Module 2 - Upper Airway Obstruction in Sleep Flashcards
What are 4 anatomical abnormalities associated with OSA?
- Adenoidotonsillar enlargement
- Micrognathia (small mandible)
- Infiltration of muscles and soft tissues (rare: myxoedema, acromegaly, neoplastic processes, mucopolysaccharidosis)
- Nasal obstruction
How is nasal obstruction associated with OSA?
It’s a contributing (not major) factor. Needs more negative pressure to breathe so there’s more collapsing force.
How does sleep impact the upper airway muscles (x5) in normal subjects?
in Non-REM sleep
Palatoglossus, genioglossus & diaphragm all normal-ish to maintain pharyngeal patency.
Levator palatini 50% reduced. Not that important because it elevates to the roof of the mouth.
Tensor palatini 75% reduced. Important for stiffening and maintaining airway by bringing soft palette onto back of the tongue. Important for sleep.
Describe the upper airway muscles reflex response to negative airway pressure?
Negative airway pressure is sensed by upper airway muscles and reflexively increase activity of upper airway muscles (genioglossus) to improve upper airway patency.
How does the upper airway muscles reflex response different from awake to sleep?
During sleep, the reflex response is markedly diminished or absent.
How do the upper airway muscles control pharyngeal patency?
Negative airway pressure is sensed by upper airway muscles and reflexively increase activity of upper airway muscles (genioglossus) to improve upper airway patency.
How does the role of the upper airway muscles control of pharyngeal patency different in OSA when awake and asleep?
When awake: OSA patients compensate for inadequate airway anatomy by increasing pharyngeal dilator muscle activity (neuromuscular compensation -> reflex).
When asleep: no neuromuscular compensation during sleep leads to airway occlusion in OSA sleep.
What are the 5 important upper airway muscles involved in maintaining pharyngeal patency?
- Genioglossus muscle
- Geniohyoid muscle
- Tensor veli palatini muscle
- Levator veli palatini muscle
- Palatopharyngeus muscle
Where is the genioglossus muscle and what does it control?
Base of the tongue, sits on soft palette
Contracts and keeps base of tongue off posterior pharyngeal wall. Important in pharyngeal patency.
Where is the geniohyoid muscle and what does it control?
From mandible to hyoid bone.
Contraction pulls tongue off pharyngeal wall. Important in pharyngeal patency
What does the tensor veli palatini muscle do?
Contraction tenses soft palette and pulls of pharyngeal wall. This is important for nasal airflow and pharyngeal patency.
What does the levator veli palatini muscle do?
Elevates soft palette, closing nasopharynx. Important for swelling and oral breathing.
What does the palatoglossus muscle do?
Contracts the soft palette putting it on the back of tongue to promote nasal breathing.
Do upper airway muscles respond in a uniform way in sleep?
No.
How do upper airway muscles respond to negative airway pressure?
A reflex activation.
What are some of the problems of using AHI as a phenotype?
- Noisy signal
- Variable definitions (e.g. hypopnea)
- Variable techniques
- Relationship to outcomes isn’t overly strong
- Night to night variability (reporting and physiological changes, body positioning and sleep depth)
- Problems of in-lab recording
- Two patients can have very different clinical characteristics
What are the phenotype names in OSA?
(e.g. Risk factors, clinical features)
Risk factors: risk factor phenotypes
Clinical features/Complications: clinical phenotypes
Physiological features: Polysomnographic phenotypes
What are the new ways that we can use to phenotype for OSA?
- Imaging of craniofacial and upper airway structures [narrowing, Box model]
- Ethnicity
- Tongue Fat %
- Mandibular Advancement (SPAM grid)
- Photography for facial phenotyping
- Pathophysiological
- PSG
- Genetic
Describe the bone-soft tissues interaction (“Box” model)
Soft tissue (small/large) + Bony enclosure (of mandible and maxilla small/large) -> Leads to -> Airway size
Obesity = large soft tissue and normal (or smaller) bony enclosure -> increased tissue pressure and smaller airway
What is the main ethnic difference in driving risk factor for OSA?
