Control of Respiration: Neural and Chemical Regulation

Control of Respiration (Neural and Chemical Regulation)

Respiration is controlled by both the involuntary and voluntary nervous systems. Involuntary control, which governs automatic breathing, is managed by the respiratory centers in the brainstem (medulla oblongata and pons), which respond to blood levels of oxygen, carbon dioxide, and pH. Voluntary control comes from the cerebral cortex and allows you to control your breathing for activities like speaking or holding your breath.

Overall Objective: To understand the neural pathways and chemical factors that regulate the rate and depth of breathing, ensuring appropriate gas exchange to meet metabolic demands and maintain blood gas homeostasis.

Objective 1: Identify and describe the key neural control centers for respiration in the brainstem.

The control of breathing is a complex process involving both voluntary and involuntary mechanisms. The involuntary, rhythmic control of breathing primarily originates in the brainstem, specifically in the medulla oblongata and the pons. These areas contain specialized groups of neurons that generate and modulate the respiratory rhythm.

I. Medullary Respiratory Centers

The medulla oblongata houses the most crucial respiratory control centers, responsible for setting the basic rhythm of breathing. These are broadly divided into two main groups: the Dorsal Respiratory Group (DRG) and the Ventral Respiratory Group (VRG).

A. Dorsal Respiratory Group (DRG)

Location:

Located in the posterior portion of the medulla, near the nucleus of the tractus solitarius.

Primary Function:

The DRG is the most fundamental and active group involved in controlling the basic rhythm of breathing, especially during quiet (eupneic) respiration. It primarily controls inspiration.

Neuronal Activity:

Contains inspiratory neurons that fire rhythmically.
These neurons generate a ramp-like signal: they start weakly and increase in intensity over approximately 2 seconds, then abruptly cease for about 3 seconds, allowing for elastic recoil and exhalation. This gradual increase helps to ensure a smooth, progressive filling of the lungs.

Innervation:

Sends efferent (motor) signals via the phrenic nerves to the diaphragm.
Sends signals via the intercostal nerves to the external intercostal muscles.
Activation of these muscles causes the diaphragm to contract and flatten, and the rib cage to expand, leading to inspiration.

Afferent Input:

Receives sensory input (afferent signals) from:

Peripheral chemoreceptors: via glossopharyngeal (CN IX) and vagus (CN X) nerves, detecting changes in PO₂, PCO₂, and pH.
Lung receptors: via vagus (CN X) nerve, detecting stretch and irritation in the lungs and airways.

This sensory input allows the DRG to modify the basic respiratory rhythm in response to physiological demands.

B. Ventral Respiratory Group (VRG)

Location:

Located in the anterior portion of the medulla, extending from the brainstem to the upper spinal cord, including the pre-Bötzinger complex.

Primary Function:

The VRG is largely inactive during quiet breathing. It becomes active and crucial for generating the respiratory rhythm only when there is an increased ventilatory demand, such as during forceful (active) inspiration and expiration.

Neuronal Activity:

Contains both inspiratory and expiratory neurons.

Inspiratory neurons: When stimulated (e.g., by intense DRG signals or strong chemoreceptor input), they send signals to accessory muscles of inspiration (e.g., sternocleidomastoid, scalenes).
Expiratory neurons: When stimulated, they send signals to the internal intercostals and abdominal muscles, which are primarily active during forceful exhalation.

Rhythm Generation (Pre-Bötzinger Complex):

Current research suggests that a small area within the VRG, known as the pre-Bötzinger complex, is the primary site responsible for generating the basic respiratory rhythm. It acts as the pacemaker for breathing, relaying signals to the DRG.

Innervation:

Inspiratory neurons: Innervate accessory muscles of inspiration.
Expiratory neurons: Innervate internal intercostal and abdominal muscles (for active expiration).

Role in Forced Breathing:

During exercise or respiratory distress, the DRG activates the VRG. The VRG then significantly increases the strength of both inspiratory and expiratory signals, leading to a deeper and more rapid breathing pattern.

