Ventilatory Control Flashcards
Explain central control
In pons:
• Pneumotaxic center = inhibitory
• Apneustic center = stimulatory
In medulla = respiratory rhythmicity center 1) Ventral respiratory group • Pacemaker cells • Expiratory center 2) Dorsal respiratory group • Primary generator of inspiration
Inspiratory and expiratory neurons are responsible for automaticity and phase switching of normal breath:
1) During inspiration = inspiratory neurons fire; expiratory neurons inactive
• Some inspiratory muscles active during end expiration to prevent airway collapse
2) During expiration = expiratory neurons fire
• Some inspiratory activity during expiration = “respiratory breaking”
• Prevents expiration from happening too fast
• With higher demands (ex. Exercise) inspiratory muscles are inactive
Peripheral chemoreceptors
- In carotid and aortic bodies
- Sensitive to pH and PaO2
- Hypoxia → stimulates receptors → ventilatory response
Central chemoreceptos
- On ventrolateral suface of medulla
- Responds most to PaCO2: increased blood PaCO2 → increased CSF H+ → decreased pH → increased ventilation
- At lower levels of PaO2 → more dramatic change in ventilation rate
- Central chemoreceptors responsible for 75% of ventilatory changes due to H+ (compared to peripheral)
- Sensitive: pH change of only 0.01 → increase of alveolar ventilation of 5 L/min
- Influenced by BBB and cerebral blood flow
- BBB:
- H+ diffuses slowly → slower ventilatory response to metabolic acidosis
- CO2 easily crosses → quick ventilatory response
- Cerebral blood flow
- Increase → washes away H+ ions → inhibitory ventilatory effect
- Decrease → accumulation of H+ → stimulates ventilation
- Input is required for rhythmic breathing
Afferent input from airways in ventilatory control
• Stretch receptors
o In airway smooth muscles
o Increased lung volume → increased stretch → signals to increase duration of expiration
o Called “Hering-Breuer reflex”
• Irritant receptors
o Between epithelial cells in airway mucosa
o Stimulated by noxious gas, dust, smoke, cold air
o Signals via vagus nerve
o Triggers cough, bronchoconstriction, and mucous secretion and increased respiratory rate
• C receptors
o In airway
o Determines bronchomotor tone/ degree of airway relaxation or constriction
Afferent input from parenchymal in ventilatory control
• J-receptors (juxta-capillary)
o In alveolar wall close to capillaries
o Increased volume of capillaries or interstitial fluid → stimulates receptors
o Signals via vagus nerve
o Triggers rapid shallow breathing
o Mechanism of disease in CHF = stimulation of J-receptors causes dyspnea
Afferent input from chest wall muscles in ventilatory control
• Muscle spindles
o Stretch receptor
o Within muscles
o Reflexively control strength/force of contraction
o Influences sensation of dyspnea with large respiratory efforts (ex: airway obstruction)
• Golgi apparatus
o In tendons of chest wall muscles
o Reflexively control strength/force of contraction
o Influences sensation of dyspnea with large respiratory efforts (ex: airway obstruction)
Afferent input from upper airway in ventilatory control
(nose, sinuses, pharynx, and larynx)
• Includes: airflow (pressure), stretch, irritation, vascularity, characteristics of CT
• Effects: sneezing, coughing, changes in breathing rate, tidal volume, mucous production, vascular engorgement, and muscular tone
“Other” afferent input in ventilatory control
• Cortical afferent input:
o Behavioral voluntary and reflexive control
o Hyperventilation with anxiety, breath holding
• Wakefulness stimulus
o Continuous tonic influence to central respiratory centers and respiratory motorneurons:
o Brainstem reticular activating formation = wake effect
• Decrease duration of exhalation
• Increase upper airway muscle dilation
• Increase respiratory pump motorneuron activity
o Most affects upper airway > respiratory skeletal muscles»_space; diaphragm
Effectors in ventilatory control
o Inspiratory muscles:
• Diaphragm!
