Respiratory Control: Johnson Flashcards
-Mechanics
-gas exchange
-gas transport
Bringing everything together with control of breathing
Everything we’ve learned so far
What is ventilatory control and what are the 3 perspectives for control for respiration?
ventilatory control refers to the generation and regulation of rhythmic breathing and modification from input from nervous system; highly regulated system
- want to minimize the amount of work that the body exerts to breathe and meet body metabolic needs
- deliver o2 to tissues and eliminate waste product CO2, thus maintaining blood gas levels, specifically to regulate arterial PCO2
- maintaining acid base
Highly regulated process
Maintains an adequate supply of O2 to the tissues
Effectively removes the waste product CO2
Maintains acid-base balance
What are the 3 major elements that comprise the respiratory control system?
SENSORS:
- peripheral chemoreceptors
- central chemoreceptors
- pulmonary mechanoreceptors
CENTRAL CONTROLLER
-medulla oblongata and pons
EFFECTORS
-respiratory muscles such as diaphragms
these will all allow the respiratory system to be in tune with body metabolic needs
The musculature generating pressure gradients for the respiratory system are all under control of what nerve?
neural inputs via phrenic nerve which is impacted by central nuclei involved in respiratory activity; now this is the sensor component that impulses via the spinal cord to unpack the activity of the respiratory musculature
What are the levels of control of the respiratory system?
- Respiratory control centers/nuclei in pons and medulla
- Central chemoreceptors (within medulla and other regions of the brain that are sensitive to levels of CO2) and Peripheral chemoreceptors(aortic and carotid bodies)
- Pulmonary mechanoreceptors/sensory nerves
-Other Receptors Nose and upper airway Joint and muscle proprioceptors Gamma system Arterial baroreceptors Pain and Temperature
What contains the primary neural circuit that generates the ventilatory pattern for respiratory activity and is referred to it as the central pattern generator?
medulla oblongata
-there is an oscillatory pattern that continues throughout life and is established in the medulla oblongata
What is the integrator?
- influences the central pattern generator
- the region that receives all signals coming from the periphery and other regions in the brain and integrates the info and sends signals to the central pattern generator which would then influence the muscles so that respiration changes accordingly; it will be modified based on the sensory inputs that are coming in
What are all the sorts of tonic input that have to be integrated to keep the respiratory system up with body demands ?
- inhibition of inspiration from the pneumotaxic center (located in the pons)
- tonic inspiratory stimulation from peripheral and central chemoreceptors
- tonic inspiratory stimulation from vagal stretch receptors
How did we localize the respiratory centers in the brain?
via brain transection experiments
Separation of the pons and medulla allowed rhythmic breathing to ensue.
Removal of the cerebrum, cerebellum and mid-brain had no important effect on breathing.
Transection of the upper pons results in decrease frequency and increased tidal volume. (Apneusis)
A section across the lower pons produced gasping (with or without intact vagus).
Transection of the lower medulla leads to complete respiratory arrest (apnea).
Where are the pneumotaxic, apneustic centers located in the brainstem? How do they change ventilatory pattern?
PNC in pons: decreases frequency of ventilation (inhibits inspiration) in turn increasing tidal volume???preventing overdistension of lungs
APC in pons: inspire holding breath for a while then expire; delays the switch off of the inspiratory ramp
major respiratory nuclei (DRG and VRG) in the medulla: increases frequency of ventilation
pattern changes if vagus nerve is intact or not
What is apnea? What is apneusis?
