HYPOXIA RESPIRATORY FAILURE M. Tatar Dept. of Pathophysiology

HYPOXIA hypoxemia anoxia ischemia

glucose 38 ATP Krebs´s cycle O2 CO2 H2O glucose 2 ATP lactate pyruvate

The aim of oxygen transport to preserve high PO2 gradient between capillaries and mitochondria Q x Hb conc. x (SaO2 – SvO2) O2 c circulation respiration erythropoiesis microcirculation Hb afinity to O2 ADP VO2 m

Classification of hypoxia (1) Hypotonic hypoxemic hypoxia -  PaO2,  CaO2; Q . Hb . ( SaO2 – SvO2) - carotid body stimulation, hyperventilation - pulmonary hypertension in chronic form - respiratory failure 2. Izotonic hypoxemic hypoxia - normal PaO2,  CaO2; Q .  Hb . ( SaO2 – SvO2) - chemoreceptors are not stimulated, lack of dyspnea - anemia, carboxyhemoglobin

Hb concentration and CaO2 interrelationship 300 100 polycythemia Hb = 20 200 100 normal Hb = 15 CaO2, ml/l 150 SaO2, % 100 anemia Hb = 10 20 60 100 120 PaO2 , mmHg

Classification of hypoxia (2) 3. Hypoextractive hypoxia - increased Hb afinity to O2 - Q . Hb . (SaO2 –  SvO2) 100 released O2 SaO2, % 50 pH = 7,4; t = 37 °C pH  7,4; t  37 °C 6 14 PaO2, kPa

Classification of hypoxia 3 4. Hypocirculatory hypoxia -  Q . Hb . (SaO2 – SvO2) - ischemic, congestive; local, general 5. Overutilization hypoxia -  demand of tissues for O2 excesses the available supply - angina pectoris, epilepsy (fatigue and cerebral depression) 6. Histotoxic hypoxia - disturbed ATP production, blocked oxidative phosphorylation - Q . Hb . (SaO2 –  SvO2) - cyanide

Respiratory failure - definition Syndrome characterized by disturbed exchange of oxygen and carbon dioxide in lung Consequences: PaO2  60 mmHg (8.0 kPa) with or without PaCO2 > 50 mmHg (6.7 kPa) - under resting condition - breathing atmospheric air at sea level Classification: 1. Hypoxemic (hypoxemia with normal or  PaCO2) 2. Hypercapnic (hypoxemia and hypercapnia)

Respiratory failure Factors determining oxygenation and ventilation are different PaCO2 must be regarded as a function of the overall ventilation of the entire lung, without regard to local inequalities of distribution of ventilation and perfusion PaO2, on the other hand, depends not only on the amount of alveolar ventilation but also on the matching of ventilation and perfusion

Respiratory failure Mechanisms responsible for gas exchange disturbances A. intrinsic lung disorders (airways, lung parenchyma) 1. Ventilation/perfusion (V´/Q´) mismatch 2. Venous admixture 3. Diffusion impairment B. extrinsic lung disorders (respiratory centre, nerve pathways, respiratory muscles, thoracic cage, pleural space) 1. Alveolar hypoventilation (overall)

 ventilatory drive PaO2 PaCO2 chemoreceptors SaO2 100 40 50 120 30 70% chemoreceptors SaO2 100% hypoxemia normocapnia hypoxemia hypercapnia

2. compartments with low V´/Q´ ratio Respiratory failure Mechanisms of hypoxemia 1. alveolar hypoventilation 2. compartments with low V´/Q´ ratio 3. right-to-left shunting of blood in compartments with zero V´/Q´ratio 4. diffusion impairment due to thickening of the alveolar-capillary membrane

Diffusion impairment – oxygen saturation of arterial blood normal PcO2 12 impaired kPa exercise rest PvO2 4 0.8 s Er contact time with A-c membrane

Respiratory failure Mechanisms enhancing hypoxemia Pure oxygen breathing:  hypoxic pulmonary vasoconstriction resorptive atelectasis ( PAN2,  resorption of O2)  central inspiratory drive

Mechanisms of hypercapnia Respiratory failure Mechanisms of hypercapnia 1. overall alveolar hypoventilation 2. critical amount of the compartments with low V´/Q´ ratio overall ventilation must increase to maintain effective alveolar ventilation (normal CO2 exchange) limits of effective alveolar ventilation:  work of breathing respiratory muscle fatigue  dead space ventilation