• Also: scalenes and parasternals, external intercostals
• Upper airway dilating muscles
• Levator and tensor palatine muscles
• Alae nasi = nasal dilator
• Gengioglossus = tongue protrusion; main upper airway dilator
• Posterior cricoarytenoid muscle = opens laryngeal aperture
o Expiratory muscles:
• Abdominal muscles and triangularis sternii
o Internal intercostals = either inspiratory or expiratory effects
• Depends on lung volume
Determinants of respiratory muscle strength
o Function of number of contractile units
o Test strength by inhaling or exhaling against an occluded airway
• Maximal static inspiratory pressure at RV = -125 cmH2O
• Maximal static expiratory pressure at TLC = +225 cmH2O
o Strength is affected by age, gender, and overall muscle development
Factors modifying muscle strength:
• Length-tension relationship
• Longer the muscle pre-contraction = stronger the contraction
• At TLC = maximal static expiratory force
• At RV = maximal static inspiratory force
- Force-velocity relationship
- Slower the contraction velocity = more force develops
- Important compensatory mechanism
- Ex: resistive loads (obstructed airway) = slows rate of contraction = increases force
Determinants of respiratory muscle endurance
o Function of capillary density, mitochondrial density, myoglobin, oxidative enzyme capacity
Sleep related changes in ventilation
• CNS controller activity
o Clinically insignificant changes:
o Switch firing pattern from inspiration to expiration
• Longer expiration relative to wake → decreased respiratory rate
o Desynchronization of firing during respiration
o Reduction in activity of some neurons to upper airway dilators
o Overall:
• No significant changes in central respiratory drive
• No changes in CNS respiratory controller output to ventilatory pump muscles
• Withdrawal of wakefulness stimulus
o Non-specific stimulatory drive
o Arises from suprapontine regions and reticular-activating system of brainstem
o Reduced activity of upper airway muscles → decreased tone → increased resistance of upper airway
o Decreases activity of intercostals and accessory muscles
o Decrease in muscle activity most prominent in REM sleep
o Diaphragm unaffected
• Respiratory chemoreceptors
o Become less sensitive to stimuli (especially during REM sleep)
o Result: need a higher CO2 level to stimulate ventilation
• Decrease in metabolic rate (CO2 production = VCO2)
• RESULT: sleep-related changes in breathing
o Alveolar hypoventilation
o 2-8 Torr increase in PaCO2
o 2-4 Torr decrease in PaO2
• Ventilatory effects more prominent during REM than non-REM
o Result: normal subjects more susceptible to breathing abnormalities during REM
o Ex: apnea, hypopnea, O2 desaturation
Effects of hypoxia
- Stimulates peripheral chemoreceptors → increase ventilation
- Offset by inhibitory responses:
- Hypoxia depresses CNS = limits ventilatory response
- Hyperventilation causes hypocapnia and respiratory alkalosis → inhibits ventilation
- Hypoxia causes decreased cerebral blood flow → less H+ accumulation → inhibit ventilation
- Result: final magnitude of hyperventilation is less than expected
Effects of acidosis
If give acid acutely:
• Stimulate peripheral chemoreceptors → increase in ventilation (2-4 hrs)
• But: only about half of total ventilation increase occurs in first 4 hrs
• BBB prevents H+ from rapidly entering CNS
o So maximal ventilatory response develops slowly
If give bicarbonate to correct:
• Less stimulation of peripheral chemoreceptor → decreased ventilation
• But: takes >2-4 hrs to return ventilation to normal
• Need additional time to return central chemoreceptors to normal [H+]
Result: gradual development of compensatory mechanisms
Effects of COPD
o Increased metabolic rate
o Increased resistive load
o Hyperinflation → weak inspiratory muscle (mechanical disadvantage)
• More susceptible to fatigue
o Normal or increased VE
o V/Q non-uniformities (increased VD/VT)
o Increased respiratory rate and decreased tidal volume
o Further increase in VD/VT, low VA
o Result: Chronic CO2 retention, decreased pH
Describe central apnea
o Absent airflow associated with no inspiratory efforts
o Often in patients with CHF, renal or neurologic disease, and periodic breathing of altitude
- In CHF:
- Increased J-receptor stimulation and hypoxemia → elevated minue ventilation
- Increased circulatory time → delay in time for blood from lungs to reach chemoreceptors in medulla → enough time to overshoot ventilation
- At high altitude:
- Effects from hypoxemia and secondary hyperventilation
- Result in high gain or higher than normal ventilation due to a change in stimuli
- Lower than normal PCO2 (from secondary hyperventilation) → increases difference awake pCO2 and pCO2 apnea threshold in sleep
Result: cenral apnea at sleep onset
o Cheyne-Stokes breathing or periodic breathing
• Abnormal pattern of breathing
• Clusters of crescendo-decrescendo breaths, separated by apneas or hypopneas
• Affected by loop gain and apnea threshold
Loop gain
- Amount of response of a system in proportion to the disturbance in the system
- High loop gain = any change in stimulus (ex: pCO2) → higher than normal ventilatory response
Factors causing high loop gains
o Hypoxia
o Metabolic acidosis
Apneic threshold
• Level of pCO2 that stimulates ventilation
• In NREM sleep = sensitive apnea threshold for CO2
o Decreased PCO2 ventilatory response during sleep → higher level of CO2 needed to stimulate breathing
• With Cheyne-Stokes breathing = need elevated apneic threshold for CO2 (like in sleep) and a high gain (to produce higher than normal ventilation at end of an apnea in order to drive CO2 below apneic threshold → causes another apnea = perpetuates cycle)
Treatment of central sleep apnea
- Treat underlying disease
- O2
- Acetazolamide, theophylline, ?sedatives?
