Block 4: 16 Respiratory Control

PRACTICE: What effect will a higher PaCO2 have on the sensitivity of the peripheral chemoreceptor to O2?

A higher PaCO2 will increase the sensitivity of the peripheral chemoreceptor to O2

Which to variables are regulated when breathing is controlled?

PaCO2 (pH) and PaO2

What is the most important regulator of ventilation in healthy individuals?

PaCO2 acting on the central chemo-recep

How does CO2 affect the ability of low PaO2 to increase ventilation?

Peri-chemo-receps are not very sensitive to PaO2 unless PaCO2 is high and pH is low (again, CO2 is the main goal, O2 is secondary) Once CO2 is high and pH is low then the threshold for O2 sensitivity decreases and O2 can act as a complementary trigger for increased ventilation

What are the primary nerves of inspiration?

Phrenic motor nerves External intercostal motor nerves

True or False: Phrenic and external intercostal motor neurons are simultaneously active during normal quiet inspiration

True; Phrenic and external intercostal motor neurons are simultaneously active during normal quiet inspiration

True or False: Ventilation correlates inversely to the pH of the CSF

True; Ventilation correlates inversely to the pH of the CSF As pH of CSF drops (due to increased CO2), ventilation increases

PRACTICE: True or false; carotid bodies and aortic bodies respond to H+.

True; carotid bodies and aortic bodies respond to H+.

PRACTICE: True or false; decreased O2 will active the peripheral chemoreceptor

True; decreased O2 will active the peripheral chemoreceptor

PRACTICE: True or false; peripheral chemoreceptors respond to H+, CO2, and HCO3-

True; peripheral chemoreceptors respond to H+, CO2, and HCO3-

PRACTICE: True or false; the central chemoreceptor becomes desensitized to CO2 under anesthesia

True; the central chemoreceptor becomes desensitized to CO2 under anesthesia

True or False: Chemoreceptor sensitivity to CO2 levels can be measured/evaluated

True; using predicted ventilation changes given known CO2 administration, a patient's ventilation can be evaluated as a way to gauge receptor sensitivity (less increase than expected? May be less sensitive!)

True or False: By administering CO2 via a mask we can generate expected normal values for ventilation due to higher CO2 levels in patients

True; when given a mask of known CO2 concentration we can measure the ventilation increase to establish normal values If a patient's ventilation increase does not match expected value then chemoreceptor sensitivity to CO2 may be impaired

What centers in the brain control expiration?

Ventral Respiratory Group (VRG)

Describe how hypoventilation triggers increase in ventilation

Hypovent = increase PaCO2 Increase PaCO2 moves across BBB, reacts with H2O and increases H+ in CSF = trigger cent-receps Increase PaCO2 also directly triggers periphs and indirectly by reacting with H2O in blood to form H+ that also triggers periphs

Describe Central Chemoreceptors

In medulla Connected to inspiratory neurons of DRG Directly activated by H+ in CSF (*but H+ must come from CO2 that has crossed BBB and reacted with H2O, as H+ itself cannot cross BBB*) Not responsive to PaO2 or PaCO2 directly Indirectly respond to CO2 since it can cross BBB and be converted to H+

Describe the Ventral Respiratory Group (VRG)

In medulla Control expiration Mediates expiration under non-rest conditions (normally passive)

Describe the Dorsal Respiratory Group (DRG)

In medulla Control inspiration Set autonomic rhythm of respiration Sensitive to H+ in the cerebrospinal fluid (CSF) Connects to phrenic nerve that innervates diaphragm

Why is increased PaCO2 not enough to increase ventilation in some cases, such as drug overdose?

In some cases, like drug overdose, the medulla is suppressed, so even with great signalling coming from the cent and periph receps the medulla cannot respond to increase ventilation

PRACTICE: In the CSF, what effect will increased pH have on alveolar ventilation?

In the CSF, increased pH will decrease alveolar ventilation (increased pH = lower CO2)

How are the DRG and VRG controlled so their firing can appropriately regulate breathing?

Through the two types of chemoreceptors

Describe Pheripheral Chemoreceptors

*Two types:* 1. Aortic bodies - in aortic arch, extend nerves to DRG 2. Carotid bodies - in bifurcation of common carotid artery to sense what goes to the brain, extend nerves to DRG Both respond to H+, PaCO2, and PaO2 of blood Depolarization creates action potential that goes to DRG to increase ventilation

What are the two types of chemoreceptors?

1. Central Chemoreceptors 2. Peripheral Chemoreceptors

Describe the sensitivity of peri-chemo-receps to O2 at higher PaCO2 and/or lower pH (>100 mmHg, <7.4)

At >normal PaCO2 and/or <7.4 pH the threshold and sensitivity of peri-chemo-receps changes at a given PO2 (lower threshold, more sensitive) (Okay, CO2 is wrong AND O2 is wrong - time to take immediate action!)

Describe the sensitivity of peri-chemo-receps to O2 at normal PaCO2 and pH (100 mmHg, 7.4)

At normal PaCO2 and pH (100 mmHg, 7.4) peripheral chemo-receps are not very sensitive to O2 (CO2 is the focus of ventilation - if CO2 good then don't mess with it much!)

Which two metabolic activities is control of breathing tightly linked to?

CO2 production O2 consumption

What does CSF have larger changes in pH in response to PaCO2 changes than blood?

CSF has a poor buffering capacity than blood

Describe the phrenic motor nerves

Cell bodies located in ventral horn of thorasic spinal cord (C3-C5) Innervate diaphragm Fire in bursts that control diaphragm contraction

Describe the external intercostal motor nerves

Cell bodies located in ventral horn of thorasic spinal cord (C3-C5) Used during normal breathing to pull the chest up/out during inspiration

What is COPD?

