|
  





|
  



` volume of air inspired and expired per
unit time is tightly controlled, both with
respect to frequency of breaths and to
tidal volume.
` Breathing is regulated so the lungs
can maintain the PaO2 and PaCO2
within the normal range, even under
widely varying conditions such as
exercise.
 

|
 

` four components :
1. chemoreceptors for O2 or CO2
2. mechanoreceptors in the lungs and
joints
3. control centers for breathing in the
brain stem (medulla and pons)
4. the respiratory muscles, whose activity
is directed by the brain stem
centers
nitiation and regulation of
breathing in the CNS
Ô


 

can also be exerted by commands from the
cerebral cortex (e.g., breath-holding or
voluntary hyperventilation), which can
temporarily override the brain stem.

Ô
 

Ô


Ô


 |

 |
 
` originates in the motor cortex, and
signaling passes directly to motor neurons
in the spine through the Ô
Ô 

Ô

` 

Ô
Ô ë 


 
 CEREBRAL CORTEX

` 
  
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` involuntary
` controlled by the medulla and pons of
the brain stem
 

|
 



` three groups of neurons or 


Ô 

ü the medullary respiratory center
‡ DRG
‡ VRG
ü the apneustic center
ü the pneumotaxic center
 * 
 
 
` Extends most of the
length of medulla
` MOSTLY: Neurons are
located within the
tractus solitarius
some - reticular
substance of medulla
Nucleus Tractus Solitarius

` Sensory termination of CN X and X

` Transmit sensory signals into the
respiratory center from:
1. peripheral chemoreceptors
2. baroreceptors
3. lung receptors
 *

` Generates basic rhythm of respiration

` contains inspiratory neurons that
innervate the diaphragm and the external
intercostals
` Despite transection at the level of medulla
ĺ still emits repetitive bursts of
inspiratory neuronal action potentials



  



` Action potential begins weakly and
increases steadily in a ramp manner for
about 2 seconds, then ceases abruptly
for the next 3 seconds
` Advantage: promotes steady increase in
the lung volume during
inspiration, rather than
inspiratory gasps



  



V
 
 



  



V
 
 
 2 qualities of the inspiratory
ramp that are controlled:
1. | 
  
  Ô
   


 
> so that during heavy respiration, the ramp
increases rapidly and therefore fills the lungs
rapidly.
2. | 
  
  Ô 


 Ô  
This is the usual method for controlling the rate of
respiration; that is, the earlier the ramp ceases,
the shorter the duration of inspiration. This also
shortens the duration of expiration. Thus, the
frequency of respiration is increased.
 [

 
 
` Located in each side of
medulla
` Found in the nucleus
ambiguus rostrally and
nucleus retroambiguus
caudally
 VENTRAL RESPRATORY
GROUP
`
Ô during normal quiet respiration
` only functions in 
Ô 

 
ü t contains neurons involved in active
exhalation and maximal inhalation

` Provide powerful expiratory signals to the

abdominal muscles during very heavy
inspiration
 VENTRAL RESPRATORY
GROUP
` The ventral respiratory neurons do not appear to
participate in the basic rhythmical oscillation that
controls respiration.
` When the respiratory drive for increased
pulmonary ventilation becomes

than
normal, respiratory signals spill over into the
ventral respiratory neurons from the basic
oscillating mechanism of the dorsal respiratory
area. As a consequence, the ventral respiratory
area contributes extra respiratory drive as well.
 VENTRAL RESPRATORY
GROUP
` these neurons contribute to both
inspiration and expiration.
` They are especially important in
providing the powerful expiratory signals
to the abdominal muscles during very
heavy expiration. Thus, this area
operates more or less as an overdrive
mechanism when high levels of
pulmonary ventilation are required,
especially during heavy exercise.
*V
 *V

V

 
| |


` Located dorsally in the nucleus

parabrachialis of the 
 
` Switches off the inspiratory ramp

` Shortens inspiratory time ĺ decrease

lung filling
` PRMARY EFFECT: 

 

ĺ increase RR
Pneumotaxic Center

` 
 
 

limits the size of the tidal volume,
regulates the respiratory rate
` controls rate and depth of breathing.

` A normal breathing rhythm persists in

the absence of this center.




