Control of Ventilation Flashcards
peripheral chemoreceptors
within carotid bodies
rapid, respond to decreased Po2 (and decrease pH and increased CO2 - mostly make more responsive)
increase ventilation
-
- An organ that senses oxygen, cannot be influenced by its own need of oxygen consumption
- The environment of the carotid bodies have to be such that this organ must always be bathed in perfect arterial blood in order to sense and control oxygen environment very closely
peripheral chemoreceptors - type I cells
glomus cells
mainly for decrease PO2
- Closely associated with carotid sinus nerve
- Will learn about nerves later on
- For now, know it is part of 9th cranial nerve (glossopharyngeal nerve)
peripheral chemoreceptors - type II cells
- Interstitial cells that wrap around glomus cells and nerve endings
- Don’t have cytoplasmic granules
- Function unknown but it is thought to be stroma and provides a histologic structure for the type I glomus cells to exist
low does low Po2 stim glomus cell
- We can see that sensing of hypoxia (low PO2) stimulates this glomus cell via 3 different mechanisms
- Heme-containing membrane proteins
- Increasing intracellular cAMP levels
- Stimulation of mitochondrion to increase levels of glutathione
BLOCK K channels (can’t leave) - increase VM - Ca channels open, NT release on nerve
glossopharyngeal nerve
from peripheral chemoreceptors to DRG (inspiration)
- The response starts at about levels at 50-60 mmHg
- Patient starts to have increased activity of the 9th cranial nerve as hypoxia is sensed by the peripheral chemoreceptors
- If we plot maximum response on nerve (y-axis) against arterial PO2 levels (x-axis)
- We see that the nerve starts firing at a greater intensity until a maximum response is reached at arterial PO2 levels of approximately 32 mmHg
- This happens in the sinusoidal manner
- How will this be translated? What will hypoxia stimulate?
- Via glossopharyngeal nerves, stimulation of respiratory centers in the brainstem will increase firing of respiratory motor neurons and minute ventilation will rise
- This is what happens when hypoxia is sensed and the mechanism to compensate for hypoxia is yet again a ventilatory response with an increase in ventilation and hopefully reestablishment of normal levels of arterial blood
Pons Respioratory Centers
apneustic center
pneumotaxic center
apneustic center
excite inspiratory center of medulla (DRG)
pneumotaxic center
inhibit inspiration - regulate volum and rate (fine tuning!!)
medullary respiratory center components
DRG
VRG
Pre Boetzinger Complex
Respiratory Rate and rhythm
in brainstem
- Small area close to ventral called the Pre-Botzinger complex
- Thought that this complex is our pacemaker
- Studied in isolation – activity of neurons is such that they fire rhythmically
DRG
inspiration
modulated by glassopharyngealnerve and vagus
only thing active in normal cycle (exhale is passive)
excited by glassophyrngeal!
inhibited by stretch receptors in lungs
-DRG does not have ability to control size of breath (in terms of intensity or time)
VRG
expiration - quiet during normal breathing (passive)
-The expiratory centers (located at VRG) are only active if we require a forced expiration
For example: running, coughing, sneezing, blowing candles, etc
receptors to PRG
(apneustic and pneumotaxic)
inhibited by stretch receptors (vagus)
- PRG is always active (even during tidal breathing) and regulates size, and volume of breath via pneuotaxic and apneustic centers
- Fine-tuning occurs here
medulla neurons
send impulses down spinal cord on opposite side
cervical neurons
via phrenic nerve to diaphragm
throacic neurons
to intercostal muscles
apnea
no breathing - if severe brainstem from spinal cord
ataxic breathing
if we separate medulla and pons
pre-boetzinger complex will generate rhythm (above VRG)
inspiration because DRG is intact
bad control over inspiratory time and tidal volume because severed from pons
ERRATIC TV
if lose pneumotactic center (still have apneustic center)
lose transition from I to E (apneustic excites inspiratory center)
- If we were to allow the apneustic center to be the only one in control over medullary centers, we would see that without the influence of the pneumotaxic center, we would have a pattern of breathing called an apneustic pattern of breathing
- Apneustic pattern of breathing: there is a poor transition of inspiration to expiration
if both parts of PRG are intact
good I-E transition
- We see a pattern of breathing with a rhythm, a controlled inspiration and exhalation with a fairly normal looking tidal breath
- Now we have all the centers exerting control over each other and generation influence over each other
- The breath would look no different from normal
What does the vagus nerve do to respiration?
