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Flashcards in 13 Control of Breathing Deck (32)
1

Voluntary and automatic control of breathing

  • Structures involved in voluntary control
  • Structures involved in automatic control

  • Structures involved in voluntary control (e.g. breathholding, phonation, swallowing)
    • Cerebral motor cortex
      • --> Brainstem motor nuclei
        • --> Diaphragm & external intercostals
          • --> Inspiration
        • --> Internal intercostals
          • --> Expiration
  • Structures involved in automatic control
    • Rhythm generator
      • --> Dorsal respiratory group
        • --> Inspiratory neurons
      • --> Ventral respiratory group
        • --> Expiratory neurons

2

Voluntary and automatic control of breathing

  • The system that regulates respiration
  • The conditions to which the respiratory control system must respond

  • The system that regulates respiration
    • Does so in a way that will maintain homeostasis under a variety of circumstances that individuals encounter under conditions of health and disease
    • Modulates these responses in such a fashion that minimizes the work of breathing
  • The conditions to which the respiratory control system must respond
    • Physiologic and metabolic changes (e.g. acid-base perturbations)
    • Changing environment (e.g. altitude)
    • Altered states or disease-related processes (e.g. sleep, obesity, and respiratory diseases)

3

Voluntary and automatic control of breathing

  • Operation of the respiratory control system reflects the integrated activity of a wide variety of...
  • Brainstem motor neurons

  • Operation of the respiratory control system reflects the integrated activity of a wide variety of...
    • Integrators, sensors, and effectors
  • Brainstem motor neurons
    • Fundamental elements of the system
    • Represent the breathing pattern generator
    • This generator sends neural signals to...
      • The chest wall (the diaphragm and accessory muscles of breathing) as
      • The upper airway muscles (to maintain patency of the upper airway during breathing and protect the lungs when swallowing)
    • The breathing pattern generator is like a pacemaker, which initiates the process of inspiration and consequently results in lung inflation and ventilation

4

Voluntary and automatic control of breathing

  • As a result of lung inflation, a number of receptors are stimulated, including...
  • The magnitude of alveolar ventilation regulates...
  • Arterial blood gas tensions and pH...
  • Cerebral motor cortex
  • Other physiologic factors that may influence the way we breathe

  • As a result of lung inflation, a number of receptors are stimulated, including...
    • Non-chemical stretch receptors located in the airways and lungs
    • Muscle spindles and tendon organs in the chest wall musculature
  • The magnitude of alveolar ventilation regulates...
    • Arterial carbon dioxide tension (PaCO2)
    • Hydrogen ion concentration
    • Arterial oxygen tension, PaO2
  • Arterial blood gas tensions and pH...
    • Feed back on the brainstem respiratory control centers to regulate respiratioin
  • Cerebral motor cortex
    • Automatic control of respiration
    • Provides input to the brainstem motor neurons in order that adjustments in breathing may be made to accommodate voluntary or behavioral activities such as phonation, swallowing, and other activities that use the same structures as does breathing
  • Other physiologic factors that may influence the way we breathe
    • Temperature, cardiovascular changes associated with exercise, etc.

5

Voluntary and automatic control of breathing

  • The rhythm generator or pacemaker exists in the...
  • Other neuronal groups within the pons and medulla responsible for initiating inspiration and expiration
  • Output from these neurons ultimately governs...
  • Other groups of neurons in the brainstem are responsible for...

  • The rhythm generator or pacemaker exists in the...
    • Pre-Bötzinger complex within the brainstem
  • Other neuronal groups within the pons and medulla responsible for initiating inspiration and expiration
    • Dorsal Respiratory Group (activate inspiratory neurons)
    • Ventral Respiratory Group (activate primarily expiratory neurons, but also some inspiratory neurons)
  • Output from these neurons ultimately governs...
    • Activity of the phrenic and intercostal motor neurons 
    • Activity of the pharyngeal and laryngeal muscles
  • Other groups of neurons in the brainstem are responsible for...
    • Integrating afferent inputs from peripheral receptors 
    • Relaying the signals to the inspiratory and expiratory motor neurons, whose activity is consequently modified

6

Regulation of respiratory centers:
The variety of factors that may stimulate the respiratory control system may be classified as...

