REGULATION OF REGULATION OF RESPIRATION RESPIRATION

ByByDr. M. Anthony David, MDDr. M. Anthony David, MD

Professor of PhysiologyProfessor of Physiology

RESPIRATORY CONTROL: A RESPIRATORY CONTROL: A SCHEMASCHEMA

SENSORSRECEPTORS

CENTER

EFFECTORS

VENTILATION

OUTPUT

INPUTFEED

BACK

FEED

BACK

PONTO MEDULLARY PONTO MEDULLARY RESPIRATORY CENTERSRESPIRATORY CENTERS

ALL ARE PAIRED & INTERCONNECTED

INFERIOR COLLICULUS

PNEUMOTAXIC CENTER

PONS

MEDULLAOBLONGATA

SPINAL CORD

INSPIRATORY NEURONS

EXPIRATORY NEURONS

APNEUSTIC CENTER

PRE BOTTZINGER COMPLEX

DORSAL GROUP OF R NEURONS

VENTRAL GROUP OF R NEURONS

RESPIRATORY CENTERSRESPIRATORY CENTERS

1. 1. PNEUMOTAXIC CENTER:PNEUMOTAXIC CENTER:• Location: Upper PonsLocation: Upper Pons• Absence causes APNEUSTIC Absence causes APNEUSTIC

BREATHING (Esp when the vagi are BREATHING (Esp when the vagi are cut)cut)

• Curtails inspiratory activity & thus can Curtails inspiratory activity & thus can increase the rate of respirationincrease the rate of respiration

APNEUSTIC CENTERAPNEUSTIC CENTER Location: Lower PonsLocation: Lower Pons Stimulates the Inspiratory Center and Stimulates the Inspiratory Center and

increases Inspirationincreases Inspiration Gets feed back from Vagi & other Gets feed back from Vagi & other

Centers.Centers.

MEDULLARY RESPIRATORY MEDULLARY RESPIRATORY CENTERSCENTERS

DORSAL GROUPDORSAL GROUP Neurons diffusely Neurons diffusely

located in the NTSlocated in the NTS All neurons are of All neurons are of

the Inspiratory the Inspiratory typetype

Generates the Generates the Inspiratory Ramp Inspiratory Ramp SignalSignal

Is autorhythmicIs autorhythmic

VENTRAL GROUPVENTRAL GROUP Has both Has both

Inspiratory & Inspiratory & Expiratory neuronsExpiratory neurons

Expiratory neurons Expiratory neurons found at Caudal & found at Caudal & Rostral ends.Rostral ends.

Inspiratory neurons Inspiratory neurons found in the central found in the central area.area.

All the respiratory centers are termed as All the respiratory centers are termed as the the BULBOPONTINE RESPIRATORY BULBOPONTINE RESPIRATORY NEURONAL COMPLEXNEURONAL COMPLEX

There is an inspiratory ramp generator There is an inspiratory ramp generator called called Respiratory Control Pattern Respiratory Control Pattern Generator: Pre Bottzinger ComplexGenerator: Pre Bottzinger Complex

RESPIRATORY CONTROL RESPIRATORY CONTROL ORGANIZATION:MODERN CONCEPTORGANIZATION:MODERN CONCEPT

The Inspiratory Off switch(IOS) is fine The Inspiratory Off switch(IOS) is fine tuned by PTC & the chemoreceptor tuned by PTC & the chemoreceptor drive.drive.

Both Both Neural & Chemical controlsNeural & Chemical controls are are well coordinated.well coordinated.

RESPIRATORY CONTROL RESPIRATORY CONTROL ORGANIZATION:MODERN CONCEPTORGANIZATION:MODERN CONCEPT

PERIPHERAL INFLUENCES ON PERIPHERAL INFLUENCES ON RESPIRATORY CONTROLRESPIRATORY CONTROL

LUNG OR PULMONARY RECEPTORS:LUNG OR PULMONARY RECEPTORS:• Receptors in and around the lungs.Receptors in and around the lungs.

CHEMORECEPTORSCHEMORECEPTORS• Peripheral ChemoreceptorsPeripheral Chemoreceptors• Central Chemoreceptors.Central Chemoreceptors.

PERIPHERAL INFLUENCESPERIPHERAL INFLUENCES

The four influences from the lungs The four influences from the lungs are:are:• Pulmonary stretch receptorsPulmonary stretch receptors• Lung irritant receptorsLung irritant receptors• J receptorsJ receptors• ProprioceptorsProprioceptors

Along with the chemoreceptors, Along with the chemoreceptors, these receptors send information to these receptors send information to the respiratory centers.the respiratory centers.