-apnea is the sensation of breathing
Apneusis is a type of breath holding pattern; it is an inspiratory cramp
What occurs with a lesion to the spinal cord (separating the spinal cord from the medulla)?
loss of motor output to the phrenic nerve
info cannot get to the diaphragm if you separate medulla from spinal cord and thus no diaphragmatic contraction
no diaphragmatic contraction you get apnea and you don’t create the pressure gradient needed to breath
What nerves have snychornized activity during the respiratory phase?
phrenic: allows for contraction of diaphragm
vagus: decreases inspiratory activity in the brain; DRG, VRG receives inputs from CN IX and X???
hypoglossal: prevent prolapse of tongue into blocking the airway
Which nerves maintain the patency of the upper airway?
hypoglossal (CN XII) prevents prolapse of tongue
airway patency: laryngeal and pharyngeal muscles are active during both inspiration and expiration; need to have an open airway to allow air in and out without obstruction these neurons help that to take place
Paraambiguus is primarily vagal motor neurons that innervate the laryngeal and pharyngeal muscles and active during both
inspiration and expiration (patency of the airway)
What is the Pre-Bötzinger Complex?
in central medulla
-very similar to SA node in heart as they are pacemaker neurons that starts off the oscillation that will eventually reach the phrenic nerve to stimulate diaphragm to contract
- every 5 seconds we usually take a breath
- these pacemaker neurons each have their own oscillatory rhythm which is then propagated through multiple synaptic connections and reaches the motorneurons responsible for the upper airway or diaphragm or anything that is involved in respiratory
What nerves are involved in inspiration?
CN IX and X (larynx and pharynx)
CN V: opening of mouth
CN VII: flaring of nostrils
phrenic nerve: diaphragm
spinal nerves reaching external intercostal muscles
all of these have coordinated activity
What nerves are involved in expiration?
internal intercostal muscles and abdominal muscles with forced expiration
What is the dorsal respiratory group?
DRG located in the dorsomedial region of the medulla and is involved primarily in inspiratory activity
integrates lots of info coming from periphery
muscle spindle sending signal to brain about status traveling from the CN IX and X
Why is CO2 and O2 important?
the body has receptors to measure the levels of CO2 and O2 and that’s how we are constantly aware of their levels and can make necessary adjustments for them to stay within physiological pH
What are the E=expiraotry
I=inspiratory neurons in the DRG and VRG?
DRG:
Ibeta: excitatory
Ialpha: inhibitory
VRG:
- Nucleus retrofacialis (E)
- nucleus paraambiguus (I,E)
- nucleus retroambiguus (E,I)
The respiratory control centers each have their own set of nuclei which are classified based on?
neurons are classified based on the place where they show their activity
Phrenic nerve activity is an indication of what?
- diaphragmatic activity establish pressure gradients to get air into alveoli
- correlates to the time where you have increase in tidal volume
- phrenic goes silent at the end of inspiration (diaphragm resumes dome shape position)
When we start breathing we start at what volume?
FRC: volume of gas in lungs after normal expiration
FRC= functional residual capacity
Nomenclature of the respiratory neurons
depending on the time in the respiratory cycle this is what the nomenclature says about the activity of the neuron
What is the function of Nucleus Tract Soilatris in DRG?
Integrates inputs from the 9th and 10th cranial nerves (glossopharyngeal and vagus)
Lung and airways (inflation/irritant receptors)
Information about PO2, PCO2, and pH from peripheral chemoreceptors and systemic BP
Pulmonary stretch receptors
What is ventral respiratory group and what is it comprised of?
located in the ventrolateral region of the medulla
have a major influence on expiratory phase
Comprised of the rostral nucleus retrofacialis, caudal nucleus retroambiguus and nucleus paraambiguus.
Contains inspiratory and expiratory neurons and their primary function is to drive spinal respiratory neurons innervating the intercostal and abdominals or upper airway muscles of inspiration.
What is the functions of expiratory neurons in VRG?
expiratory neurons project to contralateral spinal cord to drive internal intercostal and abdominal muscles to do active expiration or the forced vital capacity (FVC)maneuver
FVC maneuver: when this happens active contraction of the abdominal muscle becomes important as you need greater force than just diaphragmatic relaxation to force air to be expelled from lungs
What is the pneumotaxic center?
located in the upper pons
comprised of the Kölliker-Fuse and nucleus parabrachialis medialis which are involved in fine tuning the transition between inspiratory activity to expiration
Premature termination of inspiratory ramp
Shorten of inspiration that results in frequency modulation of breathing.
