PHYSI

OLOGY: RESP.SYSTEM /
/ Dr
.BasharTal
i
b

Thedeadspace:I ti st hespacei nwhi cht hegasexchangei snot

takingpl ace.Someoft heai rthataper sonbr eathesnev err eaches
thegasex changear easbuti nsteadgoest of il
lt her espir atory
passages.Ther espi ratorypassageswher enogasexchanget akes
placear ecal l
edt heanat omi caldeadspaces( whichconsi stof
nose,phar ynx,l ar ynx,t r
achea,br onchi,and br onchi oles).The
normalanat omi caldeadspaceai rinthey oungadul ti sabout150
ml .Thi sincr easessl i
ghtlywi thage.I tal soi ncr easesdur inga
maxi mali nspi rati
onbecauset het racheaandbr onchiexpandas
thel ungsexpand.Ther ei sanot hert ypeofdeadspaceandi s
calledphy siologicaldeadspace.Thi si sduet osomeal veol iar e
notf unctionalorar eonl ypar t
iallyfunct i
onalbecauseofabsentor
poorbl oodf lowt hr oughadj acentpul monar ycapi l
laries.Ther ef ore,
from a f unct ionalpoi ntofv iew,t hese al veolimustal so be
consi deredt obedeadspace.I nt henor malper son,al ltheal v eoli
aref unctional .Ther efore,t hev olumeofphy siol
ogi caldeadspace
i
sequal tozer o.
Total deadspace=anat omi cal D.S.+phy siological D.S.
=150+0=150ml .i.e.equal t
oanat omi caldeadspace.
Inper sonwi thpar t
iallyf unct i
onalornonf unct i
onalal veol iin
somepar tofl ungs,t hephy si
ol ogicdeadspacei ssomet imesas
muchast ent imest heanat omi caldeadspace.I ft het i
dalv ol ume
i
s500ml ,anor maldeadspaceof150ml ,andar espi rator yrat eof
12t imespermi nute, al
veol arv ent il
ati
onequal s12x( 500–150)=
4200ml /min.Al veol arv ent i
lationi samor eaccur atemeasur eof
thel evelofv entil
at ionsi ncei tt akesi ntoaccountonl yt hev ol ume
ofgast hati nterfaceswi tht her espiratoryepi thel i
um.I tcanbe
seen t hati fa subj ectt akes r apid,shal low br eat hs,t heywi ll
become hy poxaemi c despi te numer i
cally adequat e mi nute
vent i
lati
on.

Respi
rat
orypassageway
sresi
stance:.

Ther ear efourmaj orfactorst

hataffectresi
stancetoai rflow:
1.Ai r
wayr adiusisthemai ncomponentofai rwayr esistance.The
resistancechangesal ong theai r
way .Theupperai rwayof f
ers
significantfixedr esistance,whichthendecl i
nesr apidlyfrom the
fiftht hrought hetent hgenerati
onofai rwaydivisi
on.Becauset he
coll
ect i
v e cross-
sectionalarea ofl ung aciniis enor mous,t he
respiratoryzoneoft hel unghasv er
ylowr esi
stance.

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 PHYSI
OLOGY: RESP.SYSTEM /
/ Dr
.BasharTal
i
b

2.Lungv olumei sani mpor tantdet er

mi nantofai rwayr esi st
ance
becauset heov erallcross-sect i
onalar eaofai rway sv ari
eswi t
h
l
ungv olume,causi nggl obalchangesi nairwayr adi us.Atl owl ung
volume,t hecr oss-sect i
onalar eai sreducedandai rwayr esi st
ance
i
ncr eases.Forexampl e,pat i
entswi thpulmonar yfibr osishav elow
l
ung compl iance and l ow r est i
ng lung v olume;hi gh ai r
way
resistancecont ributestot heirincreasedwor kofbr eathing.
3.Tur bulentgasflow i ncreasesai rwayr esist
ance.Tur bulentflow
occur sinthel argercent ralai
rway s,wher eflowv elocityishi gh,and
atbr anchpoi ntsal ongt heconduct ingairways.Di sor ganizat i
onof
thegasst r
eam r equi r
esmor epr essuretodr i
veflowandef fecti
vel
y
i
ncr easesr esist
ance.

4.Dy nami c airway compr essi

on:Ai rway resistance increases
duringf orcedexpi r
ationbecausei ntrapl
euralpr essurebecomes
positi
v eandt heairway sarecompr essed.For cefulcont r
actionof
theexpi r
atorymuscl esincreasesbot hintr
apleur alpressureand
alveolarpr essuret o posit
ivev alues.The l argestcompr ession
forces ar e applied tol ar
gerai rway s,which hav e cart
il
aginous
suppor tt or esi
stcol l
apse.Thedi stalbronchiolesdo nothav e
cartil
aginous suppor tt o resist dy namic compr essi
on and,
therefore, ar e at r i
sk of col lapsing. Nor mal ai rways ar e
compr essedinf orcedexpirati
onandai rwayresistancer i
ses.

Thesmoot hmuscl esoft hebr onchi olesar eunderner vousand

humor al cont rol:
[A]Ner vouscont r
oloft hebr onchioles:Theonl yi mportantner vous
cont rolt ot hebr onchi ol esi sbywayofpar asy mpat het i
cv agus
ner ves f i
ber s.These ner ves secr et e acet ylcholi
ne and when
act i
vatedcausemi ldt omoder ateconst ri
ctionoft hebr onchioles
(table6. 2).I rri
tantsent er i
ngt heai rway s,suchassmoke,dust ,
sul f
urdi oxide,andsomeoft heaci dicel ement sinsmog,canal l
i
ni ti
atel ocalr eactionst hatcauseobst ructi
v econst r
ictionoft he
bronchi olesmedi atedt hr oughapar asy mpat het icref
lex .
[B]Humor alcont roloft hebronchi oles:sev er aldifferenthumor al
subst ances ar e of ten qui te act ive i n causi ng br onchiolar
const riction.Twooft hemosti mpor tantoft hesear ehi stamine,
l
eukot ri
enesandt hesubst ancecal ledsl owr eactivesubst anceof
anaphy laxis( SRA)( tabl e6. 4).Bothoft hesear ereleasedi nt he
l
ungt issuesbymastcel lsduringaller gicreact i
ons.Ther efore,they
playkeyr olesi ncausi ngt heai rwayobst ruct i
ont hatoccur si n
allergicast hma.I naddi tion,theai rwaysmoot hmuscl ei shi ghl y
responsi vet oCO2( highbl oodCO2pr oduci ngbr onchodi l
at aionand

I
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 PHYSI
OLOGY: RESP.SYSTEM /
/ Dr
.BasharTal
i
b

l
ow CO2 br onchoconstr
ict
ion).In cont r
ast to t he humor al
substancest hatconstri
ctthebr onchioles,twoot herhor mones,
epinephri
neandnor epinephr
ine,bothofwhi charesecretedbyt he
adrenalglandsi nresponset osympat heticsti
mulation,relaxthe
bronchiol
es(byact i
vati
onof2r eceptors).Theref
ore,activ
at i
onof
thesy mpatheticnervoussystem isof t
env aluabl
ei nrelaxingthe
air
way sandpr event
ingobstr
uction.

