HYPOXIAHYPOXIARESPIRATORY FAILURERESPIRATORY FAILURE

M. TatarM. Tatar

Dept. of PathophysiologyDept. of Pathophysiology

HYPOXIA

hypoxemia

anoxia

ischemia

glucose

Krebs´s cycle

O2

H2O

38 ATP

glucose

pyruvatelactate

2 ATP

CO2

The aim of oxygen transport

to preserve high PO2 gradient between capillaries and mitochondria

circ

ula

tion

ery

thro

poie

sis

r es p

irat i

on

mic

roci

rcu

lati

on

Hb

afin

ity t

o O

2

VO2m

ADPc

Q x Hb conc. x (SaO2 – SvO2)O2

Classification of hypoxia (1)

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

20 60 100 120

PaO2 , mmHg

300

200

150

Ca

O2,

ml/l

100

100

anemiaHb = 10

normalHb = 15

100

Sa

O2,

%

polycythemiaHb = 20

Classification of hypoxia (2)

3. Hypoextractive hypoxia- increased Hb afinity to O2

- Q . Hb . (SaO2 – SvO2)

6 14

PaO2, kPa

100

50

Sa

O2, % re

leas e

d O

2

pH = 7,4; t = 37 °C

pH 7,4; t 37 °C

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 - definitionRespiratory failure - definition

Syndrome characterized by disturbed exchange Syndrome characterized by disturbed exchange of oxygen and carbon dioxide in lungof 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

ClassificationClassification:1. Hypoxemic (hypoxemia with normal or 1. Hypoxemic (hypoxemia with normal or

PaCOPaCO22))2. Hypercapnic (hypoxemia and hypercapnia)2. Hypercapnic (hypoxemia and hypercapnia)

Respiratory failureRespiratory failure

PaCOPaCO22 must be regarded as a function of the must be regarded as a function of the overall overall ventilation of the entire lung, without regard to local ventilation of the entire lung, without regard to local inequalities of distribution of ventilation and inequalities of distribution of ventilation and perfusionperfusion

PaOPaO22, on the other hand, depends not only on the , on the other hand, depends not only on the amount of alveolar ventilation but also on the amount of alveolar ventilation but also on the matching of ventilation and perfusionmatching of ventilation and perfusion

Factors determining oxygenation and ventilation are Factors determining oxygenation and ventilation are differentdifferent

Respiratory failureRespiratory failure

Mechanisms responsible for gas exchange Mechanisms responsible for gas exchange disturbancesdisturbances

1. Ventilation/perfusion (V´/Q´) mismatch

1. Alveolar hypoventilation (overall)

2. Venous admixture3. Diffusion impairment

A. intrinsic lung disorders (airways, lung parenchyma)

B. extrinsic lung disorders (respiratory centre, nerve pathways, respiratory muscles, thoracic cage, pleural space)

100 40

5050

PaO2

PaCO2

100%

70%chemoreceptors

ventilatory drive

120 30

hypoxemia

hypercapniahypoxemianormocapnia

SaO2

?

2 0 4 0 6 0 8 0 1 0 0 1 2 0 m m H g

P a O 2

CC

DC

AC

BC

2 0

1 0

Vol

% O

2

h i g h V ´ A = 1 1 / 2

V ´ A / Q ´

Q ´ = 1

V ´ A = 1 / 2 l o w V ´ A / Q ´ Q ´ = 1

m o r m a l V ´ A / Q ´ V ´ A = 1 V ´ A = 1 Q ´ = 1 Q ´ = 1

50

25

20 40 60 mmHg PaCO2

Vol

% C

O2

B

A

C

low V´A=2/3 V´A/Q´ Q´ = 1

V´A=11/3

High Q´=1 V´A/Q´

Normal V´A/Q´ Q´=1 V´A=1 V´A=1 Q´=1

11/3 + 2/3 = 2

Respiratory failureRespiratory failure

Mechanisms of hypoxemiaMechanisms 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

PvO2

PcO2

Diffusion impairment – oxygen saturation of arterial blood

0.8 s Er contact time with A-c membrane

restexercise

4

12

kPa

normal

impaired

Respiratory failure

Mechanisms enhancing hypoxemiaMechanisms enhancing hypoxemia

Pure oxygen breathing:

hypoxic pulmonary vasoconstriction

resorptive atelectasis ( PAN2, resorption of O2) central inspiratory drive

Respiratory failure

Mechanisms of hypercapniaMechanisms 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