helps with volume control as well
it maintains tidal volume creating the switch from inspiratory phase to expiratory phase
What occurs to the breathing pattern with transections above the apneustic center in the lower pons? How is this clinically important?
results in apnea, apneusis, inspiratory cramp, breathholding, prolonged inspiratory gasps
clinically important when patient with head trauma present with this type of breathing allowing localization of the injury; you know apneustic breathing comes from ANC in lower pons
The respiratory cycle has two phases of the expiratory phase, what are they?
during the onset of inspiratory activity we talked about pacemaker cells (Pre-Bötzinger Complex) that sets the rhythm for diaphragmatic contraction
there’s is a positive feedback loop that causes other neurons to be recruited continuing in the inspiratory phase
phrenic nerve stops stimulation when they are shut off the diaphragm relaxes leading to phase I and II
how they break the phase and transition into expiration
end of phase II represents the beginning of phrenic nerve firing and FRC
During apneic pause what volume of air is important to maintain gas exchange?
FRC= functional reserve capacity
What are the two population of sensor that help us to maintain our respiratory activity?
peripheral and central chemoreceptors
What are peripheral chemoreceptors? Where are they located?
in the bifurcation carotid and aortic arch bodies
are uniquely sensitive to O2 levels
blood coming from left ventricle is not at PaO2 of 100 mmHg and so have to adjust that
they respond to acidic pH and increases in CO2 as well but are VERY sensitive to O2
have very little activity during normoxia; in lung diseases hypoxia (PO2) becomes the primary regulator for breathing
does not play a significant role in the regulation of normal ventilation until levels become drastically low (< 60 mmHg).
What is normoxia?
means PaO2 is normal
Which chemoreceptors control normal ventilation?
central chemoreceptors
Where are the peripheral chemoreceptors located?
in blood in the carotid body which has receptors sensing the PaO2 and sending info to the integration station telling the brain we have enough O2
What are two types of carotid body cells and what are their functions?
type I: if the blood surrounding these cells have low O2, they cause release of a transmitter that allows info to be transmitted centrally so that brain can be made aware of need to increase ventilation
Type II (glomus): contains large numbers of synaptic vesicles that contain neurotransmitters
How does the firing rate of Type I carotid body cells change with PaO2 along the nerve?
-stimulated with hypoxia (when it goes below 60)
with normal gas exchange there is no stimulation
-when blood exits LV and goes into aortic arch
Low PaO2 causes change in potassium channel configuration in type I cells in bowman cells causing what cascade?
depolarization: accumulation of positive charges within the cell causes a change in the membrane potential
you have opening voltage gated calcium channels whose calcium influx will cause fusion of transmitter vesciles to the synaptic cleft
they contain dopamine whichis released and cause info to be trnasmitted centrally
and when info gets to the brain it will cause an increase in ventilation to increase breathing to bring in more O2 to stop the initial activity (low O2) that caused the cascade to initiate activity
How do you get increased central impulses to increase O2?????
fluctuation in pH will have an additive effect on what happens to O2
- acidification increases impulses
- alkalosis decreases impulses
What are Central chemoreceptors and where are they located?
- are located within the medulla oblongata and respond to pH of CSF
- primary controller of ventilation (so the periphery are secondary until PaO2 goes below 60) AKA responsible for regulating normal respiratory activity on a breath to breath basis
acidic pH is the MOST POTENT and primary stimulus of central chemoreceptor ~7.32 pH
arterial CO2 fluctuates on a breath to breath basis causing production of hydrogen ion and this causes acidification of CSF stimulating central chemoreceptors
High levels of CO2 diffuses from the arterial blood across the blood brain barrier (BBB)
Causes the carbonic acid equation to proceed to the right to yield increased concentration of H+ ions.
