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Oxygen transport from alveoli to mithocondria Paolo Palange

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

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Oxygen transport from alveoli to mithocondria Paolo Palange

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  1. Oxygen transport from alveoli to mithocondria Paolo Palange

  2. Taylor CT, Biochem J 2008 Critical PO2 = 26 Torr Critical PO2 = 6 Torr

  3. Talk plan • Oxygen transport • Tissue hypoxia and inflammation • COPD

  4. Talk plan • Oxygen transport • Tissue hypoxia and inflammation • COPD

  5. pO2 air 150 100 50 0 alveolar O2 convection arterial capillary pO2 mmHg Diff Shunt O2 extraction PO2crit Atmosphere Mithocondria

  6. O2 Transport and e Utilizzation O2 O2

  7. V’O2 kinetics during moderate CWR exercise Training Aging

  8. (Whipp and Mahler - 1980)

  9. V’O2 – Work rate relationship V’O2 peak *  10 ml V’O2/min/watt

  10. Talk plan • Oxygen transport • Tissue hypoxia and inflammation • COPD

  11. Expression of Hypoxia-inducible Factor 1 (HIF-1) Normoxia Hypoxia

  12. Hypoxic activation of HIF1a

  13. Hypoxic activation of HIF1a

  14. HIF1-geni target Douglas and Haddad. J ApplPhysiol 2003

  15. Selective activation of inflammatory pathways by intermittent hypoxia Sustained normoxia Chronic hypoxia Intermittent hypoxia Ryan S, Circulation 2005

  16. NFkB: a major transcription factor in inflammation • TNFa • IL6 • IL8

  17. Possible cross-talk between NFkB and HIF1a? ? Taylor CT, Ann NY 2009

  18. Talk plan • Oxygen transport • Tissue hypoxia and inflammation • COPD

  19. Blue bloater (type B) Pink puffer (type A) Emphysema Chronic bronchitis Phenotypes of COPD ’60-80 Hypoxemia Hypercapnia Na+ and H2O retention Obstruction Inflammation Remodelling

  20. 100 90 80 NOTT cont 70 60 Cumulative percent survival 50 NOTT noct MRC O2 40 30 MRC controls 20 10 0 10 20 30 40 50 60 70 Time (months) LTOT SURVIVAL CURVES (%) NOTT : Ann Intern Med 1980, MRC: Lancet 1981

  21. Pathogenesisofsodium and water retention in COPD Palange P, Thorax 1998 ERS 2002

  22. Pink puffer (type A) Blue bloater (type B) Chronic bronchitis Phenotypes of COPD ’90-’10 Emphysema Low BMI Muscledysfunction Anemia ↑ TNFa Loss of capillaries Loss of alveolar walls “repair failure” Emphysema

  23. Effect of oxygen on V’O2 kinetics in a COPD patient with mild hypoxemia (PaO2 70mmHg) Palange P, J ApplPhysiol 1995

  24. Control COPD COPD COPD Controls Eur Respir J 2006

  25. COPD Controls Eur Respir J 2006

  26. * * # RespPhysiol and Neurobiol2010

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