HERING BREUER(HB) REFLEXHERING BREUER(HB) REFLEX

It is a ‘Volume’ reflex.It is a ‘Volume’ reflex. Receptors are located in between the Receptors are located in between the

smooth muscles of the small airways.smooth muscles of the small airways. These receptors are unmyelinated These receptors are unmyelinated

nerve endings.nerve endings. They are stimulated by the change of They are stimulated by the change of

shape of the Airways.shape of the Airways.

HB INFLATION REFLEXHB INFLATION REFLEX

INSPIRATION

TIDAL VOLUME >1lt

STRETCH OF THE AIRWAYS

INCREASED RESPIRATORY RATE

DECREASED TIME FOR INSPIRATION

A NEGATIVE FEEDBACK SERVOCONTROL SYSTEM

HB INFLATION REFLEXHB INFLATION REFLEX

0.5 lts 1.0 Ltrs 1.5 lts 2.0 lts 2.5 lts 3.0lts 3.5lts

INSPIRATION

TIME

TIDAL VOLUME in Liters

HB DEFLATION REFLEXHB DEFLATION REFLEX Excessive deflation of the lungs Excessive deflation of the lungs

causes Inspiration.causes Inspiration. This reflex prevents This reflex prevents AtelectasisAtelectasis.. AtelectasisAtelectasis is the collapse of the is the collapse of the

lungs.lungs. This reflex also opens up collapsed This reflex also opens up collapsed

portions of the lung.portions of the lung.

CHEMICAL CONTROL:THE CHEMICAL CONTROL:THE THREE MAIN ‘CHEMICALS’ THREE MAIN ‘CHEMICALS’

OXYGENOXYGEN• POPO22 levels in blood. levels in blood.

CARBON DIOXIDECARBON DIOXIDE::• PCOPCO22 levels in blood. levels in blood.

HYDROGEN IONHYDROGEN ION::• Concentration in blood.Concentration in blood.

COCO22 & [H & [H++] act ] act centrallycentrally while the while the Oxygen levels act on the Oxygen levels act on the peripheralperipheral chemoreceptors.chemoreceptors.

RESPIRATORY RESPIRATORY CHEMORECEPTORSCHEMORECEPTORS

CENTRALCENTRAL:: CHEMORECEPTOR ZONE:CHEMORECEPTOR ZONE:

• BILATERALBILATERAL• LOCATED IN THE MEDULLALOCATED IN THE MEDULLA• JUST BENEATH IT’S VENTRAL SURFACEJUST BENEATH IT’S VENTRAL SURFACE• HIGHLY SENSITIVE TO PCOHIGHLY SENSITIVE TO PCO22 AND [H AND [H++]]

FUNCTIONS BY STIMULATING THE FUNCTIONS BY STIMULATING THE RESPIRATORY CENTERS:RESPIRATORY CENTERS:• DRG,VRG & PTC.DRG,VRG & PTC.

CENTRAL CENTRAL CHEMORECEPTORSCHEMORECEPTORS

PRIMARY STIMULUS:PRIMARY STIMULUS:• [H[H++]]

PERHAPS THE ONLY IMPORTANT PERHAPS THE ONLY IMPORTANT DIRECT STIMULUS FOR THE CENTRAL DIRECT STIMULUS FOR THE CENTRAL CHEMORECEPTOR CELLS (MEDULLARY CHEMORECEPTOR CELLS (MEDULLARY CHEMORECEPTORS)CHEMORECEPTORS)

But these ions do not cross the Blood But these ions do not cross the Blood Brain BarrierBrain Barrier

So, the blood PCOSo, the blood PCO22 level has more level has more effect as COeffect as CO22 readily crosses the BBB. readily crosses the BBB.

STIMULATION BY STIMULATION BY CARBONDIOXIDECARBONDIOXIDE

Is not direct.Is not direct. Even the indirect effect of COEven the indirect effect of CO22 is most is most

potent. Why?potent. Why? Because COBecause CO2 2 easily crosses the BBB.easily crosses the BBB. Once it is across the BBB,Once it is across the BBB, COCO2 2 + H+ H22O HO H22COCO33 H H++ + HCO + HCO33

--

These increased HThese increased H++ ions in the brain ions in the brain stimulate the medullary stimulate the medullary chemoreceptors.chemoreceptors.

QUANTITATIVE EFFECT OF QUANTITATIVE EFFECT OF HH++ IONS IONS

The stimulatory effect of H+ ions The stimulatory effect of H+ ions increases in the first few hours.increases in the first few hours.

It then decreases in the next 1 to 2 It then decreases in the next 1 to 2 days.days.

It comes down to about 1/5It comes down to about 1/5thth the the initial effect.initial effect.

This is due to Renal readjustment of This is due to Renal readjustment of [H+] in the circulating blood.[H+] in the circulating blood.