II. Pontine Respiratory Centers (Pontine Respiratory Group - PRG)

The pons contains centers that modify and fine-tune the activity of the medullary respiratory centers, ensuring smooth transitions between inspiration and expiration. These are often collectively referred to as the Pontine Respiratory Group (PRG) and include the Pneumotaxic and Apneustic centers.

A. Pneumotaxic Center

Upper Pons (Nucleus Parabrachialis)

Primary Function: Primarily acts to limit inspiration and fine-tune the respiratory rate. It essentially "switches off" the inspiratory ramp signal from the DRG.

Effect: By shortening the inspiratory phase, it leads to:

Decreased tidal volume (shallower breaths).
Increased respiratory rate.

Analogy: Think of it as an "off switch" or a "brake" for inspiration. A strong pneumotaxic signal reduces the duration of inspiration.

Clinical Significance: Damage to this center can lead to prolonged inspiration and decreased respiratory rate.

B. Apneustic Center

Lower Pons

Primary Function: Has an excitatory effect on the medullary inspiratory neurons, particularly the DRG. It essentially prolongs inspiration.

Effect: If unopposed by the pneumotaxic center, it would lead to:

Prolonged, gasping inspirations followed by brief, insufficient expirations (a breathing pattern called apneusis).

Interaction with Pneumotaxic Center: Normally, the pneumotaxic center overrides the apneustic center, preventing prolonged inspiration and ensuring rhythmic breathing.

Clinical Significance: Damage to the pneumotaxic center or vagal nerves (which also inhibit inspiration) can allow the apneustic center to dominate, leading to apneustic breathing.

Summary of Brainstem Control

Medulla (DRG & VRG): Generates the basic rhythm of breathing. DRG for quiet inspiration; VRG for forceful inspiration/expiration and contains the pacemaker (pre-Bötzinger complex).
Pons (Pneumotaxic & Apneustic): Modulates the medullary centers. Pneumotaxic center limits inspiration and increases rate; Apneustic center prolongs inspiration.

This intricate interplay of neural centers ensures that breathing is a continuous, rhythmic process that can be finely adjusted to meet the body's changing metabolic demands.

Objective 2: Explain the roles of central chemoreceptors in regulating breathing.

The chemical control of respiration is paramount for maintaining arterial blood gas homeostasis (PCO₂, PO₂, and pH). Chemoreceptors are specialized sensory receptors that detect changes in the chemical composition of the blood and cerebrospinal fluid (CSF) and send signals to the respiratory centers in the brainstem to adjust ventilation accordingly.

Central chemoreceptors are the most potent and important regulators of ventilation under normal physiological conditions.

I. Location of Central Chemoreceptors

Primary Location: Strategically located in the ventrolateral surface of the medulla oblongata, very close to the DRG and VRG respiratory centers. This proximity allows for a rapid and direct influence on breathing patterns.

II. Primary Stimulus: Changes in Cerebrospinal Fluid (CSF) pH

(Largely driven by arterial PCO₂)

Not directly sensitive to blood CO₂: Central chemoreceptors are not directly sensitive to changes in arterial PCO₂, but rather to the pH of the cerebrospinal fluid (CSF).

The Crucial Link: Arterial PCO₂ and CSF pH

1. CO₂ freely crosses the Blood-Brain Barrier (BBB):

Unlike H⁺ and HCO₃^- ions, CO₂ is lipid-soluble and readily diffuses across the blood-brain barrier from the systemic circulation into the CSF.

2. Conversion to Carbonic Acid in CSF:

Once in the CSF, CO₂ reacts with water to form carbonic acid (H₂CO₃), a reaction facilitated by carbonic anhydrase (though less prevalent than in RBCs, it still occurs spontaneously).

CO₂ + H₂O ↔ H₂CO₃ ↔ H⁺ + HCO₃^-

3. CSF Lacks Significant Buffering Capacity:

The CSF has a very low protein concentration, meaning it has a much weaker buffering capacity compared to blood plasma. Therefore, even small changes in CO₂ entering the CSF can cause a significant change in CSF H⁺ concentration, and thus, a notable change in CSF pH.