Chinese: craniofacial restriction is bigger driver
Caucasian: obesity is biggest driver
But, BMI has a bigger influence in Chinese population due to craniofacial restriction
What is SPAM imaging?
magnetic grid of tissue imaging to find tissue deformations
check out grid photos in notes
What types of information can be taken from photography for facial phenotyping of OSA?
Angles
Areas
Volumes
How does photographic facial phenotyping perform in predicting OSA?
77% correctly classified based on
Caucasian:
Mandibular width & width angle
Neck width
Lower face width-depth angle
HongKong
Cricomental space area
Mandibular width
Mandibular plane angle
Neck soft tissue area
What are the pathophysiological phenotypes in OSA & how much are they present in disease?
Anatomical (Pcrit) 81%
Inadequate UA muscle responsiveness 36%
Low respiratory arousal threshold 37%
Oversensitive ventilatory control (high loop gain) 36%
What does it mean if someone has an oversensitive ventilatory control (high loop gain)?
They develop an exaggerated response that causes cyclical breathing
What is the primary finding regarding clinical clusters in the Icelandic study in OSA?
(# clusters, symptoms and which is more prone to comorbidities)
There are 3 clinical clusters; (1) insomnia-type 33%, (2) minimally symptomatic 25% and (3) textbook OSA with daytime sleepiness 42%
Cluster 2 more prone to hypertension, CVD, diabetes. Not based on severity as no diff in age, gender, AHI.
The European clinical phenotypes study on OSA determined there were 4 clinical types of OSA. What were they and what is their distribution?
Excessive Daytime Sleepiness (Y/N)
Insomnia (Y/N)
Roughly even distribution
What is the confounding problem when examining phenotypes for OSA?
A lot of comorbidites in OSA that have interrelationships and have bidirectional causalities.
Leads to many moderators and modifiers.
E.g. Obesity (OSA RF) is strongly related to diabetes (OSA comorbidity)
What are the conclusions on genetic research in OSA?
Inconsistent, doesn’t say much yet.
Likely many genes contributing small amounts.
What are the 5 common polysomnographic phenotypes?
- Sleep stage dependency (e.g. REM OSA)
- Position dependency (e.g. supine OSA, common)
- Apnoeas vs hypoponoeas
- Arousal index (e.g. fragmentation)
- SaO2 (fragmentation & time below threshold)
What polysomnographic phenotypes could provide information on disease burden?
- Age of onset
- Duration of disease
- Extent of sleep fragmentation and arousal intensity
- Breathing “load”
- Airflow “fingerprints”
- Hypoxic burden
- Haemodynamic effects
- Hypercapnia/acidosis
- Snoring characteristics
- Biomarkers
What is residual disease burden?
The amount of remaining AHI when treatment compliance + efficacy is considered
E.g. Residual AHI = (AHI treatment x Hours) + (AHI treatment2 x Hours) / Total sleep time hours
2 treatments could have same effect due to different efficacy and compliance (hrs)
What traits predict response to oral appliance therapy in OSA?
Lower loop gain
How can the field of OSA improve treatment?
- Shift focus from diagnosis to outcomes (e.g. chronic disease management)
- Fractionating the OSA phenotype (simple, reliable, inexpensive phenotypic tools)
- Create large-scale OSA cohorts
- Collaborate with other disciplines
What are the functions of the human upper airway?
Air transmission, swallowing, heat exchange, and vocalization.
How does NREM sleep affect upper airway muscles?
What happens in REM sleep that differs?
Reduces tonic and phasic electromyogram (EMG) activity, contributing to airway narrowing.
REM sleep further reduces activity, particularly in phasic dilating muscles like the genioglossus, leading to increased collapsibility.
Why is the activation of genioglossus and hypoglossal nerve crucial?
Crucial for airway patency during sleep.
Does gender significantly influence negative pressure reflex during wakefulness?
No, limited evidence supports gender differences in baseline muscle activity.
How does aging impact reflex responses contributing to airway collapsibility?
Aging may not affect baseline muscle activity but can decrease reflex responses to negative pressure and hypoxia.