  • Chemostimuli
    • Hypoxemia
    • Hypercapnia
    • Acidemia
  • Mechanical stimuli (e.g.)
    • Stimulation resulting from stretching the lung and chest wall
    • Irritant inhalation

7

Regulation of respiratory centers:
Chemical control of breathing:
Chemoreceptors

  • Functions
    • Sense arterial PO2, PCO2,a nd pH
    • Feed back on CNS controllers and help to regulate alveolar ventilation ot maintain PO2, PCO2, and pH homeostasis
  • 2 types
    • Peripheral
    • Central
  • Adjust ventilation to...
    • Maintain arterial PCO2
    • Minimize an excess of H+ in the blood
    • Raise arterial PO2 when it falls to dangerous levels
  • Resting ventilation
    • Proportional to metabolic rate
    • Determined by PCO2 and not PO2

8

Regulation of respiratory centers:
Chemical control of breathing

  • Chemical stimuli that evoke a response from the respiratory control system
  • These responses are designed to...
  • Both central and peripheral chemoreceptors sense...

  • Chemical stimuli that evoke a response from the respiratory control system
    • Hypoxemia
    • Hypercapnia
    • pH
  • These responses are designed to...
    • Maintain blood gas and pH homeostasis
    • This reflects the metabolic control of respiration
  • Both central and peripheral chemoreceptors sense...
    • Oxygen tension (PaO2)
    • Carbon dioxide tension (PaCO2)
    • pH (hydrogen ion concentration)

9

Regulation of respiratory centers:
Chemical control of breathing:
Peripheral chemoreceptors

  • The peripheral chemoreceptors consist of...
  • The aortic body vs. the carotid body in humans
  • Type I (Glomus) cells
  • Type II cells (sheath cells)

  • The peripheral chemoreceptors consist of...
    • Carotid bodies located bilaterally at the bifurcation of the common carotid artery
    • Aortic bodies located near the aortic arch
  • The aortic body vs. the carotid body in humans
    • The aortic body is of considerably less importance than the carotid body in terms of the control of respiration
  • Type I (Glomus) cells
    • The peripheral chemoreceptors consist of Type I (Glomus) cells
    • Act as the sensors and contain and release catecholamines from cytoplasmic vesicles
  • Type II cells (sheath cells)
    • Encircle the glomus cells in a supporting structural role

10

Regulation of respiratory centers:
Chemical control of breathing:
Peripheral chemoreceptors:
Carotid bodies

  • Very vascular
  • Facilitate sensing blood gas tensions and making rapid adjustments in respiration
  • Send afferent information related to blood gas tensions and pH to the Central Nervous System via the carotid sinus nerve and the glossopharyngeal nerve
  • Responsible for most of the ventilatory response to hypoxemia (they are also sensitive to CO2 and pH)
  • Rspond to a decrease in arterial oxygen tension (PaO2), rather than oxygen content or oxyhemoglobin saturation

11

Regulation of respiratory centers:
Chemical control of breathing:
Peripheral chemoreceptors

  • Ventilatory response to decreasing PaO2
  • With further hypoxemia below this level,...
  • Oxyhemoglobin saturation vs. ventilation
  • Under conditions when hypercapnia is also present,...

