RESPIRATORY PHYSIOLOGY #4: REGULATION OF RESPIRATION PHS101

Dr. Oliver Christian I. Arenas, MD, FPCP | February 23, 2022 2ND SEMESTER

COURSE OBJECTIVES B. CENTRAL CONTROLLER When activity of the ventral respiratory group is
1. Review functional anatomy of respiratory tract. Information is transmitted to the central controller, increased, it stimulates contraction of the accessory
2. Review mechanics of breathing in association with primarily termed as medullary center muscles and muscles in the abdomen to facilitate
pressure changes. Integrate and process information depending on the type forceful expiration
3. Discuss the nervous regulation of respiration. of ventilation needed by the body Inactive during quiet respiration
4. Discuss the role chemoreceptors (central and Composed of three cell groups:
peripheral) in the regulation of respiration. C. EFFECTOR a. Rostral nucleus retrofacialis
5. Discuss the role mechanoreceptors in regulating Changes in the activity of the effector muscles will either b. Caudal nucleus retroambiguus
respiration. cause: c. Nucleus paraambiguus
6. Correlate common clinical conditions affecting lncrease activity → Hyperventilation
regulation of respiration. Decrease activity → Hypoventilation PONTINE CENTER:
Why are changes performed? To adjust respiratory Pons neurons influence inspiration
REFERENCES issues in the body 1. Pneumotaxic center
Negative feedback mechanism Located in the nucleus parabrachialis (upper pons)
• Dr. Arenas’ powerpoint presentation
When effector muscle detected hyperventilation, it will Controls the switch off point of the inspiratory ramp
• Berne and Levy Physiology (7th ed.)
decrease the activity of the sensor Limits the duration of inspiration and increases the
• Guyton and Hall Textbook of Medical Physiology (13th
respiratory rate
ed.)
CENTRAL CONTROLLER 2. Apneustic center
REGULATION OF BREATHING IN THE CENTRAL NERVOUS Located in the lower pons
RESPIRATORY CONTROL SYSTEM
SYSTEM Prevents the switch off of the inspiratory ramp signal
A. AUTOMATIC CONTROL Increases the duration of inspiration and decreases
Primarily controls the regulation of breathing through the the respiratory rate
medullary center
1. Neural control INSPIRATORY RAMP SIGNAL:
2. Chemical control
Automatic control is divided into three centers:
1. Medullary center
2. Pneumotaxic center
3. Apneustic center

MEDULLARY CENTER:
Respiratory control system includes three basic elements 1. Dorsal respiratory group (I neurons)
Sensor Main control of breathing
Central controller Everyday activity is automatically controlled by the
Effector dorsal respiratory group
Most of its neuron are located within the nucleus of
A. SENSOR tractus solitarius
Sensor is divided into two: Generates basic rhythm of respiration
Chemical: Central and peripheral chemoreceptor Emits rhythmical inspiratory discharges: Inspiratory
Mechanical: Lung stretch receptors ramp signal Inspiratory ramp signal is the electrical activity in the
Detect changes in the environment such as changes in 2. Ventral respiratory group (E neurons) respiratory center that facilitates breathing
PCO2, PO2 and hydrogen ion concentration (acidity) Only active with exercise and forced expiration Divided into one inspiratory phase and two expiratory
Involved in forceful respiration, particularly during phase
forceful expiration

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 RESPIRATORY PHYSIOLOGY #4: REGULATION OF RESPIRATION PHS101
Dr. Oliver Christian I. Arenas, MD, FPCP | February 23, 2022 2ND SEMESTER

