Control of the respiratory system week 5 Flashcards
What is the difference btwn ventilation and respiration?
Survival depends on the continuous and reliable exchange of oxygen and carbon dioxide between air and the blood. Many mechanisms have evolved to regulate respiration and thus, ventilation. (To remind you: ventilation refers to the movement of gas into and out of the lungs– a.k.a. breathing - whereas respiration refers to all the processes involved in the exchange of gases between the cells of an organism and the external environment.)
As with any regulation system, we have sensors, a central controller, and effectors (see attached pic).
Central control of breathing is achieved by ANS at the _____ , _____, and _____ _____.
Neural output controls what 2 parameters of respiration?
- medulla and the pons (sections of the brainstem) as well as the cerbebral cortex
- Neural output controls the rate (f) adn depth of ventilation VT.
Where is the rhythm generator of the respiratory system located?
What respiratory cells are located here? What are their functions?
How is respiration controlled by inputs from airways? (specify receptors and nerve)
What is the Hering-Breuer reflex? What type of breathing pattern results after a vagotomy?
The medulla contains the inspiratory and expiratory centers.
- Inspiratory center
a. The “rhythm generator” of the respiratory system. i.e. the intrinsic firing patterns of the neurons located here generate the normal cycle of inspiration and expiration.
b. Bursts of action potentials originate here and are conducted down the phrenic nerve, stimulating contraction of the diaphragm and other inspiratory muscles. (Remember that gas flows into and out of the lungs because the diaphragm and thoracic cage create a pressure gradient.)
c. More action potentials per burst = stronger contraction/deeper breath
d. More bursts per minute = faster breathing rate
e. Usually, the body increases the number of action potentials per burst AND the frequency of bursts per minute in order to increase ventilation!
Expiratory center
a. Only active when ventilation needs to be increased (e.g. during exercise)
i. Normally, expiration is a passive process which relies on elastic recoil of the lungs and chest wall.
b. Neurons located here fire when inspiratory neurons are silent, stimulating muscles of expiration (internal intercostals and those in the abdominal wall)
The medullary respiratory center receives inputs from stretch receptors in airway smooth muscle (travels via the vagus nerve). Stretch receptors detect lung inflation-increased volume–>lung is stretched and these receptors fire. Hering-Breuer Reflex: stretch receptor stimulation terminates inspiration. This response occurs after the lungs are inflated at least 50% greater than resting values (VT of 1L or more). The reflex also responds to abrupt deflation of the lungs by increasing ventilatory rate.
Vagotomy severs these inputs which results in a vagal breathing pattern (see slide 3 of notes)
How is respiration controlled in the pons? (name and explain the functions of respiratory control centers in the pons)
How may the cortex override control of respiration by the pons and medullary centers?
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Apneustic center
a. Stimulates the inspiratory neurons, leading to increased inspiration.
b. An “apneustic breathing pattern” is characterized by prolonged (30-90 s) inspiratory efforts that are interrupted by occasional expirations. The pattern is induced upon direct stimulation of the apneustic center, or as a result of severing the connection between the apneustic center and pneumotaxic center (thus removing the inhibitory influence of the pneumotaxic center). -
Pneumotaxic center
a. Inhibits the apneustic center, cyclically terminating inspiration.
b. Controls depth of breathing.
These two centers fine-tune the patterns set by the rhythm generator in the medulla.
What 4 factors stimulate ventilation? Which is the most important factor in stimulating ventilation?
Pa,CO2 is the main factor regulating normal ventilation. Three other factors that affect ventilation are pHa, Pa,O2, and exercise.
Note that the responses to high PCO2 and exercise are linear, but the response to low PO2 is highly nonlinear.
To provide feedback on breathing, we have many receptors. What are the types of receptors that sense respiratory parameters? What are our 2 most important receptors? Where are they located?
To provide feedback on our breathing, we have stretch receptors in the smooth muscle of the airway, irritant receptors located between airway epithelial cells, joint and muscle receptors (that stimulate breathing in response to limb movement), and juxtacapillary receptors located in alveolar walls (sense engorgement of the pulmonary capillaries, and cause rapid shallow breathing). However, by far our most important sensors are central chemoreceptors - in the medulla (i.e., central nervous system) - and the peripheral chemoreceptors - in the carotid and aortic bodies (i.e., peripheral arteries).
What are irritant receptors? Where are they located? Via what nerve do they send signal?
What stimuli do they respond to? What are the responses of these receptors being stimulated?
Irritant receptors are located near airway epithelium and send afferent signals along the vagus nerve. They are stimulated by irritants like smoke, dust, rapid lung inflation, or histamine (released in asthma) and responses include coughing, sneezing, or bronchoconstriction.
Fill out the attached table.
What are central chemoreceptors stimulated by? Describe the process of stimulation in detail.
Why is the response of central chemoreceptors to their stimulus slow?
The central chemoreceptors are directly stimulated by [H+] of the CSF. However, the central chemoreceptors appear to respond to changes in Pa,CO2 and they do, but the response is indirect. How does this work? The blood-brain barrier is impermeable to ions like H+ and HCO3, but is freely permeable to CO2. When CO2 diffuses from blood to CSF, it spontaneously forms carbonic acid which dissociates into H+ and HCO3. The response is slow because there is no carbonic anhydrase in CSF to speed up this reaction. In most bodily fluids, protein would buffer changes in pH. But there is little protein in CSF. So, any changes in Pa,CO2 are translated into changes in CSF pH. If CO2 increases, pHCSF decreases, and an increase in breathing is triggered because your body wants to blow off the excess CO2. It works in the opposite manner as well – CO2 decreases => pHCSF increases and ventilation decreases.
