2.

resplrauon
!"##$#%& &"()*&%+,-. MeLabollc
processes wlLhln cells.
e.g. C
6
P
12
C
6
+6 P
2
C+ 6C
2
!
12P
2
C + 6CC
2
+ 38 A1
1. resplrauon
.%( "/01%-2". MovemenL of C
2

from envlronmenL Lo cell
(mlLochondrla) and movemenL of
CC
2
ln opposlLe dlrecuon
1wo meanlngs of Lhe Lerm
resplrauon" (boLh are correcL)
MeLabollsm: Ch 3 pages 72-90
LxLernal
resplrauon
lnLernal
resplrauon
kLSIkA1ICN
Chapters 16 and 17
external
internal
!"#$%& ()*&+,-). /*.01*#
(also called Lhe C
2
cascade)

1he sequenual serles of 'sLeps'
lnvolved ln movlng oxygen from Lhe
envlronmenL Lo mlLochondrla ln cells

CC
2
moves along Lhe same paLhway,
buL ln Lhe opposlLe dlrecuon

1he followlng serles of lecLures wlll
focus on Lhe lmporLance of
venulauon, pulmonary dluslon, and
blood gas LransporL for gas exchange
and acld-base homeosLasls
Lk1LkNAL kLSIkA1ICN
venulauon

ulmonary
uluslon


Clrculauon


1lssue
uluslon


Cellular
uullzauon
or
roducuon
kLSIkA1ICN LLAkNING C8ILC1IVLS
Differences between external and internal respiration
Major structures of the respiratory tract, and their function
Structure and gas-exchange function of the alveoli and
respiratory membrane
Role of pulmonary surfactant
The breathing cycle, different lung volumes and capacities, total
and alveolar ventilation, breathing frequency
Neural mechanisms that establish the respiratory rhythm and
those that modify it (chemoreceptors)
Transport pathways for oxygen and carbon dioxide, and the
partial pressures of each throughout the pathway
Mechanisms of oxygen and carbon dioxide transport in the blood,
including the function of haemoglobin
Relationship between CO
2
and pH in the blood
Respiratory and other compensatory mechanisms that help
maintain acid-base homeostasis
_________ zone -
no gas exchange
beLween alr &
blood here
__________ zone -
SlLe of gas exchange
AnaLomy of Lhe resplraLory LracL
llg. 16-2
conducting
respiratory
Conducung Zone.
8elnforced wlLh
_______ and smooLh
muscle
8esplraLory Zone.
Llule carulage or
smooLh muscle -
allows for ___
________ wlLh blood
llg. 16-3
AnaLomlcal feaLures
30 Mllllon alveoll - 100m
2
Surface Area
|
<
-
-
-
-
-
-
-
-
-
-
-
-
-
-