Table6. 2:Ner vousandhumor al

cont
rol
ofbronchi
olesmoothmuscl
e
contractions.
Fact
or Effect
Parasympat heticsti
mulat
ion Br
onchoconstr
ict
ion
Histami ne,leukotri
enesandSRA Br
onchoconstr
ict
ion
Lowbl oodPCO2 Br
onchoconstr
ict
ion
Highbl oodPCO2 Br
onchodil
atat
ion
Sympat het i
cst imul
ationt
othe
adrenal glands( epi
nephri
neand Br
onchodil
atat
ion
norepinephr ine)

Inacti
vi
tyofeithert
hesy mpathet
icorthepar
asympatheti
c
nervoussy stem al
l
owst heact i
onoftheothertodominat
et he
bronchialsmoothmuscleresponse.

I
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 PHYSI
OLOGY: RESP.SYSTEM /
/ Dr
.BasharTal
i
b

Thecoughr eflex:Thet rachea,br onchi ,respi

ratorybr onchioles,
and alv eoliar ev erysensi tiv
et oirritation and touch.Af ferent
i
mpul sespassf rom t her espiratorypassagesmai nlythrought he
vagusner v est ot hemedul la.Ther e,anaut omat i
csequenceof
eventsi st r
igger edbyt heneur onalcircui t
soft hemedul lacausi ng
thefollowingef fect s:
[1]About2. 5l i
ter sofai risinspi r
ed.
[2]Theepi glottiscl oses,andt hev ocalcor dsshutt ightlytoent rap
theairwi thint hel ungs.
[3]Theabdomi nalmuscl escont ractforcef ull
y,pushingagai nstt he
diaphragm whi leot herexpiratorymuscl esal socont ractforcefully
.
Consequent l
yt hepr essurei nt helungsr ai
sest oashi ghas100
mm Hgormor e.
[4]Thev ocalcor dsandt heepi glot
ti
ssuddenl yopenwi delysot hat
airunderpr essur ei nthel ungsexpl odesout war d.Ther apidly
mov i
ngai r( 75- 100mi les/hour )usual l
ycar r
ieswithi tanyf oreign
mat t
ert hati spr esenti nthebr onchi ort rachea.

Thesneezer efl
ex:Thesneezer efl
exisv er
ymuchsi milart ocough
ref
lexexceptt hatitappli
est ot henasal passageway sinst eadoft o
the l
owerr espiratorypassages.The i ni
ti
ating sti
mul us oft he
sneezer ef
lexi si r
rit
ati
oni nt henasalpassageway s,theaf f
erent
t
h
i
mpul sespassi ngint he5 cr ani alner
ve( t
rigeminalner ves)tot he
medul l
awher ether ef
lexist r
iggered.Aser iesofreact i
onssi mil
ar
tothosef ort hecoughr ef l
ext akesplace,howev er,theuv ulais
depressedsot hatl ar
geamount sofai rpassr apidlythr ought he
nose,aswel last hought hemout h,t
hushel pi
ngcl eart henasal
passagesoff or
eignmat ter.

2 :Exchange ofgases bet ween al veol

iand bl ood ( external
respi
ration)andbet weenbloodandt issues( int
ernalr
espi rat
ion).
Aftertheal veoliareventi
latedwithfreshai r,thenextst epi nthe
respi
ratorypr ocessisdif
fusionofoxy genf rom thealveoliintothe
pulmonar y blood and transported by t he blood tot he t i
ssue
capil
lariesandt henleavest het i
ssuecapi ll
ar i
esandcr osscel l
membr anet o gain entr
yi nto cel
ls.Di ff
usion ofCO2 i si nthe
oppositedirection,f
rom t
hepul monar ybloodi ntotheal
veol i
.

I
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 PHYSI
OLOGY: RESP.SYSTEM /
/ Dr
.BasharTal
i
b

Ther espi ratoryuni t

:Thepar toft her espir
at orysy stem atwhi ch
gasexchangebet weent hepul monar ybloodandt heal veol arairis
takingpl acet hroughi tsmembr ane.Itiscomposedofar espi r
ator y
bronchiol e,alveolarduct s,alveolarsacs,andal veoli( about300
mi l
li
oni nt het wolungs) .Eachal veolushasanav er agedi amet erof
about0. 2mm.Theal veol argasesar ei nclosepr oxi mityt ot he
blood oft he capi l
laries.The gaseous exchange bet ween t he
alveolar ai r and t he pul monar y bl ood occur st hrough t he
membr ane of al lt he t erminalpor tions of t he l ungs.Thi s
membr ane i s cal l
ed t he r espiratory membr ane ( pul monar y
membr ane)whi chconsi st softhef ollowinglay ers( fi
gur e6. 17):
[1]Alay eroff luidli
ningt heal veolusandcont ainingsur factant .
[2]Theal v eolarepithelium.
[3]Theepi theli
albasementmembr ane.
[4]Av eryt hinintersti
tial space.
[5]Acapi l
larybasementmembr anet hati nmanypl acesf useswi th
theepi t
hel ialbasementmembr aneandobl iteratingt hei ntersti
tial
space.
[6]Thecapi ll
aryendot hel ial membr ane.
Theav eraget hicknessoft hesel ayersi sabout0. 6mi cron.
Thet otalsur facear eaoft herespiratorymembr anei sest imat edt o
beabout100squar emet er
s,ov erwhi chaquant i
tyofbl oodof
about60- 140mlonl y(thequant i
tyofbl oodi nt hecapi ll
ar i
esi fthe

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 PHYSI
OLOGY: RESP.SYSTEM /
/ Dr
.BasharTal
i
b

l
ung atanygi v
en inst ant
)i sspr ead,cr eati
ng a f il
m 10 µ ( or
approximat el
yoner edcel ldiameterwhi chexplai
nt herapidi
tyof
respir
atoryexchangeofgases) .Inaddi ti
on,thedi amet eroft he
pulmonar ycapil
lari
esi sabout8mi cronswhi chisaboutt hesame
diameter of RBC,t heref
ore,RBC as i tpass t hrough these
capil
lari
es ar einf acti n close cont actwi tht he endot helial
membr ane.Thi s also helpi n maki ng t he gas exchange r apid
becauset hegasescan passdi r
ect l
yf r
om RBC t ot heal veoli
withoutpassingt hr
oughsi gnif
icantplasma.

Fact orst hataf fectr ateofgasdi ffusi ont hrought her espir
at or y
membr ane:
[1]Thet hicknessoft hemembr ane:Anyf act ort hatincreasest he
thickness t o mor et han t wo ort hree t imes t he nor malcan
decr easesi gni f
icantlyt her ateofgasesdi ffusion.Thi scanoccuri n
edemaoft hei nterstitialspaceoft hemembr ane,andi nsome
fibroticdi seasesoft hel ung.
[2]Thesur facear eaofr espiratorymembr ane:Whent het ot al
sur facear eai sdecr easedt oaboutonet hi
rdt oonef ourthnormal ,
exchange ofgases t hrough t he membr ane i si mpeded t oa
signi fi
cantdegr eeev enunderr estingcondi tions.Thi scanoccuri n
emphy sema oft he l ung i n whi ch manyal veolicoal esce wi th
dissol utionofmanyal veol arwal l
s.
[3]Thedi ff
usi oncoef f i
cientoft hegasi nt hesubst anceoft he
membr ane,whi chi st hewat eroft hemembr ane:Thi sdepends
pr opor ti
onal lyont hesol ubi l
i
tyoft hegasi nt hemembr aneand
i
nv erselyont hesquar er ootofi tsmol ecularwei ght.Ther efor
e, for
agi venpr essur edif f
er ence,CO2 di ff uset hr ought hemembr ane
about20t imesasr apidl yasO2.Oxy geni nt urndi ffusesaboutt wo
timesasr api dlyasni t
rogen.
[4]The pr essur e di fference bet ween t he t wo si des of t he
membr ane,whi cht endst o mov et hegasf r
om ar eaofhi gher
par ti
al pressur etoanar eaofl owpar tial pressur e.

