ICL 2.13: Control of Respiration and Sleep Related Breathing Disorders

Question 1

what is the mechanism of sleep-wake?

Answer 1

during wake, you have histamine and serotonin and norepinephrine and ACh are active

GABA is more active when you’re sleeping

Question 2

what are the typical EEG signs for the stages of sleep?

Answer 2

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

Question 3

what are the stages of sleep in a hypnogram?

Answer 3

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

Question 4

what important things happen in NREM vs. REM sleep portions of the night?

Answer 4

NREM
1. growth hormone is released

2. brain recovery
3. executive functioning

REM
1. memory consolidation

2. learning

Question 5

what are the 3 types of sleep related breathing disorders?

Answer 5

1. obstructive sleep apnea
2. central sleep apnea
3. sleep related hypoventilation or hypoxemia

Question 6

what is obstructive sleep apnea?

Answer 6

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

Question 7

what are the most common presenting complaints with obstructive sleep apnea?

Answer 7

excessive daytime sleepiness in men

insomnia, poor sleep quality, fatigue in women

Question 8

what is the pressure in the upper airway during inspiration?

Answer 8

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

Question 9

at what part of the respiratory cycle is the upper airway narrowest?

Answer 9

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

Question 10

how’s pharyngeal muscle tone effected in NREM vs REM sleep?

Answer 10

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

Question 11

what part of the airway is obstructed in obstructive sleep apnea?

Answer 11

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

Question 12

what is the function and innervation of the genioglossus?

Answer 12

innervated by hypoglossal nerve – CN XII

important pharyngeal dilator

Question 13

under what circumstances are OSA events worse? why?

Answer 13

events are usually longer and associated with more severe decreases in oxygen saturation when:

1. they occur in REM sleep

this is due to reduced muscle tone and blunted response to changes in CO2 and O2 levels

2. the individual is sleeping supine

this is due to gravity causing the tongue to fall backwards

Question 14

what are the predisposing factors for OSA?

Answer 14

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

Question 15

what are some of structural abnormalities that can cause OSA?

Answer 15

1. hypertrophied adenoids and tonsils (especially significant in
   children)
2. nasal turbinate hypertrophy (allergic rhinitis)
3. deviated nasal septum
4. enlarged or elongated uvula
5. macroglossia (large tongue, common in Down syndrome)
6. retrognathia (posterior positioning of the mandible) which causes posterior displacement of tongue
7. micrognathia (undersized jaw) which leads to posterior displacement of tongue
8. 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

Question 16

which endocrine conditions(endocrinopathies) can cause OSA?

Answer 16

1. hypothyroidism

it leads to OSA because it causes oropharyngeal airway myopathy, edema, obesity and goiters

2. acromegaly

it leads to OSA because it causes enlarged growth of the craniofacial bones, enlarged tongue and thickening/enlargement of the laryngeal area

Question 17

what are the physical exam findings with OSA?

Answer 17

1. enlarged/displaced tongue
2. increased neck circumference from excess fatty tissue
3. enlarged tonsils
4. pulmonary HTN

Question 18

what is the Mallampati classification?

Answer 18

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

Question 19

what is a Mallampati class I?

Answer 19

soft palate, fauces, uvula, and posterior and anterior pillars are visible

Question 20

what is a Mallampati class II?

Answer 20

soft palate, fauces, and uvula are visible

can’t see the back of the throat but can see part of the uvula

Question 21

what is a Mallampati class III?

Answer 21

Soft palate, fauces, and only base of uvula are visible

Question 22

what is a Mallampati class IV?

Answer 22

soft palate is not visible

Question 23

what are the tonsil size grading?

Answer 23

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

Question 24

how is pulmonary HTN associated with OSA? what are the PE findings of pulmonary HTN?

Answer 24

pulmonary HTN is a consequence of untreated OSA!

PE findings:
1. right ventricular failure = JVD, edema, ascites

2. loud P2
3. right sided S3 or S4
4. holosystolic tricuspid regurg murmur

Question 25

what are the 2 sleep questionaries?

Answer 25

1. Epworth sleepiness scale

2. sleep apnea STOP-BAND questionnaire or Berline questionnaire

Question 26

how do you diagnose OSA?

Answer 26

polysomnography (PSG)

Question 27

what is the diagnostic criteria for OSA in adults?

Answer 27

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

2. waking up choking
3. loud snoring or witnessed apnea
4. 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

Question 28

what is the diagnostic criteria for OSA in kids?

Answer 28

AHI ≥ 1 predominantly obstructive respiratory events per hour of sleep

OR

obstructive hypoventilation (≥25% of total sleep time with PaCO2 > 50 mmHg)

Question 29

how do you classify OSA severity based on AHI?

Answer 29

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

Question 30

why is AHI of 5 significant for OSA?

Answer 30

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

Question 31

what are the pathophysiology consequences of OSA on the cardiovascular system?

Answer 31

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

Question 32

how does OSA effect urination?

Answer 32

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%

Question 33

how does OSA effect metabolism?

Answer 33

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

Question 34

how does OSA effect mental health?

Answer 34

OSA is associated with higher amounts of:
1. depression

2. anxiety
3. PTSD
4. psychosis
5. bipolar

it also lowers the seizure threshold

Question 35

how do you treat OSA?

Answer 35

CPAP = continuous positive airway pressure

they blow air into the airway to open up the obstruction

Question 36

what are the benefits of using CPAP to treat OSA?

Answer 36

1. improved oxygen saturation
2. improves insulin resistance
3. improves BP
4. reduced hospital readmission of cardiac patients
5. favorable effect on stroke severity and recurrent stroke

Question 37

what is a CHADS2 score?