  • Ventilatory response to decreasing PaO2
    • There is a curvilinear ventilatory response to decreasing PaO2
    • Negligible augmentation of ventilation until PaO2 falls to approximately 60 mmHg or below
  • With further hypoxemia below this level,...
    • There is a progressive increase in ventilation
  • Oxyhemoglobin saturation vs. ventilation
    • Due to the curvilinear relationship between PaO2 and oxygen saturation, a linear relationship exists between oxyhemoglobin saturation and ventilation
  • Under conditions when hypercapnia is also present,...
    • There is an augmentation of the ventilatory response to stimulation of the peripheral chemoreceptors, such that ventilation is stimulated at PaO2 levels above 60 mmHg

12

Regulation of respiratory centers:
Chemical control of breathing:
Central chemoreceptors

  • Central chemoreceptors are located...
  • The central chemoreceptors are primarily sensitive to...
  • Once the CO2 diffuses across the blood brain barrier it...
  • H+ ions 

  • Central chemoreceptors are located...
    • Widely throughout the lower brainstem
    • The classically described area is in the ventrolateral medulla
  • The central chemoreceptors are primarily sensitive to...
    • Carbon dioxide tension (PCO2) since CO2 can rapidly diffuse across the blood brain barrier, whereas H+ and HCO3- ions are greatly restricted
  • Once the CO2 diffuses across the blood brain barrier it...
    • is rapidly hydrated in the brain extracellular fluid and disassociates to form H+ and HCO3-
  • H+ ions
    • Act as the stimulus to the central chemosensitive cells
    • Augment ventilatory drive
    • Increase alveolar ventilation

13

Regulation of respiratory centers:
Chemical control of breathing:
Central chemoreceptors

  • Approximately 70-80% of the ventilatory response to PCO2 is mediated by...
  • The remaining 20-30% is mediated by...
  • The ventilatory response to central vs. peripheral chemoreceptors
  • Resting and changes to PaCO2
  • The ventilatory response to changing PaCO2 
  • Interaction between hypercapnia and hypoxemia

  • Approximately 70-80% of the ventilatory response to PCO2 is mediated by...
    • The central chemoreceptors
  • The remaining 20-30% is mediated by...
    • The peripheral chemoreceptors
  • The ventilatory response to central vs. peripheral chemoreceptors
    • The ventilatory response to central chemoreceptor stimulation takes considerably longer than to the peripheral chemoreceptors since the blood flow to the brain is markedly less than to the carotid bodies
  • Resting and changes to PaCO2
    • The resting arterial carbon dioxide tension (PaCO2) is usually tightly controlled between 35-45 mmHg
    • Changes in PaCO2 of as little as 1 mmHg can increase ventilation by 20-30%
  • The ventilatory response to changing PaCO2
    • Linear within the range of 40-70 mmHg
  • Interaction between hypercapnia and hypoxemia
    • Positive interaction
    • The ventilatory response to hypercapnia is augmented by concomitant hypoxemia

14

Voluntary vs. automatic control of breathing

15

Regulation of respiratory centers:
Non-chemical control of breathing

  • Receptors that are located in the airways and lungs can affect respiration through...
  • There are three main groups of receptors

  • Receptors that are located in the airways and lungs can affect respiration through...
    • Afferent connections to the respiratory centers from the vagus nerves
  • There are three main groups of receptors
    • Slowly and rapidly adapting receptors that are both innervated by myelinated vagal fibers
    • J (juxtacapillary) receptors that are innervated by unmyelinated vagal C fibers

16

Regulation of respiratory centers:
Non-chemical control of breathing:
Slowly adapting stretch receptors

  • Slowly adapting receptors
    • Firing rate
    • Location
  • Stretch receptors
    • Stimulated by...
    • Location
    • Contribute to...

  • Slowly adapting receptors
    • Firing rate
      • Increases its firing rate immediately after exposure to a stimulus
      • Then the firing rate slowly decreases towards baseline levels despite continued exposure to the stimulus
    • Location
      • Among airway smooth muscle cells
  • Stretch receptors
    • Stimulated by...
      • Lung inflation
    • Location
      • In the tracheobronchial tree
    • Contribute to...
      • The regulation of the rate and depth of breathing

17

Regulation of respiratory centers:
Non-chemical control of breathing:
Slowly adapting stretch receptors

