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Case 1: Obj 33-35

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Case 1: Obj 27-32

Case 1: Obj 19-26

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Summary Case 1

L3- Regulation of Respiration Brain Stem Centre

•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

•Any physiological control system is composed of 3 interconnecting structures:

•Integrator (centre), Sensor & Effector

Picture1

The Respiratory Control System

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

Picture2

The Respiratory Centre

Present in brain stem

• 1) Medullary group of neurons (rhythmicty centre)

• 2) Pontine:

  1. Apneustic
  2. Pnemotaxic

Picture3

(I) Medullary Respiratory Neurons (Rhythmicity Centre)

•2 distinct groups of neurons;

  1. The Dorsal Inspiratory Group (DIG)
  2. The Ventral Expiratory Group (VEG)

•The 2 groups are bilaterally paired

•There is cross communication between them

  1. responsible for initiation & regulation of breathing

1 -Dorsal Inspiratory Group (DIG)

•Inspiratory neurons that discharge during inspiration & stop discharging during expiration (Inspiratory 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

Input to DIG

•The most important sensory comes from the adjacent central Chemoreceptors (chemosensitive area in medulla)

•Input from peripheral Chemoreceptors via afferent sensory of vagus (X) & glossopharyngeal (IX)

•Stimulatory input from Apneustic centre prolonging its activity

•Inhibitory input from Pneumotaxic centre terminating its activity

Output from DIG

•Efferent nerves to spinal motoneurons supplying diaphragm (C3-5) & external intercostals (T1-T12).

•Stimulatory to Pneumotaxic centre

2 -Ventral Expiratory Group (VEG)

Anterolateral to DIG

•Activated during heavy breathing; e.g. exercise

•During such conditions, the increased activity of inspiratory neurons activates the VEG

•In turn, the activated VEG discharge:

  1. – inhibiting inspiratory group
  2. – stimulating the muscles of expiration; internal intercostals (T6-L3), abdominal recti (T4-L3)

(II) Pontine Respiratory Centre

•2 pontine centres that modify the rate & The Pattern of respiration

1 -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

Picture4

2 -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

•Thus the pontine centres work in co-ordination to regulate rhythmic respiratory cycle; How

  1. Active inspiratory neurones→ ms. of inspiration & pneumotaxic centre → inhibits apneustic & DIG → initiation of expiration

•Spontaneous activity of inspiratory neurons then starts another cycle

(III) The co-ordinated work of neurons of respiratory centre (Pons & Medulla)

Picture5

Overall Control of Activity of Respiratory Centre

A). Involuntary (Automatic) Control:

  1. Chemoreceptor Reflexes
  2. Neurogenic Reflexes

B). Voluntary Control

A). Involuntary Automatic Control

I- Chemoreceptor Reflexes

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

1- Central Chemoreceptor Pathway

2- Peripheral Chemoreceptor Pathway

•These chemoreceptors sense changes in PCO2, PO2 & pH

1- Central Chemoreceptors Pathway (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 PCO2 ,H+ conc., but not to PO2

Picture6•Under normal conditions, ~75-85% of respiratory drive is due to stimulation of central chemoreceptors by CO2

•However, central chemoreceptors are directly stimulated only by H+

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

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

Picture7

2- Peripheral Chemoreceptor Pathway (Peripheral Chemoreceptors)

Picture8*Carotid n Aortic Body = Peripheral Chemoreceptors = the only sensors detecting a fall in PO2*

Stimulation of Peripheral chemoreceptors

•The carotid & aortic bodies are sensitive to  fall in PO2, an increase in PCO2 or  H+ concentration

•They maximally stimulated when PO2 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 PO2 but reduced content of O2 bound to Hb)

Picture10•if there is decreased PO2 (Hypoxia) with absence of peripheral chemoreceptors, Hypoxia will inhibit respiration

Why?

•hypoxia depresses neuronal activity including that of respiratory centre

•Hypoxia →VD of cerebral vessels → ↓PCO2 in CSF →  ↓CO2-mediated stimulation of central chemoreceptors → hypoventilation

II- Neurogenic Reflexes

  1. Hering-Breuer Inflation Reflex
  2. Hering-Breuer Deflation Reflex
  3. J-receptor Reflex
  4. Baroreceptors Reflex
  5. Cough & sneezing Reflexes
  6. Other influences (mediated via hypothalamus)

1- 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 apneustic centre →termination of inspiration

2- Hering-Breuer deflation reflex (excito-inspiratory reflex)

•Deep expiration → Deflation of the lungs → ↓activity of previous stretch receptors or stimulate other propioceptors in respiratory muscle → vagal afferent signals → inhibition of expiratory neurons

3- J-receptor Reflex

•Pulmonary emboli or oedema →juxtapulmonary-capillaries receptors →vagal afferent to respiratory centre → rapid shallow respiration

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

4- Baroreceptor Reflex

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

5- Cough, Sneezing reflexes

•Dust, smoking, irritant substances → stimulation of irritant receptors in upper airways →afferent signals via vagus (Upper airways, {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

Picture11

6- Other Influences from higher centres hypothalamus & limbic system

•Temperature: Increases respiratory rate

•Pain: Sudden pain decreases, prolonged pain increases rate

•Alcohol: Decreases rate

B). Voluntary Control of Breathing

Cortical Influence

•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)

Summary in Figures

1) Summary of the Effect of arterial PCO2 on ventilation

Picture12

2) Effect of a decreased arterial PO2

Picture13

3) Summary of Chemical Pathways stimulating Ventilation

Picture14

4) Summary Of the Overall Control of Activity of Respiratory Centre

Picture15