4. H⁺ Stimulates Chemoreceptors:

It is these increased H⁺ ions (decreased pH) in the CSF that directly stimulate the central chemoreceptors.

Relationship Summary:

Increased arterial PCO₂ → Increased CO₂ in CSF → Increased H⁺ in CSF → Decreased CSF pH → Stimulation of central chemoreceptors → Increased ventilation.

Decreased arterial PCO₂ → Decreased CO₂ in CSF → Decreased H⁺ in CSF → Increased CSF pH → Inhibition of central chemoreceptors → Decreased ventilation.

III. Mechanism of Action

Detection: Central chemoreceptors detect changes in CSF H⁺ concentration (pH).
Signal Transmission: When stimulated, these receptors send excitatory signals directly to the medullary respiratory centers (DRG and VRG).
Ventilatory Response: The respiratory centers respond by increasing the rate and depth of breathing (hyperventilation).
Restoration of Homeostasis: This increased ventilation leads to a more rapid "blowing off" of CO₂ from the blood. As arterial PCO₂ decreases, less CO₂ diffuses into the CSF, allowing CSF H⁺ concentration to fall and CSF pH to normalize. This, in turn, reduces the stimulation of the central chemoreceptors, completing the negative feedback loop.

IV. Significance in Long-Term Control of Breathing

Dominant Regulator: Under normal physiological conditions, arterial PCO₂ (and thus CSF pH) is the most powerful and closely regulated chemical stimulus for breathing. Even small changes in PCO₂ (e.g., a 1-2 mmHg increase) can significantly alter ventilation.

Acute vs. Chronic Changes

Acute Hypercapnia

Central chemoreceptors respond quickly (within seconds to minutes) to acute changes in PCO₂, causing a robust increase in ventilation.

Chronic Hypercapnia (e.g., COPD)

If high PCO₂ levels persist for several days, the kidneys compensate by retaining bicarbonate ions (HCO₃^-) in the blood. These HCO₃^- ions eventually diffuse into the CSF, buffering the excess H⁺ ions. This "normalizes" the CSF pH, even though arterial PCO₂ remains high.

Clinical Relevance: COPD & Oxygen Administration

In such patients, the central chemoreceptors become desensitized or "reset" to the chronically high PCO₂. Their primary respiratory drive then shifts from PCO₂ to the hypoxic drive (detected by peripheral chemoreceptors).

The Danger: If supplemental oxygen is administered at high concentrations to these patients, their arterial PO₂ may increase significantly, which can then depress the hypoxic drive from the peripheral chemoreceptors. Without the strong PCO₂ drive (due to desensitization) or the hypoxic drive (due to O₂ administration), the patient's respiratory drive can diminish, leading to hypoventilation, further CO₂ retention, and potentially respiratory acidosis and coma.

This is why oxygen administration in COPD patients needs to be carefully monitored and typically delivered at lower flow rates.

Insensitivity to Hypoxia: Central chemoreceptors are essentially insensitive to changes in arterial PO₂. This role is primarily handled by the peripheral chemoreceptors.

In essence, central chemoreceptors are the body's primary "CO₂ sensors," indirectly monitoring arterial CO₂ levels by sensing CSF pH, and they are crucial for maintaining CO₂ homeostasis.

Objective 3: Explain the roles of peripheral chemoreceptors in regulating breathing.

Peripheral chemoreceptors provide an additional layer of chemical control, primarily acting as the body's emergency sensors for oxygen levels and as a secondary sensor for CO₂ and pH.

I. Location of Peripheral Chemoreceptors

These are specialized sensory organs located in specific arteries outside the brain.

Carotid Bodies

Location: Small, highly vascularized structures located bilaterally at the bifurcation of the common carotid arteries (where they split into internal and external carotid arteries).