Chronic Obstructive Pulmonary Disease

What happens when a patient becomes desensitized to chronically increased CO2 levels?

Chronically high CO2 levels result in a great decrease in central chemoreceptor sensitivity to CO2 = must rely on peripheral receptor O2 info to regulate breathing instead This means that decreased O2 will greatly affect breathing, causing hyperventilation even if CO2 levels are normal or low Giving supplemental O2 is fatal because the increased O2 signals ventilation to decrease, even if as CO2 levels rise to toxic = ventilation ceases altogether, death

What are the primary muscles of inspiration?

Diaphragm: contracts to increase volume in lungs during inspiration External intercostal muscles: contract to move ribs up/out during inspiration

What centers in the brain control inspiration?

Dorsal Respiratory Group (DRG)

True or False: The central chemoreceptors can respond to an decrease in blood pH (increase in H+)

False! Even through the cent-chemo-receps do respond to H+, H+ itself cannot cross the BBB to get to them The only H+ they can respond to are those generated when extra CO2 crosses the BBB and reacts with H2O, creating more H+ in the CSF

PRACTICE: True or false; the internal intercostal muscles assist with inspiration

False, the EXTERNAL intercostal muscles assist with inspiration

True or false: Ventilation is principally controlled by the peripheral chemoreceptors

False; Ventilation is principally controlled by the CENTRAL chemoreceptor

PRACTICE: True or false; generally, the central and peripheral chemoreceptors work to antagonize one another

False; generally, the central and peripheral chemoreceptors work TOGETHER

PRACTICE: True or false; the Ventral Respiratory Group (VRG) is active during expiration

False; the Ventral Respiratory Group (VRG) is active during INSPIRATION (when not just tidal breathing)

Describe how changes in PaCO2 can affect sensitivity to PaO2

Lowered CO2 levels give lower sensitivity to O2 levels because CO2 is the goal This means that a larger changes in O2 than normal will be needed to generate a change in ventilation Want to allow CO2 to return to regular levels, even if that means sacrificing O2 levels Ex: At PCO2 of <35 mmHg the drive to breath can be over ridden even if O2 is down to 60 mmHg

Describe how changes in PaO2 can affect sensitivity to PaCO2

Lowered O2 levels give higher sensitivity to CO2 levels This means that a smaller change in CO2 than normal will be needed to generate a change in ventilation Ex: At normal PO2 of 100 mmHg a 5 mmHg change is needed for a 10 l/m change in ventilation; but at 47 mmHg only a 2.5 mmHg change is needed for a 10 l/m change in ventilation to occur

How does metabolic acidosis from exercise affect central chemoreceptor sensitivity to CO2?

Metabolic acidosis makes the central chemoreceptor more sensitive to CO2 changes Meaning less change in CO2 than normal is needed for the same change in ventilation

What determines respiratory rate? What determines depth of respiration?

Rate: Phrenic nerve inter-burst interval (longer = lower RR) Depth: Phrenic nerve burst duration (longer = more depth)

PRACTICE: What effect will reduced PO2 have on the sensitivity of the central chemoreceptor to CO2?

Reduced PaO2 will increase the sensitivity of the central chemoreceptor to CO2

How do sleep, morphine, COPD, and anesthethic agents affect central chemoreceptor sensitivity to CO2?

Sleep, morphine, COPD, and anesthethic agents lower sensitive to CO2 changes Meaning more change in CO2 than normal is needed for the same change in ventilation

Describe how hyperventilation at low altitude due to low O2 can greatly increase ventilation IF CO2 IS KEPT ARTIFICIALLY HIGH (breathing in CO2)

The body starts to hyperventilate to get more O2, and since CO2 is breathed in also CO2 does not drop Regular CO2 levels do not impact ventilation, allow peripheral O2 receptors to greatly increase ventilation

Describe why hyperventilation at low altitude due to low O2 cannot increase ventilation greatly

The body starts to hyperventilate to get more O2, however the hyperventilation decreases CO2 Decreased CO2 blunts/moderates ventilation from increase at the central receptors because it is the overriding factor Hence, ventilation can increase some but not greatly

Describe the relative contributions of central chemoreceptors to ventilation

We are most responsive to CO2 acting indirectly via the Central Chemoreceptor Decreased O2 acts only via periph and has limited affect Decreased pH acts only via periph and has limited affect Increased CO2 has the most effect as acts via both periph and central

When is ventilation the highest?

When CO2 is high and O2 is low Combined effect: central and peripheral receptors increasing ventilation from CO2 and H+ AND peripheral receptors augmenting increase in ventilation from O2

MOCK EXAM: When we arrive at high altitude, we begin to hyper-ventilate. This is due to a) decreased PaO2 b) increased PaN2 c) decreased PaN2 d) increased PaCO2 e) decreased PaH2O

a) decreased PaO2 The initial hyper-ventilation at high altitude is due to a low PaO2

MOCK EXAM: The respiratory center that controls INSPIRATION is the a) supine respiratory group (SRG) b) lateral respiratory group (LRG) c) dorsal respiratory group (DRG) d) ventral respiratory group (VRG) e) zona respiratory group (ZRG)

c) dorsal respiratory group (DRG) The respiratory center that controls INSPIRATION is the DRG

MOCK EXAM: Within peripheral chemoreceptors, the response to a drop in PaO2 is greater when a) the central chemoreceptors are also responding do a drop in arterial PaO2 b) the central chemoreceptors are responding to an increase in PaO2 c) arterial PaCO2 is also below normal d) arterial PaCO2 is above normal e) arterial PaCO2 is normal

d) arterial PaCO2 is above normal e) arterial PaCO2 is normal There is a cooperative effect on the peripheral chemoreceptors. It is most effective when PaO2 is low and PaCO2 is high