  • Blockade of the vagus nerve results in...
  • Hering-Breuer Inflation Reflex

  • Blockade of the vagus nerve results in...
    • Elimination of slowly adapting receptor afferent information
    • Loss of feedback inhibition from lung inflation
    • A deepening and slowing of the respiratory pattern
  • Hering-Breuer Inflation Reflex
    • Slowly adapting stretch receptors participate in the Hering-Breuer Inflation Reflex
    • Sustained inflation of the lung inhibits further inspiratory activity and results in a period of apnea (cessation of breathing)
    • Prominent in animals and human neonates, but has not been demonstrated to play a significant role in adult humans

18

Regulation of respiratory centers:
Non-chemical control of breathing:
Rapidly adapting stretch receptors

  • Firing rate
  • Location
  • Stimulated by...
  • Often described as...
  • Stimulation can cause...

  • Firing rate
    • Decrease their firing rate almost immediately in response to a stimulus
  • Location
    • Among the airway epithelial cells
  • Stimulated by...
    • Lung inflation
    • Exogenous factors such as particulate matter
    • Endogenous agents such as histamine and prostaglandins
  • Often described as...
    • Lung irritant receptors
  • Stimulation can cause...
    • Cough
    • Hyperpnea 
    • Bronchoconstriction

19

Regulation of respiratory centers:
Non-chemical control of breathing:
Juxtacapillary receptors

  • Location
  • Innervated by...
  • Fibers
    • Stimulated by...
    • Stimulation in the lung and the airways causes...

  • Location
    • In the pulmonary interstitial space
    • In close proximity to the pulmonary and bronchial circulations
  • Innervated by...
    • Unmyelinated vagal C-fibers
  • Fibers
    • Stimulated by...
      • Pulmonary congestion (e.g. congestive heart failure)
      • Other pathologic processes within the pulmonary interstitium (e.g. pulmonary fibrosis)
      • Bronchoconstriction, (e.g. asthma)
      • Lung inflation
      • Exogenous and endogenous agents such as capsaicin, histamine, bradykinin, serotonin and prostaglandins
    • Stimulation in the lung and the airways causes...
      • Apnea
      • Followed by rapid shallow breathing
      • Bradycardia and hypotension (pulmonary chemoreflex)

20

Integrated view of respiratory control

21

Respiratory control in altered states:
Regulation of acid / base balance

  • The regulation of CO2 has a significant impact on...
  • The lungs and the kidneys play a critical role in...
  • The Henderson-Hasselbalch equation
  • pH maintenance by [HCO3-] and PCO2
  • An alteration in pH from a change in either [HCO3-] or PCO2 can be corrected by...
  • The numerator and denominator of the equation are regulated by...

  • The regulation of CO2 has a significant impact on...
    • The acid/base status of the blood
    • The ability of the body to maintain plasma pH at 7.4
  • The lungs and the kidneys play a critical role in...
    • Maintaining the plasma pH at normal levels
  • The Henderson-Hasselbalch equation
    • pHplasma = 6.1 + log ([HCO3-] / 0.03 x PCO2)
  • pH maintenance by [HCO3-] and PCO2
    • [HCO3-] maintained at approximately 24 mmol.l-1 by the kidney
    • PCO2 regulated close to 40 mmHg by the respiratory system
    • pH is maintained at 7.4
    • Thus, pH varies directly with [HCO3-] and inversely with PCO2
  • An alteration in pH from a change in either [HCO3-] or PCO2 can be corrected by...
    • Altering the other variable to maintain the buffer ratio constant
  • The numerator and denominator of the equation are regulated by...
    • Numerator: control of [HCO3-] by the kidney
    • Denominator: control of PCO2 by the lungs

22

Respiratory control in altered states:
Regulation of acid / base balance

  • Metabolic acidosis
    • Can be caused by...
    • Can be corrected by...
  • Metabolic alkalosis
    • Can be caused by...
    • Can be corrected by...