Periodically sends inhibitory signals to say stop inspiration & start expiration & vice versa
Functionally keeps tidal volume down & rate up
what happens if both vagus nerves are cut?
Tidal volume increases
Respiratory rate decreases
Quiet Breathing Pathway
PRG - -Regulation of the pontine group tells us about or allows depth and length of inspiratory effort to occur, inhibiting the dorsal respiratory group
DRG is inhibited
Inspiratory muscles relax
passive expiration
DRG activated
inspiratory muscles contract
inspiration
forced breathing cycle
chemosensitive regions in the brainstem
- They are very close to where the VRG is
- They are stimulated by application of acid (any solution with increased H+)
chemoreceptor multiplicity
Chemoreceptor multiplicity:
Stimulus intensity
Stimulus specificity
Arousal state dependence
- Important to note: these areas of chemosensitivity are very much influenced by state of arousal
- Do you think you will respond to CO2 administration the same way when you are asleep or when you are awake?
- Absolutely not
- A disease that comes to mind – common in (but not limited to) obese patients
- Obstructive sleep apnea
- Upper areas collapse and patients remains asleep
- CO2 rises because of cessation of ventilation
- Rise generates arousal – patient wakes up, breathes, gest rid of CO2
- This repeats – apnea, arousal, fall asleep = ventilatory periodicity
CO2 and central chemoreceptors
CO2 can travel over BBB, H+ can’t
- Via hydration equation (CO2+ H2O = H2CO3 = H+ + HCO3-), influences a drop in pH in CSF (the interstitium around the chemoreceptor) and stimulates chemoreceptors to get in touch with DRG to start breathing
- That is how the chemosensitive process via increase in proton concentration at the level of the chemoreceptor area stimulates ventilation to reregulate CO2 levels in the extracellular fluid and the CSF around the chemoreceptors
response to H+
increase H+ –> increase in inspiration
ventilatory response to increasing PCo2
- We can see group of 4 subjects where the minute ventilation increased all the way up to 44L/min upon exposure to increase in PCO2
- At rest, minute ventilation is 5-6L/min
- These people are increasing 5-fold
- In another scenario, if you take a morphine addict and stimulate their brain with CO2
- Minute ventilation increase will probably be poor
- This patient won’t increase because respiratory centers won’t increase firing in this intoxicated state
effect of progesterone on ventilation
increases slope of ventilation in response to CO2
effect of narcotics on ventilation
decrease slope of compensation
what happens if we get rid of carotid bodies?
- we would get hypoxic damage to our brain and have impaired levels of arousal
- That will happen on the first day of denervation
Peripheral chemoreceptors provide tonic continuous firing
The central chemoreceptors have adaptability upon loss of the carotid input.
- We have an initial lack of response which is then regained at about day 15
- This is just an example of how we have multiplicity
- We have fail-safe mechanisms that allow us to, despite having abnormalities, maintain at the end of the day, as good of a regulation of CO2 and pH as we can
interactions between peripheral and central chemoreceptors
- The initial stimulus will be addition of HCl
- This will drop the pH
- This is sensed by peripheral chemoreceptors
- Remember – fast, acute = peripheral chemoreceptor
- Via glossopharyngeal nerves, will stimulate CNS to release acid form of CO2
- This will drop arterial PCO2
- This drop in arterial PCO2 will be sensed by brain vessels which will increase an efflux of CO2 from CSF
- Remember- BBB does not allow protons to penetrate
- PCO2 in CSF drops, producing alkalosis and increase in pH
- This decreases firing of central chemoreceptors regulating back the activity of the effector (lungs)
- This is how the loop is maintained in tight control and our patterns of breathing are regulated by feedback loops such as this
hypoxemia - responders
mostly peripheral chemoreceptors
best in chronic
hypercapnea - responders
mostly central chemoreceptors
all better in acute
metabolic acidosis responders
mostly peripheral
central hypoventilation
most people hypoventilate in sleep!
responsible for SIDS in newborns
In 1962, Severinghaus and Mitchell coined the term Ondine curse. 3 adult patients after high cervical and brainstem surgery. When awake and summoned to breathe, these patients did so; however, they required mechanical ventilation for severe central apnea when asleep.
Lack arousal responsiveness to high CO2 and low O2 during sleep
Cheyne-Stokes Breathing
- A pattern that progressively increases and then decreases and then there’s a period of apnea
- Increases, decreases, apnea – cyclical
- Apnea = period of no ventilation
- A stethograph – no longer used