Inspiratory phase begins with abrupt increase in discharge Hypoventilation SENSORS

frequency followed by a steady ramp like increase in a Result: Decrease respiratory rate A. CHEMICAL RECEPTORS
firing rate through the remainder of inspiration How to compensate? Prolong inspiration time,
Takes about 2 seconds for the electrical brain activity then expiration time
to facilitate inspiration Limit the activity of the pneumotaxic center
End of inspiration is signaled by a switching of event due by increasing the activity of the apneustic
to the increase activity of the pneumotaxic center center
Recall: Pneumotaxic center limits inspiration time Why? Apneustic center prolongs inspiration
Increase activity of the pneumotaxic center will time
end inspiration time to enter Phase I of the
expiration B. VOLUNTARY CONTROL
At the start of expiration, there are still some paradoxical Located in the cerebral cortex and sends impulses to the
activity of the inspiratory motor neurons re s p i r a t o r y m o t o r n e u ro n s v i a t h e d o r s o l a t e r a l
Activity tends to slow down or break the early phase of corticospinal tracts
expiration Responsible for conscious, voluntary control
What to do? Augment the muscles of inspiration to Can temporarily override the automatic brain centers
Chemoreceptor responds to a change in the chemical
slow down or break the early phase of inspiration (pons and medulla)
composition of the blood or other fluid around it
Inspiratory action potential ceases completely Can never be the primary control of respiration
Detect changes in the environment such as changes
Inspiratory muscle tone falls down Why? Capable to command the brain to stop
in hydrogen concentration, carbon dioxide and
Inspiratory activity is completely absent during breathing which can be fatal
oxygen
Phase II of expiration When is voluntary control used? Deep diving
The chemical control of respiration lies in the
In deep diving, an individual has a tendency to go
chemoreceptor systems
QUALITIES OF THE INSPIRATORY RAMP THAT ARE back to gasp for air which is due to voluntary
CONTROLLED: control
1. CENTRAL CHEMORECEPTOR SYSTEM
1. Rate of increase of the ramp signal
Also known as medullary chemoreceptors
During heavy respiration, the ramp increases rapidly EFFECTORS
Activated by an increase in pCO2 and H+ concentration
and therefore fill the lungs rapidly Muscles of respiration:
Not affected by hypoxemia
2. Limit the point at which the ramp suddenly ceases Diaphragm
Usual method for controlling respiration rate Intercostal muscles
2. PERIPHERAL CHEMORECEPTOR SYSTEM
Does not need to wait for 2 seconds to cease or Abdominal muscles
Involves the aortic and carotid bodies
stop inspiration Accessory muscles (i.e. sternocleidomastoid)
Activated by an:
The earlier the ramp ceases, the shorter the duration of All of these muscles contract depending on the type of
Increase in pCO2
inspiration compensation to be performed
Stimulates both the central (stronger) and
Shortens expiration, thus an increase in respiratory lncrease respiratory rate → Increase activity of muscles
peripheral chemoreceptors
rate of inspiration (i.e. diaphragm, accessory muscles)
Most potent stimulus
Hyperventilation Forceful expiration → Increase activity of abdominal
Increase H+ concentration
Result: Increase respiratory rate which indicates muscles and intercostal muscles
a higher chance of hyperventilation Normal quiet expiration → No active muscle involved H2O + CO2 → H2CO3 → H+ + HCO3
How to compensate? Limit the point at which Why? Relaxation of the diaphragm and elastic Direct stimulus to the respiratory center
the ramp suddenly ceases recoil of the lungs Why? pCO2 can be converted to hydrogen ion
Increase the activity of the pneumotaxic and bicarbonate
center Hydrogen ion increases blood acidity
Rate of increase of ramping of the signal that Stimulates the central and peripheral (stronger)
fills up the lungs rapidly chemoreceptor

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 RESPIRATORY PHYSIOLOGY #4: REGULATION OF RESPIRATION PHS101
Dr. Oliver Christian I. Arenas, MD, FPCP | February 23, 2022 2ND SEMESTER

