ICL 2.13: Control of Respiration and Sleep Related Breathing Disorders Flashcards
what is the mechanism of sleep-wake?
during wake, you have histamine and serotonin and norepinephrine and ACh are active
GABA is more active when you’re sleeping
what are the typical EEG signs for the stages of sleep?
awake = alpha waves; 8 to 12 eps
NREM stage 1 = theta waves; 3-7 eps
NREM stage 2 sleep spindles and K complexes; 12-14 eps
NREM stage 3 = delta waves
REM sleep = low voltage, random, fast sawtooth
what are the stages of sleep in a hypnogram?
stage 1-4
4-5 REM cycles each night and they get longer throughout the night so most of your REM sleep is in the last 1/3 of the night
most of the NREM sleep is in the first 1/3 of the night
what important things happen in NREM vs. REM sleep portions of the night?
NREM
1. growth hormone is released
- brain recovery
- executive functioning
REM
1. memory consolidation
- learning
what are the 3 types of sleep related breathing disorders?
- obstructive sleep apnea
- central sleep apnea
- sleep related hypoventilation or hypoxemia
what is obstructive sleep apnea?
it’s characterize by complete (apnea) or partial (hypopnea) upper airway obstruction events that last for at least 10 seconds
these events often result in reductions in blood oxygen saturation and are usually terminated by brief arousals from sleep
snoring between apneas typically reported by bed partners
witnessed episodes of gasping or choking and body movements that disrupt sleep
what are the most common presenting complaints with obstructive sleep apnea?
excessive daytime sleepiness in men
insomnia, poor sleep quality, fatigue in women
what is the pressure in the upper airway during inspiration?
the upper airway is a collapsible tube vulnerable to closure during breathing
to keep it open it’s a balance of forces; the forces keeping it open have to be greater than the ones promoting collapse
during inspiration the upper airway has sub-atmospheric pressures which exert a collapsing force on the upper airway so anything that leads to a decrease in upper airway size sets up a condition where the airspace is even more vulnerable to collapse in inspiration
at what part of the respiratory cycle is the upper airway narrowest?
at the end of expiration
this effect increases the demand on upper airway muscles to maintain adequate airflow during the subsequent inspiration
significant enlargement of the upper airway does NOT necessarily occur in inspiration despite pharyngeal muscle activation, likely because the narrowing effects of inspiratory suction pressures offset the dilating effects of upper airway muscle activation
how’s pharyngeal muscle tone effected in NREM vs REM sleep?
pharyngeal muscle tone is reduced from wakefulness to non-REM sleep and REM sleep
so our airways are more narrow when we sleep compared to when we’re awake
then during REM, those muscles are totally paralyzed so the airway is even more narrow
what part of the airway is obstructed in obstructive sleep apnea?
in NREM sleep, the airway obstruction occurs almost always at the level of the soft palate
the obstruction also extends caudally to regions behind the tongue in about half the patients with OSA
in REM sleep, the lower level of obstruction extends to even more caudal levels compared to NREM sleep, likely due to greater suppression of pharyngeal muscle activity in REM sleep
what is the function and innervation of the genioglossus?
innervated by hypoglossal nerve – CN XII
important pharyngeal dilator
under what circumstances are OSA events worse? why?
events are usually longer and associated with more severe decreases in oxygen saturation when:
- they occur in REM sleep
this is due to reduced muscle tone and blunted response to changes in CO2 and O2 levels
- the individual is sleeping supine
this is due to gravity causing the tongue to fall backwards
what are the predisposing factors for OSA?
obesity
fat deposits around the pharynx lead to increased large neck size/neck circumference which surround the airway!
so if the neck circumference is over 17 inches in men or 16 inches in women that’s a predisposing factor for OSA
also sisceral or abdominal obesity reduces lung volume and therefore caudal traction on the pharynx
what are some of structural abnormalities that can cause OSA?
- hypertrophied adenoids and tonsils (especially significant in
children) - nasal turbinate hypertrophy (allergic rhinitis)
- deviated nasal septum
- enlarged or elongated uvula
- macroglossia (large tongue, common in Down syndrome)
- retrognathia (posterior positioning of the mandible) which causes posterior displacement of tongue
- micrognathia (undersized jaw) which leads to posterior displacement of tongue
- fluid displacement from the legs into the upper body, as can occur with recumbency, increases neck cirumference and pharygeal resistance that may predispose to OSA especially in fluid overload states, such as heart and renal failure
which endocrine conditions(endocrinopathies) can cause OSA?