- CPAP
- Bilevel positive airway pressure (BiPAP)
- Adaptive Servo-Ventilation (AVS)
Obstructive apnea
o Absence of airflow in presence of progressively increasing inspiratory efforts against an occluded airway
o Site of obstruction = level of palate or base of tongue
• Vulnerable region
• No cartilaginous support
• Loss of wakefulness stimulus in sleep → decrease in muscle tone
• Greatest impact is on upper airway dilating muscles → increased collapsibility of upper airway
o Usually superimposed on smaller than normal upper airway
• Due to obesity, bulky upper airway structures (large tongue or uvula), small facial bone structure (especially narrow or short mandible and maxilla)
• Increased risk with increased neck size (> 18’’), nasal airway obstruction, heredity
o Occlusion results when force of suction in UA produces sub-atmospheric pressure in supraglottic space that overcomes dilating force of UA muscles = closes airway by retracting tongue or passive palate
o During obstruction:
• Increasing pCO2, falling pO2 → stimulates chemoreceptors
• Get increased ventilatory drive with increased intrathoracic pressure generation
o Restoration of airway • Associated with arousal • Re-instatement of wakefulness stimulus • Genioglossus muscle or tensor palatini activated → opens airway o Cycle repeats
Treatment of obstructive apnea
- CPAP
- Weight loss, supine sleep preclusion, avoidance of sedatives and alchohol
- Dental appliances
- Surgeries (uvulo-palato-pharyngoplasty, tracheostomy)
Symptoms and health consequences of sleep apnea
o Cardiovascular and cerebrovascular disease:
• HT
• Coronary artery disease, MI, arrhythmias, CHF
• Stroke
o Problems with daytime functioning
• Daytime sleepiness, pervasive fatigue
• Motor vehicle and work-related accidents
• Psychosocial and decreased cognitive function
• Mood disorders
List the factors that can contribute to respiratory muscle fatigue.
• Fatigue occurs when energy demands of muscle are exceeded by ability of blood to supply
• Inspiratory demands = determined by work of breathing and strength of muscle
o Greater the work performed by muscle = more susceptible to fatigue
• Factors causing fatigue = factors determining energy availability
o Oxygenation
o Blood supply
• Ex: cardiogenic shock → decreased blood flow → respiratory muscle dysfunction
o Nutrition
Describe the determinants of CO2 retention
Abnormalities in arterial PCO2 define ventilatory status
PaCO2 = (VCO2)K/(VA)
• VA = VE (1 – VD/VT)
• VCO2 = production of CO2
• VA = portion of minute ventilation (VE) not participating in gas exchange
Mechanisms of CO2 retention Increased metabolic rate: • Fever, stress, exercise Low (overall) minute ventilation (VE) • Decreased central drive • Increased mechanical loads (lung, chest wall) • Weak respiratory muscles High dead space/alveolar ventilation ratio • Emphysema, pulmonary embolism Abnormal breathing pattern • Low tidal volume, high frequency
Explain the consequences of quadriplegia on ventilation and gas exchange.
(respiratory muscle weakness)
o Decreased chest expansion → decreased VT
o Rapid and shallow breathing → increased VD/VT and decreased VA
o Reduced diaphragmatic excursion
o Decreased muscle endurance
o Decreased or inefficient ventilation (VE), decreased VA
o Lower lung volumes → atelectasis (collapse/closure of lung) → V/Q mismatch
o Result: increased PaCO2, decreased pH
Explain the consequences of diaphragmatic paralysis on ventilation and gas exchange.
o Most commonly seen in NM disease
o Low lung volume
• High VD/VT requires high VE for adequate VA
• High respiratory rate to achieve increased VE
o Low respiratory muscle strength
• Dependence on intercostal and other accessory respiratory muscles
• Working at maximal capacity
• Increases fatigue
o Orthopnea without heart failure
o CO2 retention
o Respiratory muscle fatigue at lower demand level
o Susceptible to REM sleep-related hypoventilation and O2 desaturation
• REM inhibits intercostal and accessory muscles
• Only diaphragm remains but ineffective = can’t maintain ventilation
• Need nocturnal mechanical ventilation
Describe dyspnea
• Uncomfortable sensation, “air hunger”
Perception that work of breathing is:
o Greater than expected/normal
o Greater than comfortable performed
o Produces less volume of air displaced than expected
• Occurs due to excessive sensory feedback
o Caused by a mismatch between sense of volume displacement being less than expected for the level of motor output and muscle tension developed
