Peripheral and central control of breathing

What controls breathing?

Central neural controller: 1. medulla-pattern or respiratory rhythm generator 2. Pons 3. Other central pattern generator for the control of respiration. •It's activity is influenced by other CNS regions and input from sensors. •The output drives the motor neurons that innervate the respiratory muscles.

What to central and peripheral chemo receptors do? What do lung stretch receptors do?

Sense change in partial pressures Lung ventilation is sensed by lung stretch receptors. chemorecetpros always win in terms of not letting you hyperventilate at least over the long term

Peripheral Chemoreceptors

Sensitive to blood oxygen, carbon dioxide and pH Carotid -glossopharyngeal n.(CN IX) (more influential than aortic) Aortic -vagus n. Bipolar neurons Endings are in chemoreceptors. Cell bodies in ganglia. Terminate in the hindbrain nucleus of the solitary tract (NTS)

What would happen if only the diaphragm contracted?

the rib cage muscles would be pulled inward (called retraction).

Reason that chemoreceptors can get accurate info about arterial O2

•Blood flow to the carotid sinus is very high per gram of tissue, so PO2 remains constant. That is, there is little difference between the arterial and venous PO2 in the capillaries that perfuse the chemoreceptors. Therefore the arterial PO2 can be accurately monitored.

A reduction in PCO2 changes the threshold and sensitivity for PO2. Eg: hyperventilation before diving and shallow water blackout

•Hyperventilation decreases PCO2, increases pH and constricts cerebral vasculature. •Breath holding and underwater dive •PO2 falls but drive to breath is reduced because of low PCO2. •CNS hypoxia from low oxygen plus initial cerebral vasoconstriction causes loss of consciousness. •Changes in ambient pressure contribute to blackout as the diver is ascending to the surface

What does VRG do?

•Includes the Pre-Botzinger complex that probably has all the main components of the central pattern generator •Inspiratory and expiratory neurons interact via inhibitory interneurons so that muscles of inspiration and expiration are not simultaneously active.

What are the basic requirements for rhythmic breathing? (4)

•Inspiratory muscles must contract in synchrony: quiet vs. active respiration •Expiratory muscles must contract in synchrony: active respiration only •Inspiratory and expiratory muscles must not contract simultaneously - expiratory drive inhibits inspiration •Rate and depth have to be modulated

What does DRG do?

•Provide rhythmic drive to phrenic motor neurons in contralateral spinal cord via projections to VRG •Considered to primarily influence inspiration •May project directly to spinal inspiratory motor neurons (this is controversial)

Ventilatory response (compensation) to hypoxemia is dependent on both Pao2 and PCO2

Prior to respiratory compensation: Altitude: Low Pao2, normal PCO2 Diffusion limitation: low Pao2 with no or smaller effect on PCO2 Shunt: low Pao2, slightly elevated PCO2 Ventilation-perfusion imbalance: low Pao2, high PCO2 Hypoventilation: low Pao2 high PCO2 Ventilatory response (compensation) to hypoxemia is dependent on both Pao2 and PCO2 The ventilatory response is rapid and the PCO2 obtained with the respiratory compensation tells you about ventilation status (hypo- or hyper-ventilation).

What are the secondary muscles of expiration & their nerves?

Recruited during exercise Internal intercostal muscles: intercostal n. Abdominal muscles: spinal n. all of the expiratory motor neurons have cell bodies in the spinal cord.

What are the secondary muscles of inspiration & their nerves?

Recruited during exercise Larynx & Pharynx: Vagus (CN X) & glossopharyngeal (CN IX) Tongue: Hypoglossal nerve (CN XII) SCM, trapezius: Accessory nerve (CXI) all of the primary and some of the secondary inspiratory motor neurons have cell bodies in the spinal cord.

Other receptors

Respiratory reflexes from muscles tendons and joints important in control of ventilation, especially during exercise. Lung Legs, arms etc. Pain receptors: Somatic pain generally causes hyperpnea Visceral pain causes apnea or decreased ventilation

What are lung receptors?

Vagal mechanical and chemosensitive afferent modulators of medullary control of respiration Afferent neurons enter the CNS via the vagus (CN X) and terminate in the NTS

*The reduced pH in metabolic acidosis activates the peripheral chemoreceptors and shifts the line to the left

causes reduced PaCO2 and elevated ventilation Less sensitive to CO2 under sleep, even more under deep anesthesia

What would happen if only the external intercostal muscles contracted?

diaphragm is pulled upward.

When are expiratory neurons inactive?

during normal tidal volume breathing Expiratory neurons recruited by other inputs when needed.