What histologic changes in upper airway muscles are associated with OSA?
Edema
mucosal gland hypertrophy
neurogenic injury
changes in muscle enzyme activity
leukocytic inflammation.
Why is craniofacial structure crucial for upper airway patency?
Various abnormalities are linked to OSA, affecting pharyngeal airway size and function.
How can intrinsic properties of the upper airway affect collapsibility?
Intrinsic compliance, influenced by various factors, modifies the collapsing effect of transmural pressure.
What challenges does sleep pose to the ventilatory system?
Reduces activity of upper airway dilators, leading to decreased upper airway caliber and increased collapsibility.
What happens to upper airway resistance during NREM sleep?
Increases, reaching highest values in slow-wave sleep.
How is collapsibility measured during sleep?
Measured by critical closing pressure (P crit), it increases during sleep and is related to the propensity for airway collapse.
How does hormonal activity influence upper airway collapsibility?
Leptin, associated with decreased upper airway collapse, can influence collapsibility.
How does upper airway resistance change between Non-REM and REM sleep?
No significant increase in resistance during REM sleep compared with NREM sleep in normal humans.
What are examples of sensors involved in ventilatory regulation?
Sensors include central and peripheral chemoreceptors, vagal pulmonary sensors, and chest-wall and respiratory muscle afferents.
What role does the central controller play in ventilatory regulation?
The central controller receives information from sensors and generates an automated rhythm of respiration, constantly modified in response to receptor input.
What are the effectors in ventilatory regulation?
Effectors include respiratory motoneurons and muscles which alter minute ventilation and gas exchange according to the signals from the central controller.
Where are the DRG and VRG located?
The Dorsal Respiratory Group (DRG) and Ventral Respiratory Group (VRG) are located within the medullary ventilatory center.
What functions do the DRG and VRG serve?
The DRG primarily regulates inspiration, while the VRG controls both inspiratory and expiratory neurons, particularly during forced expiration.
What role do pontine influences play in respiratory control?
Pontine influences regulate and coordinate inspiratory and expiratory control, with the pneumotaxic center affecting inspiration duration and the apneustic center terminating inspiratory efforts.
What are the types of chemoreceptors involved in ventilatory regulation?
Chemoreceptors include central chemoreceptors in the ventrolateral surface of the medulla and peripheral chemoreceptors in the carotid and aortic bodies.
What are the types of pulmonary mechanoreceptors?
Pulmonary mechanoreceptors include PSRs, J-receptors, and bronchial c-fibers, which respond to inflation, dyspnea, and pulmonary inflammation respectively.
How does respiration differ during sleep compared to wakefulness?
Respiration during sleep shows changes in ventilation, response to CO2 and O2, and effects on upper-airway muscles and positional changes.
What are examples of drugs that can impair respiration?
Alcohol, anesthetics, narcotics, and sedative-hypnotics are drugs that can impair respiration by reducing hypoxic and hypercapnic ventilatory responses and depressing upper-airway muscle tone.
What respiratory disorders are associated with sleep disturbances?
Respiratory disorders such as asthma, COPD, restrictive lung disease, kyphoscoliosis, obesity hypoventilation syndrome, pregnancy, neuromuscular disorders, and obstructive sleep apnea can cause sleep disturbances.
How do respiratory patterns differ between NREM and REM sleep?
NREM sleep typically exhibits more regular respiratory patterns with decreased tidal volume, while REM sleep shows increased frequency and reduced regularity in respiration.
How do positional changes during sleep affect breathing?
Nonupright positions can significantly alter breathing mechanics, with the supine position potentially increasing airway compromise.
How do ventilatory responses differ between wakefulness and sleep in response to increased airway resistance?
Reductions in minute ventilation are more pronounced during NREM sleep compared to wakefulness in response to increased airway resistance.
What symptoms characterize nocturnal asthma?
Nocturnal asthma presents with repetitive arousals, breathlessness, coughing, and wheezing during sleep.
What contributes to hypoxemia in COPD during sleep?