s
m
o
o
L
h

m
u
s
c
l
e

-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
>
|

|
<
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-

c
a
r
u
l
a
g
e

-
-
-
-
-
-
-
-
-
-
-
-
-
-
>
|

cartilage
gas exchange
lmporLanL Conducung Zone luncuons
1he 'eplgloms' aL Lhe openlng of larynx
prevenLs food from enLerlng Lrachea.
Larynx also conLalns Lhe __________.
Carulage and smooLh muscle provlde
sLrengLh, whlch prevenLs alrway collapse
durlng lnsplrauon
Warms alr Lo 37
o
C and humldles lL Lo
100 relauve humldlLy
Cleanses alr - eplLhellum creaLes mucus
and sweeps lL upwards (Lhe mucus
escalaLor"), ___________ lngesL parucles
SmooLh muscle ln bronchloles consLrlcL/relax Lo vary reslsLance Lo alr ow
SnS ===> nL ===>
2
-adrenerglc recepLors - bronchodllauon
SnS ===>ACP ===>muscarlnlc recepLors - bronchoconsLrlcuon
vocal chords
macrophages
1he 8esplraLory Zone - slLe of C
2
& CC
2
exchange wlLh blood
Alveoll are arranged ln
clusLers connecLed by pores
Lo allow equallzauon of
________ ln Lhe lungs
1ype l cells = eplLhellal layer
1ype ll cells = produce surfacLanL
Macrophages = engulf forelgn
parucles and paLhogens
llg. 16-3
pressure
31" 4"()*&%5,&6 7"89&%-"
1he 8esplraLory Zone - slLe of C
2
& CC
2
exchange wlLh blood
llg. 16-4
SeparaLes Lhe alr ln Lhe
alveoll from blood ln Lhe
caplllarles
LxLremely Lhln
Alveoll accompllsh 90
of gas exchange
8esplraLory bronchloles
Alveolar ducLs
Cnly 10 of exchange
8educed by __________
(e.g., emphysema)
1he alveolar surface ls molsL
! Plgh _____________ aL alr-waLer
lnLerface
Alveoll are small (radlus ~ 0.1 mm)
Surface Lenslon creaLes an lnnaLe
Lendency for alveoll Lo collapse
Lelace's Law: ressure necessary Lo prevenL collapse = 21 / r
1= surface Lenslon, r = alveolus's radlus
1he 8esplraLory Zone - slLe of C
2
& CC
2
exchange wlLh blood
lung disease
surface tension
Alveolar 1ype ll Cells" secreLe surfacLanL (a proLeln + phosphollpld =
________-llke subsLance) whlch reduces surface Lenslon by up Lo 90
negauve pressure ouLslde Lhe alveoll (-4 mm Pg below aLmospherlc
pressure) ln Lhe lnLrapleural space also helps Lo hold Lhe alveoll open
1he oLher funcuon of Lhe lnLrapleural space ls Lo serve as exlble,
lubrlcaLed connecuon beLween Lhe lungs and Lhe Lhoraclc wall
lacLors prevenung alveolar collapse
1. WlLhouL surfacLanL a
smaller alveolus wlll
collapse
2. SurfacLanL ls more
hlghly concenLraLed ln
smaller alveoll, reduclng
1 = no collapse
noLe: 8esplraLory ulsLress Syndrome" (8uS) ln pre-maLure bables ls due Lo
lnadequaLe surfacLanL.
1.
2.
ulmonary surfacLanL
Loolbox, p. 467/463
detergent
ressure ln lnLrapleural space - 736mmPg
(-4mmPg relauve Lo ouLslde alr)
ChesL Wall and leural Sac
arleLal pleura
Auached Lo Lhorax
lnLrapleural space
lluld (mucus)
vlsceral pleura
Auached Lo lung wall
ressure ln Alveoll - 760mmPg
(same as ouLslde alr)
!,-(*:"& % )%+2&$ 34&$
;-, %*&<,=> %?"& "/1%#%+,-@A
llg. 16-7
llg. 16-8
ChesL Wall and leural Sac
llg 16-9
neumoLhorax - a rupLure whlch connecLs
Lhe __________ space Lo Lhe ouLslde
aLmosphere.
1he exlble, lubrlcaLed connecuon creaLed by Lhe _______ pressure ln Lhe
lnLrapleural space ensures LhaL when Lhe Lhorax changes slze durlng
breaLhlng, Lhe lungs wlll follow
1hls ellmlnaLes Lhe negauve pressure and
breaLhlng becomes lneecuve and Lhe
lung may collapse.
Lach lung has lLs own pleural sac, so Lhe
opposlLe lung wlll noL collapse
(-))
intrapleural
8reaLhlng Cycle - alveolar pressure and volume
Lxpanslon of chesL wall
durlng lnsplrauon reduces
alveolar pressure (
alv
)
! numbers shown are Lhe
:*B"&"-0"( from
aLm

(aLmospherlc pressure)
8ebound of chesL wall
durlng explrauon
lncreases alveoll pressure
Alr ow =
aLm
-
alv
8
8oyle's Law
ressure o 1 / volume
llg 16-10
lnhalauon - Always an _____ process (resL and exerclse)
8reaLhlng Cycle
LxLernal lnLercosLal muscles pull rlbs upwards and ouLwards
ulaphragm shorLens and moves _____
sLernum
WlLh lnhalauon:
1. 1horaclc volume lncreases
2. Lung volume lncreases
3. negauve pressure ls creaLed
4. Alr ows ln from aLmosphere
llg 16-11
acitve
down
- lnLernal lnLercosLal muscles
conLracL Lo pull rlbs ln and down
- Abdomlnal muscles conLracL,
pushlng guLs" ln and
dlsplaclng dlaphragm upwards
Lxhalauon - ______ durlng quleL
breaLhlng (l.e., aL resL)
Lxhalauon - ______ durlng lnLense
breaLhlng (e.g., exerclse)
- uue Lo elasuc recoll of Lhoraclc
& lung componenLs
8reaLhlng Cycle
WlLh Lxhalauon:
1. 1horaclc & lung volumes decrease
2. osluve pressure ls creaLed
3. Alr ows ouL Lo aLmosphere
passive
active
SplromeLry - lung volumes and capaclues
ulmonary funcuon
can be assessed by
measurlng lung
volumes and capaclues
by splromeLry
llg 16-13
1ldal volume (v
1
) = AmounL of alr breaLhed ln and ouL on a slngle breaLh ~ 0.S L
lnsplraLory 8eserve volume (l8v) = Maxlmum lnhaled above a normal lnhalauon ~ 3 L
LxplraLory 8eserve vol. (L8v) = Maxlmum exhaled beyond a normal exhalauon ~ 1 L
8esldual volume (8v) = volume of alr ln lungs LhaL cannoL be exhaled ~ 1.2 L
lnsplraLory CapaclLy (lC) = Maxlmum lnhaled above a normal exhalauon ~ 3.S L
luncuonal 8esldual CapaclLy (l8C) = volume ln lungs aer a normal exhalauon ~ 2.2 L
vlLal CapaclLy (vC) = Maxlmum lnhaled aer a maxlmal exhalauon ~ 4.S L
1oLal Lung CapaclLy (1LC) = vC + 8v, ~ S.7 L
Spirometer record
llg 16-16
1oLal venulauon (v
1oL
) = 1oLal alr ow lnLo (and ouL of) Lhe _________
______ per mlnuLe ('mlnuLe venulauon')