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 PHYSI
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/ Dr
.BasharTal
i
b

Vent i
lati
on – per fusion r ati
o( VA/Q) :I tist he r atio of
venti
lati
onofagi venal v eolust oi tsbl ood per f
usion.I fsome
alv
eoliar ewel lv enti
latedbuthav enooral mostnobl oodf l
ow,
VA/Q =i nf i
nity.Ther efore,t he al veol
ar ai r has t he same
composi ti
onandconcent rationoft hehumi difiedinspir
edai r(PO2
=149mm Hg,PCO2 =0mm Hg) .Ifsomeal veolihavel i
ttl
eorno
venti
lati
onbutexcel l
entbl oodf low,VA/ Q =zer o.Ther efore,the
alv
eolaraircomest oequilibri
um wi tht hev enousbl oodgases( PO2
=40mm Hg,PCO2 =45mm Hg)wi thoutf urthergasesexchange
becauset her ei snonew gascomi ngf rom t heext eri
orai rt othe
alv
eoli.Atar at i
oofei t
herzer oori nfinit
y,t herewi l
lbenopr oper
exchangeofgasest hrough t her espiratorymembr anesoft he
aff
ectedal veoli.Whenal veolarv entilati
oni snor malf oragi ven
alv
eolusandbl oodf l
owi sal sonor malf ort hesameal v eolus,the
VA/Qi salsosai dt obenor mal( VA/ Q=1. 0).ThemeanVA/ Qfor
theent i
relungi s0. 93( r
ange0. 8-1) .
I nnor malper soni nt heupr i
ghtposi t
ion, bothbloodf l
owand
alv
eolarv ent i
lati
onar econsi der abl ylessi nt heupperpar toft he
l
ungt hani nt hel owerpar t.Howev er,bloodf low isdecr eased
considerably mor et han v ent il
ation because t he low- pressure
pulmonar ycapi l
lari
esatt hel ungapi cesar ecompr essedbyt he

Fi
gur
e6.
18:
Vent
il
ati
on–per
fusi
onr
ati
o(VA/
Q)atdi
ff
erentr
egi
onsoft
hel
ung.
hi
gher-pressurelungalveoli
.Therefore,atthetopoft helung,VA/ Q
i
shi gher( >1.
0)t hant heidealv al
ue,whi chcausesamoder ate
degreeofphy si
ologi
cdeadspacei nt hisareaofthel ung( fi
gure
6.
18A&B) .Wi t
hani ncreasephysiologicaldeadspace, venti
lat
ion
becamewast edv ent
il
ationleadi
ngt osev eremuscularfatiguewith
hi
ghal veolarPO2 andl ow PCO2.VA/ Qequalt oinfini
tydoesnot

VI
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/ Dr
.BasharTal
i
b

occuri nt henor mall ungbuti nsteadoccur sonl yi nabnor mal

condi t i
onssuchasi nsomel ungdi seases( pulmonar yembol ism) ,
af al li n ar teri
alpr essur e( fol
lowing hemor rhage)orbr eathing
agai nstahi ghpr essur easoccur swhenaper soni sbl owi ngona
musi cali nstrument .Br eat hingagai nstahi ghpr essur ecausesa
compr ession oft hepul monar ycapi l
lari
esbyt hehi gh al veol ar
pressur e.
 Whenev erVA/ Qi sbel ow nor mal( i.
e.l ow v entilationand
normalper f
usi on)asi nt hebaseoft hel ung,t hev ent i
lationi snot
enought opr ov i
det heO2 neededt ooxy genat et hebl oodf l
owi ng
throught heal veol arcapi ll
ar i
esandconsequent l
yl eadst ol owPO2
(hypoxemi a)andhi ghPCO2.Ther efor e,acer tainf ractionoft he
venousbl oodpassi ngt hrought hepul monar ycapi llari
esdoesnot
becomeoxy genat ed( wast edper f
usion) .Thi sf ractionofbl oodi s
calledphy siologicalshunt edbl ood( v enousbl oodt hatpassest o
thesy st emicci rcul ationwi thoutf i
rstbei ngoxy genat edint hel ungs)
asi toccur snor mal lyint hebot tom oft hel ungwi thVA/ Q <0. 8
ti
mest hei dealv al ue( f i
gur e6.18A&B) .Al so,someaddi t
ional
bloodf l
owst hrought hebr onchi alvessel srat hert hant hrought he
alveol arcapi ll
aries,nor mal l
yabout2% oft hecar diacout put,t his
too i s unoxy genat ed,i .e.anat omi calshunt ed bl ood.The t otal
quant it
at i
ve amount of
shunt ed bl ood i s cal led t he
phy siol ogical-anat omi cal
shunt .

Compensat ory mechani sms

format chi ng the v entil
ation
andbl oodf l
ow ( per
fusion)i n
alveoli
:
Forpr operVA/ Q( t
obe
equalt o 1) ,i .
e.,forpr oper
blood oxy genation,t he r i
ght
propor ti
onofai randcapi ll
ary
blood shoul d be availabl
et o
eachal veolus.Localchanges
i
nt het oneofsmoot hmuscl es
ofbr onchiol esandpul monar y
vesselshel pt omai nt ai
nt his
equili
br i
um through t wo Figure6.
19A:AdjustmentofVA/
Q
mechani sms: whentheal
veol
arbloodfl
owishigh
andt
heai
rf
lowi
slow.

VI
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 PHYSI
OLOGY: RESP.SYSTEM /
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.BasharTal
i
b

[1]LocalbloodPO2:I fanal veol usi srecei

vingtool i
ttl
eai rforits
blood supply,the blood and t i
ssue O2 wi l
lbe decr eased.A
decreased O2 concentration int hepul monaryv esselcausesa
constri
cti
ont othesev esselsandv i
cev er
sa( t
heopposi teeffect
thatexer t
ed on sy st
emi c ar teries).By thisl ocalmechani sm,
perfusi
oncanmat chventilat
ion( figure6.19A).
[2]LocalbloodPCO2:Ifanal v eolusi srecei
vi
ngt oomuchai rforits
blood suppl y
,the bl ood CO2 wi l
lbe washed out and t he
concentrat
ionofCO2i nthebl oodandi nthesurroundi ngtissuewi l
l
be low.Consequent l
yt he ai rway s supplyi
ng t he alveolus ar e
exposed t ot hi
sl ow t issue CO2 concent r
ation and become
constri
ctedandv i
cev ersa.Byt hislocalmechani sm,v entil
ati
on
canbemat chedtobloodsuppl y( f
igure6.19B).

