2021A15 Describe the respiratory responses to hypoxaemia in both the awake and the anaesthetized patient.

 

List:

·       Intro and importance

·       Hyperventilation: sensor, integrator, effector

·       Hypoxic pulmonary vasoconstriction

·       Sympathetic outflow

 

Intro: hypoxaemia

Definition

·  PaO2 < 60mmHg

Responses

·  Increased alveolar ventilation -> ↑PaO2

·  Hypoxic pulmonary vasoconstriction

o Improved V/Q matching -> ↑PaO2

o ↑PVR

·  ↑SNS output -> ↑cardiac output -> DO2

Effect of anaesthesia on responses

·  Suppression of all responses

·  Dose-dependent effects

High risk if:

·  Alone (e.g. post-op ward at night)

·  CO2-insensate (e.g. severe COPD, OSA, OHS)

·  Sensitive to resp depression (e.g. elderly, neonate)

·  Respiratory depressant drugs (e.g. morphine)

·  Sedated (e.g. midazolam)

·  Synergistic respiratory depressant drugs (e.g. benzo+ opioid)

 

Alveolar hyperventilation:

 

Sensor:

Structure

·  Peripheral chemoreceptors

o Carotid bodies (CNIX Hering’s nerve)

o Aortic bodies (CNX)

·  Type 1 glomus cell: responsive to ↓pO2, ↑pCO2, (↓pH carotids only)

·  Type 2 sustentacular cell: support

·  Blood flow 2000mL/min/100g -> supply by dissolved O2 only

Function

·  ↓ PaO2 -> closure of K+ channel -> depolarisation -> ↑afferent to resp centre

·  Response is minimal until PaO2 <100mmHg, profound <50mmHg

·  Response is rapid, <1 second

Effect of anaesthesia

·  Volatiles:

o ↓Chemoreceptor afferents is the most important resp effect

o 1 MAC: ablated response

o 0.1 MAC: significant depression of response

o Hence need for O2 supplementation post-op for safety

             

 

·  Propofol:

o ↓Chemoreceptor afferents

o Less potent than volatiles

 

Controller:

Structure

·  Respiratory centre, medulla

·  Multiple cell types: dorsal inspiratory, ventral expiratory, pre-Botzinger pacemakers

·  Afferents via nucleus tractus solitarius

·  Efferents via nucleus ambiguus and dorsal motor nucleus of CNX

Function

·  ↑Stimulation -> ↑amplitude and frequency of neuronal output to effectors

·  ↓PaO2 is synergistic with ↑PaCO2 and ↓pH

Effect of anaesthesia

·  Suppression:

o General anaesthesia (↑GABA/glycine activity)

o Opioids (μ receptor agonist in resp centre – most important opioid effect)

o Neuraxial: ↓input to reticular activating system -> ↓conscious state, ↓resp centre output

·  Stimulation:

o Pain -> ↑input to reticular activating system -> ↑resp centre output

 

Effector:

Muscles

·  Primary inspiratory: diaphragm, external intercostals, pharyngeal dilators

·  Accessory inspiratory: e.g. sternocleidomastoid

·  Expiratory: e.g. internal intercostals, abdominals (normally inactive)

Function

·  ↑Respiratory centre output -> ↑RR, VT -> ↑VA -> ↑PaO2

·  Completion of negative feedback loop

Effect of anaesthesia

·  Volatile:

o Skeletal muscle relaxation (inhibit nAChR)

o Inhibit a-motor neuron (↑GABA/↑glycine)

o Affects intercostals > diaphragm

·  Propofol:

o As for volatiles

o But less potent: ↓glycine activity, ↓spinal cord effect

·  Benzodiazepines:

o Skeletal muscle relaxation

·  Neuraxial:

o Inhibit α-motor neuron (intercostals)

o No effect on diaphragm unless C-spine level

·  Paralysis:

o No effector response

·  Position:

o Supine, Trendelenburg -> ↑work of breathing -> impaired effector

·  Apparatus dead space (tubing distal to Y piece):

o ↓VA for a given MV

 

Hypoxic pulmonary vasoconstriction:

Aim

·  Match ventilation with perfusion, ↑PaO2

Mechanism

·  Vasoconstriction ∝ 1 / (PAO20.6 x PvO20.4)

Biphasic response

·  Phase 1: onset immediate, plateau 5 mins

o ? Inhibition of K+ channel

o ? ↓mitochondrial ROS

o ? ↓ATP:ADP

·  Phase 2: onset 40 minutes, plateau 2 hours

o ? ↑↓COX, LOX production

o ? ↑hypoxia-inducible transcription

Effect of anaesthesia

·  Volatile:

o Inhibit L-Ca2+ channel, ↑NO release, ↓medulla SNS output

o Generalised vasodilatation including pulmonary

·  Propofol:

o Similar mechanisms

o Less potent, preferred in one lung ventilation

 

Sympathetic response:

Stimulus

·  ↓PaO2 <50mmHg -> CNS acidosis

Response

·  ↑SNS output

·  ↑HR, ↑contractility, venoconstriction -> ↑preload

·  ↑Cardiac output -> ↑O2 delivery

·  No change to PaO2

Effect of anaesthesia

·  Volatiles, propofol:

o ↓SNS output from medulla (↑GABA, glycine activity)

o Inhibit L-Ca2+ on heart, blood vessels

o ↑Nitric oxide release

o Dose-dependent suppression of baroreceptor response (propofol > volatiles)

·  Opioids, benzodiazepines:

o ↓SNS output

·  Neuraxial:

o ↓SNS output below block upper limit

 

 

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