Innervation: Send afferent (sensory) signals to the medulla oblongata via the glossopharyngeal nerve (CN IX).

Significance: Because they sample blood going to the brain, they are particularly important for ensuring adequate oxygen supply to the brain.

Aortic Bodies

Location: Scattered along the aortic arch.

Innervation: Send afferent signals to the medulla oblongata via the vagus nerve (CN X).

Significance: Monitor the arterial blood that will be distributed to the rest of the body.

II. Primary Stimuli: Severe Decreases in Arterial PO₂ (Hypoxia)

Oxygen Sensitivity: Peripheral chemoreceptors are the body's primary and most important sensors for detecting changes in arterial oxygen levels.

The Critical Threshold

They are relatively insensitive to changes in PO₂ until arterial PO₂ falls below a critical threshold, typically around 60-70 mmHg.

Below this level, their firing rate increases sharply and exponentially. This means they act more as an "emergency" oxygen sensor rather than a fine-tuner of normal PO₂.

Why 60-70 mmHg?

This corresponds to the steep part of the oxygen-hemoglobin dissociation curve. Below this point, a small drop in PO₂ leads to a significant decrease in hemoglobin saturation and oxygen content, which could rapidly become life-threatening.

Response to Hypoxia: When activated by low PO₂, they send strong excitatory signals to the DRG, leading to a significant increase in ventilation (hyperventilation).

III. Secondary Stimuli: Increases in Arterial PCO₂ and H⁺ (Decreased pH)

PCO₂ Sensitivity

While central chemoreceptors are the dominant sensors for PCO₂, peripheral chemoreceptors also respond to increases in arterial PCO₂.

Their response to CO₂ is faster but quantitatively less powerful (about 20-30%) than that of the central chemoreceptors. This means they contribute to the overall ventilatory response to hypercapnia, particularly in its initial, acute phase.

pH Sensitivity

Peripheral chemoreceptors are directly sensitive to changes in arterial H⁺ concentration (pH), independent of PCO₂.

This is especially important in metabolic acidosis (e.g., diabetic ketoacidosis), where H⁺ levels rise without a primary increase in PCO₂. In such cases, the peripheral chemoreceptors are crucial for stimulating hyperventilation to "blow off" CO₂, thereby attempting to raise blood pH.

IV. Mechanism of Action

Detection: Peripheral chemoreceptors monitor the arterial blood for changes in PO₂, PCO₂, and pH.
Signal Transmission: Upon stimulation (e.g., significant drop in PO₂, rise in PCO₂ or H⁺), they generate action potentials that are transmitted via the glossopharyngeal (carotid bodies) and vagus (aortic bodies) nerves to the medullary respiratory centers (primarily the DRG).
Ventilatory Response: The medullary centers, receiving this input, increase the firing rate of inspiratory neurons, leading to an increased rate and depth of breathing (hyperventilation).
Integrated Response: The overall ventilatory response to hypercapnia and acidosis is a combined effect of both central and peripheral chemoreceptor activity.

V. Significance in Immediate, Emergency Responses and Clinical Relevance

Hypoxic Drive & COPD Oxygen Therapy

Hypoxic Drive: As mentioned in our previous discussion on central chemoreceptors, in individuals with chronic hypercapnia (e.g., severe COPD), the central chemoreceptors become desensitized to high PCO₂. In these patients, the hypoxic drive (stimulation of peripheral chemoreceptors by low PO₂) becomes the primary stimulus for breathing.

Clinical Point Revisited:

If a COPD patient with chronic hypercapnia is given high concentrations of supplemental oxygen, their arterial PO₂ rises significantly. This rise in PO₂ removes the hypoxic stimulus from the peripheral chemoreceptors, thus diminishing their main remaining drive to breathe.

This can lead to severe hypoventilation, worsening hypercapnia, respiratory acidosis, and potentially coma or death. Therefore, oxygen therapy in these patients must be carefully managed to avoid suppressing their crucial hypoxic drive.