Figure6.19B: AdjustmentofVA/Qwhen
thealveolarbloodflowissmallandt
he
airf
lowisl ar
ge.

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 PHYSI
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.BasharTal
i
b

3:Tr ansportofoxygenandcar bondioxi

deinthebl oodandbody
fl
uids:I ti
si mport
anttounder standthedif
ferencebet weenthe
parti
alpressureofagasandt hegascontentofaliquid.Thepar
tial
pressureoft hegasrepresentsthepressur
eitwoul dexertinthe
gasphase.Thegascont entrepresent
sthevolumeoft hegasper
unitvolumeofl i
qui
dthatispresent.

 Gasescanmov efrom onepoi nttoanot herbydi ffusion,

whi chisdr i
venbyt hepr essur edi fferencebet weent hetwopoi nts.
Thus,O2 di ffusesf rom theal v eoli( PO2 =104mm Hg)i ntot he
pulmonar ycapi ll
arybl ood( PO2 =40mm Hg)wher eitcombi nes
withHb( fi
gure6. 20) .Thenf rom t hesy stemiccapi l
lari
es( PO2=95
mm Hg)O2di ffusest oandequi l
ibrat ewi t
hintersti
ti
al fl
uidO2of40
mm Hgandt hendi ffusestot hecel ls(PO2=23mm Hg) .Ther efore,
PO2 oft hebl oodl eav i
ngt het issuescapi l
l
ariesandent eringt he
veinsi sabout40mm Hg.Conv ersel y
,whenO2 i smet abol i
zedi n
thecel l
s,thePCO2r isestoahi ghv alue( PCO2=46mm Hg) , which
causesCO2t odi ffusei ntothei nter stit
ialfl
uidwi thPCO2of45mm
Hgandt heni tdi ffusest oandequi l
ibrat
ewi thCO2 ofbl oodi n
ti
ssuecapi l
l
ar i
es( PCO2=40mm Hg)andcombi neswi thchemi cal
subst ancesi nt hebl oodt hati ncr easeCO2 t ransport.Ther efore,
PCO2 oft hebloodl eav i
ngt het i
ssuecapi l
lar
iesandent eringt he
veinsi sabout45mm Hg.Si milarly, i
tdi f
fusesoutoft hebl oodi nto
theal veolibecauset hePCO2 i nt heal v
eoli(40mm Hg)i sl ower
thant hatinthepul monar ycapi l
larybl ood( 45mm Hg) .

X
 PHYSI
OLOGY: RESP.SYSTEM /
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.BasharTal
i
b

Fi
gure6.20:Par
ti
alpr
essur
eofoxy
genandcar
bondi
oxi
dei
nthebl
oodand
bodyfl
uids.

About98%oft hebl oodt hatent ersthel eftat

ri
um f rom the
l
ungspassest hrought healveol arcapi ll
ari
esandbecomesf ull
y
oxygenat ed ( PO2 = 104 mm Hg)and 2% passes t hr ough the
bronchi alci
r culation( deadspace) ,whi chr epresent
st heshunt ed
bloodbypassi ngt hegasexchangear easandhasaPO2aboutt he
sameoft henor malv enousbl ood( PO2 =40mm Hg) .Thi sblood
combi nesi nt hepul monar yveinswi ththeoxy genatedbl oodf r
om
theal veolarcapi ll
aries.Thi smi xingoft hebloodi scalledv enous
admi xtureofbl ood,andi tcausest hePO2oft hebloodpumpedby
thelefthear tintot heaor tatofal ltoabout95mm Hg.

Transport of O2 int he blood: Nor mal l

y about 97% of O2
tr
anspor t
edf r
om thelungst ot hetissuesi scarr
iedinchemi cal
combinationwithHbinRBCandt heremai ni
ng3%i scarri
edint he
di
ssolvedst at
einthewat eroft heplasmaandcel l
s.Theper cent
oftheHbt hatisboundwi thO2 (percentsat ur
ationoft heHb)
i
ncreasesast hePO2 increase,plot
ti
ngt hepercentsat urati
onof
Hbagai nstt
hePO2wi l
lproduceO2–Hbdi ssoci
ati
oncurve.

XI
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.BasharTal
i
b

O2-Hbdi ssociat
ioncur v e:Theoxy gen-Hbdi ssociationcur v
ei sa
grapht hatshowst heper centsat urati
onofhemogl obinatv ari
ous
partialpr essuresofoxy gen.I tisanS–shapedcur vewi t
hast eep
slopebet ween10and60mm HgPO2 andaf latpor ti
onbet ween
70and100mm HgPO2( figure6.21A) .AtaPO2of60mm Hg, 90%
oft het otalHbi scombi nedwi thO2.Fr om thispoi nton,af urther
i
ncr easei nPO2pr oducesonl yasmal lincreasei nO2bi ndi
ng.Since
thebl oodi nthear ter
iesusual lyhasaPO2ofabout95mm Hg, one
canseef r om t
hedi ssociationcur vethatt heusualO2sat urati
onof
arterial bloodisabout97%( i.
e.19. 4ml ofO2/100ml ofblood).On
theot herhand,i nnor malv enousbl oodr eturni
ngf rom thet i
ssues
thePO2i sabout40mm Hgandt hesat urati
onofHbi sabout75%
(i
.e.14. 4ml ofO2/100ml ofbl ood)..
Fact orst hatcauseshi ft
ingoft heO2- Hbdi ssociati
oncur ve:Ther e
aresev eralfactorswhi chcandi splacet hedi ssociati
oncur vei n
onedi rectionort heother .6.21B) .

Fi
gur
e6.
21:
O2-
Hbdi
ssoci
ati
oncur
ve.

Thef act
or sthatdisplacethecur vetot heri
ght,whichmeansthat
atanygiv enPO2, Hbhasl essaf fi
nityforO2 are(fi
gure6.
22):
+
[1]I
ncreased[ H ]wit
hpHdecr easingfrom 7.4to7.
2.
[2]I
ncreasedCO2concent r
ation.
[3] I
ncreased 2, 3-
diphosphogl ycerate (2,
3-DPG) which is a
phosphat ecompoundnor mal lypresenti nt
hebloodbutindi
ffer
ing
concentrati
onsunderdi fferentcondi t
ions.

XI
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.BasharTal
i
b

[
4]I
ncr
easedbl
oodt
emper
atur
e.

Fi
gur
e6.
22:
Fact
orst
hatcauseshi
ft
ingoft
heO2-
Hbdi
ssoci
ati
oncur
vet
other
ight
.

Thefactorsthatshif
tthecur vetotheleft,
whichmeanst hatatany
gi
venPO2, Hbhasmor eaffi
nityforO2,are(fi
gure6.22)
:
+
[
1]Decreasei n[
H ]wi t
hani ncreaseinpHf rom 7.
4t o7.
6.
[
2]DecreasedCO2concent r
ation.
[
3]Decreased2, 3-di
phosphoglycerat
e( 2,
3-DPG)asi nstoredblood
underbl
oodbankcondi ti
ons.
[
4]Decreasedbl oodtemperature.
[
5]Thepr esenceoflargeamountofHb- F.

