Dr . Nahid Sherbini

Consultant IM &Pulmonary

KFH ,Medina ,Saudi Arabia

Breathing is controlled by the central

neuronal network to meet the metabolic

demands of the body

– Neural

– Chemical

Keep arterial levels of O2 & CO2 constant.

Match perfusion by pulmonary blood

flow with ventilation of the lungs with

overall metabolic demand.

Control of Breathing

Central neurons determine minute

ventilation (VE) by regulating tidal

volume (VT) and breathing

frequency (f).

VE = VT x f

Definition:

A collection of functionally similar neurons

that help to regulate the respiratory

movement.

Higher respiratory center: cortex,

hypothalamus & limbic system.

Medulla & Pons :

Basic respiratory center: produce and

control the respiration.

Spinal cord: motor neurons.

Affect rate and depth of ventilation

Influenced by:• higher brain centers

• peripheral mechanoreceptors

• peripheral & central chemoreceptors

Voluntary breathing center

Cerebral cortex.

Automatic (involuntary) breathing center

– Medulla

– Pons

CAN BYPASS LOWER CENTERS.

SPEECH,SINGING,COUGHING, BREATH

HOLDING .

Voluntarily – speaking, blowing, whistling, pushing, defecation.

Voluntary control is bilateral – cannot contract half of diaphragm or larynx.

Descend via pyramidal tracts.

Destroy voluntary control without losing involuntary control can be.. i.e. stroke

To larynx and bronchi

To respiratory muscles

Nucleus parabrachialis medialis (part of PRG)

Dorsal respiratory group

– nucleus of the solitary tract

Pons

Medulla

Ventral respiratory group

- Nucleus ambiguus

- Nucleus retroambigualis

PRG = pontine respiratory group

Rhythmicity center:

• Controls automatic

breathing.

• Interacting neurons

that fire either during

inspiration

(I neurons) or

expiration

(E neurons).

I neurons located primarily in dorsal respiratory group (DRG):• Regulate activity of phrenic nerve.

E neurons located in ventral respiratory group (VRG):• Passive process.

Activity of E neurons inhibit I neurons.• Rhythmicity of I and E neurons may be due to

pacemaker neurons

Inspiratory Muscles

Expiratory Muscles

Inspiratory Neurons

Expiratory Neurons

• This implies that each group exhibits “self-inhibition” – they can switch themselves off.

• Stops breathing getting stuck in inspiration or expiration.

Apneustic center (lower pons) – to

promote Inspiration.

Pneumotaxic center (upper pons)

– inhibits apneustic center & inhibits

inspiration

-helps control the rate and pattern of

breathing.

Pons

Medulla

Cuts off

Produces apneustic effect – long, powerful inspirations

Stops breathing since no automated output to respiratory system – cause of death

DRG

VRG

pons

medulla

Neural Control

of Breathing –

Respiratory

neurons

Neural Control

of Breathing –

The efferent

pathway

Phrenic n.

muscle supply

autonomic

DECENDING BULBOSPINAL FIBRES

ARE IN THE VENTRAL AND LATERAL

COLUMNS.

RESP NEURONS ARE IN VENTRAL Horn

EXP NEURONS -VENTROMEDIAL

INSP NEURONS- LATERAL

ASCENDING SPINORETICULAR FIBRES

CARRY PROPRIOCEPTIVE INPUTS TO

STIMULATE RESP CENTRE.

BILAT CERVICAL CORDOTOMY

LEADS TO RESPIRATORY

DYSFUNCTION (SLEEP APNEA).

Diaphragm controlled directly by motor neurons – “C3,4 & 5 keeps the diaphragm alive”.

Motor neurons take turns to stimulate different groups of muscle fibres active to minimise fatigue.

Due to poor supply of muscle spindles , control comes from DRG &VRG.

And this explains why rare to feel fatigue in diaphragm.

Larynx movements are synchronized with breathing.

Superior and recurrent laryngeal nerves are branches of vagus nerve.

Expiration – vocal cords together.Inspiration – vocal cords apart.

Automatic rhythm that we can override consciously.

Opera singers try and maximise control of breathing using these muscles.

Control of breathing affected profoundly by vagus nerves (Cranial Nerve X).

Two of these run down either side of neck and torso, near trachea.

