regulation of respiration, mmmp

Dr. Nisreen Abo-elmaaty

Regulation of Respiration

Dr. Nisreen Abo-elmaaty

The Respiratory system in human performs a critical task

That is to regulate & respond to O2

demands Maintaining a constant O2 & CO2 in the

blood Therefore, regulation of respiration is

critically important for Homeostasis

Dr. Nisreen Abo-elmaaty

Integrator (Centre) → neural network in brainstem Sensors → The main are chemosensors

sensing changes in CO2, O2 & pH

Other contributors: in the lungs, cardiovascular, skeletal muscles, tendons of respiratory muscles,

Effector → respiratory muscles

Inspiration; diaphragm &external intercostals Expiration; internal intercostals & abdominal recti

The Respiratory Control System

Dr. Nisreen Abo-elmaaty

The Respiratory Centre

• Present in brain stem

• Medullary group of neurons (rhythmicty centre)

• Pontine: Apneustic Pnemotaxic

Dr. Nisreen Abo-elmaaty

Medullary Respiratory Neurons(Rhythmicity Centre)

2 distinct groups of neurons; The Dorsal Inspiratory Group (DIG) The Ventral Expiratory Group (VEG)• The 2 groups are bilaterally paired• There is cross communication between them responsible for initiation & regulation of

breathing

Dr. Nisreen Abo-elmaaty

• Inspiratory neurons that discharge during inspiration & stop discharging during expiration (Respiratory Rhythm generator)

• They generate a Ramp Signal;

they initiate inspiration with a weak burst of action potentials that gradually increase in amplitude, then ceases for the next 3 sec. until a new cycle begins

• This provides a gradual increase in lung volume during inspiration

Medullary Respiratory NeuronsDorsal Respiratory Group (DRG)

Dr. Nisreen Abo-elmaaty

Medullary Respiratory NeuronsInput & Output of DRG

DRG

Central chemoreceptors

Peripheral chemoreceptors

Pneumotaxic centreApneustic centre

-+

+

Spinal motoneurons

Cervical (3,4,5) & Thoracic (1-12)

Dr. Nisreen Abo-elmaaty

Medullary Respiratory NeuronsVentral Respiratory Group (VRG)

• Anterolateral to DRG• Activated during heavy breathing; e.g.

exercise • During such conditions, the increased activity

of inspiratory neurons activates the VRG• In turn, the activated VRG discharge: - inhibits inspiratory group - stimulates the muscles of expiration; internal

intercostals (T6-L3), abdominal recti (T4-L3)

Dr. Nisreen Abo-elmaaty

Pontine Respiratory Centre

2 pontine centres that modify

The rate & The Pattern of respiration

Dr. Nisreen Abo-elmaaty

Pontine Respiratory Centres

Apneustic centre:• In the lower 1/3 close to

medullary groups• sends stimulatory

discharge to inspiratory neurons promoting inspiration

• Removal of its stimulatory effect→ respiration becomes shallow & irregular

Dr. Nisreen Abo-elmaaty

Pontine Respiratory Centres

Pneumotaxic centre• In upper 2/3 of pons• Its major role is regulation of

respiratory volume & rate• Controlling cessation of

inspiratory ramp signal from DIG;

• Switch-off DIG & apneustic centre → expiration occurs

• Hypoactivation of this centre →prolonged deep inspiration with limited brief expiration

• Hyperactivation →shallow inspiration

Dr. Nisreen Abo-elmaaty

How Pontine Respiratory Centres work to regulate rhythmic respiratory cycle?