` is an abnormal breathing pattern with

prolonged 

 
followed by brief expiratory movement
` Produced when apneustic center is
stimulated
  Ô| 

` Located in the  
 

` Stimulation of these neurons apparently
excites the inspiratory center in the
medulla, prolonging the period of action
potentials in the phrenic nerve, and
thereby prolonging the contraction of the
diaphragm.
| 
|
|
  




 |

|  |  
` located in the brain stem, are the most
important for the minute-to-minute
control of breathing
` located on the ventral surface of the
medulla, near the point of exit of the
glossopharyngeal (CN X) and vagus
(CN X) nerves and only a short distance
from the medullary inspiratory center.
 |
  
 
  

| 

` The medullary chemoreceptors respond

Ô to changes in the pH of CSF
and indirectly to changes in arterial Pco2
` communicate directly with the
inspiratory center
` exquisitely   to Ô 
   Ô

|
 |

|  |  
` communicate directly with the inspiratory center

Decreases in the pH of CSF produce increases

in breathing rate (hyperventilation)

ncreases in the pH of CSF produce decreases

in breathing rate (hypoventilation).
 |
  
 
  

| 

` Primary direct stimulus:
  
` BUT H+ ions do not cross
BBB
` indirect effect: CO2
react with the water of the
tissues to form carbonic
acid, which dissociates into
hydrogen and bicarbonate
ions; the hydrogen ions
then have a potent direct
stimulatory effect on
respiration

  |


| 
| 


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(
 Auantitative Effects of Blood PCO2
and Hydrogen on Concentration on
Alveolar Ventilation
` marked increase in
ventilation caused by
an increase in Pco2 ×





between 35 and 75 mm
Hg.
` This demonstrates the
tremendous effect that
carbon dioxide changes
have in controlling
respiration.
 Auantitative Effects of Blood PCO2
and Hydrogen on Concentration on
Alveolar Ventilation
` the change in
respiration in the
normal blood pH range
between 7.3 and 7.5 is
less than one-tenth as
great
 Ô | :

` ncreases RR but only for 1-2 days

` After which ĺ renal adjustment of the
H+ ion concentration by increasing
blood HCO3
` Ô  | 
Ô Ô 
   Ô 
 Ô Ô 
 




   Ô
Ô
 Ô
  
 

|  |  
` Primarily detect
changes in 
1. carotid bodies
2. aortic bodies
 | 
* *


` located bilaterally in the

bifurcation of the common
carotid arteries
` Afferent nerve fibers pass
thru Hering¶s nerves ĺ
CN X ĺ dorsal respiratory
area of medulla
` Contains most of the
receptors
  
| *


` Located along the arch of

aorta
` Afferent fibers pass thru
the CN X ĺ to the dorsal
medullary respiratory area
|
  

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`   |
- which synapse directly or indirectly with
the nerve endings
- might function as the chemoreceptors
and then stimulate the nerve
endings
- other studies suggest that the nerve
endings themselves are directly
sensitive to the low Po2.
 Carotid body oxygen sensor releases
 



when decrease in PO2

  
 

 
| *

` Respond weakly than carotid bodies

` PO2 especially between
60 and 30mm Hg strongly stimulates
the carotid bodies.
` This is the range wherein the Hb
saturation decreases.
` no effect on ventilation as
long as the arterial Po2
remains greater than 100
mm Hg

` But at pressures lower

than 100 mm Hg,
ventilation approximately
doubles when the arterial
Po2 falls to 60 mm Hg
‡ Changes in arterial blood composition detected
by peripheral chemoreceptors ĺ Ô
 

 
 

* Ô
 

 

if arterial Po2 is between 100 mm Hg and 60
mm Hg, the breathing rate is virtually
constant.

if arterial Po2 is   !

  the
breathing rate increases in a very
steep and linear fashion
‡ Changes in arterial blood composition detected
by peripheral chemoreceptors ĺ Ô
 

 
 


Ô
 

 Ô 
- effect is less important than their
response to decreases in Po2.
‡ Changes in arterial blood composition detected
by peripheral chemoreceptors ĺ Ô
 

 
 

"* Ô
 



± This effect is independent of changes in the arterial
Pco2 and is mediated 6
 by chemoreceptors in the
carotid bodies (not by those in the aortic bodies).
± Thus, in metabolic acidosis, in which there is
decreased arterial pH, the peripheral chemoreceptors
are stimulated directly to increase the ventilation rate
(the respiratory compensation for metabolic acidosis

 

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 1. LUNG STRETCH
RECEPTORS
` Mechanoreceptors located in the
muscular portions of the walls of the
bronchi and bronchioles throughout the
lungs
` transmit signals through the   into the
dorsal respiratory group of neurons when
the lungs become overstretched.
 u×
 
×  ×
 

` when the lungs become overly inflated,

the stretch receptors activate an
appropriate feedback response that
"switches off" the inspiratory ramp and
thus stops further inspiration.
` The reflex decreases breathing rate by
prolonging expiratory time.
 u
 

