Dr

Dr.Gyanendra
Gyanendra Agrawal
SeniorResident
DeptofPulmonaryMedicine

OXYGENANDCARBONDIOXIDE
CASCADE

Introduction
Introduction
Oxygen indispensableforlife
Substrateusedinthegreatestquantity
Substrate used in the greatest quantity
Nostoragesystem
Continuoussupplyrequired
C i
l
i d

Carbondioxide majorbyproductofenergy

metabolism

Mechanisms of oxygen transport

Mechanismsofoxygentransport
Convection(bulkflow)
Diffusion
Diffusion
Chemicalcombinationwithhemoglobin
30100foldincreaseinO2 transport
1520foldincreaseinCO2 transport
p

Oxygen Cascade
OxygenCascade
Uptakeinthelungs
Carryingcapacityofblood
Carrying capacity of blood
Globaldeliveryfromlungstotissue
Regionaldistributionofoxygendelivery
Diffusionfromcapillarytocell
Diffusion from capillary to cell
Cellularuseofoxygen

Oxygen Cascade
OxygenCascade
Uptakeinthelungs
Carryingcapacityofblood
Carrying capacity of blood
Globaldeliveryfromlungstotissue
Regionaldistributionofoxygendelivery
Diffusionfromcapillarytocell
Diffusion from capillary to cell
Cellularuseofoxygen

Oxygen uptake in the lungs

Oxygenuptakeinthelungs
InspiredO2 concentration
Barometricpressure
Barometric pressure
Alveolarventilation
DiffusionofO2 fromalveolitopulm capillaries
Distributionandmatchingofventilationand
Distribution and matching of ventilation and

perfusion

Alveolar ventilation
Alveolarventilation
Dependsonrateofbreathingandtidal

volume(V
volume
(VT)
Hyperbolicrelationshipbetweenalveolar
venttn andP
d PAO2
Affectedbydisordersofrespiratorycentre

andrespiratorymuscles
Highfrequencyventilationallowslowertidal
volumes while maintaining MV
volumeswhilemaintainingMV

Third gas effect

Thirdgaseffect
Administrationofnitrousoxide

Largequantitiesofmoresolublegasreplacesmaller
q
quantitiesoflesssolublenitrogen
g

Net transfer of inert

Nettransferof
inert gasfromalveoliintobody
gas from alveoli into body

Temporary increase in O2 concentration

TemporaryincreaseinO
FINK EFFECT
FINKEFFECT

Diffusionfromalveolitopulmonary
Diffusion
from alveoli to pulmonary
capillaries
p

O2 diffusion=
diffusion

K x S/d x P
KxS/dxP

Diffusionfromalveolitopulmonary
Diffusion
from alveoli to pulmonary
capillaries
p
PAO2 ismaindeterminantofPaO2
(Aa)gradientdescribestheoverallefficiency

of oxygen uptake
ofoxygenuptake
Capillarybloodisfullyoxygenatedbefore

traversingdistanceofalveolarcapillary
g
p
y
interface

V/Q matching
V/Qmatching
Trueshuntv/s
effectiveshunt

Clinicalcorrelates
Cli i l
l
HighPEEPstrategy
Prone ventilation
Proneventilation

BMJ1998;317:13026

Hypoxemia
Hypoxemia

BMJ1998;317:13026

Oxygen Cascade
OxygenCascade
Uptakeinthelungs
Carryingcapacityofblood
Carrying capacity of blood
Globaldeliveryfromlungstotissue
Regionaldistributionofoxygendelivery
Diffusionfromcapillarytocell
Diffusion from capillary to cell
Cellularuseofoxygen

Carriage of O2 inblood
CarriageofO
in blood

2%inplasma
98%inhemoglobin

Hemoglobin saturation
Hemoglobinsaturation
ExtenttowhichtheHb

iscombinedwithO
is
combined with O2
DependsonPO2 ofthe
blood
Phenomenonof

cooperativity
ti it
P50~28mmHg
Rapidandreversible
reaction

Factors affecting OEC

FactorsaffectingOEC
pH

Oxygenhemoglobindissociationcurve
Oxygen
hemoglobin dissociation curve
(Oxyhemoglobin equilibriumcurve)

PCO2
Temperature
2,3DPG
PercentageoffetalHb

Chest2005;128:554S560S

Bohr Effect
BohrEffect
ChristianBohr(1855
Christian Bohr (1855

1911)
EffectofP
Eff t f PCO2 onOEC
OEC
Conceptofpermissive
hypercapnia

2 3 Diphosphogleycerate
2,3
FormedintheRapoportLuebering shuntof

theglycolytic
the
glycolytic pathway
DPGmutase activityincreasedathighpH
DecreasedDPG instoredblood
Increasedin anemia
highaltitude

Oxygen content (CaO2)

Oxygencontent(CaO
TotalamountofO2 presentin100mlofblood
(
(1.34xHb
xSaO2)+(0.003xPaO
) (
2)