Active dorsal medullary inspiratory neurones→ stimulatory discharge to ms. Of inspiration & pneumotaxic centre → activated pneumotaxic centre inhibits apneustic & DRG → initiation of expiration

• Then, the spontaneous activity of inspiratory neurons starts another cycle

Dr. Nisreen Abo-elmaaty

The co-ordinated work of neurons of respiratory centre

+

Dr. Nisreen Abo-elmaaty

Overall Control of Activity of Respiratory Centre

A). Involuntary (Automatic) Control: I- Chemoreceptor Reflexes II- Neurogenic Reflexes B). Voluntary Control

Dr. Nisreen Abo-elmaaty

A). Involuntary Automatic ControlI- Chemoreceptor Reflexes

Chemical regulation of activity of Respiratory centre which involves 2 pathways:

1- Central Chemoreceptor Pathway

2- Peripheral (Arterial) Chemoreceptor Pathway

These chemoreceptors sense changes in PaCO2, PaO2 & pH

Dr. Nisreen Abo-elmaaty

1- Central Chemoreceptors Pathway Its receptors: Central chemosensitive area• Lying just beneath

ventral surface of medulla

• Relaying most important sensory input about changes in their close environment to respiratory centre in medulla & pons

• Most sensitive to change in PaCO2 ,H+ conc., but not to PaO2

Dr. Nisreen Abo-elmaaty

• Under normal conditions, ~75-85% of respiratory drive is due to stimulation of central chemoreceptors by PaCO2

• However, the direct stimulant for neurons of central chemoreceptors is only H+ ions

• But H+ can not cross blood brain barrier while CO2 can

• So, how central chemoreceptors are stimulated by an increase in arterial PCO2?

1- Central Chemoreceptors Pathway Central chemosensitive area

Dr. Nisreen Abo-elmaaty

More sensitive to changes in CSF than to changes in cerebral blood

Dr. Nisreen Abo-elmaaty

2- Peripheral Chemoreceptor PathwayPeripheral (Arterial) Chemoreceptors

Peripheral chemoreceptors are the only sensors detecting a fall in PO2

Dr. Nisreen Abo-elmaaty

2- Peripheral Chemoreceptor Pathway Stimulation of Peripheral chemoreceptors

• The carotid & aortic bodies are sensitive to

fall in PaO2, an increase in PaCO2 or H+

concentration• They maximally stimulated when

PaO2 decreases below 50-60mm Hg• They detect changes in dissolved O2

but not in the O2 that is bound to Hb (e.g. in anaemia there is normal PaO2 but reduced content of O2 bound to Hb)

Dr. Nisreen Abo-elmaaty

What if Carotid bodies are removed?

• if there is decreased PaO2 (Hypoxia) with absence of peripheral chemoreceptors Hypoxia would inhibit respiration

Why?• hypoxia depresses neuronal activity

including that of respiratory centre• Hypoxia →VD of cerebral vessels

→↓PaCO2 in CSF →↓CO2-mediated stimulation of central chemoreceptors → hypoventilation

Dr. Nisreen Abo-elmaaty

A). Involuntary Automatic ControlII- Neurogenic Reflexes

Hering-Breuer Inflation Reflex Hering-Breuer Deflation Reflex J-receptor Reflex Cough & sneezing Reflexes Baroreceptors Reflex Other influences (mediated via

hypothalamus)

Dr. Nisreen Abo-elmaaty

Neurogenic Reflexes originating from the respiratory system1- Hering-Breuer inflation reflex (inhibito-inspiratory reflex)

• Over-Inflation of lungs→ stimulation of slowly adapting stretch receptors in smooth muscles of large & small airways →afferent vagal signals → inhibitory to medullary and pontine inspiratory network →termination of inspiration

• This reflex in not important in normal adults. It is more important & powerful in neonates.

Dr. Nisreen Abo-elmaaty

Neurogenic Reflexes originating from the respiratory system 2- Hering-Breuer deflation reflex (excito-inspiratory reflex)

• Deep expiration → Deflation of the lungs → ↓activity of previous slowly adapting stretch receptors or stimulate other propioceptors in respiratory muscle → decreasing afferent vagal signals to respiratory centres→ increase in the activity of inspiratory neurons →↑ rate of breathing

Dr. Nisreen Abo-elmaaty

Neurogenic Reflexes originating from the respiratory system 3- J-receptor Reflex

• Pulmonary emboli or oedema or congestion → stimulation of juxtapulmonary-capillaries receptors →impulses along vagal afferent → respiratory centre → rapid shallow breathing

• These receptors are responsible for the sensation of air hunger (Dyspnea; shortness of breath)