 Shif
toftheO2-Hbdi
ssoci
at i
oncur
vebychangesinthebl
ood
+
CO2 and[H ]isimport
antt oenhanceoxygenat
ionoft he
bl
oodi nthelungsandal sotoenhancerel
easeofoxygen
fr
om thebloodi nthetissues.Thi
siscalledBohrEffect

XI
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.BasharTal
i
b

whichcanbedef inedast heef fectofCO2concent rati

onand
+
[H ]ontheaf fi
nit
yofHbt oO2.
Ast hebl oodpassest hrought hel ungs,CO2 di ffusesf rom
thebloodi ntot heal veol i
.Thisr educest hebl oodPCO2 andal so
+
decreasest he[ H ]becauseoft her esul ti
ngdecr easei nbl ood
carbonic aci
d.Bot ht hese ef fect s shi ftt he O2-Hb di ssociation
curvet otheleftandupwar d,i.e.Hbnow hasahi gheraf f
ini
tyt o
combi newithO2.Ther ef orethequant ityofO2 t hatbi ndswi tht he
Hbatanygi venal veol arPO2 becomesconsi derablyi ncreased,
thusal l
owinggr eat erO2 t r
anspor ttot het i
ssues.Thenwhent he
bloodr eachest het i
ssuecapi llariesexact lytheopposi t
eef fect
occurs.CO2 enter i
ngt hebl oodf rom t het issuewi l
lshi f
tt hecur ve
ri
ghtwar danddi splacesO2 f rom Hb,t her efor
edel iversO2 t ot he
ti
ssueatahi gherPO2t hanwoul dot her wiseoccur .

Ther ol
eof2, 3–DPG:I tishi ghlychar gedani onthatbi ndst ot he
chainsofdeoxy genat edHbbutnott ot hoseofoxy Hbasf ollow:
HbO2 + 2, 3-DPG  Hb- 2,3-DPG + O2.I nt hi
s equi l
ibrium,an
i
ncreasei ntheconcent rationof2, 3-DPGshi f t
sther eact i
ont ot he
ri
ght,causingmor eO2t obel i
ber ated.
Thenor mal2, 3-DPGi nt heRBCkeepst heO2- Hbdi ssoci ation
curveshiftedslightlytot her i
ghtal lthetime.I nhy poxiccondi ti
ons
thatlastlongert hanaf ew hour s,thequant i
tyof2, 3-DPGi nt he
RBCi ncreasesconsi derably ,thusshi ft
ingt hecurv eev enf arthert o
theright
.Thi scausesO2 t ober eleasedt ot hetissueasmuchas
10 mm Hg O2 pr essur et han woul d be the case wi thoutt his
i
ncreased 2, 3-
DPG.Thi s mechani sm mi ghtbe i mpor tantf or
adaptati
ont ohy poxia.Howev er,thepr esenceoft heexcess2, 3-
DPGal somakesi tdi ffi
cul tfort heHbt ocombi newi thO2 i nt he
l
ungswhent heal veolarPO2 i sr educed,t herebyof tencr eatingas
muchhar m asgood.Thy roidhor mones,gr owt hhor mone,and
androgensi ncreaset heconcent rati
onof2, 3-DPGi nt heRBCand
henceP50.2,3-DPGi sv erypl ent i
fulinRBC.

Ther ol
eofHb- F:Thegr eat
eraffi
nit
yofHb- FthanHb- AforO2
faci
li
tat
est hemov ementofO2 from themothertothefet
us.The
causeoft hi
sgreateraff
ini
tyist
hepoorbindi
ngof2,3-DPGbythe
poly
peptidechainsthatrepl
acechainsinHb-F.

TransportofO2 i
nt hedissolvedst
ate:About0.
17mlofO2 i s
normal l
ytr
anspor
tedinthedissol
vedstat
etotheti
ssuesbyeach
100mlofbl ood( 3% ofthet ot
altr
anspor
tedO2).Ifaper son
breathesO2atver
yhighalveol
arPO2,t
heamountthentranspor
ted

XI
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OLOGY: RESP.SYSTEM /
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.BasharTal
i
b

i
nthedi
ssol
vedst
atecanbecomev
eryhi
gh.

Combi nat
ion ofHb with CO:CO hasaf fini
tyof230 timest o
combi ne wi
th Hb than O2 do and f
orm carboxyHb.A pati
ent
poisonedwithCOcanbet r
eatedbyadministr
ati
onpureO2,forO2
athighalveol
arpressuredispl
acesCOf r
om itscombinat
ionwith
Hbf armorerapi
dlythancanO2att hel
owpressureofatmospher
ic
O2

Transpor tofCO2i nt hebl ood:Undernor malr estingcondi ti

onsan
av erageof4mlofCO2i st ranspor tedf r
om t het i
ssuest ot helungs
i
neach100mlofbl ood.CO2 di ffuseoutoft het issuecel lsinthe
gaseousf orm.Onent eringt het issuecapi llaries,t heCO2 i nthe
venous bl ood ( fi
gur e 6. 23)wi l
lbe car ried t ot he l ung i nt he
followi ngway s:
[1]About7% ofal lCO2 t ranspor t
edt ot hel ungsi sina
dissol v edst ateint hebl ood( pl asmaandRBCs) .
[2]About70%ofCO2r eactwi thwat erinsi det heRBCt of or
m
car boni caci d,ar eact ioncat al yzedbyt heenzy mei nRBCcal l
ed
car boni canhy drasewhi chaccel er atest hisr eact ionabout5000-
fold.Thi sallowst remendousamount sofCO2t or eacti nasmal l
fractionofasecondwi thRBCwat erev enbef oret hebl oodl eaves
thet i
ssuecapi l
laries.I nanot hersmal lf r
act ionofasecondt he
car boni caci df ormedi nt heRBC di ssociatesi nt ohy drogenand
+
bicar bonat ei ons.Mostoft hehy drogeni ons( theH gener ated
cannot escape due t o cel lmembr ane i mper meabi li
ty)t hen
combi newi tht hedeoxy Hb( mai nl yt hei mi dazol egr oupsoft he
globi n pol ypeptide chai n)i nt he RBC because deoxy Hb i sa
power fulaci d-basebuf fer.I nt urn,manyoft hebi carbonat eions
diffusei nt othepl asmawhi lechl or i
dei onsdi ffusei ntot heRBCt o
taket hei rplacet hroughbi car bonat e–chloridecar r i
erpr oteininthe
RBCcel lmembr ane.Thus, thechl or i
decont entoft hev enousRBC
i
sgr eat ert hant hatofar ter ialcel l
s,aphenomenoncal l
edt he
-
chl orideshi ft.Alloft hebi car bonat eandClgener atedf oll
owing
CO2 car riagebyt her edcel li ncr easest hei ntracel l
ul arosmot i
c
pressur e.Thi scausest hecel lt oswel lwithext r
aH2Ot hatdi f
fuses
throught hecel lmembr ane.Thi si swhyt hehaemat ocr i
t( Hct)of
venousbl oodi ssome3%hi ghert hani nar t
er i
al blood.