- hypothyroidism
it leads to OSA because it causes oropharyngeal airway myopathy, edema, obesity and goiters
- acromegaly
it leads to OSA because it causes enlarged growth of the craniofacial bones, enlarged tongue and thickening/enlargement of the laryngeal area
what are the physical exam findings with OSA?
- enlarged/displaced tongue
- increased neck circumference from excess fatty tissue
- enlarged tonsils
- pulmonary HTN
what is the Mallampati classification?
it’s used to examine the pharynx in patients with suspected OSA
just have the person open their mouth as wide as possible with their tongue out but without making any noise to see how much you can see their uvula
class III and IV are clinically significant
class III = you can only see the base of the uvula
class IV = you can’t see any of the uvula
what is a Mallampati class I?
soft palate, fauces, uvula, and posterior and anterior pillars are visible
what is a Mallampati class II?
soft palate, fauces, and uvula are visible
can’t see the back of the throat but can see part of the uvula
what is a Mallampati class III?
Soft palate, fauces, and only base of uvula are visible
what is a Mallampati class IV?
soft palate is not visible
what are the tonsil size grading?
tonsil size 1: tonsil are hidden within the pillars
tonsil size 2: tonsils extend to the pillars
tonsil size 3: tonsils extend beyond the pillars but not the midline
tonsil size 4: tonsils extend to the midline
tonsil size 3 and 4 is clinical significant
how is pulmonary HTN associated with OSA? what are the PE findings of pulmonary HTN?
pulmonary HTN is a consequence of untreated OSA!
PE findings:
1. right ventricular failure = JVD, edema, ascites
- loud P2
- right sided S3 or S4
- holosystolic tricuspid regurg murmur
what are the 2 sleep questionaries?
- Epworth sleepiness scale
2. sleep apnea STOP-BAND questionnaire or Berline questionnaire
how do you diagnose OSA?
polysomnography (PSG)
what is the diagnostic criteria for OSA in adults?
apnea-hypopnea index (AHI)
(# apneas + # hypopneas) ÷ total sleep time
AHI >5 obstructive respiratory events/hour AND at least one of the following:
1. daytime sleepiness
- waking up choking
- loud snoring or witnessed apnea
- diagnosis of hypertension, a mood disorder, cognitive dysfunction, coronary artery disease, stroke, congestive heart failure, atrial fibrillation, or type 2 diabetes mellitus
OR ADH >15 regardless of additional symptoms
what is the diagnostic criteria for OSA in kids?
AHI ≥ 1 predominantly obstructive respiratory events per hour of sleep
OR
obstructive hypoventilation (≥25% of total sleep time with PaCO2 > 50 mmHg)
how do you classify OSA severity based on AHI?
AHI = apnea-hypopnea index
ADULT
mild = 5-15
moderate = 15-20
severe = 30+
CHILD
mild = 1-5
moderate = 5-10
severe = 10+
the greater the severity, the higher the chance of sudden cardiac death at night
why is AHI of 5 significant for OSA?
your risk of HTN and cardiovascular disease increases a lot
survival also starts to decrease at this number
for women under 70, your mortality also increases at this point
what are the pathophysiology consequences of OSA on the cardiovascular system?
hypoxia, increased PCO2, CNS arousals and negative intrathoracic pressures seen in sleep apnea can cause:
decreased O2 delivery, endothelial dysfunction, pulmonary vasoconstriction, sympathetic activation and increased transmural pressure of L and R ventricles
those ultimately lead to organ dysfunction, vasoconstriction, thrombosis, inflammation, increased RV after load, increased systemic vascular resistance, changes in RV and LV preload and afterload and excess lung water and pulmonary edema
this is so important to know how OSA effects the cardiovascular system!! they have a 25% risk of atrial fibrillation even after ablation
how does OSA effect urination?
increased night time urination
when you have occluded breaths and your upper airway starts to collapse you have increased negative intrathoracic pressure which increases venous return to the right ventricle
this causes distention of the RA and RV so the heart falsely thinks it’s in heart failure and will release ANP
ANP inhibits ADH and aldosterone secretion which causes diuresis
treating with CPAP decreases nighttime urination 50%
how does OSA effect metabolism?
intermittent hypoxia and sleep fragmentation from OSA result in activation of the sympathetic nervous system, oxidative stress and inflammation
those factors result in obesity, insulin resistance, glucose intolerance, dyslipidemia, nonalcoholic fatty liver disease and metabolic syndrome
how does OSA effect mental health?