Regulate receptors which are most involved in respiration:• Slowly-adapting pulmonary stretch receptors (PSR’s)

• Rapidly-adapting (irritant) receptors (RAR’s)

• C-fibre receptors (J receptors)

Paintel et al (1970) :

Propose J receptors function TO LIMIT

EXERCISE WHEN INTERSTITIAL

PRESSURE INCREASES(J REFLEX)

MECHANISM:

INHIBITION OF RESP MOTOR

NEURONS.

• + when pulmonary caps are

engorged or pulmonary edema.

create a feeling of dyspnea

UNMYELINATED NERVE ENDINGS .

RESPONSIBLE FOR BRONCHOSPASM IN ASTHMA.

INCREASED TRACHEOBRONCHIAL SECRETIONS.

MEDIATORS:HISTAMINE, PROSTAGLANDINS ,

BRADYKININ.

Herring-Breuer Inflation reflex• stretch receptors located in wall of airways• + when stretched at tidal volumes > 1500 ml• inhibits the DRG

Inflation

Apnoea

Phrenic nerve activity

Lung volume

Safety threshold that

triggers reflex

Airway Receptors:

Slowly adapting (stretch - ends

inspiration)

Rapidly adapting (irritants -

cough)

Bronchial c-fiber (vascular

congestion - bronchoconstriction)

Parenchymal c-fiber (irritants -

bronchoconstriction)

Xth n.

Reflex Control of

Breathing –

Neural receptors

afferents

EXPT ANIMAL STUDIES

Rapid shallow breathing pattern in

response to bronchospasm is mediated

through vagal afferents.

MECHANORECEPTORS - SENSE

CHANGES IN LENGTH ,TENSION AND

MOVEMENT.

ASCENDING TRACTS IN ANTERIOR

COLUMN OF SPINAL CORD TO RESP

CENTRE IN MEDULLA.

SENSE CHANGES IN MSL LENGTH.

INTERCOSTALS > DIAPHRAGM .

REFLEX CONTRACTION OF MUSCLE IN RESPONSE TO STRETCH.

INCREASE VENTILATION IN EARLY STAGES OF EXERCISE.

SENSE DEGREE OF CHEST WALL

MOVT.

INFLUENCE THE LEVEL & TIMING OF

RESP ACTIVITY.

Neural control Beta receptors causing dilatation

Parasympathetic-muscarinic receptors causing constriction

NANC nerves (non-adrenergic, non-cholinergic)○ Inhibitory release VIP and NO bronchodilitation

○ Stimulatory bronchoconstriction, mucous secretion, vascular hyperpermeability, cough, vasodilation “neurogenic inflammation”.

Local factors• histamine binds to H1 receptors-constriction

• histamine binds to H2 receptors-dilation

• slow reactive substance of anaphylaxsis-

constriction-allergic response to pollen

• Prostaglandins E series- dilation

• Prostaglandins F series- constriction

Monitor changes in

blood PC02, P02, and

pH.

Central:

• Medulla.

Peripheral:

• Carotid and aortic

bodies.

Control breathing

indirectly.

RESPONSE TO HYPERCAPNIA

• 20-50% CAROTID BODIES

• 50-80% CENTRAL CHEMORECEPTORS

CO2, H+

Control of

Breathing by

Central

chemoreceptors

Central

chemoreceptors

major regulators of

breathing

CO2, H+

Central

chemoreceptors

Resp

neurons

VE

Carotid

body

O2

Chemical

Control of

Breathing –

Peripheral

chemoreceptorsIXth n.

CO2

pH

~10% contribution

to breathing

CO2 tension in blood (mm Hg)

35 40 45

VE

5

50

(L/min)quiet breathing

hypercapnia

CO2 drives ventilation

CO2 tension in blood (mm Hg)

35 40 45

VE

5

50

(L/min)

Hypoxia is a weak ventilatory

stimulus

blood pO2 =

100 mmHg

blood pO2 =

50 mmHg

Are not stimulated directly by changes in

arterial PC02.

H20 + C02 H2C03 H+

Stimulated by rise in [H+] of arterial blood.• Increased [H+] stimulates peripheral

chemoreceptors.

NO CHANGE CAROTID BODY ACTIVITY TILL PaO2 < 75mmHg.

