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High Altitude Physiology and Pathophysiology : from Organism to Molecule Part I : Oxygen sensing Jean-Marc Pequignot UMR 5123: PHYSIOLOGIE intégrative, cellulaire et moléculaire CNRS, Université Claude Bernard Lyon I, France

High Altitude Physiology and Pathophysiology : … · High Altitude Physiology and Pathophysiology : from Organism to Molecule Part I : Oxygen sensing Jean-Marc Pequignot UMR 5123:

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Page 1: High Altitude Physiology and Pathophysiology : … · High Altitude Physiology and Pathophysiology : from Organism to Molecule Part I : Oxygen sensing Jean-Marc Pequignot UMR 5123:

High Altitude Physiology andPathophysiology : fromOrganism to Molecule

Part I : Oxygen sensing

Jean-Marc PequignotUMR 5123: PHYSIOLOGIE intégrative, cellulaire et moléculaire CNRS,

Université Claude Bernard Lyon I, France

Page 2: High Altitude Physiology and Pathophysiology : … · High Altitude Physiology and Pathophysiology : from Organism to Molecule Part I : Oxygen sensing Jean-Marc Pequignot UMR 5123:

Hypoxic Hypoxic chemoreflexchemoreflex

Low arterial PO2

Carotid Bodies sense Low PO2

Sympatheticnervous system

Other central pathways

Central integration in brainstem sites

Respiratory motoneurons

Increased ventilation

HematopoieticPathway (Hb)

Page 3: High Altitude Physiology and Pathophysiology : … · High Altitude Physiology and Pathophysiology : from Organism to Molecule Part I : Oxygen sensing Jean-Marc Pequignot UMR 5123:

Cellular elements of the carotidbody

The anatomical localization of thecarotid body

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Ultrastructure of the glomus cells

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The firing rate in response to gradual increase of hypoxia level

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Measurement of hypoxic ventilatoryresponse

Page 7: High Altitude Physiology and Pathophysiology : … · High Altitude Physiology and Pathophysiology : from Organism to Molecule Part I : Oxygen sensing Jean-Marc Pequignot UMR 5123:

Chemoreception / chemotransduction

Page 8: High Altitude Physiology and Pathophysiology : … · High Altitude Physiology and Pathophysiology : from Organism to Molecule Part I : Oxygen sensing Jean-Marc Pequignot UMR 5123:

Peripheral chemosensitivity : a model for O2 sensing

Page 9: High Altitude Physiology and Pathophysiology : … · High Altitude Physiology and Pathophysiology : from Organism to Molecule Part I : Oxygen sensing Jean-Marc Pequignot UMR 5123:

O2 sensing and chemotransductionin the carotid body

Page 10: High Altitude Physiology and Pathophysiology : … · High Altitude Physiology and Pathophysiology : from Organism to Molecule Part I : Oxygen sensing Jean-Marc Pequignot UMR 5123:

Catecholamine responses to hypoxia in the carotid body

Page 11: High Altitude Physiology and Pathophysiology : … · High Altitude Physiology and Pathophysiology : from Organism to Molecule Part I : Oxygen sensing Jean-Marc Pequignot UMR 5123:

Hypoxia

Functional reorganization

Cell dysfunctions

Pathophysiology

Cellular phenotypicremodeling

Acclimatization

Page 12: High Altitude Physiology and Pathophysiology : … · High Altitude Physiology and Pathophysiology : from Organism to Molecule Part I : Oxygen sensing Jean-Marc Pequignot UMR 5123:

Cell Plasticity

Page 13: High Altitude Physiology and Pathophysiology : … · High Altitude Physiology and Pathophysiology : from Organism to Molecule Part I : Oxygen sensing Jean-Marc Pequignot UMR 5123:

Catecholaminergic response to hypoxia in the carotid body

Page 14: High Altitude Physiology and Pathophysiology : … · High Altitude Physiology and Pathophysiology : from Organism to Molecule Part I : Oxygen sensing Jean-Marc Pequignot UMR 5123:

Model of ventilatory acclimatizationto hypoxia

Page 15: High Altitude Physiology and Pathophysiology : … · High Altitude Physiology and Pathophysiology : from Organism to Molecule Part I : Oxygen sensing Jean-Marc Pequignot UMR 5123:

Mount Everest in utero (Sir John Barcroft, in 1930s)

Page 16: High Altitude Physiology and Pathophysiology : … · High Altitude Physiology and Pathophysiology : from Organism to Molecule Part I : Oxygen sensing Jean-Marc Pequignot UMR 5123:

Fetus vs. Adult chemosensitivity

Page 17: High Altitude Physiology and Pathophysiology : … · High Altitude Physiology and Pathophysiology : from Organism to Molecule Part I : Oxygen sensing Jean-Marc Pequignot UMR 5123:

Role of dopamine in carotid body resetting

Page 18: High Altitude Physiology and Pathophysiology : … · High Altitude Physiology and Pathophysiology : from Organism to Molecule Part I : Oxygen sensing Jean-Marc Pequignot UMR 5123:

Neonatal maturation of thechemosensitivity

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