Dr. Nisreen Abo-elmaaty

Neurogenic Reflexes originating from the respiratory system 4- Cough, Sneezing reflexes

• Dust, smoking, irritant substances → stimulation of irritant receptors in upper airways (nose, larynx, bronchi)→afferent signals via vagus (larynx, cough}) or trigeminal or olfactory (nose, sneezing) → respiratory centre → deep inspiration followed by forced expiration against closed glottis →opening of glottis →forceful outflow of air (help removal of irritants)

Dr. Nisreen Abo-elmaaty

Neurogenic Reflexes from other systems Baroreceptor Reflex

• Acute ↑in ABP → stimulation of baroreceptors →afferent signals via X & IX → inhibitory to respiratory centre → decrease rate & depth of respiration → ↓venous return → ↓COP → ↓ABP

Dr. Nisreen Abo-elmaaty

Dr. Nisreen Abo-elmaaty

Neurogenic Reflexes Other Influences from higher centershypothalamus & limbic system

• Temperature: Increases respiratory rate• Pain: Sudden pain decreases, prolonged

pain increases rate• Alcohol: Decreases rate• Exercise; increases breathing rate (higher

cortical centers)

Dr. Nisreen Abo-elmaaty

• Through descending tracts from the cerebral cortex to motor neurons of the respiratory muscles (dorsolateral corticospinal tracts)

• This provides CNS the ability to override the automatic regulation of respiration for short time e.g. holding breath but the involuntary control will take over (↑ PCO2, H+), or deliberate hyperventilation (↓PCO2)

B). Voluntary Control of BreathingCortical Influence

Dr. Nisreen Abo-elmaaty

Now, can U explain what u have read about Luke?• His respiratory rate of 22/min• His PaO2 was 61 mm Hg• His PaCO2 was 31 mm Hg

Dr. Nisreen Abo-elmaaty

Summary in Figures

Dr. Nisreen Abo-elmaaty

The Effect of ↑ PaCO2 on ventilation

Dr. Nisreen Abo-elmaaty

Effect of a decreased PaO2

Dr. Nisreen Abo-elmaaty

Summary of Chemical Pathways stimulating Ventilation

Dr. Nisreen Abo-elmaaty

Summary Of the Overall Control of Activity of Respiratory Centre

Dr. Nisreen Abo-elmaaty

Now, You should ask yourself if you know the followings:

• General organization of respiratory control system• Localization & description of brain stem centres

involved in regulation of breathing• The sensors that sense changes in PaO2, PaCO2 & H+

• The effects of changes in PaO2, PaCO2 & H+ on breathing

• The list of reflexes that affect the breathing pattern

Dr. Nisreen Abo-elmaaty

Dr. Nisreen Abo-elmaaty

Mark the following T or FRespiratory chemoreceptors:

a). in the carotid and aortic bodies are most important in the ventilatory response to an elevated PCO2 b. in the carotid and aortic bodies are strongly stimulated by the low arterial O2 content in anaemic patients c). in the medulla are responsive to changes in arterial PCO2 d. transducer a chemical changes into electric signals e. may be sensitive to H+

Dr. Nisreen Abo-elmaaty

Choose the best answer

– Voluntary apnea for 90 seconds will

  a. Increase arterial PCO2

  b. Decrease arterial PO2

  c. Stimulate the arterial chemoreceptors

  d. Stimulate the central chemoreceptors

  e. All of the above

Dr. Nisreen Abo-elmaaty

• What is the function of the Apneustic centre in the brain?

a) monitor changes in CO2, O2 & H+ ions

b) sends inhibitory signals to Inspiratory area in medulla

c) sends stimulatory signals to Inspiratory area in medulla

d) monitors changes in blood pressure

Dr. Nisreen Abo-elmaaty

– Stimulation of which of the following receptors should result in decreased ventilation?

  a. Aortic chemoreceptors

  b. Carotid chemoreceptors

  c. Central chemoreceptors

  d. Hering-Breuer inflation (stretch) receptors

Dr. Nisreen Abo-elmaaty

THANK U