CaO
C O2=20vol
20 l %
%

C O2 =15vol
CvO
15 l %

O2contentdecreasedin
Hypoxemia(lowPO
yp
(
2)
Anemia(lowHb)
Hypercarbia,acidemia,hyperthermia(lowSaO
yp
,
, yp
(
2))

Effect of anemia and CO

EffectofanemiaandCO
Anemia Hb O2

carryingcapacityof
blood& O2 content

CarbonMonoxide
affinityforHb 250fold

relativetoO
relative
to O2
CompeteswithO2 binding
Lshift interferewithO2
unloadingattissues
Severetissuehypoxia

Oxygen Cascade
OxygenCascade
Uptakeinthelungs
Carryingcapacityofblood
Carrying capacity of blood
Globaldeliveryfromlungstotissue
Regionaldistributionofoxygendelivery
Diffusionfromcapillarytocell
Diffusion from capillary to cell
Cellularuseofoxygen

Oxygen delivery (DO2)

Oxygendelivery(DO
QuantityofO2 madeavailabletobodyinone

minute O2 deliveryorflux
minute
delivery or flux
EqualtocardiacoutputXarterialoxygen
content
t t
DO2 isapproximately1000mL/min

Oxygen consumption (VO2)

Oxygenconsumption(VO
TotalamountofO2 consumedbythetissues

per unit of time

perunitoftime
VO2 =10xCOx(CaO
= 10 x CO x (CaO2 CvO2)

NormalrestingO
g 2 consumption~250mL/min
p
/

inadulthumans
OER=VO2/DO2

DO2 VO2 relationship

Jindal SK,Agarwal R.OxygenTherapy.2nd Ed.pp78

DO2 VO2 relationshipincriticallyill

relationship in critically ill
SlopeofmaximumOERis
lesssteep

Reducedextractionof
oxygenbytissues

Doesnotplateau
(consumptionremains
supply dependent even
supplydependenteven
atsupranormallevels
of DO2)
ofDO

CriticallevelofDO
ca e e o O2 rangefrom
a ge o
2.1to6.2mL/min/kg
BMJ1998;317:13026

Mechanismscausingfailureofglobal
Mechanisms
causing failure of global
oxygendelivery
yg
y
Reductionincardiacoutput
Reduction in cardiac output
Fallinhemoglobinconcentration
Failureofoxygenuptake

byblood
y

Failure of oxygen delivery

Failureofoxygendelivery

RelativeeffectsofchangesinPaO2,Hb andCOonDO2 inacriticallyill

Thorax2002;57:170177

DO2 duringexercise
during exercise
Duringexercise
O2 requirementmaybe20times
q
y
Bloodremainsincapillaryblood<Ntime

Butsaturationnotaffected
FullsaturationinfirstofNtime
Increaseddiffusioncapacity
Additionalcapillariesopenup
V/Qratioimproves
Dilatationofbothalveoliandcapillaries
OECshiftstoright
OEC shifts to right CO2,pH,temp,2,3DPG
CO2 pH temp 2 3 DPG

Oxygen Cascade
OxygenCascade
Uptakeinthelungs
Carryingcapacityofblood
Carrying capacity of blood
Globaldeliveryfromlungstotissue
Regionaldistributionofoxygendelivery
Diffusionfromcapillarytocell
Diffusion from capillary to cell
Cellularuseofoxygen

RegionaldistributionandOxygen
Regional
distribution and Oxygen
consumption
p

Perfusionpressureisanimportantdeterminant
Chest 2005; 128:554S560S
Chest2005;128:554S
560S

Oxygen Cascade
OxygenCascade
Uptakeinthelungs
Carryingcapacityofblood
Carrying capacity of blood
Globaldeliveryfromlungstotissue
Regionaldistributionofoxygendelivery
Diffusionfromcapillarytocell
Diffusion from capillary to cell
Cellularuseofoxygen

Cellular use of oxygen

Cellularuseofoxygen
Importantforaerobicmetabolism
EMPpathway
EMP pathway
Krebscycle

Canbeinhibitedbycellularmetabolicpoisons
b hb db
ll l
b l
Exogenous(e.g.cyanide)or
Endogenous(e.g.endotoxins insepticshock)

Clinical features of tissue hypoxia

Clinicalfeaturesoftissuehypoxia

Dyspnea
Alteredmentalstate
Tachypnea orhypoventilation
Arrhythmias
y
Peripheralvasodilatation
Systemichypotension
y
yp
Coma
Cyanosis(unreliable)
y
(
)
Nausea,vomiting,andgastrointestinal
disturbance

Issues in critically patient

Issuesincriticallypatient
Disorderedregionaldistributionofbloodflow
Bothbetweenandwithinorgans
Both between and within organs
Lossofautoregulation
Useofvasopressors
U
f

Capillarymicrothrombosis afterendothelial

damage
CytokinesinduceddisorderedcellularO
Cytokines induced disordered cellular O2 use

