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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.