 
6 



` not activated until the tidal volume
increases to more than three times
normal (>§ 1.5 liters per breath).
Therefore, this reflex appears to be
mainly a protective mechanism for
preventing excess lung inflation rather
than an important ingredient in normal
control of ventilation.
 # 
Ô 

Ô 

` Mechanoreceptors located in the joints
and muscles detect the movement of
limbs and instruct the inspiratory center to
increase the breathing rate.
` nformation from the joints and muscles is
important in the early (anticipatory)
ventilatory response to exercise.
 "



Ô 

` rritant receptors for noxious chemicals and
particles are located between epithelial cells
lining the airways.
` nformation from these receptors travels to the
medulla via myelinated CN X and causes a
reflex constriction of bronchial smooth muscle
and an increase in breathing rate.
` cause coughing and sneezing
` They may also cause bronchial constriction in
such diseases as asthma and emphysema
` These receptors are

` nhaled dust, noxious gases, or
cigarette smoke stimulates 



Ô 
 in the trachea and large
airways that transmit information
through myelinated vagal afferent
fibers.
` These receptors are also known as

 
Ô 

 -#|  
` Uuxtacapillary (U) receptors are located in
the alveolar walls and, therefore, are 


× ×
` transmit their afferent input through
unmyelinated, vagal C fibers.
 #|  
` Engorgement of pulmonary capillaries with
blood and increases in interstitial fluid
volume may activate these receptors and
produce an increase in the breathing rate.
` For example, in    


blood "backs up" in the pulmonary
circulation, and U receptors mediate a
change in breathing pattern, including rapid
shallow breathing and dyspnea (difficulty in
breathing).
 5. CHEST WALL RECEPTORS

` located in the intercostal muscles, rib joints,

accessory muscles of respiration, and tendons,
` they respond to changes in the length and tension
of the respiratory muscles.
` they provide information about lung volume and
play a role in terminating inspiration. They are
especially important in individuals with increased
airway resistance and decreased pulmonary
compliance because they can augment muscle
force within the same breath

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Regulation of Respiration
during exercise
` ncrease in ventilation during exercise
` Results from neurogenic signals
transmitted directly into the brain stem
respiratory center at the same time
that signals go to the body muscles to
cause muscle contraction
 [


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 Chronic Breathing of Low Oxygen

Stimulates Respiration Even More-The
Phenomenon of "ÔÔ
 "
` on ascent to a mountain slowly, over a
period of days rather than a period of
hours, they breathe much more deeply
and therefore can withstand far lower
atmospheric oxygen concentrations than
when they ascend rapidly. This is called
 ××× .
 "ÔÔ
 "

` The reason for acclimatization is that,

within 2 to 3 days, the respiratory center
in the brain stem loses about four fifths
of its sensitivity to changes in Pco2 and
hydrogen ions.
 "ÔÔ
 "

` nstead of the 70 percent increase in

ventilation that might occur after acute
exposure to low oxygen, the alveolar
ventilation often increases 400 to 500
percent after 2 to 3 days of low oxygen;
this helps immensely in supplying
additional oxygen to the mountain
climber.



 



 |    


` The person breathes deeply for a short interval

and then breathes slightly or not at all for an
additional interval, with the cycle repeating
itself over and over

` is characterized by slowly waxing and waning

respiration occurring about every 40 to 60
seconds
Cheyne-Stokes breathing
 | 

 



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‡ When a person overbreathes, thus blowing
off too much carbon dioxide from the
pulmonary blood while at the same time
increasing blood oxygen, it takes several
seconds before the changed pulmonary
blood can be transported to the brain and
inhibit the excess ventilation.
 | 

 



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Therefore, when the overventilated blood finally
reaches the brain respiratory center, the center
becomes depressed to an excessive amount. Then
the opposite cycle begins. That is, carbon dioxide
increases and oxygen decreases in the alveoli.
Again, it takes a few seconds before the brain can
respond to these new changes. When the brain
does respond, the person breathes hard once again
and the cycle repeats
 | 

 



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` occurs in patients with 
×
× 
because blood flow is slow, thus delaying the
transport of blood gases from the lungs to the
brain
 | 

 



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‡ This means that a change in blood carbon
dioxide or oxygen causes a far greater
change in ventilation than normally
4 


 
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‡ This means that a change in blood carbon
dioxide or oxygen causes a far greater
change in ventilation than normally



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 DURNG SLEEP««

` approximately a third of normal individuals

have brief episodes of apnea or
hypoventilation that have no significant
effects on arterial Po2 or Pco2. The apnea
usually lasts less than 10 seconds, and it
occurs in the lighter stages of slow-wave
and rapid eye movement (REM) sleep.
 CLNCAL ABNORMALTES
OF BREATHNG
` Related to sleep apnea
1. obstructive sleep apnea