Acute Hypoxemia:

The peripheral chemoreceptors are vital for triggering a rapid ventilatory response to acute hypoxemia (e.g., at high altitude, during suffocation).

Metabolic Acidosis:

They are the sole chemoreceptors to respond to changes in pH that are not caused by changes in PCO₂ (i.e., metabolic acidosis), driving the compensatory hyperventilation (Kussmaul breathing) seen in conditions like diabetic ketoacidosis.

In summary, while central chemoreceptors are the primary sensors for CO₂ and pH via CSF, peripheral chemoreceptors are indispensable for detecting critically low oxygen levels and for responding to metabolic acid-base disturbances, making them vital for acute and emergency respiratory regulation.

Objective 4: Describe the various lung and airway receptors that influence breathing.

Beyond the central control in the brainstem and chemical feedback from chemoreceptors, a variety of mechanoreceptors and irritant receptors located within the lungs and airways provide sensory input that modifies the breathing pattern. These receptors relay information predominantly via the vagus nerves (CN X) to the medullary respiratory centers.

I. Pulmonary Stretch Receptors (Slowly Adapting Receptors)

Location: Found in the smooth muscle of the airways (trachea, bronchi, and bronchioles).
Stimulus: Activated by distension or stretching of the lung tissue during inspiration. As the lungs inflate, these receptors fire with increasing frequency.

Reflex: The Hering-Breuer Reflex

Mechanism: When these receptors are significantly stimulated (i.e., during deep inspiration, or in infants even during normal inspiration), they send inhibitory signals to the inspiratory neurons of the DRG.

Effect: This inhibition terminates inspiration and therefore prolongs the expiratory phase. It acts as a protective mechanism to prevent overinflation of the lungs, particularly important in newborns and during exercise in adults. In resting adults, it may not play a major role until tidal volume exceeds approximately 1.5 liters.

Adaptation: They are "slowly adapting" because they continue to fire as long as the stretch is maintained.

II. Irritant Receptors (Rapidly Adapting Receptors)

Location: Located in the epithelium of the entire airway, from the trachea to the terminal bronchioles.
Stimulus: Activated by a wide variety of noxious stimuli:
- Mechanical irritants (e.g., dust, foreign particles)
- Chemical irritants (e.g., smoke, fumes, sulfur dioxide, ammonia)
- Cold air
- Inflammatory mediators (e.g., histamine, prostaglandins)

Protective Reflexes:

Bronchoconstriction: Narrows the airways, limiting further entry of irritants.
Coughing: A forceful expulsion of air to clear the airways.
Sneezing: Similar to coughing, but typically for irritants in the nasal passages.
Hyperpnea/Shallow Breathing: Increased rate or shallow pattern depending on the irritant.

Adaptation: They are "rapidly adapting" because they respond vigorously to the onset of a stimulus but then quickly decrease their firing rate even if the stimulus persists.

III. J-Receptors (Juxtacapillary Receptors)

Location: Located in the alveolar-capillary walls, in the interstitial space between the pulmonary capillaries and the alveoli.
Stimulus: Activated by an increase in interstitial fluid volume or pressure (e.g., pulmonary edema, pneumonia, left heart failure) and by chemical agents such as histamine.

Reflexes & Response:

Rapid, Shallow Breathing (Tachypnea): Increases the respiratory rate but with reduced tidal volume.
Bronchoconstriction (sometimes).
Dyspnea: Sensation of shortness of breath. Thought to be a major contributor to the feeling of breathlessness in conditions like pulmonary edema.

Physiological Role: Their precise physiological role is still debated, but they are thought to be important in sensing pathological changes in the lung interstitium.

Receptor Type	Function/Reflex
Pulmonary Stretch	Prevent overinflation, modulate inspiratory duration (Hering-Breuer).
Irritant	Protect airways from noxious stimuli, trigger cough/bronchoconstriction.
J-Receptors	Respond to interstitial fluid changes, contribute to dyspnea and rapid shallow breathing.