Issues in critically patient

Issuesincriticallypatient
DecreasedO2carryingcapacityofblood
Phlebotomy
Hemorrhagesecondarytotrauma/surgery
Inflammation
I fl
i
Nutritionaldeficiencies
Decreasederythropoietinproduction

AltereddissociationprofileofOEC
p
Acidosis,fever
Decreased2,3DPG
Decreased 2 3 DPG

Issues in critically patient

Issuesincriticallypatient
CardiacdysfunctioninICUpatients
Underlyingorganicheartdisease
Underlying organic heart disease
InsufficientDO2 tothecoronarycirculation,

precipitatedbyanemia
precipitated
by anemia
Subendocardial ischemiafromLVH
Compromisedmyocardialcontractilityfromthe
i d
di l
ili f
h
effectsofinflammatorycytokines
Inappropriateintravascularfluidstatus

CARBONDIOXIDE CASCADE

Blood transports more CO2 thanO

BloodtransportsmoreCO
than O2
CO2 istwentyfoldmoresolublethanO2 inplasma
CO2 contentreflectsthesumofCO2 inthebloodinall

threeforms

CaCO2=48vol%CvCO2=52vol%
Eachtimebloodcirculatesthroughthebody,4vol%
g
y,

ofCO2 isremovedfromthetissuesanddeliveredto
thelungstobeexhaled

Dissolved CO2
DissolvedCO
Only5%oftotalarterialcontentispresentin

theformofdissolvedCO
the
form of dissolved CO2
0.3mlofCO2/100mlinabsoluteterms
Duringheavyexercisemayincreaseupto
sevenfold

Carbonic anhydrase (CA)

Carbonicanhydrase
KeyenzymeinCO2 transport
Catalyzesreactioninbothdirection(~5000
Catalyzes reaction in both direction (~5000

fold)
Notpresentinplasma
7isozymes
y
CAIIinRBCsandCAIVmembranebound
isozyme presentinpulmonarycapillaries
present in pulmonary capillaries
Inhibitedbythiazides andacetazolamide

Chloride shift
Chlorideshift
Hamburgerin1918
HCO3 exchangewithCl
exchange with Cl ionsacrossRBC
ions across RBC

membrane
Passiveprocess
P i
Mediatedbymembraneboundproteinband3
Band3anchoringsiteforankyrin andspectrin

CO2 boundascarbamate
bound as carbamate
CO2 reactsdirectlywithHb
Reversiblereactionwithaloosebond
Reversible reaction with a loose bond
Dependson
O2 satn ofHb and2,3DPG(bindingtoHb)
H+ concn ((bothHb &plasmaproteins)
p
p
)

However,Hb desat andinH+ concn work

in opposite direction
inoppositedirection

Haldane Effect
HaldaneEffect

JBSHaldane[18921964]

ChristiansenJ,DouglasCG,HaldaneJS.JPhysiol 1914;48:24471

Molecular basis for Haldane Effect

MolecularbasisforHaldaneEffect
ReducedHb isbetterthan
oxygenatedHb in
combiningwith
1.H+ ions
2.CO2 toformcarbamino
compounds

inturnassistingbloodtoload
moreCO
CO2 fromthetissues
f
h i

Haldane Effect
HaldaneEffect
BindingofO2 withhemoglobintendsto

displace CO2 fromtheblood

displaceCO
from the blood
Leadsto uptakeofCO2 inthetissuesand

releaseofCO22 inthelungs
ApproximatelydoublestheamountofCO
Approximately doubles the amount of CO2

releasedfromthebloodinthelungsandthat
pickedupinthetissues
i k d i th ti

Coupledtransportwithintheredcellin
Coupled
transport within the red cell in
p p
peripheraltissues

NEngJMed1998;338:23947

Influence of CO2 onbloodpH

InfluenceofCO
on blood pH
Carbonicacidbicarbonatebuffersystem

resists blood pH changes

resistsbloodpHchanges
IfH+ concentrationsinbloodbegintorise,excess

H+ removedbycombiningwithHCO
removed by combining with HCO3
IfH+ concentrationsbegintodrop,carbonicacid
dissociates releasing H+
dissociates,releasingH

Hypercapnia
Signsofventilatory failure:
Tachypnea
Acidemia
Increasedpulsus paradoxus
Hyperinflation
Somnolence/Decreasedmentalstatus

Hypercapnia
yp
p Etiologies
g
PaCO2
2

VCO2
RR(VT VD)

VCO2 (Hypermetabolism)

VT

Fever
Seizures
Sepsis
Hyperalimentation

Skeletalmuscleweakness
Impairedneuromusculartransmission
Lung/chestwallcompliance
Airwayobstruction
COPD
Asthma
Obstructivesleepapnea
Obst
uct e s eep ap ea

RR(Centralhypoventilation

(
yp
)
Drugs
Brainstemlesions
Obesityhypoventilationsyndrome

VD
ExcessivePEEP