= 1ldal volume (v
1
) x 8reaLhlng lrequency (f
8
)

e.g., 6730 ml/mln = 430 ml x 13 / mln
AnaLomlcal uead Space - Lhe volume of alr le ln Lhe conducung zone
aer each breaLh - leads Lo Lhe dlerence beLween v
1oL
and v
A

e.g., 4300 ml/mln = [ 430 ml - 130 ml ] x 13/mln
A|veo|ar venn|anon d|ctates gas exchange
Alveolar venulauon (v
A
) = 1oLal alr ow lnLo (and ouL of) Lhe
______ per mlnuLe
= [v
1
- uead Space volume (v
u
)] x f
8

venulauon
respiratory
system
alveloi
AnaLomlcal
uead Space
llg 16-19
300 ml of new" alr ls mlxlng wlLh
Lhe 2300 ml funcuonal resldual
capaclLy, whlch conLalns old" alr
D||unon = 300 m| new = ~ 10
300 m| new + 2S00 m| o|d
! Cnly ~ _____ replacemenL of alveolar alr per breaLh aL resL
Consequence: Alveolar C
2
ls lower and alveolar CC
2
ls hlgher Lhan ln
ouLslde alr
lncreases ln udal volume (e.g., durlng exerclse) brlng alveolar C
2
and
alveolar CC
2
values closer Lo Lhose ln ouLslde alr
1he funcuonal resldual capaclLy
lncludes Lhe volume remalnlng ln
boLh Lhe conducung zone (l.e.,
anaLomlcal dead space) & alveoll
10
Alveolar venulauon (v
A
) = f
8
x (v
1
- v
u
)
= 12 breaLhs/mln x (300 ml - 130 ml)
= 4200 ml/mln

uoubllng f
8
: v
A
= 8,400 ml/mln
uoubllng v
1
: v
A
= 10,200 ml/mln
It |s beuer for gas exchange to |ncrease V
1
than to |ncrease f
k
50670 3%*8+ .- * $)%*.%) 69,)-:%9%&. 6& $*+ %"70*&$%;
6&7)%*+%+ 6& 28*3 :-349% -) 6&7)%*+%+ 6& <)%*.06&$ =)%>4%&7#?
D|us|on of gases
C1%5 :*05%5"( 51" :*B$(*,- ,D
2%("( %0&,(( 51" &"()*&%5,&6
8"89&%-" E
venulauon

ulmonary
uluslon


Clrculauon


1lssue
uluslon


Cellular
uullzauon
or
roducuon
D|us|on of gases
1: Membrane Lhlckness
A: Surface area
k: ermeablllLy gas consLanL
uluslon raLe = k ! A ! A
1
: arna| pressure grad|ent
C1%5 :*05%5"( 51" :*B$(*,- ,D
2%("( %0&,(( 51" &"()*&%5,&6
8"89&%-" E
llg 17-2
arual ressure - A measure of Lhe _____________
______ of gas molecules
ualLon's Law:
1oLal pressure = sum of parual pressures
1oLal (baromeLrlc) alr pressure = 760 mm Pg = 760 1orr
=
n2
+
C2
+
CC2
+
P2C
= 363 + 130 + 0.2 + 47 (depends on 8P)

1orr" = ln honour of 1orrlcelll,
lnvenLor of baromeLer
arna| pressure of gases
dluse
Cases dlssolve accordlng Lo Lhelr parual pressures, not
reacL necessarlly accordlng Lo Lhelr concenLrauons
thermodynamic activity
ln Lhe alr phase, we can calculaLe parual pressure as
arual ressure = 1oLal ressure ! volume (Mole) lracuon
8emember:
Lqual moles of gases occupy equal volumes
1 mole of any gas occuples 22.4 L aL S.1..
ury 8oom Alr:

C2
= 760 1orr x 21 (210 ml C
2
/ 1000 ml alr)
= 160 1orr

CC2
= 760 1orr x 0.03 (0.3 ml CC
2
/ 1000 ml alr)
= 0.23 1orr
arna| pressure of gases
ln a uld phase, Lhe slLuauon ls more compllcaLed
1he parual pressure of a gas
LhaL ls dlssolved ln a llquld ls
equal Lo Lhe parual pressure of
LhaL gas ln Lhe alr phase wlLh
whlch Lhe uld ls ln _________
Penry's ConcenLrauon of = arual ! SolublllLy
Law: a dlssolved gas ressure CoeclenL

C2
= 130 1orr
C2
= 130 1orr

C2
= 0 1orr
C2
= 130 1orr
arna| pressure of gases
llg 17-3
[Cxygen] ln waLer = 130 1orr x =
0.034 ml C
2
3.1 ml C
2

1000 ml waLer . 1orr 1000 ml waLer
[Cxygen] ln alr = 21 of every llLre of alr =
210 ml C
2