Decrease in pO2 4. JOINT AND MUSCLE RECEPTORS 2. Increased tidal volume to increase distention of
Least potent stimulus Activated by muscular contraction airways
Stimulates the peripheral chemoreceptors Involved in early stimulation during exercise Activates the inspiratory ramp signal that leads to
Between the carotid and aortic body, the carotid When working out, individuals experience gasping for increase activity of the pneumotaxic center
body is more sensitive to hypoxemia air due to the activation of joint and muscle receptors Result: Rapid filling of gas that increases tidal
volume and increase distention of the airway
B. MECHANICAL RECEPTORS C. OTHER FACTORS AFFECTING BREATHING 3. Increase in ventilatory rate
1. LUNG STRETCH RECEPTORS 1. LIMBIC SYSTEM AND HYPOTHALAMUS How? Increase activity of the pneumotaxic center
Located in the smooth muscles of the airways Alter the breathing system that indicates more chances of air to go in and out
Stimulated by overdistention of the lungs Examples: Affective states, strong emotions such as rage 4. Increase cardiac output
When the lung parenchyma expands, the airways also and fear
expands resulting to the activation of the lung stretch Causes changes in breathing pattern such as episodes
PARAMETER RESPONSE TO EXERCISE
receptors of shortness of breathing resulting to hyperventilation
What is their relationship? Lung parenchyma is O2 consumption Increased
connected or adjacent to the airways 2. RETICULAR ACTIVATING SYSTEM (RAS)
Involved in vagal system (Herring Breuer reflex) Modulates the brainstem controller by affecting the state CO2 production Increased
Involves stimulation of stretch receptors of alertness
Activated if the lungs are overinflated (TV = 1.5 L) Ventilation rate Increased
Activated until the tidal volume is increased three RESPIRATORY ACID-BASE BALANCE
times the normal Arterial pO2 and pCO2 No change
RESPIRATORY ACIDOSIS RESPIRATORY ALKALOSIS
Protective mechanism of preventing overinflation of
the lungs No change during
Hypoventilation Hyperventilation
Herring Breuer reflex causes the lungs to collapse moderate exercise
Why? Overdistention of the lungs at 1.5 L or more Arterial pH
Accumulation of CO2 in the Excessive loss of CO2 in the
At 1.5 L, the Herring Breuer reflex is activated by the Decreased during
tissues tissues
lung stretch receptors resulting to ceasing further strenuous exercise
• pCO2 increases • pCO2 decreases
expansion or distention of the lungs to prevent • pH decreases • pH increases Venous pCO2 Increased
barotrauma and pneumothorax • Plasma HCO3- increases • Plasma HCO3- decreases
Pulmonary blood flow and Increased
2. IRRITANT RECEPTORS Example: Chronic Example: High altitude cardiac output
Located in the airway epithelial cells and carina obstructive pulmonary climbing
Stimulated by noxious stimuli disease (COPD) More evenly distributed
Stimulation results to coughing and sneezing V/Q ratio
throughout the lung

3. JUXTACAPILLARY (J) RECEPTORS VENTILATION AND EXERCISE

Physiologic dead space Decreased
Located in the alveoli close to the capillaries Exercise involves the joints and muscles receptors to make
Stimulated by engorgement of pulmonary capillaries up for the increase demand for oxygen and metabolic
Clinical correlation: Pulmonary congestion, pulmonary demand RESPONSES TO HIGH ALTITUDE
edema due to heart problem or heart failure, fluid Both perfusion and ventilation are increase through the ACUTE RESPONSES
overload following: In hypoxemia, alveolar PO2 is decrease at high altitude
Patients with these type of conditions presents 1. Increased recruitment of capillaries to increase the due to decrease barometric pressure
shortness of breathing area for gas diffusion Result: Arterial PO2 is decrease
Increased blood flow resulting to better perfusion As compensation, the peripheral chemoreceptors are
and effective gas diffusion activated that leads to hyperventilation (acute
response)

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 RESPIRATORY PHYSIOLOGY #4: REGULATION OF RESPIRATION PHS101
Dr. Oliver Christian I. Arenas, MD, FPCP | February 23, 2022 2ND SEMESTER

