Oxygen transport from alveoli to mithocondria

Paolo Palange

Taylor CT, Biochem J 2008

Critical PO2 = 26 Torr

Critical PO2 = 6 Torr

Talk plan

• Oxygen transport

• Tissue hypoxia and inflammation

• COPD

Talk plan

• Oxygen transport

• Tissue hypoxia and inflammation

• COPD

pO2

150

100

50

0

pO

2 mm

Hg

Atmosphere Mithocondria

arterial capillary

Diff Shunt

air

alveolar

O2 extraction

PO2crit

O2 convection

O2 Transport and e Utilizzation

O2

O2

V’O2 kinetics during moderate CWR exercise

Training

Aging

(Whipp and Mahler - 1980)

10 ml V’O2/min/watt

V’O2 peak

V’O2 – Work rate relationship

*

Talk plan

• Oxygen transport

• Tissue hypoxia and inflammation

• COPD

Expression of Hypoxia-inducible Factor 1 (HIF-1)

Normoxia Hypoxia

Hypoxic activation of HIF1a

Hypoxic activation of HIF1a

Douglas and Haddad. J Appl Physiol 2003

HIF1-geni target

Chronic hypoxia Intermittent hypoxia

Selective activation of inflammatory pathways by intermittent hypoxia

Ryan S, Circulation 2005

Sustained normoxia

NFkB: a major transcription factor in inflammation

- TNFa- IL6- IL8

?

Taylor CT, Ann NY 2009

Possible cross-talk between NFkB and HIF1a?

Talk plan

• Oxygen transport

• Tissue hypoxia and inflammation

• COPD

Phenotypes of COPDBlue bloater (type B)

Chronic bronchitis

Pink puffer (type A)

Emphysema

’60-80

HypoxemiaHypercapniaNa+ and H2O retention

Obstruction Inflammation Remodelling

100

Time (months)

Cum

ulat

ive

perc

ent s

urvi

val

10

NOTT cont

90

80

70

60

50

40

30

20

10

020 30 40 50 60 70

MRC O2

NOTT noct

MRC controls

LTOT SURVIVAL CURVES(%)

NOTT : Ann Intern Med 1980, MRC: Lancet 1981

Pathogenesis of sodium and water retention in COPD

ERS 2002Palange P, Thorax 1998

Phenotypes of COPD

Blue bloater (type B)

Chronic bronchitis

Pink puffer (type A)

Emphysema

’90-’10

EmphysemaLow BMIMuscle dysfunctionAnemia↑ TNFa

Loss of capillariesLoss of alveolar walls“repair failure”

Effect of oxygen on V’O2 kinetics in a COPD patient with mild hypoxemia (PaO2 70mmHg)

Palange P, J Appl Physiol 1995

COPD Controls

Control

COPD

COPD

Eur Respir J 2006

COPD Controls

Eur Respir J 2006

Resp Physiol and Neurobiol 2010

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