1000 ml alr
1he capac|ty of water to ho|d C
2
|s much |ower than that of a|r
equilibrium
Carbon dloxlde ls abouL ___ more soluble Lhan C
2
ln waLer
1he capac|ty of water to ho|d CC
2
|s comparab|e to that of a|r
lor boLh C
2
and CC
2
(and all
gases) Lhey dluse accordlng Lo
Lhelr parual pressures, noL
accordlng Lo Lhelr concenLrauons
[CC
2
] ln waLer = 0.3 1orr x =
0.67 ml CC
2
0.2 ml CC
2

1000 ml waLer . 1orr 1000 ml waLer
[CC
2
] ln alr = 0.03 of every llLre of alr =
arna| pressure of gases
0.3 ml CC
2

1000 ml alr
20
D|us|on of gases
uluslon raLe = k ! A ! A
1
D|us|on occurs down the gas'
parna| pressure () grad|ent:


C2
= A|veo|ar
C2
- 8|ood
C2



CC2
= 8|ood
CC2
- A|veo|ar
CC2

F*B"&"-0"( *- )%&+%# )&"(($&"
9"5=""- %#G",#* %-: 9#,,:
:&*G" :*B$(*,-
llg 17-2
1he parual
pressure of C
2

drops wlLh each
sLep ln Lhe C
2

LransporL
paLhway
C
2
aL Lhe
___________
musL remaln
hlgh enough Lo
supporL A1
synLhesls
Cxygen cascade
venulauon

ulmonary
uluslon


Clrculauon


1lssue
uluslon


Cellular
uullzauon
C
2
arual ressure (ka)
1here ls a mlnlmum
C2
aL whlch
mlLochondrla can funcuon
mitochondria
1. Alveolar parual pressures are
very dlerenL from ouLslde alr
C
2
160
CC
2
0.3
100
40
2. arual pressures are very slmllar
ln alveolar alr and Lhe blood leavlng
Lhe lungs (sllghLly less ln blood)
100
40
3. arual pressures are Lhe same ln
blood leavlng Lhe lungs and
enLerlng Lhe ______________beds
100
40
2. ul. velns
3. SysLemlc arL.
4. arual pressures ln cells very
dlerenL from blood
1. Alveolar alr
4. cells
46 40
All ln
mmPg
(1orr)
46 40
3. SysLemlc velns
3. arual pressures are Lhe same ln
venous" blood leavlng Lhe sysLemlc
caplllarles & enLerlng Lhe
pulmonary caplllary beds
46 40
3. ul. ArL.
1. ALmospherlc alr
llg 17-4
See 1able 17-1
C
2
and CC
2
parual pressures
systemic capillary
llg 17-3
C
2
and CC
2
parual pressures
uluslon ls rapld aL lungs and blood equlllbraLes ln ~0.23 seconds wlLh
alveolar alr.
Leaves a large safeLy margln" Lo accommodaLe lncreases
ln Lhe raLe of blood ow
____ - physlcally dlssolved ln plasma and 88C cyLoplasm
____ - chemlcally comblned wlLh haemoglobln (Pb)
280 x 10
6
Pb molecules per 88C
4 C
2
molecules bound per Pb molecule
~ 10
9
C
2
molecules per 88C
~ 3 x 10
9
88C's per ml of blood
~ 3 x 10
18
C
2
molecules per ml of blood (aL 100 saLurauon)
Pb dramaucally lncreases Lhe blood's ablllLy Lo carry C
2
(relauve Lo
plasma/waLer), so lL ls comparable Lo alr (0.21 ml C
2
per ml of alr)
1ransporL of oxygen ln Lhe blood
~ 6 x 10
23
C
2
molecules per mole, ~ 22.4 llLres per mole
~ 0.2 ml C
2
per ml of blood
1.5
98.54
Pb exhlblLs Lhe properLy of allosLerlc modulauon = blndlng aL one
slLe on a molecule aecLs blndlng aL a second slLe, usually by
changlng Lhe shape of Lhe molecule."
Pb ls a _______ (M.W. ~ 68,000), composed of 4 slmllar unlLs
Lach unlL conslsLs of a heme" rlng sLrucLure LhaL blnds 1 C
2

and a polypepude chaln (globln") LhaL blnds CC
2
, P
+
, phosphaLes, eLc.
llg 13-3
Paemoglobln (recall lecLures 6 & 7)
1 Pb proLeln = 4 globlns (2o chalns and 2 chalns) + 4 hemes
tetramer
1ransporL of oxygen vla haemoglobln
As blood passes Lhrough Lhe lungs
Lhe hlgh C
2
promoLes Lhe
formauon of _____________"
llg 17-6
Pb leavlng Lhe lungs ls ~98
saLuraLed wlLh C
2
. AlmosL all of Lhe
blndlng slLes are occupled
llg 17-7
oxyhemoglobin
1ransporL of oxygen vla haemoglobln
As blood passes Lhrough Lhe ussues,
Lhe low C
2
promoLes Lhe
formauon of ________________"
llg 17-6
Pb becomes desaLuraLed aL Lhe
ussues. AL resL, only 73 of Lhe
blndlng slLes of Pb are occupled by
C
2
aer leavlng Lhe ussues

llg 17-7
deoxyhemoglobin
1. C
2
bound Lo Pb does not
conLrlbuLe dlrecLly Lo blood C
2
,
only dlssolved C
2
does
2. C
2
bound Lo Pb does conLrlbuLe
Lo Lhe LoLal concenLrauon of C
2
LhaL ls avallable Lo

