Respiratory Physiology III- Regulation of Ventilation

• can we override the chemoreceptor reflexes?

  no.

  
  

  we can only temporarily alter our respiratory performance:

  You can hold your breath voluntarily only until elevated PCO2 in the blood and CSF activates the chemoreceptor reflex, forcing you to inhale.
• what happens if an extremely strong-willed child continues to hold their breath?

  they will turn blue and pass out from hypoxia, but once they are unconscious, normal breathing automatically resumes
• Respiration can also be affected by stimulation of portions of the limbic system. what does this mean?

  emotional and autonomic activities such as fear, and excitement may affect the pace and depth of respiration.
• Higher brain centre control is not a requirement for ventilation.

  
  

  so, what happens if the brainstem above the pons is severely damaged?

  essentially normal respiratory cycles continue.
• can conscious and unconscious thought processes also affect respiratory activities?

  yes

  -> voluntary control of ventilation falls into this category.
• what is a common example of a protective reflex?

  Coughing
• what does the Hering-Breuer reflex prevent?

  stretch receptors in the walls of the bronchi and bronchioles of the lungs are stimulated by the pulmonary stretch and are associated with lung inflation terminating inspiration in a reflex that prevents overinflation of the lung.
• explain the process of bronchoconstriction

  - Inhaled particles or noxious gases stimulate irritant receptors in the airway mucosa.

  
  

  - the irritant receptors send signals through sensory neurons to integrating centres in the CNS that trigger bronchoconstriction.
• what is bronchoconstriction mediated by?

  mediated through parasympathetic neurons that innervate bronchiolar smooth muscle.
• what are key examples of physical protective reflexes?

  - bronchoconstriction

  - Hering-Breuer reflex
• what responds to physical injury or irritation of the respiratory tract and to overinflation of the lungs?

  physical protective reflexes
• when does low PO2 becomes the primary chemical stimulus for ventilation?


  e.g. patients with severe chronic lung disease, such as COPD, have chronic hypercapnia and hypoxia.

  
  

  
  

  Their arterial PCO2 may rise to 50-55 mmHg (normal is 35-45) while their PO2 falls to 45-50 mm Hg (normal 75-100). Because these levels are chronic, the chemoreceptor response adapts to the elevated PCO2.

  Most of the chemical stimulus for ventilation in this situation then comes from low PO2, sensed by the carotid body chemoreceptors.

  
  

  If these patients are given too much O2, they may stop breathing because their chemical stimulus for ventilation is eliminated.
• when the central chemoreceptor response adapts to chronically high PCO2, what do the peripheral chemoreceptors do?

  the response of peripheral chemoreceptor to low arterial PO2 remains intact over time.

  (so PO2 stays high)
• what happens when plasma PCO2 remains elevated for several days?

  the chemoreceptors initially respond by increasing ventilation.

  however eventually ventilation falls back toward normal rates as the chemoreceptor response adapts.

  
  

  -> The adaptation appears to be due to increased cerebrospinal fluid bicarbonate concentrations that buffer the H+.
• the central chemoreceptors only respond to increases in arterial PCO2

  
  

  TRUE/FALSE

  FALSE

  
  

  the central chemoreceptors respond to decreases in arterial PCO2 as well as to increases
• how do the centrak chemoreceptors respond to changes in PCO2?

  1. arterial PCO2 increases, CO2 crosses the blood-brain barrier (BBB) and activates the central chemoreceptors.

  
  

  2.CO2 that diffuses across the BBB into the Cerebrospinal fluid (CSF) and is converted to bicarbonate and H+.

  
  

  -> pH changes in the plasma do not usually influence the central chemoreceptors directly.

  HOWEVER, plasma PCO2 enters the CSF READILY, whilst plasma H+ crosses the BBB very slowly and therefore has little direct effect on the central chemoreceptors.

  
  

  3. The receptors signal the control network to increase the rate and depth of ventilation, thereby enhancing alveolar ventilation and removing CO2 from the blood.
• why is PCO2 the most important chemical controller of ventilation?

  because it is mediated both through the peripheral and central chemoreceptors located in the medulla.
• how do carotid body cells respond to PO2 below 60mmHg?

  - a stimulus inactivates K+ channels and depolarises the receptor cell.