XV
 PHYSI
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.BasharTal
i
b

[3]Ther emai ni
ng23%ofCO2ar etranspor tedtot helungsby
combi nation wi t
h pl asma pr ot
eins and wi th Hb i nf orm of
carbami nohaemogl obi n(HbCO2) .Thi scombi nat i
onofCO2 wi th
Hbi sar eversiblereact i
ont hatoccur swi thav eryloosebond,so
thattheCO2 i seasi l
yr eleasedi ntot heal v
eol iwher et hePCO2 i s
l
owert hanint het i
ssuecapi l
lar
ies.
Car bondi oxi
de’sabi li
tytobi ndt o hemogl obini s affected
byt heamountofoxy genboundt ohemogl obi n.Thesmal lerthe
amountofoxy genboundt ohemogl obi n,thegr eat ertheamountof
carbondi oxidet hatcanbi ndt oit,andv i
cev ersa.Thi srelat
ionship
i
scal ledt heHal daneef fect.Int hel ungs,bi ndingofoxy genwi th
Hbt endst odi splaceCO2f rom thebl ood.Hal daneef fect,
therefore,
canbedef inedast heef fectofO2 concent ration( PO2)ont he
affi
nit
yofHbt oCO2.Thi sef f
ectcanbeex plainedasf oll
ow:

Fi
gur
e6.
23:
Transpor
tofCO2i
nthebl
ood.
1.Binding ofoxy gen t o Hemogl obin appearst o di
rectly
reducet heaffinityoftheprotei
nf orcarbondi oxi
dei ntheform of
carbami nohemogl obin. Consequently, bindi
ng of oxy gen t o
hemogl obin di spl
aces hemogl obin-
bound car bon di oxide,
faci
lit
atingeli
mi nati
onofcar bondioxi
dei nthelungs.
2.Bindi
ng ofoxy gen rendersHemogl obin a mor e aci
di c
+
mol ecul
et husr esult
inginther el
easeoff r
eehy drogenions( H) .

XVI
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.BasharTal
i
b

Thehi gherconcentrat
ionoff r
eehy drogenionsf ol
lowi ngoxygen
bindi
ngpushest hereversibleequil
i
brium betweenbi carbonateand
carbondi oxi
deint hedi r
ect i
onofcar bondi oxi
de.Consequent ly
,
bindi
ng of oxy gen t o hemogl obin f aci
l
itat
es conv ersi
on of
bicar
bonat etocarbondi oxideinthepul monarycirculationandin
turnenhancescarbondi oxideeli
mination.

4:Thecont rolandr egulationofr espiration:Ther espir

ationi s
cont r
olledbyt her espi ratorycent erandi sr egul atedbyv arious
factors.
Respi rator ycent eri slocat edi nt hebr ainwhi chiscomposed
oft hreemaj orgr oupsofneur onsl ocatedbi l
at erall
ywi thint he
reti
cularf ormat ionoft hemedul l
aobl ongat aandponsandt hese
are( f
igur e6. 24) :
[1] The dor sal
respirator ygr oup( DRG)
ofneur ons:Thi sgr oup
ofneur onsi sl ocat edi n
the medul l
a wi thint he
nucleus oft he t ract us
soli
tor i
uswhi chi sal so
thesensor yt er mi nat i
on
of bot ht he v agal( X
cranial ner v e) and
glossophar y ngeal
nerves( IX)t ransmi tti
ng
sensor ysi gnal si ntot he
respiratorycent erf r
om
the per ipher al
chemor ecept or s,
mechanor ecept ors,
barorecept or s and
severaldi ffer entt ypes
ofrecept orsi nt hel ung.
DRG i sr esponsi blef or
the basi c r hy thm of
respiration by
autonomous r epet i
tive
bursts of i nspi rat or y Fi gure6.24: Br
ainrespirator
ycenter
.
action pot ent ials. The
nervesi gnal f rom DRGi stransmi t
tedt o:
 Thei nspi rator ymuscl es( t
hr oughcont ralateral phr
enic.
 Toext ernal inter cost almuscl est hroughspi nal motoneur ons.
XVI
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 PHYSI
OLOGY: RESP.SYSTEM /
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.BasharTal
i
b

 Tot hev ent r

al respi rator ygr oup.
Thener vesi gnalf rom DRGbegi nsv eryweakl yatf i
r standi ncr ease
steadi lyi nar ampf ashi onf orabout2sec( figure6. 25) .Theni t
abrupt l
yceasesf orappr oximat el ythenext3sec,andt henbegi ns
againf orst i
llanot hercy cle, andagai nandagai n.Theadv ant ageof
thisist hati tcausesast eadyi ncr easei nt hev olumeoft hel ungs
duringi nspi r
at ion, rat hert hani nspi ratorygasps.
[2]Thev ent ralr espi ratorygr oup( VRG) :Theseneur onsar e
l
ocat ed i nt he medul la and i nnervat e mai nl yi nspirator y and
expirat or yaccessor ymuscl es.VRGr emai nsalmostt ot
allyi nact ive
during nor malqui etr espi r
at i
on.Whent her espi ratorydr ivef or
i
ncr eased pul monar yv ent i
lation becomes gr eatert han nor mal
(suchasdur ingexer cise) ,respi ratorysi gnalsf rom DRGspel lov er
i
nt ot he VRG.As a consequence,t he VRG cont r
ibutes t ot he
respirat or ydr iveaswel l
.
[3]Thepneumot axicgr oup: Thi sgr oupofneur onsi sl ocatedwi thin
theupperponsandt heyt ransmi ti mpul sescont inuousl yt ot he
dorsalr espi rat orygr oupofneur ons.Thepr imar yef fectoft hesei s
to cont rolt he swi tch of fpoi ntoft he inspi rat oryr amp,t hus
cont rollingt hedur at i
onoft hef ill
ingphaseoft hel ungcy cle.When
thepneumot axicsi gnal sar est rong,i nspirat
ionbecomeshal low
andshor t(mi ghtl astf orasl i
ttl
eas0. 5sec) ,andi ncr easet her at e
ofbr eat hing,butwhent hepneumot axi csignal sar eweak,t he
i
nspi rat oryr ampmi ghtcont inuet orisef orper hapsasl ongas5- 10
secandpr olongandf il
lst hel ungswi t
hagr eatai rleadi ngt oa
deepandl ongi nspi rationwi thadecr easei nt her at eofbr eat hi
ng.
Ther ef oret her espi rator yr ateisdecr eased.

XVI
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OLOGY: RESP.SYSTEM /
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.BasharTal
i
b

[
4]Apneusti
ccenter
:Thisislocat
edi nthelowerpons.Theroleof
t
he apneust
ic cent
eris stil
lunclear,butitseems t o pr
olong
i
nspi
rat
ionbyst i
mulat
ingt heDRG.Dur i
ngforcedbreathi
ng,the

Fi
gur
e6.25:Rampf ashi
onofi
nspi
rat
oryact
ionpot
ent
ial
soft
hedor
sal
respi
rat
ory
gr
oupofneurons.
apneusti
ccent er
sadj
ustthedegr
eeofsti
mul
ationinr
esponseto
sensoryinfor
mationf
rom thev
agusner
veconcerni
ngtheamount
oflunginfl
ati
on.

Regulationofr espi r
ator ycenteract i
v i
ty:Ther espir
ator
ycenters
andconsequent lythev enti
lati
oncanber egulatedbyt hefoll
owing
factors:
[1]Chemi calregulati
onofr espirati
onmedi atedt hroughchangesin
+
PCO2, [H],andPO2.
[2] Per i
pheral r ecept ors and pr oprioceptors r egul
ati
on of
respir
ation.
[3]Braincentersr egulationofr espi
ration.
[4]Mot orcort
exr egulat ionofrespirati
on.
[5]Vasomot orcent err egulati
onofr espiration.
[6]Bodyt emper atureregul ati
onofr espirati
on.