These receptors act as sophisticated sensors within the respiratory system, providing essential feedback to the brain to adjust ventilation and activate protective reflexes, ensuring both efficient gas exchange and the integrity of the airways.

Objective 5: Identify other factors that influence respiratory control.

Beyond the primary medullary and pontine centers, chemoreceptors, and pulmonary reflexes, several other physiological and psychological factors can exert significant influence over the rate and depth of respiration. These often involve higher brain centers or specialized sensory receptors throughout the body.

I. Voluntary Control (Cerebral Cortex)

Mechanism: The cerebral cortex, particularly the motor cortex, can temporarily override the brainstem's automatic respiratory centers. This allows for conscious control over breathing.

Examples:

Holding Breath (diving).
Talking, Singing, Playing Wind Instruments.
Breath-holding for medical procedures (X-ray).
Voluntary Hyperventilation/Hypoventilation.

The "Breaking Point":

This voluntary control is ultimately limited. If CO₂ levels rise too high (or O₂ levels fall too low) during breath-holding, the involuntary drive from the medullary centers (primarily via central chemoreceptors sensing CO₂) will eventually become so strong that it overrides voluntary inhibition, forcing a breath.

II. Hypothalamic Influence (Emotion, Pain, Temperature)

Mechanism: The hypothalamus, a key brain region for regulating homeostatic functions and emotional responses, can influence the respiratory centers.

Emotion:

Strong emotions (e.g., fear, anxiety, anger, excitement) can cause changes in breathing patterns (e.g., gasping, hyperventilation, sighing). Mediated by pathways from the limbic system to the hypothalamus.

Pain:

Sudden severe pain often causes a brief period of apnea followed by rapid, shallow breathing. Prolonged pain typically leads to an increase in respiratory rate.

Temperature:

Increased Body Temperature (Fever): Increases respiratory rate (hyperpnea). Mechanism to increase heat loss.
Decreased Body Temperature (Hypothermia): Generally decreases respiratory rate and depth.

III. Proprioceptors & V. Muscle Stretch Receptors (Exercise)

Location: Sensory receptors located in muscles, tendons, and joints throughout the body.

Mechanism: The "Anticipatory Response"

When movement begins (e.g., at the start of exercise), these proprioceptors send excitatory signals to the medullary respiratory centers, causing an immediate increase in ventilation. This anticipatory response ensures that ventilation increases before there are significant changes in blood gases or pH due to increased metabolic activity.

Significance: This "neurogenic drive" is a significant contributor to the rapid increase in breathing observed at the onset of exercise.

IV. Baroreceptors (Blood Pressure)

Location: Carotid sinuses and aortic arch.

Increased BP: Stimulation inhibits respiratory centers → temporary decrease in rate/depth.
Decreased BP: Reduced stimulation excites respiratory centers → increase in rate/depth.

Significance: Plays a role in integrated cardiovascular/respiratory homeostasis, though less powerful than chemoreceptors.

VI. Irritation of Upper Airways

Receptors: Free nerve endings in nose, pharynx, larynx, trachea.

Reflexes: Sneezing, coughing, bronchoconstriction, temporary apnea. Similar to lung irritant receptors but specific to the upper tract.

These diverse influences demonstrate that respiration is not merely an automatic process driven by basic chemical needs, but a highly adaptable system integrated with our emotional state, physical activity, and protective reflexes.

Objective 6: Explain how the body responds to changes in PCO₂, PO₂, and pH to maintain respiratory homeostasis.

The respiratory system works tirelessly to maintain arterial partial pressures of carbon dioxide (PCO₂) and oxygen (PO₂), and arterial pH within very narrow physiological limits. This is achieved through a sophisticated negative feedback system involving chemoreceptors and medullary respiratory centers.

I. Response to Hypercapnia (Increased Arterial PCO₂)

Definition: Hypercapnia is an abnormally high level of CO₂ in the arterial blood (PaCO₂ > 45 mmHg). It typically occurs due to hypoventilation (inadequate removal of CO₂).

