oxygen transport from alveoli to mithocondria paolo palange
DESCRIPTION
Oxygen transport from alveoli to mithocondria Paolo Palange. Taylor CT, Biochem J 2008. Critical PO 2 = 26 Torr. Critical PO 2 = 6 Torr. Talk plan. Oxygen transport Tissue hypoxia and inflammation COPD. Talk plan. Oxygen transport Tissue hypoxia and inflammation - PowerPoint PPT PresentationTRANSCRIPT
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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