The kidneys increase blood HCOThe kidneys increase blood HCO33.. This bicarbonate binds with the free This bicarbonate binds with the free

HH++ ions in the blood & decreases their ions in the blood & decreases their concentration.concentration.

Bicarbonate also diffuses slowly past Bicarbonate also diffuses slowly past the BBB and decreases the Hthe BBB and decreases the H++ ions in ions in the brain.the brain.

Therefore the effect of HTherefore the effect of H++ ions is: ions is:• POTENT: AcutelyPOTENT: Acutely• WEAK : Chronically.WEAK : Chronically.

QUANTITATIVE EFFECT OF QUANTITATIVE EFFECT OF HH++ IONS IONS

EFFECT OF COEFFECT OF CO22

Change in PCOChange in PCO22 between 35 to between 35 to 75mmHg causes peak increase in 75mmHg causes peak increase in alveolar ventilation.alveolar ventilation.

Change in the normal range Change in the normal range causes less than tenth of change causes less than tenth of change in alveolar ventilation.in alveolar ventilation.

EFFECT OF OXYGENEFFECT OF OXYGEN

The partial pressure of The partial pressure of Oxygen has no effect on the Oxygen has no effect on the medullary chemoreceptors.medullary chemoreceptors.

It only has an effect on the It only has an effect on the peripheral chemoreceptors.peripheral chemoreceptors.

PERIPHERAL PERIPHERAL CHEMORECEPTORSCHEMORECEPTORS

There are two pairs of chemoreceptors:There are two pairs of chemoreceptors:• Aortic BodiesAortic Bodies: located at the arch of : located at the arch of

aorta.aorta.• Carotid bodiesCarotid bodies: located at the : located at the

branching of the common carotid branching of the common carotid arteries.arteries.

Their functions are:Their functions are:

• To detect changes in the POTo detect changes in the PO22

• To transmit nervous signals to the To transmit nervous signals to the Respiratory Centers. Respiratory Centers.

These bodies have two types of These bodies have two types of special cells called special cells called glomus cellsglomus cells..

The type 2 glomus cells have special The type 2 glomus cells have special ion channels sensitive to POion channels sensitive to PO22..

They fire the nerve endings and They fire the nerve endings and send signals via:send signals via:• Aortic bodies: Vagi.Aortic bodies: Vagi.• Carotid bodies: Hering nerve & Carotid bodies: Hering nerve &

Glossopharyngeal nerve.Glossopharyngeal nerve.

PERIPHERAL PERIPHERAL CHEMORECEPTORSCHEMORECEPTORS

Both these bodies receive their own Both these bodies receive their own special blood supply through minute special blood supply through minute arteries, directly from the trunk.arteries, directly from the trunk.

Their blood flow is roughly Their blood flow is roughly 20 times 20 times their own weighttheir own weight..

THEY ARE ALL THE TIME EXPOSED THEY ARE ALL THE TIME EXPOSED ONLY TO ONLY TO ARTERIAL BLOODARTERIAL BLOOD..

POPO22 stimulates these stimulates these chemoreceptors strongly.chemoreceptors strongly.

PERIPHERAL PERIPHERAL CHEMORECEPTORSCHEMORECEPTORS

ARTERIAL POARTERIAL PO22 & IMPULSES & IMPULSES IN AORTIC BODYIN AORTIC BODY

POPO22 especially between 60 and especially between 60 and 30mm Hg strongly stimulates the 30mm Hg strongly stimulates the carotid bodies.carotid bodies.

This is the range wherein the Hb This is the range wherein the Hb saturation decreases.saturation decreases.

EFFECT OF POEFFECT OF PO22

When PCOWhen PCO22 & [H & [H++] are kept ] are kept constantly normal,constantly normal,

There is no effect if the POThere is no effect if the PO22 is is >100mmHg>100mmHg

If it falls below 100mmHg, If it falls below 100mmHg, ventilation doubles upto 60 ventilation doubles upto 60 mmHg.mmHg.

It increases upto 5 times at very It increases upto 5 times at very low POlow PO22 levels levels

COCO22 & H & H++

They also stimulate the peripheral They also stimulate the peripheral chemoreceptors.chemoreceptors.

But their effects on the central or But their effects on the central or medullary chemoreceptors are more medullary chemoreceptors are more powerful.powerful.

PCOPCO22 stimulates the peripheral stimulates the peripheral chemoreceptors 5 times as rapidly as chemoreceptors 5 times as rapidly as it stimulates the central ones.it stimulates the central ones.

So this is responsible for the rapid So this is responsible for the rapid response to COresponse to CO22 at the onset of at the onset of exercise.exercise.