High Altitude Physiology and Pathophysiology : … · High Altitude Physiology and Pathophysiology...

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

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)

Cellular elements of the carotidbody

The anatomical localization of thecarotid body

Ultrastructure of the glomus cells

The firing rate in response to gradual increase of hypoxia level

Measurement of hypoxic ventilatoryresponse

Chemoreception / chemotransduction

Peripheral chemosensitivity : a model for O2 sensing

O2 sensing and chemotransductionin the carotid body

Catecholamine responses to hypoxia in the carotid body

Hypoxia

Functional reorganization

Cell dysfunctions

Pathophysiology

Cellular phenotypicremodeling

Acclimatization

Cell Plasticity

Catecholaminergic response to hypoxia in the carotid body

Model of ventilatory acclimatizationto hypoxia

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

Fetus vs. Adult chemosensitivity

Role of dopamine in carotid body resetting

Neonatal maturation of thechemosensitivity