Answer 37

risk of stroke associated with atrial fibrillation

Chronic heart failure

HTN

Age >65

DM

Stroke history

Question 38

what are the effects of weight loss on OSA?

Answer 38

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

Question 39

what is a BPAP?

Answer 39

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

Question 40

what is IPAP and EPAP?

Answer 40

IPAP
1. maintains or augments ventilation (stabilizes O2 and decreases PCO2 especially during sleep)

2. decreases work of breathing and rests accessory muscles
3. 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)

2. promotes alveolar recruitment, enhancing oxygen exchange (same as PEEP)
3. for OSA, EPAP is titrated to resolve obstructive apneas

Question 41

what’s the difference between CPAP and BPAP?

Answer 41

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

Question 42

when is the patient switchedfrom CPAP to BPAP?

Answer 42

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

Question 43

what are the surgical alternatives to treating OSA?

Answer 43

1. tonsillectomy
2. adenoidectomy
3. septoplasty
4. tracheostomy

Question 44

how does upper airway stimulation work for treating OSA?

Answer 44

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

Question 45

what is the etiology of pediatric OSA?

Answer 45

1. adenotonsillar hypertrophy = big tonsils (most common)
2. craniofacial anomalies
3. neuromuscular disorders
4. obesity

first line treatment is adenotonsillectomy

Question 46

what is the most common presentation of pediatric OSA?

Answer 46

1. neurobehavioral issues
   ex. developmental delay, poor school performance, ADHD*, inattention, impairment in concentration, aggressive behavior
2. growth impairment due to suppression of slow wave sleep that is causing impairment of related growth hormone release

Question 47

what are the effects of sleep deprivation on growth hormone, cortisol, TSH and prolactin?

Answer 47

GH = decreased

cortisol = unchanged

TSH = increased

prolactin = decreased

Question 48

what controls your breathing when you’re asleep?

Answer 48

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

Question 49

what is your central control of breathing?

Answer 49

both of these are in the medulla

1. 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

2. ventral respiratory group (VRG) which have both inspiratory neurons (rostral) and expiratory neurons (caudal)

Question 50

what is the Pre-Botzinger complex?

Answer 50

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

Question 51

how does the Pre-Botzinger complex work?

Answer 51

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

Question 52

what is the range of PCO2 that your body allows for before regulating respiration?

Answer 52

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

Question 53

what is central sleep apnea?

Answer 53

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

Question 54

what are the 3 main central sleep apnea syndromes?

Answer 54

1. Central Sleep Apnea with Cheyne-Stokes Breathing
2. Central Apnea Due to Medical Disorder without Cheyne-Stokes Breathing
3. Central Sleep Apnea Due to a Medication or Substance

Question 55

what is central sleep apnea with cheyne-stokes breathing?

Answer 55

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

Question 56

what is the apnea threshold?

Answer 56

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

Question 57

what kind of unstable ventilation do you see with central sleep apnea with cheyne-stokes breathing?

Answer 57

1. 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

2. 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

Question 58

central sleep apnea with cheyne-stokes breathing?

Answer 58

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

Question 59

what is central apnea due to medical disorder without cheyne-stokes breathing?

Answer 59

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

Question 60

what is central apnea due to a medication or substance?

Answer 60

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

Question 61

what is Biot breathing?

Answer 61

ataxic(irregular) breathing with variable tidal volumes and rate seen in opiate-induced central sleep apnea

Question 62

how do you treat central sleep apnea?

Answer 62

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

Question 63

what happens to the respiratory rate and airflow during NREM vs REM sleep?

Answer 63

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

Question 64

what is sleep related hypoventilation?

Answer 64

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

Question 65

what is sleep related hypoxemia?

Answer 65

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

Question 66

what can cause sleep related hypoventilation and hypoxemia?

Answer 66

it can occur without apnea or hypopnea for the following reasons:

1. impaired gas exchange between the alveoli and blood
2. failure of inhaled air to reach the entire lung
3. failure of the lungs to properly inflate

Question 67

which conditions cause hypoventilation?

Answer 67

1. COPD

mechanical disadvantage to the diaphragm

2. ILD or fibrosis

altered lung volumes (e.g., reduced functional residual capacity) and abnormal ventilation/perfusion relationships

3. 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

Question 68

when is hypoventilation the most severe?

Answer 68

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

Question 69

what is daytime hypoxemia?

Answer 69

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

Question 70

what are the consequences of chronic hypercapnia and hypoxemia?

Answer 70

1. CO2 toxicity
2. pulmonary HTN –> cor pulmonale
3. nocturnal sudden cardiac death

Question 71

what is obesity hypoventilation syndrome (OHS)?

Answer 71

1. 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

2. 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!

Question 72

how do you diagnose obesity hypoventilation syndrome?

Answer 72

OHS can be diagnosed by:

1. the presence of hypoventilation during wakefulness aka daytime hypercapnia = PaCO2 > 45 mmHg
2. BMI > 30
3. diagnosis of exclusion –> requires that no other coexisting disease may account for the hypercapnia present, including severe OSA

Question 73

what is COPD/OSA overlap syndrome?

Answer 73

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

Question 74

what is the pathway involved in producing sleep-related hypoxemia and hypercapnia in COPD and OSA overlap syndrome?

Answer 74

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!

Question 75

how do you treat hypoventilation?

Answer 75

1. noninvasive ventilation
2. invasive volume ventilation via tracheostomy
3. nocturnal oxygen therapy for sleep related hypoxemia

Question 76

is sleep apnea related to COVID?

Answer 76

not that we know

but using a CPAP may increase the risk of spreading the virus to others…