dluse
As dlscussed
earller, dluslon ls
a funcuon of Lhe
parual pressure
gradlenL, whlch ls
dlcLaLed by Lhe
dlssolved oxygen
fracuon.
1ransporL of oxygen ln Lhe blood
[C
2
]=[C
2
] [C
2
]<[C
2
]
- - - - - - - - - - - - - - - -
le
2+
le
2+

le
2+
le
2+
- nP
2

- nP
2

- nP
2

- nP
2

-
-
-
-
- - - - - - - - - - - - - - - -
- - - - - - - - - - - - - - - -
- - - - - - - - - - - - - - - -





C
2

C
2

C
2

C
2

Pemes Cloblns
CC
2

CC
2

CC
2

CC
2

P
+
P
+
P
+
P
+
P
+

P
+
P
+
P
+
P
+
P
+



P
+
, CC
2
, & phosphaLe are negauve allosLerlc modulaLors of C
2
blndlng
C
2
ls a negauve allosLerlc modulaLor of P
+
, CC
2
, & phosphaLe blndlng
1herefore C
2
ls a _______ allosLerlc modulaLor for furLher C
2
blndlng
________ co-operauvlLy: Lhe 1
sL
C
2
helps Lhe 2
nd
, & Lhe 2
nd
helps Lhe 3
rd
,
Lhe 4
th
ls noL helped
A funcuonal" model of Pb
lncrease ln LemperaLure weakens Lhe lonlc bond beLween le
2+
and C
2

allosteric
+
AllosLerlc co-operauvlLy ls Lhe reason for Lhe ________ (S-shaped) C
2

equlllbrlum curve" (also called Lhe C
2
dlssoclauon curve") of Lhe blood.
1
2
3
4
llg 17-8
1he Pb-oxygen equlllbrlum curve
0
30
100
130
200
m
l

C
2

p
e
r

1
0
0
0

m
l

b
l
o
o
d

v
e
n
o
u
s

r
e
s
e
r
v
e

Loadlng polnL
unloadlng polnL
a
C2
v
C2

AL resL, only
23 of Lhe C
2

bound by Pb ls
ooaded aL
Lhe ussues. 30
ml of C
2
leaves
each L of blood
73 of Lhe C
2

remalns as a
venous
reserve"
AL resL
sigmoidal
1he Pb-oxygen equlllbrlum curve
llg 17-8
1he anlLy of Pb for
C
2
aecLs Lhe shape of
Lhe curve
C
2
anlLy ls quanued
by calculaung Lhe
30
"
- Lhe
C2
aL whlch Pb
ls _____ saLuraLed

S0
~ 2S 1orr
~ 32 1orr
~ 42 1orr
Pb wlLh a hlgher
anlLy has a lower
30
50
1. llaL reglon aL Lop provldes an lmporLanL ___________for C
2
loadlng lf
arLerlal
C2
(a
C2
) falls (e.g., hlgh aluLude, resplraLory dlsease, eLc.)
1
2. knee and sLeep parL ls
ldeally locaLed Lo enhance C
2

unloadlng durlng exerclse,
wlLh only a relauvely small
decrease ln venous
C2
(v
C2
)
and Lherefore ussue
C2

2
v
C2
resL
v
C2
exerclse
3. resL 40 1orr
! ~73 Pb-C
2
exerclse 20 1orr
! ~33 Pb-C
2

Lxerclse
1he Pb-oxygen equlllbrlum curve
3
llg 17-8
safety margin
1he 8ohr sh|h lmproves C
2
unloadlng durlng exerclse:
1. An lncrease ln v
CC2
shls
Lhe curve Lo Lhe rlghL
! Caused by lncreased
ussue ____________
2. A decrease ln venous pP also
shls Lhe curve Lo Lhe rlghL
! [P
+
] lncreases from lacuc
acld and CC
2
producuon
ln Lhe ussues:
CC
2
+ P
2
C ! P
+
+ PCC
3
-

(we wlll come back Lo Lhls)
1he Pb-oxygen equlllbrlum curve
llg 17-10
CO2 production
lncreases ln blood
LemperaLure shl Lhe
curve Lo Lhe rlghL, and Lhus
enhance unloadlng of C
2
Acuve muscle warms up,
lncreaslng Lhe LemperaLure
of blood ln Lhe caplllarles
Increases |n temperature lmprove C
2
unloadlng durlng exerclse:
1he Pb-oxygen equlllbrlum curve
llg 17-10
1he comblned eecLs of
LemperaLure and Lhe 8ohr
shl durlng exerclse can
lncrease C
2
unloadlng Lo
90 (l.e., venous reserve
reduced Lo 10)
Crganlc phosphaLe molecules are also lmporLanL _______ allosLerlc
modlers of C
2
blndlng, buL play llule role durlng exerclse
Mammals - 2,3-dlphosphoglyceraLe (2,3-uC)
8lrds - l
3
(lnoslLol penLaphosphaLe)
llsh & amphlblans - A1 & C1
lncreases ln 88C [phosphaLe] generally shl Lhe curve Lo ____.
1he Pb-oxygen equlllbrlum curve
leLal mammals use a dlerenL Pb Lhan adulL mammals, ln whlch 2 gamma
chalns are used lnsLead of 2 beLa chalns
leLal Pb ls lnsensluve Lo 2,3-uC and Lherefore
has a hlgher anlLy for C
2
Lhan maLernal Pb
! faclllLaLes C
2
Lransfer across Lhe placenLa
1 feLal Pb = 2o chalns + 2 chalns + 4 heme groups
-
right
1here |s a |ot more CC
2
than C
2

