Respiratory Control: An Overview

Lecture 1: Introduction to Respiratory Control

• Alveolar ventilation is determined by the frequency of breathing and the depth of respiration (tidal volume).
• Frequency of breathing dictates respiratory rate.
• Respiratory neurons are concentrated bilaterally in two areas of the medulla: the nucleus tractus solitarius (NTS) and various nuclei in the ventral respiratory group (VRG).
• Nucleus Tractus Solitarius houses signals from mechanoreceptors.
• The dorsal respiratory group (DRG) and VRG are key areas for respiratory control.
• The brainstem, specifically the pons and medulla, is critical for breath regulation, with the hypothalamus also playing a role.
• At rest, the typical breathing rate is 12 breaths per minute.
• More motor units recruited yields a stronger response

Medullary Respiratory Center and Neural Control

• The pre-Bötzinger complex sets the basic rhythm of respiration.
• The medulla sets the basic rhythm of respiration, specifically the pre-Bötzinger complex
• Inspiratory neurons stimulate inspiratory muscles, while expiratory neurons stimulate expiratory muscles.
• The pneumotaxic center (PRG) in the pons coordinates breathing patterns and smooth transitions between inspiration and expiration
• Pontine respiratory groups receive visceral afferent fibers and put the breaks on inhalation
• The DRG houses the majority of inspiratory neurons.
• The inspiratory and expiratory neurons communicate within the inspiratory-expiratory complex.

Respiratory Reflexes

• The Hering-Breuer inflation reflex prevents overinflation of the lungs via stretch receptors.
• Trigeminal, olfactory stimulation of receptors in the nasal mucosa triggers sneezing and bronchoconstriction.
• Stimulation of the nasal and face trigeminal receptors causes apnea.
• J receptors in pulmonary vessels mediate pulmonary chemoreflexes, resulting in tachypnea or apnea and bronchoconstriction.
• The arterial chemoreceptor reflex, triggered by low PaO2, high PaCO2, and low pHa, increases systemic arterial blood pressure and promotes hyperpnea, bronchoconstriction, and dilation of the upper airway.
• Muscle spindles, tendon organs, proprioreceptors provide respiratory controller with feedback.

Hypercapnia and Ventilation

• Hypercapnia (increased PaCO2) is a potent stimulus for ventilation.
• Carbonic anhydrase drives the reaction CO2 + H2O ↔ H2CO3 ↔ H+ + HCO3-.
• The effect of hypoxia on ventilation in response to CO2 is potentiation
• The same start PP of CO2 increases alveolar ventilation increases
• Ventilation increases as alveolar ventilation increases
• Conditions cause a greater increase in alveolar ventilation
• Hypoxia potentiates the ventilatory response to CO2.
• Ventilation reduces CO2 levels.

Metabolic Acidosis and Ventilatory Response

• The body responds to restore the acid and produce bicarbonate.
• Increased PaCO2 makes ventilation levels increase
• Hypoxia increases the ventilatory response to metabolic acidosis, whereas depressants decrease it
• Metabolic acidosis potentiates the ventilatory response.
• There is potentiated ventilatory response when there is hypoxia
• Metabolic acidosis can lead to deep anesthesia.

Feedback Control in Respiration

• Sensors, controller, disturbaces and regulated variables all affect the respiratory system
• Chemoreceptors respond to arterial blood gases and pH and in location of the carotid sinus
• Central chemoreceptors, located in the medulla, respond to PCO2, H+, and sense changes in CSF, but not O2, and the central respiratory controller is in the medulla.

Types and Patterns of Ventilation

• Eupnea is normal quiet breathing.
• Hyperpnea is increased respiratory rate and/or volume due to increased metabolism, like exercise
• Hyperventilation is increased respiratory rate and/or volume without increased metabolism from blowing up a balloon
• Hypoventilation is decreased alveolar ventilation from asthma
• Tachypnea is rapid breathing, but decreased depth like panting
• Dyspnea is the subjective feeling of difficulty breathing
• Apnea is the cessation of breathing

Carotid Body Oxygen Sensors

• Decreases in PO2 causes a signal toward medullary centers

Ventilatory Response to Hypoxia

• The ventilatory response to hypoxia increases
• Responding starts at ~80mmHg when there is hypercapnea
• Starts to adjust ventilation when PaO2 ≤ 60mmHg
• Ventilatory responses potentiate hypoxia.
• A buildup of CO2 causes ventilation

Work of Breathing

• Minute ventilation increases with more breaths
• Minute ventilation is ~6L/min normally
• Inhalation and exhalation are active processes and require energy usually 3% of total expenditure
• The amount of breathing may need to become mouth breathing.
• Resistive work is from tissue resistance, airway resistance, etc.
• A compromised elasticity needs work to expand the lungs
• Exercise, altitude all require an increase in CO.

Work of Breathing: Factors Influencing

• Work of breathing can increase due to a number of factors.
• Decreased pulmonary compliance, as seen in pulmonary fibrosis.
• Increased airway resistance, as in COPD, emphysema or chronic bronchitis.
• Decreased elastic recoil, as with emphysema.
• Work of breathing increases due to exercise
• Increased cardiac output should be coupled with increased alveolar ventilation.
• An increased need for ventilation due to increased altitude or exercise
• Metabolic increases due to exercise are additional stressors

Minute Ventilation and Limitations

• The resp system can keep up by increased ventilation 25%
• Minute ventilation can increase 25x during exercise, but CO can be only 4-6x

Impact of Exercise on Pulmonary Blood Flow

• During exercise, pulmonary blood flow increases, facilitated by recruitment and distention due to perfusion
• During exercise diffusion through alveolar capillary membrane increases

Gas Exchange Optimization

• V/Q ratio becomes more uniform from bottom to top to deliver better mixture.
• Also due to recruitment and distention SA for gas exchange

Oxygen and Carbon Dioxide Transport During Exercise

• Unloading O2 at tissue to T due to right shifting TH, TCO2 and T temp
• The buildup of CO2 aids in a shift
• The tissue becomes more metabolizing needing more 02

Acid-Base Balance and Ventilation

• Blow off more CO2 due to T ventilation
• Ventilation increases chemoreceptors

Total Air Pressure and Altitude

• Total air pressure decreases at high altitude.
• As altitude T, ventilation increases and PCO2 falls.
• Arterial PO2 and the brain are affected at altitude.
• Central chemoreceptors are not arterial

Unacclimatized Individuals at High Altitudes

• Alveolar PO2 decreases leading
• The hypoxia will lead to deteriorization of the NS function
• Deteriorization of NS is primarily due to hypoxia

Acute Mountain Sickness

• Acute mountain sickness is due to hypoxia alkalosis or cerebral edema or pulmonary edema
• PCO2 = H+

Control of Breathing at Altitude

• Lower alveolar PO2 occurs at higher altitude
• Alveolar ventilation rate increases which in turn can increase arterial chemoreceptors hyperventilation

Central vs Peripheral Responses at Altitude

• Raising the set point promotes a sympathetic response which increased HR, CO and systemic BP

Alveolar Changes and Pulmonary Vasoconstriction

• Decreased PO2 in alveoli leads to alveolar hypoxia creating hypoxic pulmonary vasoconstriction

Pulmonary Edema and Capillary Stress

• The combined effect increasepulmonary edema.
• The increased hydrostatic pressure leads to stress failure and makes them leaky
• High blood pressure could damage the capillaries