  • Metabolic acidosis
    • Can be caused by...
      • Production of ketone acids in diabetes
      • Lactic acid in shock
      • Loss of alkaline secretions such as bile
      • Failure to generate adequate HCO3- in kidney (renal acidosis)
    • Can be corrected by...
      • An increase in alveolar ventilation
  • Metabolic alkalosis
    • Can be caused by...
      • Loss of acid secretions from the stomach
    • Can be corrected by...
      • A decrease in alveolar ventilation and retention of CO2

23

Respiratory control in altered states:
Regulation of acid / base balance

  • Respiratory acidosis
    • Can be caused by...
    • Can be corrected by...
  • Respiratory alkalosis
    • Can be caused by...
    • Can be corrected by...

  • Respiratory acidosis
    • Can be caused by...
      • Hypoventilation (respiratory obstruction or drugs/toxins)
      • High inspired CO2
    • Can be corrected by...
      • Slow replacement of Cl- by HCO3- in the kidneys over a time course of days
  • Respiratory alkalosis
    • Can be caused by...
      • Hyperventilation
      • Hypoxic exposure at altitude
      • Nervousness/anxiety
    • Can be corrected by...
      • The kidney excreting HCO3- in an alkaline urine and a slow restoration of pH over many days if the hyperventilation persists

24

Respiratory control in altered states:
Ondine's curse

  • The regulation of breathing is dependent on...
  • Ondine's curse
  • Results from...
  • Children
  • Adults

  • The regulation of breathing is dependent on...
    • Both voluntary and automatic control of the muscles of respiration
  • Ondine's curse
    • Lose the ability for automatic control of respiration while maintaining voluntary control
    • Affects only a few hundred people worldwide
  • Results from...
    • Brainstem lesions in critical respiratory control centers
    • Genetic predisposition
  • Children
    • Need cntinuous ventilatory support
  • Adults
    • Ventilation is usually required only during sleep

25

Respiratory control in altered states:
Heart-lung transplantation

  • Routinely in heart-lung transplantation,...
  • Vagal innervation to the heart and lungs
  • Cough response

  • Routinely in heart-lung transplantation,...
    • The donor heart is attached to the right atrium of the recipient
    • The donor lungs are attached above the carina to the recipient’s trachea
  • Vagal innervation to the heart and lungs
    • Vagal innervation of both the heart and lungs are lost
    • Loss of vagal efferent innervation to the heart causes an increase in resting heart rate
    • Loss of vagal afferent innervation from the lungs does not significantly influence the rate and depth of breathing under normal conditions
  • Cough response
    • There is no longer a cough response to stimulation of the smaller airways
    • But since the trachea remains innervated it can still elicit a normal cough response

26

Respiratory control in altered states:
Cough, sneeze, yawn, and hiccup

  • Coughing and sneezing
  • Cough
  • Sneeze
  • Hiccup
  • Yawning

  • Coughing and sneezing
    • Reflex responses that help maintain a patent airway and expel irritants
  • Cough
    • Deep inspiration followed by a forced expiration against a closed glottis
    • Builds up large pressures until the glottis is suddenly opened and the air escapes
  • Sneeze
    • Series of superimposed inspirations in the presence of an open glottis
    • Followed by a rapid expiration of air at several hundred miles per hour
  • Hiccup
    • Spasmodic contraction of the inspiratory muscles timed exactly with sudden closure of the glottis
    • Appears to serve no useful purpose
    • Resembles the pattern of response seen in newborns learning to suckle
  • Yawning
    • Another respiratory action that has no obvious physiologic function
    • Deep inspiration followed by a slow expiration over a 5-6 sec period
    • Associated with boredom and tiredness and has a ‘contagious’ effect
    • 'Stretches’ the lung to open up under-ventilated and collapsed portions

27

Respiratory control in altered states:
Breathing during sleep

  • During normal sleep
  • In non-REM sleep there is...
  • Blood gases during REM sleep 