Hypoxemia in COPD during sleep results from hypoventilation, ventilation/perfusion mismatching, and/or reduction of lung volume, exacerbated in REM sleep.
How does pregnancy affect sleep-disordered breathing?
Pregnancy tends to increase snoring prevalence but has less effect on apnea-hypopnea frequency.
How do neuromuscular disorders affect respiration during sleep?
Neuromuscular disorders can cause hypoventilation, oxygen desaturation, and apneas/hypopneas during sleep.
What characterizes obesity hypoventilation syndrome during sleep?
Obesity hypoventilation syndrome during sleep results from increased work of breathing and metabolic demands, leading to hypoxemia.
How does REM sleep exacerbate obstructive sleep apnea?
REM sleep exacerbates obstructive sleep apnea by increasing upper-airway narrowing and breathing work, leading to hypoxemia and hypercapnia.
What is alveolar hypoventilation, and how is it defined?
Alveolar hypoventilation is defined as PaCO2 ≥ 45 mm Hg during wakefulness, with nocturnal hypoventilation indicated if sleeping PaCO2 is ≥ 10 mm Hg higher than awake.
What PaO2 value on room air indicates severe hypoxemia?
A PaO2 < 55 mm Hg on room air indicates severe hypoxemia, suggesting the need for oxygen therapy.
How is PAO2 calculated, and what value is assumed for the respiratory exchange ratio (R)?
The alveolar gas equation computes PAO2 from FiO2 and PaCO2, assuming a respiratory exchange ratio (R) of 0.8.
What are some causes of hypoxemia?
Hypoxemia can result from low FiO2 (fraction of inspired oxygen), low barometric pressure (high altitude), hypoventilation (increased PaCO2), ventilation-perfusion mismatch, or shunt.
What complications can arise from hypoxemia?
Hypoxemia may occur from hypoventilation without affecting the A-a gradient, whereas lung disease causing increased PaCO2 is associated with an increased A-a gradient.
How is oxygen mainly carried in the blood, and what factors affect its saturation?
Oxygen is mainly carried by hemoglobin, with saturation affected by temperature, pH, and other factors. Abnormal hemoglobins, like those in sickle cell disease, can alter this relationship.
What happens when the oxygen dissociation curve shifts left or right?
A left shift reduces oxygen release to tissues, while a right shift increases it. Various factors like temperature, pH, and abnormal hemoglobins influence these shifts.
What factors influence PaCO2 levels?
PaCO2 is related to metabolic rate and alveolar ventilation, with minute ventilation minus dead space ventilation determining alveolar ventilation.
How does ventilation change during sleep, and why?
Ventilation decreases during sleep due to decreased CO2 production, increased upper airway resistance, decreased chemosensitivity, and loss of wakefulness stimulus.
What are some tests used to assess ventilatory control?
Chemoreceptors like carotid body and medullary chemoreceptors respond to changes in PaO2, PaCO2, and [H+]. Hypercapnic hypoxemia is a potent stimulus. Sensitivity of chemoreceptors can be measured using rebreathing methods.
What does mouth occlusion pressure measure, and how is it assessed?
Mouth occlusion pressure (P0.1) measures respiratory drive and is measured 0.1 second after inspiration start. It is assessed during rebreathing with intermittent airway occlusion.
How do ventilatory control parameters change during different sleep stages?
Hypercapnic and hypoxic ventilatory responses are reduced during NREM sleep compared to wakefulness and further decreased during REM sleep compared to NREM sleep.
How does CPAP treatment alter ventilatory control in patients with obstructive sleep apnea (OSA)?
CPAP treatment in OSA patients alters the position of the oxygen dissociation curve without changing its slope. This is attributed to reduced nocturnal PaCO2 accumulation and bicarbonate (HCO3) compensation.
How are pH, PaCO2, and HCO3 related in acid-base physiology?
pH is related to serum bicarbonate (HCO3) and PaCO2 through the Henderson-Hasselbalch equation. Compensation involves changes in HCO3 in the same direction as PaCO2 changes to minimize alterations in the PaCO2-to-HCO3 ratio, while pH remains outside the normal range.