Hyperventilation thru stimulation of peripheral receptors ABNORMAL PATTERNS OF BREATHING Respiratory muscles relax that leads to decrease
A. CHEYNE-STROKES BREATHING respiratory drive
CHRONIC RESPONSES Result: Increase CO2 retention but does not causes
Hypoxemia stimulates renal production of erythropoietin any complication
Result: Increase red blood cell production, Hgb Inspiration tends to collapse the upper airway due to
concentration, O2 carrying capacity and O2 blood negative pressure
content ln mild cases lead to snoring
Tendency to develop polycythemia In extreme cases, closing of the upper airway leads to
sleep apnea
PARAMETER RESPONSE
B. OBSTRUCTIVE SLEEP APNEA
↓ due to decreased Characterized by periods of hyperventilation alternating Muscles of the upper airway (generally the hypopharynx)
Alveolar PO2 with periods of apnea (waxing and waning respiration)
barometric pressure are depressed during sleep more than the diaphragm,
Observed in hypoxia, central nervous system disease, causes upper airway to close during inspiration
Arterial PO2 ↓ hypoxemia chronic heart failure, drug overdose and sleep at high Occurs to obese or overweight patients
altitudes, central sleep apnea syndrome In a lying or supine position, the muscles of the upper
↑ hyperventilation due to Pattern of breathing: Apnea → Hyperventilation airway obstructs the potency of the airway resulting to
Ventilation rate
hypoxemia snoring and apnea episode
B. BIOT’S BREATHING (ATAXIC) When obstructive sleep apnea is associated with extreme
↑ respiratory alkalosis due
Arterial pH obesity, it is called obesity hypoventilation syndrome
to hyperventilation
(OHS) or Pickwickian syndrome
Pickwickian is the first patient diagnosed with OHS
↑ increased red blood cell
Hemoglobin concentration Characterized by prolonged periods of apnea A congenital abnormality that manifests obesity and
concentration
interrupting normal respiratory cycles short stature
2,3-DPG concentration ↑ Caused by damage to the medulla oblongata due to Due to hypoxemia, the patient may also manifest
stroke, trauma or pressure on the medulla mental retardation
O2-Hb dissociation curve Shifts to the right; ↓ affinity Pattern of breathing: Apnea → Normal quiet breathing Why? Brain is unable to develop during childhood
No compensation
Pulmonary vascular ↑ due to hypoxic C. CENTRAL ALVEOLAR HYPOVENTILATION
resistance vasoconstriction C. KUSSMAUL BREATHING Also referred to as Ondine’s curse
Myth of Ondine
↑ secondary to increased A water nymph who fell in love with a mortal lover
Pulmonary arterial pressure pulmonary vascular He swore to her that his “every waking breath would
resistance be a testimony of his love”
Upon witnessing his adultery, she cursed that if he
Deep, faster and labored breathing pattern often
If chronic hypoxemia takes place in relation to an should fall asleep, he would forget to breathe
associated with severe metabolic acidosis, particularly
obstructive lung disease, there is presence of persistent A genetic abnormality or may be caused by trauma,
diabetic ketoacidosis (DKA)
hypoxic vasoconstriction space occupying lesion or stroke that damages the
Patient feels an urge to breathe deeply, an “air hunger”,
Increase pulmonary vascular resistance and automatic center of the brain
and it appears almost involuntary
pulmonary arterial pressure Result to central alveolar hypoventilation syndrome
Occurrence indicates presence of pulmonary Treatment: Continuous positive airway pressure (CPAP) or
CLINICAL ABNORMALITIES OF BREATHING
hypertension and possible right sided heart failure mechanical respirator or ventilator during sleeping
A. SLEEP APNEA
During sleep, there is a normal tendency to relax

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 RESPIRATORY PHYSIOLOGY #4: REGULATION OF RESPIRATION PHS101
Dr. Oliver Christian I. Arenas, MD, FPCP | February 23, 2022 2ND SEMESTER

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