OSA is associated with higher amounts of:
1. depression
- anxiety
- PTSD
- psychosis
- bipolar
it also lowers the seizure threshold
how do you treat OSA?
CPAP = continuous positive airway pressure
they blow air into the airway to open up the obstruction
what are the benefits of using CPAP to treat OSA?
- improved oxygen saturation
- improves insulin resistance
- improves BP
- reduced hospital readmission of cardiac patients
- favorable effect on stroke severity and recurrent stroke
what is a CHADS2 score?
risk of stroke associated with atrial fibrillation
Chronic heart failure
HTN
Age >65
DM
Stroke history
what are the effects of weight loss on OSA?
helps treat OSA!
you can decrease fatty tissue surrounding airway so the size of the airway improves
weight loss or weight loss + CPAP reduced CRP, insulin resistance and serum TG levels
what is a BPAP?
BPAP = bilevel positive airway pressure device
it provides higher pressure during inspiration (IPAP) and lower pressure during expiration (EPAP)
that’s because during inspiration there’s more forcing acting to collapse your airway so you want higher pressure being given by the BPAP to prevent that whereas during expiration it’s not as needed
the machine is monitoring patient’s flow so it’ll turn IPAP off to allow the patient to exhale
what is IPAP and EPAP?
IPAP
1. maintains or augments ventilation (stabilizes O2 and decreases PCO2 especially during sleep)
- decreases work of breathing and rests accessory muscles
- for OSA, IPAP is titrated to resolve obstructive hypopneas, respiratory effort-related arousals (RERAs), and snoring
EPAP
1. splints the upper airway (same as CPAP)
- promotes alveolar recruitment, enhancing oxygen exchange (same as PEEP)
- for OSA, EPAP is titrated to resolve obstructive apneas
what’s the difference between CPAP and BPAP?
CPAP set at 4 cmH2O mean that whether you’re inhaling or exhaling you’re going to be getting 4 cmH2O
with BPAP or 9/4 that means when you inhale you’ll get 9 cmH2O and when you exhale you’ll get 4 cmH2O
pressure support = IPAP - EPAP = 9-4 = 5
when is the patient switchedfrom CPAP to BPAP?
if the patient can’t tolerate CPAP therapy
OR
if there are continued obstructive respiratory events at 15 cm H2O of CPAP for either adult or pediatric patients during the titration study
what are the surgical alternatives to treating OSA?
- tonsillectomy
- adenoidectomy
- septoplasty
- tracheostomy
how does upper airway stimulation work for treating OSA?
it’s like a pacemaker for your respiratory system and when it senses an obstruction happening, it sends a signal that stimulates your hypoglossal nerve which causes tongue protrusion
what is the etiology of pediatric OSA?
- adenotonsillar hypertrophy = big tonsils (most common)
- craniofacial anomalies
- neuromuscular disorders
- obesity
first line treatment is adenotonsillectomy
what is the most common presentation of pediatric OSA?
- neurobehavioral issues
ex. developmental delay, poor school performance, ADHD*, inattention, impairment in concentration, aggressive behavior - growth impairment due to suppression of slow wave sleep that is causing impairment of related growth hormone release
what are the effects of sleep deprivation on growth hormone, cortisol, TSH and prolactin?
GH = decreased
cortisol = unchanged
TSH = increased
prolactin = decreased
what controls your breathing when you’re asleep?
there’s a lot of inputs that contribute to regulation of breathing and during sleep a lot of them are diminished or absent so the predominant inputs during sleep are the peripheral and central chemoreceptors
what is your central control of breathing?
both of these are in the medulla
- dorsal respiratory group (DRG)
key site of integration of sensory information from the lung located in the nucleus of the solitary tract (NTS) which is the site of the first central synapse for afferents from arterial chemoreceptors and lung and airway receptors
- ventral respiratory group (VRG) which have both inspiratory neurons (rostral) and expiratory neurons (caudal)
what is the Pre-Botzinger complex?
part of the ventral respiratory group (VRG)
these neurons have pacemaker-like properties that are though to be important to the generation of the basic respiratory rhythm, and to the expression of rhythmic neuronal activity elsewhere in the respiratory network
how does the Pre-Botzinger complex work?
this complex expresses neurokinin-1 receptors which are the receptors for substance P which increases respiratory rate!
it also expresses μ opioid receptors, which slows respiratory rate
NREM sleep and general anesthesia are the most vulnerable states for respiratory rate depression produced by opioids at the pre-Bötzinger complex
what is the range of PCO2 that your body allows for before regulating respiration?