  • During normal sleep
    • There is a reduction in tidal volume without any increase in breathing frequency
    • As a consequence of the reduced tidal volume, minute ventilation falls relative to wakefulness
  • In non-REM sleep there is...
    • (1) a reduction in PaO2 by 3-10 mmHg and a reduction in oxyhemoglobin saturation by less then 3%
    • (2) an increase in PaCO2 anywhere from 2-9 mmHg
  • Blood gases during REM sleep
    • Variable since this sleep stage is a non-homogeneous condition consisting of both phasic REM and tonic REM sleep
    • The irregularity in breathing during REM sleep is due to loss of accessory muscles such as the intercostals
    • Ventilation becomes solely dependent on the diaphragm

28

Respiratory control in altered states:
Breathing during sleep

  • The ventilatory response to hypercapnia
    • During non-REM sleep
    • During REM sleep
  • The ventilatory response to hypoxemia
    • During non-REM sleep
    • During REM sleep

  • The ventilatory response to hypercapnia (increased PaCO2)
    • During non-REM sleep
      • Diminished compared to wakefulness
    • During REM sleep
      • Further reduction
  • The ventilatory response to hypoxemia (oxyhemoglobin desaturation)
    • During non-REM sleep
      • Reduced relative to wakefulness
    • During REM sleep
      • Further reduction

29

Respiratory control in altered states:
The depression of respiratory control systems during sleep can lead to significant breathing problems

  • Obstructive sleep apnea
  • Cheyne- Stokes respiration
  • Factors involved in the pathogenesis of Cheyne-Stokes respiration

  • Obstructive sleep apnea
    • The most common breathing problem
    • Associated with reduced tone of the upper airway respiratory muscles leading to periods of airway collapse during sleep
  • Cheyne- Stokes respiration
    • Characterized as waxing and waning periods of hyperventilation and apnea
    • Sometimes described as crescendo-decrescendo breathing
    • Most commonly seen in people ascending to high altitude or in patients with severe heart failure
  • Factors involved in the pathogenesis of Cheyne-Stokes respiration
    • (1) pulmonary congestion
    • (2) a delay in circulation time between the lungs and central chemoreceptors due to cardiac insufficiency in heart failure patients
    • (3) alterations in the threshold for PaCO2 to stimulate breathing, potentially accounting for the increased susceptibility to develop this breathing pattern during sleep

30

Respiratory control in altered states:
Severe obesity

  • Overweight & obesity in the US population
  • Severe obesity
  • The majority of obese individuals
  • A small proportion of severely obese individuals

  • Overweight & obesity in the US population
    • 66% is characterized as overweight or obese (body mass index > 25 kg/m2)
    • 35% is obese (body mass index > 30 kg/m2)
  • Severe obesity
    • Leads to mechanical loads on the respiratory system
    • May result in under-ventilation of parts of the lung
  • The majority of obese individuals
    • Can increase their respiratory drive to maintain PaCO2 at normal levels
  • A small proportion of severely obese individuals
    • Respiratory system is unable to compensate
    • Leads to elevated PaCO2 levels (obesity-hypoventilation syndrome)
    • Subsequently leads to Pickwickian Syndrome
      • Hypoxia, polycythemia, pulmonary hypertension, and right-sided heart failure

31

Respiratory control in altered states:
Severe obesity

  • Obesity
  • An impairment of the respiratory control system
  • Leptin
  • Adipose tissue

  • Obesity
    • Since only a small proportion of severely obese people develop obesity-hypoventilation, it is likely that obesity is not the only predisposing factor
  • An impairment of the respiratory control system
    • May also be required for severely obese individuals to develop obesity hypoventilation
  • Leptin
    • Important satiety/metabolic regulator
    • Produced by adipocytes
    • Acts on neuronal groups in the hypothalamus
    • Can also alter central respiratory control mechanisms
  • Adipose tissue
    • May directly impact respiratory control mechanisms
    • Rich source of endocrine and signaling factors
    • May play a role in determining whether respiratory control mechanisms are able to compensate for the mechanical loads imposed by severe obesity

32

Respiratory plasticity

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