|n the b|ood
1. 10 ls physlcally dlssolved ln
plasma and 88C cyLoplasm
1
2
2. 30 blnds Pb Lo form
carbamlno-CC
2

3
3. 60 ls LransporLed as PCC
3
-

lon, malnly dlssolved ln plasma
Carbonlc anhydrase (CA), whlch caLalyzes Lhe above reacuon, ls Lhe
second mosL abundanL proLeln ln eryLhrocyLes aer Pb
38
3A. 8uered
by Pb
38. Moves lnLo plasma
ln exchange for Cl
-
1ransporL of carbon dloxlde ln Lhe blood
CC
2
+ P
2
C P
2
CC
3
PCC
3
-
+ P
+
CA
fasL
3A
llg 17-11
8oLh of Lhese reacuons shl Lhe C
2

equlllbrlum curve Lo Lhe rlghL,
Lhereby helplng Lo unload C
2
.
8and 3" proLeln for Cl
-
/PCC
3
-

exchange = ___________
llg 17-11
MosL blcarbonaLe LransporLed ln
plasma
urlvlng pressure for dluslon:
Cells (>46 1orr) ! caplllary (40 1orr)
PCC
3
-
1ransporL of carbon dloxlde ln Lhe blood
chloride shift
8oLh of Lhese reacuons shl Lhe C
2

equlllbrlum curve Lo Lhe le, Lhereby
helplng Lo load C
2
.
llg 17-11
urlvlng pressure for CC
2
8lood (46 1orr) ! alveoll (40 1orr)
Lungs
Cl
-
/PCC
3
-
exchange reversed
8lcarbonaLe moves from plasma
Lo rbc and converLed Lo CC
2
1ransporL of carbon dloxlde ln Lhe blood
31" H%#:%-" IB"05
1he addluon of C
2

Lo Lhe Pb helps Lo
______ CC
2
and P
+

aL Lhe pulmonary
caplllarles
1he removal of C
2
from Lhe Pb helps Lo load CC
2
and P
+
aL Lhe
sysLemlc caplllarles
AlLhough Lhese eecLs are small aL resL, Lhey become more
pronounced durlng exerclse
'Mlrror lmage' of
Lhe ____ LecL
(boLh are negauve
allosLerlc eecLs)
llg 17-12
1ransporL of carbon dloxlde ln Lhe blood
Bohr
unload
1ransporL of gases ln Lhe blood
As blood passes Lhrough pulmonary caplllarles:
lncreaslng C
2
, uecreaslng CC
2
and [P
+
]
1he C
2
equlllbrlum curve shls le, whlch
accenLuaLes C
2
loadlng and CC
2
unloadlng
As blood passes Lhrough sysLemlc caplllarles:
uecreaslng C
2
, lncreaslng CC
2
and [P
+
]
1he C
2
equlllbrlum curve shls rlghL, whlch
accenLuaLes C
2
unloadlng and CC
2
loadlng
1he 8ohr and Paldane LecLs (as well as
LemperaLure eecLs) faclllLaLe gas exchange aL
resL, and are exaggeraLed durlng exerclse
48
1ransporL of gases ln Lhe blood
J$#8,-%&6 !%)*##%&*"( K6(5"8*0 !%)*##%&*"(
llg 17-13
Cenerauon of breaLhlng rhyLhm
A Lyplcal person Laklng 13 breaLhs per mlnuLe wlll
lnsplre hundreds of mllllons of umes ln Lhelr llfeume

50*. $%&%)*.%+ .0%+% <)%*.0+?
Cenerauon of breaLhlng rhyLhm
K*:" G*"=
llg 17-13
L&,-5 G*"=
Cenerauon of breaLhlng rhyLhm
re-8tz|nger
Comp|ex (8C)
1he cenLral rhyLhm generaLor" ls
composed of a rhyLhmlcally
acuve group of neurons ln Lhe
re-8Lzlnger Complex (8C) ln
Lhe venLro-laLeral medulla
PypoLhesls 1: lndlvldual neurons
sponLaneously depolarlze Lo
generaLe acuon poLenuals, Lhus
acung llke pacemakers
PypoLhesls 2: Complex
lnLeracuons beLween neurons ln
a neLwork generaLe Lhe a rhyLhm
Cenerauon of breaLhlng rhyLhm
1he rhyLhmlclLy cenLer ln Lhe
medulla lncludes Lhe 8C along wlLh
lnsplraLory and explraLory neurons
lnsplraLory (l) neurons ln Lhe u8C and
v8C (shown ln blue) re durlng
lnsplrauon (ln response Lo Lhe 8C)

k
h
y
t
h
m
|
c
|
t
y


C
e
n
t
e
r


l neurons
L neurons
LxplraLory (L) neurons ln Lhe v8C
(shown ln yellow) re durlng %0+G"
exhalauon (e.g. exerclse)