At normal PCO2 and pH the peripheral chemoreceptors are not very sensitive to Po2. Elevations in PCO2 and/or decreased pH change the threshold and sensitivity of the receptors to Po2.

if you have two or more things telling you to breathe more, it will have synergistic effect e.g. if oxygen is low and co2 is high...breathe more

2.There is a central pattern generator that drives activity of the motor neurons that innervate the muscles involved in respiration. The activity of the pattern generator is controlled by input from central and peripheral chemoreceptors and other inputs (lung stretch receptors etc).

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CO2 enters CNS, combines with water to form carbonic acid which dissociates. H+ stimulates central chemoreceptors.

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Central chemoreceptors detect changes in cerebral spinal fluid (CSF) hydrogen ion concentration, which is directly linked to the partial pressure of carbon dioxide in the brain.

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High sensitivity: 2-5 mmHg increase in Pco2 can more than double alveolar ventilation via stimulation of the central chemoreceptors. The central chemoreceptors are not sensitive to Po2 or blood pH.

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Pontine centers can modulate the activity of the central pattern generator.

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The DRG receives afferent input and projects to the VRG. The VRG contains neurons that control the muscles of respiration and also contains the pattern generator.

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The brain integrates input from the peripheral and central chemoreceptors. A reduction in PO2 decreases the threshold and increases the sensitivity to PCO2

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The control of breathing is tightly linked to metabolic activity. PO2, PCO2 and pH can all influence respiration.

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Under normal resting conditions CO2 acting through H+ at the central chemoreceptors is the primary drive to breathing. PO2 acting at the peripheral chemoreceptors influences respiration when PO2 is below normal or when pH is low and/or PCO2 is high.

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blood gas partial pressure affect chemoreceptors, which feed into DRG and feedback to control lung ventilation

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What are the sensors that send signal to medulla?

1. Peripheral chemoreceptors 2. Central chemoreceptors 3. Lung and other receptors

Why are central chemoreceptors so sensitive?

CSF has a poor buffering capacity relative to blood, so initial pH change can be large. Ventilation is well correlated to the pH of the CSF. In the short-term this is reflective of arterial PCO2. At rest in healthy individuals Pco2, via stimulation of the central chemoreceptors, is the most important regulator of ventilation.

Central chemoreceptors

Chemoreceptors in medulla that sense changes in CO2 and pH levels in CSF or interstitial fluid in the brain. They surround the respiratory center (in medulla) and send signals to respiratory center

Function of Pneumotaxic center (now called pontine respiratory groups)

Can directly affect apneustic center or bypass it and directly affect VRG •Located in ROSTRAL pons •Electrical stimulation in late inspiration facilitates the termination of inspiration. Can inhibit apneustic center and also bypass apneustic ctr and project directly to VRG •Probably not important for generating normal breathing, but can influence it.

Peripheral chemoreceptors

Carotid and aortic body are a cluster of chemoreceptors made of glomus cells (neuron like) that sense systemic changes in O2, CO2 and pH and secrete neurotransmitters to nearby neurons that send signals to the respiratory center in the medulla. Carotid body sends info via CN9 and aortic body sends info via CN 10. Carotid body gets a LOT of blood flow. Highly perfused. 2L/min/100g

What happens in COPD?

Eg: COPD (e.g. emphysema) •Chronic retention of CO2 •Reduced sensitivity of central chemoreceptors to PCO2 •Main drive to ventilation is hypoxia at peripheral chemoreceptors •Giving patient supplemental O2 can remove hypoxic drive •Ventilation decreases, PCO2>100 mmHg •PCO2 now acts centrally as narcotic to depress respiration •Death from hypoventilation

Lung stretch receptors (PSR; slowly adapting pulmonary stretch receptors)

Responsible for the Hering-Breuer Inflation Reflex Mechanoreceptors located in the smooth muscle of the airways Neural discharge dependent on lung inflation Increases with inflation, decreases with deflation Continuous discharge with sustained inflation (i.e. slowly adapting) Reflex effect: Terminates inspiration, prolongs expiration. Prevents overinflating lung. Generally insensitive to chemicals except increased airway CO2 will decrease their activity. Important at large tidal volumes (>800 ml) in adults Probably important for normal breathing in babies

How would you breathe more frequently?

Make bursts closer together

How would you breathe more deeply, ie increase tidal volume?

Make bursts last longer

What are pontine centers? What are they called?

Alter respiratory rhythm. Not essential for normal breathing. Apneustic and Pneumotaxic centers

What is the Ventral respiratory group (VRG)? What does it include?

aka Expiratory center. Includes pre-Botzinger complex. About 2/3 are inspiratory (I) neurons, 1/3 expiratory (E). Contains most of the neurons in the pattern (rhythm) generator. Also includes nucleus ambiguus. I and E neurons stimulate spinal motor neurons, which in turn control muscles of respiration.