1.Chemi calr
egul at
ionofr espi
rat
ion:
+
[
A][ CO2]and[H] :SurplusofCO2orH+st i
mulaterespi
rat
orycenter
i
ndirectl
yt hr
oughcent ralchemoreceptors(locatedbil
ater
all
yi n
themedul laclosetot heexitofcranialnerv
esI XandX)whi chi s
+
highlysensit
ivet o changesi nH concent ration,and i
tint urn

XI
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 PHYSI
OLOGY: RESP.SYSTEM /
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.BasharTal
i
b

exci t
est heot herpor ti
onsoft her espi r
at orycent ercausi nggr eat l
y
i
ncr easedst rengt hofbot ht hei nspi ratoryandexpi rat orysi gnal st o
the r espi rat or y muscl es.The r esul t
ing i ncr ease i nv entil
at i
on
i
ncr easest heel imi nati
onofCO2f r om t hebl ood; thi sal sor emov es
+
H f rom t hebl oodbecausedecr easedCO2 al sodecr easest he
bloodcar boni caci d.About80% oft hedr i
v ef orv ent i
lationi sa
resultofst i
mul ationoft hecent ralchemor ecept or s.Howev er ,H+
does noteasi l
y cr oss ei ther t he bl ood- br ain bar ri
er or t he
blood–cer ebr ospi nalf luidbar rier.Fort hisr eason,changesi nH+
concent rat ioni nt hebl oodact ual l
yhav econsi derabl yl essef fecti n
stimul atingt hechemosensi t
iv eneur onst handochangesi nCO2.
Thi sisbecauseCO2passest hr oughbl ood–br ainbar rierandbl ood
-cerebr ospi nalf lui
dbar ri
erv eryeasi ly(figure6. 26) .Consequent ly,
whenev ert hebl oodCO2concent rat ioni ncreases, thePCO2i nbot h
thei nt erstitialf lui
doft hemedul laandi nt hecer ebr ospi nalf luid
alsoi ncrease.I nbot hoft hesef l
ui dst heCO2 i mmedi atelyr eact s
+
witht hewat ert of orm car boni caci dwhi chdi ssoci at esi nt oH and
+
bicar bonat es.Thus,par adoxi cal ly,mor eH ar er eleasedi ntot he
respir atory
chemosensi ti
v e
sensor yar eawhent he
blood CO2
concent rat ion
i
ncr eases t han when
the blood H+
concent rat ion
i
ncr eases. For t hi
s
reason, respi ratory
cent er act i
vity i s
affect ed consi der ably
mor e by changes i n
blood CO2 t han by
changesi nbl oodH+.
The st imul atory
effectofi ncr easedCO2
onr espi rat i
onr eaches Fi gure6. 26: Chemi cal r
egul ationof
i
t s peak wi thinaf ew r espiration, eff
ectof[ CO2].
mi nut es af ter an
i
ncr ease i n bl ood PCO2.Ther eaf ter,t he st i
mul at i
on gr adual l
y
decl i
nesf ort henextonet ot woday st oasl itt
leasone- fif
tht he
i
nit i
alef fectdue t o adapt at ion oft he r ecept or s.Ther efore,a
changei nbl oodCO2concent rat i
onhasav er ypot entacut eef fect
oncont rolli
ngr espi rati
onbutonl yaweakchr oni cef fectaf teraf ew

XX
 PHYSI
OLOGY: RESP.SYSTEM /
/ Dr
.BasharTal
i
b

day
s’adapt
ati
on.

[B]PO2:Arteri
alPO2doesnothav easi
gni
ficantdi
rectef
fectonthe
respir
atorycenteroft hebrai
nincont r
oll
i
ngr espi
rati
on.Inst
ead,i
t
acts either ent i
rel
y or al most
enti
rely on peri
pher al
chemor eceptor
s l ocated in t he
caroti
d and aor t
ic bodies,and
theseint urntransmitappropri
at e
nervoussi gnal
st other espi
rator y
centerf orcont r
olofr espi
rati
on
(fi
gure6.27).

Peripher alchemor ecept or

sar e
sensitivet o:
 P O2
 P CO2
 p H
 B l
oodf l
ow Figure6.27:Respirat
or ycontr
ol byper
ipher
al
 T emperature chemor eceptorsinthecar ot
idandaorticbodi
es.
Thecar otidbodiesar esuppl iedby
the aut onomic ner vous sy stem,whi ch appear st o al tert heir
sensitivity to hy poxia by r egul
at i
ng bl ood f low t o t he
chemor eceptor:
 S ympatheticact i
onv asoconstricts,increasi ngsensi ti
vit
yt o
hy poxi
a
 P arasympatheticact ionv asodilates,r educi ngsensi ti
vi
tyt o
hy poxi
a.
Car otidbodiesar el ocatedbi l
aterall
yi nt hebi fur
cat ionsoft he
commoncar oti
dar teri
es,andt heiraf fer
entnev erfiber spasst o
thegl ossophar yngealner vesandt hencet ot hedor salr espi r
at ory
areaoft hemedul l
a.
Aor ti
cbodi esar elocatedal ongt hear choft heaor ta,andt heir
afferent ner vef ibers pass t hrough t he v agit ot he dor sal
respiratoryarea.

Whenthear t
erialPO2f al
l
sbel ownormallevelof100mm Hg,
orwhent hebloodpr essur
esuf fi
cientl
ylow causi
ngal ow blood
fl
ow (even though const i
tuents ofblood do notchange) ,the
chemoreceptors wi ll be st i
mulated, and become st rongly
sti
mulat
edwhenar teri
alPO2 <60mm Hgcausi ngt healv eol
ar
venti
l
ati
ont oincreaseonl y1.5t o1. 7fol
d.Ani ncreaseinei t
her
+
CO2 orH concent rati
onalsoexci testhechemor eceptorsandi n