1he 8C ln Lhe pons conLalns l, L, and
mlxed neurons LhaL ne-Lune" Lhe
acuvlLy of Lhe rhyLhmlclLy cenLer,
faclllLaLe Lhe Lransluon beLween lnsp.
and exp., and conLrol breaLhlng depLh

to kesp|ratory Musc|es
l, L, & mlxed
neurons
Cenerauon of breaLhlng rhyLhm
1he lnsplraLory muscles
(dlaphragm and exLernal
lnLercosLals) are
lnnervaLed by Lhe phrenlc
and exLernal lnLercosLal
nerves, respecuvely
LxplraLory muscles
(lnLernal lnLercosLals) are
lnnervaLed by Lhe
lnLernal lnLercosLal
nerve, buL are only
acuvaLed Lo conLracL
durlng heavy breaLhlng
llg 17-14
neural conLrol of breaLhlng
to kesp|ratory Groups
|n medu||a and pons
varlous sensory recepLors provlde
lnpuL Lo Lhe resplraLory cenLers ln
Lhe bralnsLem Lo regulaLe breaLhlng
CenLral and perlpheral
chemorecepLors sense chemlcal
slgnals (CC
2
, C
2
, pP, glucose, eLc.)
ulmonary sLreLch recepLors sense
Lhe degree of lung lnauon
LLc.
CenLral chemorecepLors
More sensluve and accuraLe Lhan
perlpheral chemorecepLors
MonlLors cerebral splnal uld (CSl)
pP and CC
2
(Lhrough Lhe lauer's
aecL on pP vla carbonlc anhydrase)
CC
2
can cross Lhe blood-braln barrler
buL P
+
cannoL, so arLerlal CC
2
(buL
noL arLerlal pP) ls also sensed
lncreases ln CSl CC
2
also occur when neural meLabollsm lncreases, whlch
would necesslLaLe hlgher raLes of breaLhlng and gas exchange
MonlLor CC
2
/pP (noL C
2
) ln medulla near Lhe rhyLhmlclLy cenLer
CenLral chemorecepLors are Lhe mosL lmporLanL sensor conLrolllng
venulauon, causlng lL Lo lncrease ln response Lo lncreases ln CC
2
llg 17-20
ons
Medulla
Caroud
chemorecepLors
Aoruc
chemorecepLors
erlpheral (arLerlal") chemorecepLors (CC
2
, pP, and C
2
)
Closso-pharyngeal (l)
(aerenL branches)
vagus ()
(aerenL branches)
SumulaLe an lncrease ln venulauon
ln response Lo a rlse ln arLerlal
CC
2
, supporung Lhe cenLral
chemorecepLors

lncrease venulauon ln response Lo a
decrease ln arLerlal pP (l.e.,
lncreased [P
+
])
Malnly a ne-Lunlng, back-up and
safeLy sysLem whlch becomes more
lmporLanL durlng speclal
clrcumsLances
lncrease venulauon ln response Lo a
decrease ln arLerlal C
2


MonlLor arLerlal C
2
aL a seLpolnL ~ 100 1orr
! SumulaLe venulauon ln response Lo large decreases ln C
2

(small changes do noL cause a large eecL)
ChemorecepLors
MedlaLed
enurely by
perlpheral
chemorecepLors
Pb saLurauon
sLarLs dropplng
erlpheral recepLors are very lmporLanL aL hlgh aluLudes, where
Lhe C
2
of amblenL alr ls much lower
llg 17-19
Figure 13.35
MedlaLed almosL enurely by
perlpheral chemorecepLors
(P
+
does noL easlly cross
blood-braln barrler)
pP change noL due Lo CC
2

(e.g. lacLaLe durlng exerclse)
MedlaLed largely by Lhe
cenLral chemorecepLors
venulauon LecLs of CC
2

ChemorecepLors
llg 17-19
llgure 17.21
ChemorecepLor 8eexes
1. MosL lmporLanL:
PCC
3
-
+ P
+
P
2
CC
3
2. roLeln buer:
roL
-
+ P
+
[Link]
Acld-base regulauon - Lhe conLrol of LCl and lCl pP
7.00 " " 7.20 " 7.40 ! 7.60 ! ! 7.80
normal pP range
LCl (pPa)~7.4, lCl~7.0
uepresslon of nervous
sysLem & coma
Cver-exclLablllLy of nervous
sysLem & LeLany of muscles
lnpuLs of acld 8lood buers CuLpuLs (compensauon)
uleLary and
meLabollc
sources.
CC
2
acLs as
an acld
1. 8esplraLory sysLem
rapldly changes breaLhlng
Lo alLer explrauon of CC
2