What is the dorsal respiratory group (DRG)? Where is it? What does it include?

aka Inspiratory center. Neurons primarily inspiratory (active during inspiration). Includes the nucleus of the solitary tract (NTS-important for autonomic function)

What are the 3 types of lung receptors

3 types 1, Lung stretch receptors (Slowly adapting pulmonary stretch receptors; PSR) 2.Rapidly adapting receptors (RAR) Lung C fibers Pulmonary C-fibers or J-receptors (juxtapulmonary) Bronchial C-fibers

Higher brain centers, other systems interact with the control of respiration. Where do these inputs go? Examples

1.Other inputs important for breathing when you are awake 2. Requirements for singing, talking, eating 3. Limbic centers: fear can stimulate respiration 4. Increased body temperature can stimulate respiration 5. Pain can stimulate respiration (e.g. slapping newborns) 6. Central command with exercise -- Inputs can go to medullary respiratory centers or directly to spinal motor neurons and can be inhibitory or excitatory

What is apneustic breathing?

Apneustic breathing: inspire for along time, short expiration time

What is the apneustic center? Function?

Apneustic center •Located in CAUDAL pons •Electrical stimulation excites medullary inspiratory center, produces tonic contraction of diaphragm (makes inspiration longer). •keeps the switch in the inspiratory position.

Diving and "barometric" pressure

Barometric pressure increases as you go below the water surface. It has the same effect on the PAO2 and PaO2 as does putting a patient in a hyperbaric chamber. For example at a depth of 35 ft, PB doubles to 1520 mmHg. What is PaO2? Estimate it from the alveolar gas equation: PAO2= [(1520-47) * .21] - (40/.8) = 309-50 = 259 mmHg On the ascent PaO2 is falling both because the person is utilizing O2 for metabolism and because the "PB" value in the alveolar gas equation is decreasing.

What are the effectors of central pattern generator?

Brain sends signals to motor neurons that control respiratory muscles

Where does DRG receive input?

DRG receives afferent input from central and peripheral chemoreceptors about the state of blood gases, and from other receptors such as lung stretch receptors.

What are the 2 types of respiratory neurons? Where are they located?

Dorsal & ventral. Medulla

External intercostal muscles and diaphragm must contract simultaneously. What neurons must be active?

For normal quiet inspiration the phrenic and external intercostal motor neurons are simultaneously active.

What is the effect of chronic increases in pCO2?

However, the blood brain barrier can actively transport HCO3- from blood into CSF, so pH changes can be buffered over time. A chronic elevation in arterial PCO2 will not be associated with decreased CSF pH. The increased buffering capacity of the CSF will reduce the sensitivity of the central chemoreceptors to changes in PCO2.

Where are the external intercostal motor nerves located?

In the ventral horn of the thoracic spinal cord. Used during quiet breathing

Normal quiet breathing

Inspiration is active-depends on muscle contraction Expiration is passive Therefore, the motor nerves that drive the muscles of INSPIRATION must be rhythmically activated in a way that can be controlled by blood gas values.

The control of breathing is tightly linked to metabolic activity: Carbon dioxide production and oxygen consumption

PaCO2 (pH) and PaO2 are the regulated variables Reflexes produce changes in respiration in order to regulate these variables. We can, to some extent voluntarily control our breathing to eat, speak, etc.

What innervates the diaphragm?

Phrenic motor nerves innervate the diaphragm and the cell bodies are in the ventral horn of the thoracic spinal cord (C3-C5). The phrenic nerve fires in bursts. *injury to spinal cord above C3 will stop respiration. Heart can still pump though.

Role of sleep

Sleep depresses breathing because of the reduction of inputs other than the chemoreceptors. We become more dependent on them. Set-point of chemoreceptors changes during sleep so that we are less sensitive to them. If central chemoreceptors are not functioning, breathing will stop (central sleep apnea). What might cause this to happen? other than genetics, narcotics, drugs etc Sleep can lead to disturbances in airway patency that can lead to obstructive sleep apnea.

Chemoreceptors

The central and peripheral chemoreceptors link metabolism (O2 consumption and CO2 production) to ventilation.

Central Chemoreceptors

The central chemoreceptors are located on the ventral surface of the medulla. The blood-brain barrier separates the central chemoreceptors in the medulla from the arterial blood. Blood brain barrier is impermeable to charged molecules but freely permeable to CO2. CO2 enters CNS and dissociates. H+ stimulates central chemoreceptors.

What stimulates peripheral chemoreceptors?

They are sensitive to the partial pressures of oxygen and carbon dioxide, and to hydrogen ion (H+) concentration in the arterial blood. Reflex response: Ventilation (L/min) increases when: PCO2 increases pH decreases PO2 decreases

The chemosensitive cells in the carotid body are called glomus cells.

They have neuron-like characteristics. Depolarizing the cells triggers action potentials.