40 +/- 4 mmHg
if it varies any more than this your brain will start signaling to your lungs to either breath faster or slower to regulate CO2 levels
what is central sleep apnea?
centrally driven respiratory events are primarily due to a temporary loss of output from the pontomedullary pacemaker that generates breathing rhythm, resulting in loss of the respiratory pump muscles = diaphragm, thorax, abdomen
on polysomnography (PSG), there is an absence of respiratory effort during the cessation of airflow
what are the 3 main central sleep apnea syndromes?
- Central Sleep Apnea with Cheyne-Stokes Breathing
- Central Apnea Due to Medical Disorder without Cheyne-Stokes Breathing
- Central Sleep Apnea Due to a Medication or Substance
what is central sleep apnea with cheyne-stokes breathing?
CSA-CSB is recurrent central apneas or central hypopneas alternating with a respiratory phase exhibiting a crescendo-decrescendo pattern of flow (or tidal volume)
so there’s periods of breathing too fast followed by slow breathing
a vast majority of patients with CSA-CSB have either systolic or diastolic heart failure!!
it occurs more commonly in the supine position because of an increase in pulmonary congestion, reduction in vital capacity and pulmonary compliance = orthopnea
what is the apnea threshold?
the level of CO2 that results in the absence of breathing
so it’s the absolute set point and sensitivity is different between individuals
if your normal pCO2 is 36-44 mmHg but your CO2 goes to 50 or 52, you start to hyperventilate
eventually you’ll get to a point where you’re hyperventilating so much that you can’t compensate anymore for the increased pCO2 and you die
what kind of unstable ventilation do you see with central sleep apnea with cheyne-stokes breathing?
- CSA-CSB have unstable ventilation
in heart failure the heart is so weak that blood is pumped slower throughout the body so blood with high CO2 levels takes a longer time to reach the body sensors – this means that the CO2 level continues to rise for longer before the single increase breathing is triggered
this leads to increased “mixing gain” = the time required for a change in alveolar CO2 to mix with the blood in the heart and the arteries before reaching the chemoreceptors –> so in people with CHF they have an increase in mixing gain
- they are hypersensitive to changes in CO2 levels so they will start to hyperventilate at a CO2 of 40.0001 = increased “controller gain”
pCO2 will be normal or low on ABG because they’re hyperventilating
central sleep apnea with cheyne-stokes breathing?
people with pulmonary congestion due to CHF have increased sympathetic tone and stimulation of vagal irritant receptors in the lungs
this lead to an increase in the responsiveness of the peripheral and central chemoreceptors and hyperventilation
the hyperventilation leads to arousal from sleep and PaCO2 being driven below the apnea threshold
this causes central apnea
so then your body stops breathing to make the PaCO2 to go up and eventually it gets high enough that it’ll trigger your peripheral and central chemoreceptors again and the whole cycle starts all over
what is central apnea due to medical disorder without cheyne-stokes breathing?
a brainstem lesions of developmental, vascular, neoplastic, degenerative, demyelinating, or traumatic origin that causes dysfunction of ventral ventilatory control centers
ex. Chiari malformation, brainstem stroke, multiple system atrophy
what is central apnea due to a medication or substance?
Opioid use: respiratory depression that occurs through action of the drugs on the mu-receptors located on Pre-Botzinger Complex neurons on the ventral surface of the medulla
at low doses, tidal volumes decline, whereas at higher doses, respiratory rate and rhythm generation are suppressed (respiratory arrest)
chronic opioid use is a risk factor for the development of central sleep apnea and ataxic breathing
what is Biot breathing?
ataxic(irregular) breathing with variable tidal volumes and rate seen in opiate-induced central sleep apnea
how do you treat central sleep apnea?
treat the underlying problem!!!
whether that be treating the CHF or opiates etc.
other options include CPAP, nocturnal oxygen therapy, BPAP, or adaptive servo ventilation therapy
what happens to the respiratory rate and airflow during NREM vs REM sleep?
