18- Respiratory Chemoreceptors and Neuromodulation Flashcards
chemoreceptor neurons
DEFINITION: Neurons whose discharge rate is altered by changes in PO2 or PCO2 in their environment.
LOCATION: Respiratory chemoreceptors are found in the carotid bodies and within the brainstem.
carotid body location and innervation
1) located bilaterally at the bifurcation of carotid arteries
2) innervated by 9th cranial nerve.
carotid sensory mechanism
within TYPE 1 (glomus) cells which release neurotransmitters that activate sensory nerve endings
- chemoreceptor is type 1
- the sensory nerve endings go back to the petrosal ganglion cell bodies which project to the 9th cranial nerve
Sensory mechanism involves…
changes in K+ and Ca2+ channels that lead to release of neurotransmitters
- atp
- acetylcholine
- dopamine
- norepinephrine
relationship between decreased PaO2 and carotid chemoreceptor activity
curvilinear relationship
- response is augmented by increasing PaCO2
- impulse frequency increases as PO2 is lowered and the degree is dependent upon the existing CO2
carotid impulse frequency relationship to PaCO2
- linearly related
- response is augmented by decreasing PaO2
as PaO2 increases what happens to spike activity and ventilation?
as PO2 increases there is not much of a change higher up until you go lower and past normal (100) is when you have a big increase in spike activity of carotid chemoreceptor activity
Surgical denervation of carotid chemoreceptors causes
hypoventilation after denervation then there is some plasticity and PCO2 and O2 come back to the nomal levels again with some time
role of carotid chemoreceptors
- Provide excitatory input to the respiratory network of neurons.
- Are the body’s major or only site of hypoxic chemoreceptors,
- Stabilize breathing to minimize breath-to-breath variations in PaCO2 and PaO2
- Mediate high altitude ventilatory acclimatization
- if we go to high altitude the chemoreceptors become much more active and their impulse frequency for a given PO2 is increased which gives us a great increase in breathing, which partially compensates for the lower atmospheric O2
CO2 H+ Chemoreceptors
have multiple sites that can be activated by an increase in PCO2
-most notable is the retrotrapezoidal nucleus (aka. ventral lateral medulla)
-hypothesized to determine physiologic functions in addition to breathing
Congenital Central Hypoventilation Syndrome
characterized by:
1) Central sleep apnea
2) Absent CO2/H+ chemoreceptor sensitivity
3) Absent carotid hypoxic chemoreceptor sensitivity
4) Normal exercise hyperpnea
5) Normal airway reflexes and respiratory mechanics
Absence of chemosensitivity due to abnormal retrotrapezoid nucleus (major site of chemosensitivity)
Conclusions:
- in addition to the chemoreceptor input to respiratory neurons, there must be other important inputs determining respiratory neuron excitability
- these other inputs must not be present during sleep. There is strong evidence that this input is from neuromodulators.
Neurotransmitters
A major means of neuronal communication is by release at the presynaptic terminal of neurochemicals which then enter through ion channels the post synaptic neuron to elicit an action potential.
-through ion channels that stimulate or inhibit post synaptic membrane
glutamate
major fast-acting neurotransmitter
-excitatory (leads to depolarization)
GABA
fast acting inhibitory neurotransmitter
Neuromodulators
- change effectiveness of neurotransmitters
- bind to G-protein receptors on the postsynaptic membrane that alter membrane potential
- elicit a cascade of reactions to change the membrane potential thereby increasing or decreasing the possibility of eliciting discharge by neurotransmitters.
discuss the state-dependent activity of neurons producing neuromodulators
-it is a reduction in these neuroexcitatory modulators that decrease excitability of neurons in rhythm and the pattern generating network which is what results in being wake/sleeping and the different stages of sleep
Neuromodulators
- raphe pallidus
- locus coeruleus
- rostral pontine nuclei (LGT/PPT & FTG)
- Raphe pallidus: source of serotonin
- locus coeruleus source of norepinephrine
- rostral pontine nuclei (LGT/PPT and FTG) are sources of acetylcholine
Three excitatory stimuli that sustain activity of rhythm and pattern generating neurons
- Carotid Chemoreceptors
- State-dependent Neuromodulation
- Retrotrapezoid Nucleus
all go to the Respiratory Controllers
-apnea can result from deficit in excitation or an increase in inhibition
Central Sleep Apnea
defined as cessation of airflow and absence of changes in esophageal pressure (Pes) and respiratory muscle activity
Cheyne-Stokes breathing due to…
delay in change of blood PCO2 and PCO2 at brain chemoreceptors
Obstructive Sleep Apnea
cessation of airflow in spite of activity of respiratory muscles and changes in esophageal pressure
-typically due to tongue falling behind soft palate at base of tongue
mixed vs obtrusive apnea
mixed apnea: where rhythm generator stops
obstructive apnea: rhythm generator is operative but no flow
Obstructive Sleep Apnea (OSA)
- Major control of breathing clinical condition in USA (15% of adults)
- The airway obstruction is not life-threatening but the fractionated sleep, hypoxemia, increased sympathetic nerve activity, acute and chronic arterial hypertension, daytime somnolence, and psychiatric disorders are major problems.
Treatments for SDB/OSA:
1. Positive pressure breathing.
2. Mechanical device is inserted to the back of the mouth. 3. Surgery to remove portions of the tongue and/or oral
pharynx.
4. Tracheotomy is created in some patients (putting in an opening below the larynx or below the level of occlusion so that ventilation doesn’t suffer at night)
Sudden Infant Death Syndrome (SIDS)
a) most SIDS infants die of central sleep apnea
b) SIDS occurs in 1 out of every 2000 births in the USA
c) the deaths occur most frequently between 2 and 4 months of age
d) evidence that in SIDS infants, there is a deficit in mechanisms by which serotonin in the medulla provides an excitatory drive to breath, specifically to respiratory/physiologic response to an elevated PaCO2.
how to tell if the lungs are working properly
normal PaO2 level means the lungs are fine