  
  

  - depolarisation opens voltage-gated Ca2+ channels, and Ca2+ entry causes exocytosis of neurotransmitter onto the sensory neuron.

  
  

  - in the carotid bodies, neurotransmitters initiate action potentials in sensory neurons leading to the brain stem respiratory networks, signalling them to increase ventilation.
• carotid body cells respond to PO2 below 60mmHg.

  TRUE/FALSE

  TRUE
• do situations like anaemia and CO poisoning affect PO2 of the arterial blood?

  no, therefore do not stimulate increased ventilation.

  
  

  Both these conditions decrease the amount of oxygen bound to Hb.
• what can alter function of the carotid bodies?

  unusual physiological conditions, such as ascending to high altitude, and pathological conditions, such as COPD, heart failure, and obstructive sleep apnoea.
• why is oxygen not an important factor in modulating ventilation under normal circumstances?

  because arterial PO2 must fall to less than 60 mmHg before ventilation is stimulated.

  
  

  (this large decrease in PO2 is equivalent to ascending to an altitude of 3000 m)
• what affect will activate the carotid and aortic glomus cells and increase ventilation?

  - reduction of plasma pH

  - increase of PCO2
• Above 10kPa the effects of narcosis (state of unconciousness) are seen, and minute ventilation starts to fall.

  
  

  TRUE/FALSE

  TRUE
• Doubling the PACO2 causes minute ventilation to decrease by 4x.

  
  

  TRUE/FALSE

  FALSE

  
  

  Doubling the PACO2 causes minute ventilation to increase by 4x.
• there is a relatively linear increase in minute ventilation as PACO2 increases between 5 and 10kPa.

  TRUE/FALSE

  TRUE
• what happens when glomus cells in the carotid bodies are activated?

  they trigger a reflex increase in ventilation.
• what type of cells do the peripheral chemoreceptors contain?

  glomus cells
• what are the primary peripheral chemoreceptors?

  The carotid bodies in the carotid arteries are the primary peripheral chemoreceptors.

  
  

  (they are located close to the baroreceptors involved in reflex control of blood pressure.)
• The peripheral chemoreceptors act faster and sense changes in the periphery.

  TRUE/FALSE

  TRUE
• where are the peripheral chemoreceptors?

  in the carotid and aortic bodies

  (mediate 30% of responses)

  
  

  ->sense changes in the PO2, pH, and PCO2 of the plasma.
• what are the primary central chemoreceptors?

  The primary central receptors lie on the ventral surface of the medulla, close to neurons involved in respiratory control.
• where are the central chemoreceptors?

  in medulla in brain

  (mediate 70% of responses)

  
  

  -> respond to changes in the concentration of CO2 in the cerebrospinal fluid.
• what homeostatic reflexes ensure PO2 and PCO2 are kept within a narrow range?

  chemoreceptors:

  - central chemoreceptors

  - peripheral chemoreceptors

  
• ventilation:

  
  

  what happens to the rate and depth of breathing if PCO2 increases?

  rate and depth of breathing increases

  (ventilation increases)

  so, rate of co2 production matches rate of co2 removal
• ventilation:

  
  

  what happens to the rate and depth of breathing if PO2 decreases in the atrial blood?

  rate and depth of breathing increases

  (ventilation increases)
• forced breathing:

  
  

  inspiratory neurons are not inhibited during active expiration.

  TRUE/FALSE

  FALSE

  
  

  inspiratory neurons are inhibited during active expiration.

  (so there seems to be some communication between inspiratory and expiratory neurons)
• forced breathing:

  
  

  how does forced breathing occur?

  In forced breathing, increased activity of inspiratory neurons stimulates accessory muscles, such as the sternocleidomastoids.

  
  

  Contraction of these accessory muscles enhances expansion of the thorax by raising the sternum and upper ribs.

  (air is taken in)

  
  

  With active expiration, expiratory neurons from the VRG activate the internal intercostal and abdominal muscles.
• forced breathing:

  
  

  many neurons of the VRG function primarily during forced breathing.

  TRUE/FALSE

  TRUE
• quiet breathing:

  
  

  Many neurons of the VRG remain inactive during quiet respiration.

  TRUE/FALSE

  TRUE