HCO3- controlled by the choroid plexus
What are the areas identified that are sensitive to CO2 or hydrogen ions concentration ?
rostal
medial
caudal
cells in the medulla oblongata
How do you increased CO2?
hypoventilation
increase in production of H+ ions via carbonic acid equation which in turn stimulates central chemoreceptors causing increase in ventilation causing CO2 to be removed
the increase in CO2 level that initiated the cascade will then go back down to normal range
How does central chemoreceptor induce increase in O2? When during a normal respiratory cycle would you expect CO2 to become slightly elevated just enough to cause a stimulation for the next inspiratory effort?
CO2 builds up in the arterial blood
the CO2 gets to BBB and crosses over causing an increased production of hydrogen ions via the carbonic acid equation
which will in turn stimulate the central chemoreceptor
when it is stimulated it triggers us to breathe
during apneic pause, no gas is going into or out and thus CO2 will just rise just enough to stimulate central chemoreceptors
this is why we are dependent on CO2 for our respiratory drive ??
What is the most important regulator of ventilation?
CO2 is the most important regulator of ventilation compared to PO2 and pH of the arterial blood.
CO2 fluctuates just enough for you to take your next breath.
The rate and depth of breathing are controlled such that arterial CO2 remains within near 40mmHg during rest, increased activity and sleep.
What experiments can determine your control of respiration?
Breathing into a bag
- Oxygen held constant
- CO2 gradually rises
- Ventilation increases in a linear fashion as CO2 increases.
CO2 will build up in the bag causing you to hyperventilate.
What happens at the onset of inspiration?
-inspiratory neurons
-changes in tidal volume
-pacemaker cells are setting the rhythm and when they firing the info is transferred to brain for
the diaphragm to contract resulting in increase in tidal volume
inspiration shuts off resulting in expiratory phase
apneic pause (CO2 increases triggering pacemaker cells sensitive to CO2 which then stimulates the diaphragm to contract and start inspiration again
How does gas partial pressure in different compartments affect ventilation????
At any PaCO2 level, ventilation increases more as the PaO2 decreases.
The ventilatory response to hypercapnia is enhanced by hypoxia
in diseased states because of the inability to regulate your ventilation properly gases will be out of the physiological range
for PaO2 the lower the O2 level the greater your firing rate at any given level of CO2
How is ventilation dependent on PO2?
once you get to 60 mmHg of O2 you have increased firing of peripheral and central chemoreceptors
How is ventilation dependent on PCO2?
in a normal individual when PaCO2 increases above 40 mmHg ventilation will increase
With acidosis you expect increase in what?
ventilation
CO2 is acidic
What is the normal range for PCO2?
35-45 mmHg
if not within this range you get acid base imbalance
How do patients with lung diseases switch to having O2 as their primary regulator of ventilation?
When you have lung disease states (emphysema, COPD) the patient HAS gas exchange issues and so they are not able to generate pressure gradients and can have hypoventilation, increasing CO2, and in drop O2
they develop a tolerance for high CO2 and the increase in CO2 is no longer significant enough to cause contraction of diaphragm to start the next breath (to create an inspiratory drive)
then O2 drops and you transition to a hypoxic drive to breath
this why you give a low fraction of inspired O2 to help get O2 in
the key is to NOT give too much O2 as the peripheral chemoreceptors are thinking that they do not need to breathe anymore; so pt needs to remain slightly hypoxic to maintain breathing (talked about in past lecture)
What is Herring-Breuer reflex?
- involves slowly adapting stretch receptors which are volume regulators
- volume regulators as lung begins to stretch when you get to a certain degree they are stimulated and thus you expire preventing over expansion
becomes important when you have larger than normal tidal volumes
What is the diving reflex?
cold water on the nose triggers a very brief apnea
this is how you teach babies to swim
cessation of breathing and bradycardia occur; this reflex provide protection from aspiration of water during the initial stages of drowning.
Sneezing triggers what receptors?
activates irritant receptors (rapidly adapting) taking in a huge breath forcing it out through air and mouth moving out foreign material
Triggers deep inspiration followed by an explosive expiration through the mouth and nose; helps to remove foreign material.
Aspiration or sniff reflex is elicited by what?