2. 8enal sysLem slowly
(hours Lo days) excreLes
or reabsorbs P
+
or PCC
3
-
! 8educes buL does noL
ellmlnaLe pP changes
llg 19-24
MN ."-"&%# ;"O$*#*9&*$8@ "O$%+,-P PCC
3
-
+ P
+
P
2
CC
3


pP = pk + log [anlon of an acld] = pk + log [PCC
3
-
]
[acld] [P
2
CC
3
]
1he ma[or pr|nc|p|es of ac|d-base regu|anon can be understood by
fo||ow|ng the CC
2
]nCC
3
-
system
8lcarbonaLe 8uer SysLem of Lhe 8lood
1he relauonshlp beLween CC
2
and pP (Lhe CC
2
/PCC
3
-
buer sysLem)
can be descrlbed by Lhe Penderson-Passelbalch Lquauon
QN !%&9,-*0 R-16:&%(" 4"%0+,-P P
2
CC
3
P
2
C + CC
2


ulssolved [CC
2
] = CC
2
! SolublllLy CoeclenL (oCC
2
)

H"-:"&(,-SH%(("#9%#01 pP = pk' + log [PCC
3
-
] = 6.1 + log [PCC
3
-
]
IO$%+,- D,& T#,,:P [CC
2
] CC
2
! oCC
2
~ConsLanL
8egulaLed by breaLhlng (fasL)
CA
****
pP = 7.4 = 6.1 + log [PCC
3
-
]
40 ! 0.03

ArLerlal pP ls regulaLed aL 7.4 by
keeplng [PCC
3
-
]:[CC
2
] aL ~20:1
8lcarbonaLe 8uer SysLem of Lhe 8lood
pn = 6.1 + |og [nCC
3
-
]
CC
2
! oCC
2
oCC
2
= 0.03 mM/1orr

ArLerlal CC
2
= 40 1orr
ArLerlal pP = 7.4
C1%5 *( 51" 0,-0"-5&%+,- ,D 9*0%&9,-%5" *- %&5"&*%# 9#,,:E
7.4 - 6.1 = log [PCC
3
-
]
40 ! 0.03

10
(7.4 - 6.1)
= [PCC
3
-
]
40 ! 0.03

[PCC
3
-
] = 40 ! 0.03 ! 10
(7.4 - 6.1)


= 24 mM
[CC
2
] = CC
2
! oCC
2
= 40 ! 0.03
= 1.2 mM
1he CC
2
/blcarbonaLe buer sysLem dlcLaLes pP ln Lhe blood (and
wherever Lhere ls carbonlc anhydrase). CLher buer sysLems (e.g.,
proLelns, phosphaLe, nP
3
) remaln ln equlllbrlum (lsohydrlc rlnclple)
Acld-8ase dlsLurbances and compensauons

CC
2
+ P
2
C P
2
CC
3
P
+
+ PCC
3
-
_________________ - lf CC
2
excreuon by Lhe resplraLory sysLem ls
less Lhan producuon ('_____________') ! neL P
+
and PCC
3
-
bulldup
kldney slowly compensaLes by accumulaung PCC
3
-
(lncreased reabsorpuon)
and excreung P
+
Lo brlng [PCC
3
-
]:[CC
2
] back Lo ~20:1 and Lhus resLore pP
8esplraLory Alkalosls - lf CC
2
excreuon by Lhe resplraLory sysLem
exceeds producuon ('hypervenulauon') ! neL P
+
and PCC
3
-
loss
kldney slowly compensaLes by excreung PCC
3
-
and
accumulaung P
+
Lo help resLore pP

CC
2
+ P
2
C P
2
CC
3
P
+
+ PCC
3
-
[nCC
3
-
] < 20
[CC
2
]
[nCC
3
-
] > 20
[CC
2
]
CA
CA
respiratory acidosis
hypoventilation
Acld-8ase dlsLurbances and compensauons
________________ - lf an acld (P
+
) oLher Lhan CC
2
ls added Lo Lhe
blood (e.g. lacuc acld) , reacuon ls drlven Lo le ! CC
2
bulldup
venulauon lncreases qulckly Lo compensaLe, whlch lowers
arLerlal CC
2
(and Lhus [CC
2
]) and helps reduce [P
+
]
MeLabollc Alkalosls - lf a base (CP
-
, PCC
3
-
) ls added Lo Lhe blood, lL
forms or adds PCC
3
-
, drlvlng Lhe reacuon le ! neL P
+
loss
venulauon decreases qulckly Lo compensaLe, whlch lncreases arLerlal CC
2

and helps malnLaln pP

CC
2
+ P
2
C P
2
CC
3
P
+
+ PCC
3
-
CA
[nCC
3
-
] < 20
[CC
2
]

CC
2
+ P
2
C P
2
CC
3
P
+
+ PCC
3
-
CA
[nCC
3
-
] > 20
[CC
2
]
metabolic acidosis
llg 19-28
Acld-8ase dlsLurbances and compensauons
Acld-8ase dlsLurbances and compensauons
50*. 6+ .0% 70*33%&$% .- *768@<*+% <*3*&7%
*. 06$0 *32.48%+; *&8 0-1 6+ 6. -:%)7-9%?