VENTILATION MARKEDLY INCREASED When

PaO2<50mmHg

RAPID PHASE- RAPID INCREASE IN VE

WITHIN SECONDS DUE TO

ACIDIFICATION OF CSF.

SLOWER PHASE- DUE TO BUILDUP OF

H+ IONS IN MEDULLARY

INTERSTITIUM.

CHRONIC HYPERCAPNIA- WEAKER

EFFECT DUE TO RENAL RETENTION

OF HCO3 WHICH REDUCES THE H+.

VENTILATORY RESPONSE TO ALV O2

CO2 POTENTIATES

VENTILATORY

RESPONSE TO

HYPOXEMIA .

BOTH HYPOXEMIC

AND HYPERCAPNIC

RESPONSES

DECREASE WITH

AGEING AND

EXERCISE

TRAINING.

Normal level of HCO3- = 25 mEq/L

Metabolic acidosis (low HCO3-) will

stimulate ventilation (regardless of CO2

levels).

Metabolic alkalosis (high HCO3-) will

depress ventilation (regardless of CO2

levels) .

EFFECT OF PaCO2 & pH ON

VENTILATION

SENSATION OF DYSPNEA WHEN

INCREASED RESP EFFORT DUE TO

“LENGTH- TENSION

INAPPROPRTATENESS”

REMOVAL OF FLUID RESTORES THE

END EXP MSL FIBRE LENGTH

RESTORES THE LENTH TENSION

RELATIONSHIP RELIEF.

SV & CO decreasedCoronary blood flow decreasedRepolarization of heart impairedOxyhemoglobin affinity increasedCerebral blood flow decreasedSkeletal muscle spasm & tetanySerum potassium decreased

• (common thread in most of above is hypocapnic alkalosis)

Effect of brain edema• depression or inactivation of respiratory centers

Effect of Anesthesia/Narcotics• respiratory depression

sodium pentobarbital

morphine

BILATERAL CAROTID BODY

RESECTION

CAROTID ENDARTERECTOMY

REDUCES VE.

30% DECREASE IN RESPONSE TO

HYPERCAPNIA.

59Y FEMALE COPD,CVA ( OLD)CAROTID ENDARTERECTOMY 1YR

ELECTIVE CE (R) DONEPREOP ABG ON R/A- 7.43/50/48/31DAY 3 EXTUBATED O2 3L/MINDAY5: SOMNOLENT AND CONFUSEDABG- 7.28/62/69/31BiPAP INITIATED IMPROVEDABG-7.38/72/54/36

COPD WITH HYPERCAPNIA &

WORSENING RESP ACIDOSIS FULL

OXYGEN THERAPY• LOSS OF HYPOXIC DRIVE

• WORSENING V/Q MISMATCH

PHYSIOLOGIC DEAD SPACE

• CO2 CARRYING CAPACITY AS

OXYGENATION OF Hb IMPROVES

( HALDANE EFFECT)

PERIODIC BREATHING PATTERN WITH

CENTRAL APNEAS.

Causes

1. BILATERAL SUPRAMEDULLARY

LESION

2. CARDIAC FAILURE

3. HIGH ALTITUDE

4. SLEEP

Response to hypoxia and

hypercapnia.

Response to

MECHANORECEPTORS

Pa O2 AND PaCO2 BY 4-8 mmHg

HYPOTONIA OF UPPER AIRWAY-

OBSTR SLEEP APNEA.

HYPOTONIA OF SKELETAL& RESP

MUSCLES- (Ventilation DEPENDS ON

DIAPHRAGM)

PHASE I - IMMED VE WITHIN

SECONDS,NEURAL IMPULSES MSL

SPINDLES, JOINT PROPRIOCEPTORS .

PHASE II- WITHIN 20-30 SEC VENOUS

BLD FROM MSL,SLOW VE(

VENTILATION LAGS BEHIND CO2).

PHASE III - PULM GAS EXCHANGE

MATCHES THE METAB RATE TO

MAINTAIN STABLE O2, CO2, PH.

PHASE IV - BEGINS AT ANAOERBIC

THRESHOLD, O2 CONSUMTION> O2

DELIVERY AND LACTIC ACID

ACCUMULATES.

VENTILATORY RESPONSE TO EXERCISE