Control of Ventilation

Question 1

peripheral chemoreceptors

Answer 1

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

Question 2

peripheral chemoreceptors - type I cells

Answer 2

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)

Question 3

peripheral chemoreceptors - type II cells

Answer 3

• 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

Question 4

low does low Po2 stim glomus cell

Answer 4

• 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

Question 5

glossopharyngeal nerve

Answer 5

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

Question 6

Pons Respioratory Centers

Answer 6

apneustic center

pneumotaxic center

Question 7

apneustic center

Answer 7

excite inspiratory center of medulla (DRG)

Question 8

pneumotaxic center

Answer 8

inhibit inspiration - regulate volum and rate (fine tuning!!)

Question 9

medullary respiratory center components

Answer 9

DRG

VRG

Question 10

Pre Boetzinger Complex

Answer 10

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

Question 11

DRG

Answer 11

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)

Question 12

VRG

Answer 12

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

Question 13

receptors to PRG

Answer 13

(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

Question 14

medulla neurons

Answer 14

send impulses down spinal cord on opposite side

Question 15

cervical neurons

Answer 15

via phrenic nerve to diaphragm

Question 16

throacic neurons

Answer 16

to intercostal muscles

Question 17

apnea

Answer 17

no breathing - if severe brainstem from spinal cord

Question 18

ataxic breathing

Answer 18

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

Question 19

if lose pneumotactic center (still have apneustic center)

Answer 19

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

Question 20

if both parts of PRG are intact

Answer 20

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

Question 21

What does the vagus nerve do to respiration?

Answer 21

Periodically sends inhibitory signals to say stop inspiration & start expiration & vice versa

Functionally keeps tidal volume down & rate up

Question 22

what happens if both vagus nerves are cut?

Answer 22

Tidal volume increases

Respiratory rate decreases

Question 23

Quiet Breathing Pathway

Answer 23

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

Question 24

forced breathing cycle

Answer 24

Question 25

chemosensitive regions in the brainstem

Answer 25

- They are very close to where the VRG is - They are stimulated by application of acid (any solution with increased H+)

Question 26

chemoreceptor multiplicity

Answer 26

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

Question 27

CO2 and central chemoreceptors

Answer 27

CO2 can travel over BBB, H+ can't ## Footnote - 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

Question 28

response to H+

Answer 28

increase H+ --\> increase in inspiration

Question 29

ventilatory response to increasing PCo2

Answer 29

- 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

Question 30

effect of progesterone on ventilation

Answer 30

increases slope of ventilation in response to CO2

Question 31

effect of narcotics on ventilation

Answer 31

decrease slope of compensation

Question 32

what happens if we get rid of carotid bodies?

Answer 32

- 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

Question 33

interactions between peripheral and central chemoreceptors

Answer 33

- 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

Question 34

hypoxemia - responders

Answer 34

mostly peripheral chemoreceptors best in chronic

Question 35

hypercapnea - responders

Answer 35

mostly central chemoreceptors all better in acute

Question 36

metabolic acidosis responders

Answer 36

mostly peripheral

Question 37

central hypoventilation

Answer 37

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

Question 38

Cheyne-Stokes Breathing

Answer 38

- 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