Aspiration or sniff reflex: elicited by stimulation of mechanical receptors in nasopharynx to the pharynx.
What is the difference between irritant and slowly adapting pulmonary stretch receptors?
irritant receptors (rapidly adapting):
- found in the trachea, impulses transmitted via myelinated vagal afferents
- stimulation results in increased airway resistance, reflex apnea, and coughing
pulmonary stretch receptors (Slowly adapting):
- respond to mechanical stimulation
- transmit info via myelinated afferents
- significant in people with OPD; help with respiration by delaying the onset of inspiration (you need more time to get the air out), explaining the long, slow expiratory effort
- essential to minimize airway compression during expiration
caliber of airway initial expansion initially helped to move air in and out of bronchial tree helping to overcome the disease but as disease progresses????
In which patients are juxta-alveolar or J receptors very important?
- SOB dyspnea in CHF pts
- pt is not getting enough proper gas exchange
- associated with edema or inflammatory states
Sensory receptors are important in what individuals?
Important in individuals with increased airway resistance and decreased compliance; help to augment muscle force within the same breath. (increased work of breathing; stiff lung)
receptors are embedded in muscles (rib joints, tendons) constantly detecting the stretch and the states of the respiratory musculature
sensory receptors involved in detecting volume and participating in regulating the length of respiratory cycle: termination of inspiration is involved here
What components are taken out to produce apneic breathing?
sensory inputs
What is the Cheyne-stokes respiration?
it is due to overshooting and undershooting of signal
crescendo decrescendo breathing
hypothesize it has something to do with brain detecting the level of blood gases over unshooting them
Characterized by a varying tidal volume and respiratory frequency that progressively increase over several breaths
Common in individuals with head trauma, CNS disease states and increased intracranial pressure; persons sleeping at high altitude
UNKNOWN mechanism
Possibly associated with low blood flow to the brain with period of overshooting and undershooting ventilatory effort in response to PCO2
What is Central Alveolar Hypoventilation (Odine’s Curse)?
-discusses a curse that was placed on a subject that the only way they would breath is if they were alert and awake
so you have sufficient voluntary control over ventilation
distractions such as watching TV or playing poker results in severe hypoventilation or apnea
pt has to consciously remind yourself to breath and have to rely on diaphragmatic pacing and mechanical ventilation to maintain breathing
What occurs in CENTRAL sleep apnea?
in order to get airflow you need a pressure gradient which needs diaphragmatic contraction
there is decreased ventilatory drive
no respiratory effort as the diaphragm is not stimulated to contract and thus you get a flat line leading to long periods where you have apnea
may possibly be linked to decreased hypercapnic response during sleep
What is OBSTRUCTIVE sleep apnea?
- obstruction in airway that prevents airflow
- often associated with obesity
snoring: partial obstruction
nothing: complete obstruction ALLAN (ask him)
so SNORING proceeds complete occlusion of airway
no problem with the central component as diaphragm is being stimulated to contract
-impacts PaO2 and PaCO2 as airway is obstructed
What is the most common cause of death in infants under 1 year?
SIDS
- unknown cause
- elevated CO2
- involves serotonin neurons
- altered cardiorespiratory control
lay baby facing up not down so they can breathe
What are chemical regulations of the medullary respiratory control center?
- central chemoreceptors: PCO2/pH of the interstitial fluid and CSF
- peripheral chemoreceptors: PaO2 via carotid and aortic bodies
What are neural regulations of the medullary respiratory control center?
- impulses from cerebral cortex/limbic system hypothalamus and pons
- proprioceptive afferent from joints in limbs
- baroreceptors (aortic arch)
- vagal receptors in lungs: J-receptors, stretch, and irritant
- afferent impulses for sneezing, yawning, swallowing, coughing, and vomiting
What is the similarity between chemical and neural regulation of medullary respiratory control center?
all of these inputs will come into the control center and be integrated to meet body’s demand by innervating phrenic nerve to contract diaphragm and intercostal nerves to contract the intercostals