Consequences:

Respiratory Acidosis: As CO₂ combines with water to form carbonic acid (H₂CO₃) which then dissociates into H⁺ and HCO₃^-, the H⁺ concentration in the blood increases, causing a drop in pH.
Direct effect on tissues: High CO₂ can have narcotic effects on the brain at very high levels.

Body's Response:

1. Central Chemoreceptors (Dominant Role):

Increased PaCO₂ readily diffuses across the blood-brain barrier into the CSF. In the CSF, CO₂ is converted to H⁺, leading to a decrease in CSF pH. This decreased CSF pH strongly stimulates the central chemoreceptors in the medulla.

2. Peripheral Chemoreceptors (Secondary, Faster Role):

Increased PaCO₂ also directly stimulates the peripheral chemoreceptors (carotid and aortic bodies). This response is faster but less powerful than the central chemoreceptor response to CO₂.

Physiological Outcome:

Overall Effect: Both sets of chemoreceptors send strong excitatory signals to the medullary respiratory centers (DRG and VRG).
Ventilatory Outcome: The respiratory centers respond by dramatically increasing the rate and depth of breathing (hyperventilation).
Restoration of Homeostasis: This increased ventilation "blows off" excess CO₂ from the lungs, reducing PaCO₂ back towards normal. As PaCO₂ falls, CSF pH rises, and the stimulation of chemoreceptors decreases, completing the negative feedback loop.

Summary: Increased PaCO₂ is the most powerful ventilatory stimulus. A rise of just 1-2 mmHg in PaCO₂ can double ventilation.

II. Response to Hypoxemia (Decreased Arterial PO₂)

Definition: Hypoxemia is an abnormally low level of O₂ in the arterial blood (PaO₂ < 80 mmHg).

Body's Response:

Peripheral Chemoreceptors (Exclusive Role):

Central chemoreceptors are insensitive to changes in PO₂.
The peripheral chemoreceptors (carotid and aortic bodies) are the only chemoreceptors that directly sense arterial PO₂.
They become significantly stimulated when PaO₂ drops below approximately 60-70 mmHg. Their firing rate increases exponentially below this threshold.

Physiological Outcome:

Overall Effect: Stimulated peripheral chemoreceptors send excitatory signals to the medullary respiratory centers.
Ventilatory Outcome: The respiratory centers respond by increasing the rate and depth of breathing (hyperventilation).
Restoration of Homeostasis: This increased ventilation brings more oxygen into the alveoli, raising PaO₂ back towards normal.

Summary: Decreased PaO₂ is a potent ventilatory stimulus, but only when it falls significantly below normal levels. It acts primarily as an emergency mechanism.

III. Response to Acidosis/Alkalosis (Changes in Arterial pH)

Definition: Acidosis (pH < 7.35) or alkalosis (pH > 7.45) refers to an imbalance in arterial blood pH.

Metabolic Acidosis

Decreased pH, Normal/Decreased PaCO₂

Primary Role: Peripheral chemoreceptors are directly sensitive to increased H⁺.

Secondary Role: Central chemoreceptors play a delayed, indirect role if acidosis is prolonged.

Outcome: Marked increase in ventilation (hyperventilation), often characterized by deep, rapid breaths known as Kussmaul respiration.

Restoration: "Blowing off" CO₂ reduces H⁺ concentration, raising pH back toward normal.

Metabolic Alkalosis

Increased pH, Normal/Increased PaCO₂

Primary Role: Decreased H⁺ (increased pH) inhibits peripheral chemoreceptors.

Outcome: Decreased ventilation (hypoventilation).

Restoration: Hypoventilation leads to CO₂ retention, increasing H⁺ concentration and lowering pH back toward normal.

Objective 7: Identify and describe common abnormal breathing patterns and their physiological basis.

Understanding normal quiet breathing (eupnea) is essential, but equally important is the ability to recognize and interpret deviations from this pattern.

I. Eupnea (Normal Breathing)

Quiet, effortless, rhythmic breathing (12-20 breaths/min). Generated by medullary centers maintaining homeostasis.