NREM = decreased respiratory rate during the transition from wake to NREM
REM = increased respiratory rate during REM sleep occasionally exceeding the waking level
airflow is lower than during wake or NREM in REM sleep
what is sleep related hypoventilation?
reduction in the amount of air flow
this leads to elevated carbon dioxide levels and an increase in PaCO2 over 55 mmHg for 10+ minutes during sleep
OR
these is a 10+ mmHg increase in PaCO2 during sleep in comparison to an awake supine value to a value exceeding 50 mmHg for 10+ minutes
what is sleep related hypoxemia?
hypoxemia = low oxygen level
diagnosis of sleep related hypoxemia is reserved for patients who have low oxygen but normal carbon dioxide levels during sleep
PSG, home sleep study or nocturnal oximetry shows the arterial oxygen saturation (SpO2) during sleep of ≤88% in adults or ≤90% in children for ≥5 minutes
what can cause sleep related hypoventilation and hypoxemia?
it can occur without apnea or hypopnea for the following reasons:
- impaired gas exchange between the alveoli and blood
- failure of inhaled air to reach the entire lung
- failure of the lungs to properly inflate
which conditions cause hypoventilation?
- COPD
mechanical disadvantage to the diaphragm
- ILD or fibrosis
altered lung volumes (e.g., reduced functional residual capacity) and abnormal ventilation/perfusion relationships
- extrathoracic restrictive lung disease like ALS, kyphoscholiosis, obesity
abnormal ventilatory pump (secondary to reduced muscle strength or anatomic distortion of the chest wall structures) that is unable to meet the ventilatory requirements of maintaining PaCO2 at or below 45 mmHg
when is hypoventilation the most severe?
REM sleep
this is due to reduced activation of the intercostal and accessory muscles which causes a disproportionate ventilatory burden placed on the diaphragm
someone with COPD or ALS need their diaphragm and their intercostal muscles to breath to bring in their tidal volume so if these patients go into REM, these muscles are paralyzed which puts an extra burden on the diaphragm to bring in the diaphragm all on its own
decreased minute ventilation and tidal volume: REM > NREM > wake
what is daytime hypoxemia?
if sufficiently severe, may place the patient near or on the steep portion of the oxyhemoglobin curve, where even relatively small decrements in arterial oxygen tension result in large decrements in oxyhemoglobin saturation
what are the consequences of chronic hypercapnia and hypoxemia?
- CO2 toxicity
- pulmonary HTN –> cor pulmonale
- nocturnal sudden cardiac death
what is obesity hypoventilation syndrome (OHS)?
- increased CO2 production
mass loading of adipose tissue on the respiratory pump increases the work of breathing particularly in the supine position which increases the amount of oxygen needed to breath
- reduced CO2 elimination
there’s reduced alveolar ventilation due to an overall decreased level of ventilation –> there’s also maldistribution of ventilation with respect to pulmonary capillary perfusion = increased in physiologic dead space
there’s also blunted central respiratory drive/hypercapnic ventilatory response because with obesity there’s leptin resistance from increased leptin levels which leptin normally is what stimulates ventilation!
how do you diagnose obesity hypoventilation syndrome?
OHS can be diagnosed by:
- the presence of hypoventilation during wakefulness aka daytime hypercapnia = PaCO2 > 45 mmHg
- BMI > 30
- diagnosis of exclusion –> requires that no other coexisting disease may account for the hypercapnia present, including severe OSA
what is COPD/OSA overlap syndrome?
sleep studies should be considered in COPD patients with obesity, snoring, or morning headache associated with nocturnal oxygen therapy to assess for the presence of associated OSA
the clinical course and prognosis of such “overlap patients” were worse than for patients suffering from COPD or untreated OSA alone
patients with untreated overlap syndrome had increased mortality compared with the group with overlap syndrome treated with CPAP and with the group of patients without OSA
what is the pathway involved in producing sleep-related hypoxemia and hypercapnia in COPD and OSA overlap syndrome?
so you start with a OSA that is caused by obesity, smoking etc. that causes upper airway resistance
then with COPD you have impaired respiratory mechanisms and compromised control of breathing
these two combined cause V/Q and hypoventilation which subsequently cause hypoxemia and hypercapnia!
how do you treat hypoventilation?
- noninvasive ventilation
- invasive volume ventilation via tracheostomy
- nocturnal oxygen therapy for sleep related hypoxemia
is sleep apnea related to COVID?
not that we know
but using a CPAP may increase the risk of spreading the virus to others…