XXI
 PHYSI
OLOGY: RESP.SYSTEM /
/ Dr
.BasharTal
i
b

this wayi ndirect l

yi ncr eases r espirator yact i
vity .Howev er,t he
directef fectsofbot ht hesef act orsi nt her espi rator ycent eri tsel f
aresomuchpower fult hant heiref fect smedi at edt hrought he
chemor ecept ors.
Thecauseoft hepooref fectofPO2 changesonr espi rat or y
+
cont rolincompar i
sont ot hoseofCO2andH concent r
ati
oncanbe
expl ainedasf ollow:Thei ncr easei nv ent il
at i
ont hatdoesoccur
whent hePO2 f all
sbl owsof fCO2 f rom t hebl oodandt her efor e
decr easest hePCO2,att hesamet imei tal sodecr easest heH+
concent rat i
on.Ther efor e,t het wopower fulr espi ratoryst i
mul ant s
wer edecr easedandt her eforeexer tinhibi tor yef fectst hatoppose
theexci tator yef fectoft hedi mi nishedO2..
Whent heconcent rationofCO2 andH+ ar epr eventedf rom
changi ng,t hedecr easedbl oodPO2 wi l
li ncr easet hev entil
at ion8
+
to10t i
mesasgr eataswhent heCO2 andH concent rationdo
changeandopposet hePO2ef fect .Thus, undernor malcondi tions,
thePO2mechani sm pl ay sonl ysmal lrolei ncont rol ofrespi r
at i
on.
Whenaper sonf ir
stascendst ohi ghal titudes, thedimi nished
O2 int heai rstimul atest heO2 l ackcont rolsy stem ofr espi rat i
on
(table6. 4) .Ther espi rationatf irstincr easest oamaxi mum ofonl y
aboutt wo- t
hirdsabov enor mal .Thecauseoft hissl ightincr easei s
+
the power fulopposi ti
on ef fect s oft he CO2 and H cont rol
mechani smsont heO2 l ackmechani sm.Howev er,ov ersev er al
day s,t her espi rator ycent ergr adual lybecomesadapt edt ot he
dimi nishedCO2 sot hati tsopposi t
ionef fectt ot heO2 cont roli s
gradual l
yl ost ,andal v eolarv ent i
lationt henr isest oashi ghasf ive
tosev ent i
mesnor mal .Thi si spar toft heaccl imat i
zationt hat
occur sasaper sonsl owl yascendsamount ain.

2. Per ipheral r ecept ors and pr opr i

oceptors r egulati
on of
respi ration( figure6. 28) :
[
A]St retch r ecept or s:Locat ed int he walloft he br onchiand
bronchi olet hatt ransmi tsignalst hrought hev agii ntot hedor sal
respi rator y gr oup of neur ons when t he l ungs become
over stret ched.Thesesi gnalsaffecti nspir
ati
oni nmucht hesame
wayassi gnal sfrom t hepneumot axiccent er
,thati s,theyl i
mitthe
durat ionofi nspi r
at ion.Ther efore,whent helungsbecomeov erly
i
nf l
at ed,t hest retchr eceptorsact i
vateanappr opriatef eedback
responset hatswi tchesof fthei nspi r
atoryrampandt husl i
mi t
s
furtheri nspi rati
on.Thi si scall
edt heHer i
ng-Breueri nflat
ionreflex.
I
nhumanbei ngs, thisr efl
expr obablyi snotactivatedunt i
lthetidal
volume i ncreases t o greater t han appr oximat ely 1. 5 li
ters.
Ther ef ore, t
hisr efl
exappear stobemai nl
yapr otectivemechani sm
XXI
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 PHYSI
OLOGY: RESP.SYSTEM /
/ Dr
.BasharTal
i
b

for pr ev ent i
ng excess l ung i nfl
at i
on r at her t han i mpor tant
i
ngr edi enti nt henor mal cont rolofv ent ilation.
[B]( j
uxt acapi l
lar y)recept or s:Theser ecept or sar el ocat edi nt he
alveol arwal ls,cl ose t ot he capi ll
ar i
es and ar e st imul at ed by
distensi on oft he pul monar yv essel s( e.g. ,as caused by l eft
vent ri
cul arf ai l
ure,pul monar yembol izat ion,andcer t
ainchemi cals
ordr ugs) .Theser ecept orsi niti
ater eflexescausi ngr api d,shal l
ow
breat hing( t
achy pnea) .
[C]Chestwal lr ecept ors:Thi scandet ectt hef or cegener atedby
the r espi r
at orymuscl e dur ing br eat hing.I ft he f orce r equi red
distendi ngt hel ungsbecomesexcessi ve( eitherasar esul tofhi gh
airwayr esistanceorl ow compl iance) ,t hei nf ormat ionf rom t hese
recept or sgi vesr i
se t ot he sensat i
on ofdy spnea ( diffi
cul tyi n
breat hing) .
[D]Irritantr ecept ors:Thosear elocatedbet weent heepi t
hel ialcel l
s
oft hel argeai rway sandar est i
mul atedbysmoke,noxi ousgases,
and par ticulates i nt he i nspired ai r .These r ecept or si nit
iate
refl
exes t hat cause coughi ng, br onchoconst r
icti
on, mucus
secr etion, andbr eathehol ding( i.
e.,apnea) .
[E]Joi ntpr opriocept or s:Thosear el ocat edi nt hej ointcapsul es
andt r
ansmi texci t
atoryi mpul sest other espir atorycent er .
[F]Touch,t hermal ,andpai nr ecept ors:Canal sost imul at et he
respi r
at or ycent er.Forexampl e,irri
tant si nt henasalcav i
tycan
i
nitiateasneezer efl
ex.I naddi ti
on,t hr ought heser ecept or sone
canobser vet her espirator yresponsewhencol dwat eri sspl ashed
onto a per son,and al so t he common pr act ice ofswat ing a
newbor nbabyont hebut t
ocks.

3.Braincentersregul
ationofrespirati
on:
[A]Reti
cularActi
vatingSystem (RAS):Locatedintheret
icular
system oft he brain stem;its activi
tyi s associ
ated wit
ht he
"awake"or"conscious"state.Whenact ive,i
tsimulatesrespi
ratory
ventil
ati
on.When RAS act iv
ityisr educed,as dur ing sleep,
ventil
ati
onisreducedandPCO2i ncreasesbyaf ewmmHg.
.
[B]LimbicSystem:Respirator
ychangesi nemot i
on.

4.Mot orcor t
ex regulat
ion ofr espirati
on:Respirat
ion can be
controll
ed v ol
untari
ly
, and t hat one can hy perventi
lat
e or
hypov ent
il
atetosuchanext entthatser i
ousderangement sinPCO2,
pH and PO2 can occuri nt hebl ood.Thi sismedi ated bythe
nervouspat hwayf orv ol
untarycont r
olpassesdi rect
lyf rom t
he
motorcor texand ot herhighercent ers downwardt hrough t
he
XXI
II
 PHYSI
OLOGY: RESP.SYSTEM /
/ Dr
.BasharTal
i
b

corti
cospinaltr
actt ot hespinalneuronst hatdr i
vether espirat
or y
muscles.
5.Vasomot orcent err egulat
ionofr espir
ation:Thev asomot or
centerthatcontrolperipheralvasoconstri
ctionandhear tactivit
yi s
closel
yr el
atedtor espir
atorycent eri
nt hemedul l
a.A moder at e
degreeofspi l
lov erofner vesi gnal
soccur sbetween t het wo
centers.Theref
ore,almostanyf actorthatincreasestheact ivi
tyof
thev asomot orcent eralso hasatl eastamoder ateef fecton

Figur
e6.28:Cent
ral
,per
ipher
alr
ecept
orsandpr
opr
iocept
orsr
egul
ati
onof
respi
rat
ion.
i
ncr
easi
ngr
espi
rat
ion.

6.Bodytemper atur
eregulati
onofrespi
r at
ion:Anincreaseinbody
temperat
ureincreasestherateofr
espirati
ondirectl
ybyi ncr
easi
ng
respi
rat
orycenteractiv
ityandindi
rectl
ybyi ncreasi
ngt hecell
ular

XXI
V
 PHYSI
OLOGY: RESP.SYSTEM /
/ Dr
.BasharTal
i
b

met
aboli
sm and ev ent
ual
l
yenhances t
he chemi
calst
imul
ifor
i
ncr
easedrespi
rat
ion.

XXV