2. central sleep apnea

 SLEEP APNEA
SYNDROME
` the duration of apnea is abnormally prolonged,
and it changes arterial Po2 and Pco2.
` two major categories of sleep apnea
 
Ô   
- the most common of the sleep apnea
syndromes
- it occurs when the upper airway (generally the
hypopharynx) closes during inspiration.
Although the process is similar to what
happens during snoring, it is more severe,
obstructs the airway, and causes cessation of
airflow.
 SLEEP APNEA
SYNDROME
` Ô 
  
- occurs when the ventilatory drive to the
respiratory motor neurons decreases
- The degree of hypercapnia and
hypoxemia in individuals with central
sleep apnea is less than that in
individuals with OSA, but the same
complications (polycythemia, etc.)
can occur when central sleep apnea
is recurrent and severe.
 CENTRAL ALVEOLAR
HYPOVENTLATON
` also known as Ondine's curse
` is a rare disease in which voluntary breathing is
intact but abnormalities in automaticity exist.
` the most severe of the central sleep apnea
syndromes. As a result, people with CAH can
breathe as long as they do not fall asleep. For
these individuals, mechanical ventilation or, more
recently, bilateral diaphragmatic pacing (similar to a
cardiac pacemaker) can be lifesaving.
 Hypoxemia and Hypoxia
` Hypoxemia - a decrease in arterial Po2.
` Hypoxia - decrease in O2 delivery to, or
utilization by, the tissues.
` Hypoxemia is one cause of tissue hypoxia,
although it is not the only cause.
‡  
± barometric pressure (Pb) is decreased, which
decreases the Po2 of inspired air (PiO2) and
of alveolar air (PaO2).
± At high altitude, breathing supplemental O2
raises arterial Po2 by raising inspired and
alveolar Po2.
‡    
± decrease alveolar Po2 (less fresh inspired air
is brought into alveoli).
± breathing supplemental O2 raises arterial Po2
by raising the alveolar Po2.
‡ *   Ô (e.g., fibrosis,
pulmonary edema)
± increase diffusion distance or decrease
surface area for diffusion. Equilibration of O2
is impaired, PaO2 is less than PAO2, and the
A - a gradient is increased, or widened.
‡ breathing supplemental O2 raises arterial
Po2 by raising alveolar Po2 and increasing
the driving force for O2 diffusion.
‡ [
  Ô always cause hypoxemia and
increased A - a gradient.
± high V/A regions - high Po2
± low V/A regions - low Po2
‡ high V/A regions have blood with a high Po2,
blood flow to those regions is low (i.e., high
V/A ratio) and contributes little to total blood
flow.
‡ Low V/A regions, where Po2 is low, have the
highest blood flow and the greatest overall
effect on Po2 of blood leaving the lungs. n
V/A defects
‡ supplemental O2 can be helpful, primarily
because it raises the Po2 of low V/A regions
where blood flow is highest.
‡     (right-to-left cardiac shunts,
intrapulmonary shunts) always cause hypoxemia
and increased A - a gradient.
‡ Shunted blood completely bypasses ventilated
alveoli and cannot be oxygenated. Because
shunted blood mixes with, and dilutes, normally
oxygenated blood (nonshunted blood), the Po2
of blood leaving the lungs must be lower than
normal.
‡ Supplemental O2 has a limited effect on the
Po2 of systemic arterial blood because it can
only raise the Po2 of normal nonshunted blood;
the shunted blood continues to have a dilutional
effect.
 Brain Edema Depresses the
Respiratory Center
` the damaged brain tissues swell,
compressing the cerebral arteries against the
cranial vault and thus partially blocking
cerebral blood supply.

` Occasionally, can be relieved temporarily by

intravenous injection of hypertonic solutions
such as highly concentrated mannitol
solution. These solutions osmotically remove
some of the fluids of the brain, thus relieving
intracranial pressure and sometimes re-
establishing respiration within a few minutes.
   

` Perhaps the most prevalent cause of respiratory

depression and respiratory arrest is overdosage
with anesthetics or narcotics. For instance,
sodium pentobarbital depresses the respiratory
center considerably more than many other
anesthetics, such as halothane. At one time,
morphine was used as an anesthetic, but this
drug is now used only as an adjunct to
anesthetics because it greatly depresses the
respiratory center while having less ability to
anesthetize the cerebral cortex.
 

| 

 Brainstem Respiratory
Centers
` Dorsal Respiratory Group - Auiet inspiration

` Ventral Respiratory Group - Forceful

inspiration and active expiration

` Pneumotaxic Center - nfluences inspiration

to shut off

` Apneustic Center - Prolongs inspiration

A