic5s La* tells us that diffusion is also proportional to soluility. The soluility of

C0-is -# times higher than the soluility of 0 -, *hich ma5es up for the smaller driing force 7partialpressure gradient8.

$igure %. C0-diffusion from aleolar air into capillary lood.

4ottom line: In normal individuals2 blood is in the *ulmonar, ca*illar, bed long enough

1or both !.and 8!.to com*letel, e;uilibrate across the airFblood inter1ace0


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$igure %


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More on&L

The driing force &+28! ' +v28!) does 90T determineDL The driing force &+28! ' +v28!) does 90T

determineDL The driing force &+28!' +v28!) does 90T determineDL The driing force &+28!' +v28!)

does 90T determineDL The driing force &+28!' +v28!) does 90T determineDL The driing force

&+28!' +v28!) does 90T determineDL The driing force &+28!' +v28!) does 90T determineDL

6e *ant to measure DL *hich is a global indication of ho* *ell diffusion happens in oneparticular suectpatient 738. Lets compare her *ith another suect B. 6hose lungs *or5 the est

6e *ant numers Put some 0-7or C08 into oth lungs and measure ho* much goes into the lood in

(.H minute That isDL 6e see that 3 transferred 7ia diffusion8 1HH ml 0-min and B transferred #HH ml0-min. 0), no* *e 5no* that 3 has etter lungs =ight 6rong 6e chec5 and see that *hen *e

s/uirted our measured amount of 0-into 3 eerything *ent fine, ut efore *e gae 0-to B, the tue *e

used crac5ed. Turns out P3,0-in 3 *as (HH torr, ut P3,0-in B *as only "H torr. Both had P,0-H torr.

?o the driing force *as #H torr for 3, ut only -H torr for B. 9o *onder 6hen *e correct for this, *esee that in fact B has etter lungs

Lets loo5 at another e+ample. Lets say *e cant decide *hich of t*o race cars to uy, 3 and B.

6e *onder *hich has a more po*erful engine. ?o *e drie each car for 1 minutes full$out. 3 goes miles, ut B goes only ! miles. Vreat, lets uy car 3 F it is oiously etter >mmm. Lets loo5 a it

closer. 6e droe car 3 on a leel stretch of deserted high*ay. Car B *e droe straight up from Dener

into the =oc5y Mountains. Maye this *as not a completely fair test 6e re$test car B on the same leelhigh*ay, and it goes % miles in one minute. :n order to test ho* *ell diffusion occurs in the lungs, *e

hae to e sure the test is fair. ?o lets correct for the pressure gradient

III.' Alveolar "as #(uations

?o no* that *e 5no* (8 ho* to use partial pressure gas la*s to measure 0 -and C0-pressures in the

respiratory system, -8 that minute entilation is different from aleolar entilation, and !8 ho* to 5eep

trac5 of aleolar entilation, *e are in a position to determine alveolar gas content.

:t might seem oious that aleolar gas content depends on entilation. But it also depends on

metaolism 70- consumption and C0- production8 of the organism. 4or any gien metaolic rate,

aleolar entilation V37not total minute entilation, VE8 *ill estalish the aleolar gas leels according to

E;0 ?and $ig0 %?.

E;uation @%0 lveolar Gas E;uation:

+2!." +I2!.H &+28!.FR) J )

P:,0-< P0-of inspired air < 4:,0-7Patm$ P>-08

4:,0-< fraction of inspired air that is 0-

Patm< atmospheric pressure 7QH torr at sea leel8

P>-0< *ater apor pressure 7#Q torr at !QoC8

=R < respiratory /uotient, respiratory e+change ratio 7GH."8

9< small correction factor


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$ig0 %?assumes a constant metaolic demand. Clearly, increasing V3increases P3,0-and decreases P3,C0-.

3n important point is that doubling Vdecreases +28!.b, K but does N!T double +2!.0 This is

understandale if you rememer that increasing V3results in oth of the aleolar gases approaching their

alues in inspired air 7P:,0-< (1H torr, P:,C0-< H torr8. :f P3,0-is already (HH torr, you cannot doule itF the

highest P3,0-you can get at sea leel is (#% torr.

\These cures *ere calculated *ith E/s. !H$(" and !H$(! of Boron & Boulpaep, -HH!, assuming =R < H." and VC0-< -HH

mlmin].

$igure %?. Dependence of 3leolar Vas Content on 3leolar 2entilation =ate


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Respiratory Physiology Lecture Questions

Lecture #' 2entilation and Vas E+change

These /uestions are intended to proide you *ith a means of determining *hether you are getting the

messages that are eing deliered in class. *o attempt has been ma+e to make these (uestionscomparable to the (uestions ou ,ill encounter on the #$am in either their format or their +egree of

+ifficult. The Practice E+am *ill proide you *ith a sampling of /uestions that are intended to esimilar to the E+am.

(. The partial pressure of a gas in a li/uid is e/uialent to the content of that gas in the li/uid 7T48.

-. :n calculating the partial pressure of o+ygen in the trachea you need to consider the presence of'

a. nitrogen. *ater

c. oth a and

d. neither a nor

!. ;nder normal conditions, e/uiliration of aleolar P0-and PC0-*ith lood P0-and PC0-occurs

*ithin the first half of the pulmonary capillary 7T48.

#. During a respiratory cycle 7inspiration$e+piration8 in a normal indiidual, aleolar P0-fluctuates

et*een'

a. (HH and #H mm >g

. (HH and H mm >g

c. (HH and %" mm >g

d. #H and !" mm >g

e. none of the aoe aleolar P0-is held appro+imately constant y a refle+

1. 6hich of the follo*ing contriutes to the diffusing capacity of the lungs 7DL8 for o+ygen 7in anormal, healthy indiidual at rest8'

a. aleolar surface area. the partial pressure gradient et*een the aleolar space and the lood

c. the concentration of hemogloin in the lood

d. all of the aoe

e. none of the aoe

. The *or5 to oercome'

a. elastic recoil decreases as tidal olume decreases

. air*ay resistance increases as reathing fre/uency increases

c. oth a and are correctd. neither a nor is correct

Q. Pressures in the respiratory system are measured relatie to atmospheric pressure 7T48.


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3ns*ers

(. 4

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Lecture 4 RespiratoryPhysiology Ventilation & Gas Exchange

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