II. Apnea

Cessation of breathing.

Voluntary: Breath-holding.
Reflexive: Pain, cold shock.
Pathological: Sleep apnea, brainstem lesions, opioid overdose.

III. Dyspnea

Subjective sensation of "shortness of breath." Complex sensation involving increased effort, ventilatory demand mismatch, and chemoreceptor stimulation. Common in heart failure, COPD, anxiety.

IV. Tachypnea

Rapid breathing (>20/min). Caused by acidosis, hypoxemia, fever, anxiety, pain.

V. Bradypnea

Slow breathing (<12/min). Caused by CNS depression (opioids), hypothermia, metabolic alkalosis.

VI. Hyperpnea & VII. Kussmaul Respiration

Hyperpnea: Increased depth/rate to meet metabolic demand (exercise, altitude).

Kussmaul: Deep, rapid, labored breathing. Specific compensatory mechanism for severe metabolic acidosis (DKA) to blow off CO₂.

VIII. Cheyne-Stokes Respiration

Cyclical pattern: gradual increase in volume/rate, then decrease, then apnea. Repeats.

Mechanism (Unstable Feedback Loop): Heart failure/brain injury → Slow blood flow → Delayed signal to brain → Overshoot (hyperventilation) → Undershoot (apnea) → Cycle repeats.

IX. Biot's (Ataxic)

Irregular shallow breaths followed by irregular apnea. Indicates severe medullary damage (stroke, trauma). Pre-terminal.

X. Apneustic

Prolonged inspiratory pauses, short expirations. Indicates pontine damage disrupting the pneumotaxic center.

Physiology: Control of Respiration Exam

Control of Respiration Exam

Test your knowledge with these 30 questions.

Control of Respiration: Neural and Chemical Regulation

Control of Respiration (Neural and Chemical Regulation)

I. Medullary Respiratory Centers

A. Dorsal Respiratory Group (DRG)

B. Ventral Respiratory Group (VRG)

II. Pontine Respiratory Centers (Pontine Respiratory Group - PRG)

A. Pneumotaxic Center

B. Apneustic Center

Summary of Brainstem Control

I. Location of Central Chemoreceptors

II. Primary Stimulus: Changes in Cerebrospinal Fluid (CSF) pH

The Crucial Link: Arterial PCO2 and CSF pH

Relationship Summary:

III. Mechanism of Action

IV. Significance in Long-Term Control of Breathing

Acute vs. Chronic Changes

Acute Hypercapnia

Chronic Hypercapnia (e.g., COPD)

Clinical Relevance: COPD & Oxygen Administration

I. Location of Peripheral Chemoreceptors

Carotid Bodies

Aortic Bodies

II. Primary Stimuli: Severe Decreases in Arterial PO2 (Hypoxia)

The Critical Threshold

III. Secondary Stimuli: Increases in Arterial PCO2 and H+ (Decreased pH)

PCO2 Sensitivity

pH Sensitivity

IV. Mechanism of Action

V. Significance in Immediate, Emergency Responses and Clinical Relevance

Hypoxic Drive & COPD Oxygen Therapy

I. Pulmonary Stretch Receptors (Slowly Adapting Receptors)

II. Irritant Receptors (Rapidly Adapting Receptors)

III. J-Receptors (Juxtacapillary Receptors)

I. Voluntary Control (Cerebral Cortex)

II. Hypothalamic Influence (Emotion, Pain, Temperature)

III. Proprioceptors & V. Muscle Stretch Receptors (Exercise)

IV. Baroreceptors (Blood Pressure)

VI. Irritation of Upper Airways

I. Response to Hypercapnia (Increased Arterial PCO2)

Body's Response:

II. Response to Hypoxemia (Decreased Arterial PO2)

Body's Response:

III. Response to Acidosis/Alkalosis (Changes in Arterial pH)

Metabolic Acidosis

Metabolic Alkalosis

Control of Respiration Exam