*This is the control system for normal breathing.*
The central chemoreceptors are directly stimulated by [H+] of the CSF, but the pH of CSF usually reflects Pa,CO2.
We noted that the response of central chemoreceptors to changes in Pa,CO2 are linear. How sensitive are central chemoreptors to their stimulus?
How does the sensitivity change with hypoxia? What are possible reasons why this occurs?
Why do central chemoreceptors adapt to chronic changes in PCO2? How long does this adaptation take? In what situations may it occur?
- The response is linear (see attached pic)
a. Increasing or decreasing PA,CO2 by 1 torr changes ventilation by 4 L/min (a huge change!).
b. The system is very sensitive to small changes in PA,CO2.
c. The system’s response – the slope (change in ventilation/change in PA,CO2) – is even steeper if there is also hypoxia (+ and Ï in Fig. 70). Why There might be several explanations: maybe hypoxia affects the chemoreceptor itself, or higher integrating sites play a role, or there are acid-base changes in the blood which are secondary to hypoxia. Curves are also shifted up and to the left, which means the ventilatory response is greater at a lower PA,O2 for a given PA,CO2. Multiple stimuli combine synergistically – the response is greater than simply adding the two individual responses. Note: In the experiments where PA,O2 = 37 mm Hg or 47 mm Hg, the PA,CO2 response flattens at low PA,CO2. This is because at these low Pa,O2 levels, the peripheral chemoreceptors kick in.
The central chemoreceptors adapt to chronic changes in PA,CO2 (takes days). This may occur in many pulmonary diseases, such as edema, COPD, etc. (elevated PA,CO2) or high altitude (low PA,CO2).
a. The increased central chemoreceptor response to a maintained change in PA,CO2 disappears over a period of days.
b. A non-respiratory mechanism regulates CSF pH, which eventually restores [H+] to normal (buffer). Thus, the stimulus for the central chemoreceptor disappears.
Response of the central chemoreceptor response is reduced in what 4 situations/types of people?
We know that peripheral chemoreceptors respond to hypoxia, hypercapnia, and acidocis. Of these 3, which is the most important response?
At what PO2 do these cells respond?
Where are these chemoreceptors located? What name is given to these cells?
How do these cells respond to decreased O2 content?
The peripheral chemoreceptors respond to hypoxia (low Pa,O2), hypercapnia (high Pa,CO2), and acidosis (low pHa). However, the most important response is to hypoxia. They respond to severely reduced Pa,O2 (less than 60 torr). It is logical, therefore, that they are located where they have access to arterial blood. One group is the carotid bodies, at the bifurcation of each common carotid artery (main sensor in man). The other group is the aortic bodies, just under the aortic arch. The chemoreceptor cells are called glomus cells.
These chemoreceptors do not respond to decreased O2 content! In anemia, a pts Hb is still fully saturated (even though O2 content is reduced) so these receptors do not fire.
We know that the response of peripheral chemoreceptors to PaO2 is non-linear. What is the consequence of this?
How is the response of these receptors changed with hypercapnia and acidosis?
The response is highly nonlinear. (see attached). Small decreases in Pa,O2 provide only a small stimulation. But if Pa,O2 falls below about 60 mm Hg, response increases dramatically.
Remember that this response is not adaptable. This response kicks in during life-threatening situations so we would not want the response to adapt.
The peripheral chemoreceptors respond mainly to hypoxia (low Pa,O2), but this response is also modulated (increased) by hypercapnia (high Pa,CO2), and acidosis (low pH) (see attached).
When does the peripheral chemoreceptor response kick in?
What change occurs to arteral blood gasses (PaO2, PACO2, pHa) during exercise? What is the effect of exercise on ventilation? What receptors respond to increase ventilation during exercise?
There is no significant change in the arterial blood gases (Pa,O2, Pa,CO2, pHa) during exercise. We do not know how exercise increases ventilation, but it does so very effectively!
Explanation of attached graphs:
- Arterial % Hb saturation stays constant during Subject N8’s exercise, although mixed venous % Hb saturation decreases (because the muscles are extracting O2 from the blood). After exercise stops, venous % Hb saturation returns to normal.
- Patient C10 has subnormal arterial and venous hemoglobin saturation at rest.
- Mixed venous % Hb saturation dramatically decreases during exercise in the patient with impaired cardiac function. The patient can’t increase cardiac output; muscles can only use what the heart delivers. Since the heart isn’t pumping well enough, almost all of the oxygen is taken up by the muscles, and venous O2 saturation is extremely low.
- Arterial % Hb saturation (a result of pulmonary gas exchange) either does not change significantly or perhaps actually improves in Patient C10 during exercise!
Bottom line: Pa,O2 does not change during exercise, and therefore cannot be the trigger for increased ventilation.
What are the changes in ventilation at initiation and termination of exercise believed to be caused by? During exercise?
The changes in breathing here, at initiation and termination of exercise, are quite rapid! The response occurs before the results of exercise could change blood gases, for example, and thus they are believed to be mediated neurally. The more gradual changes in between might be mediated by blood borne or humoral substances travelling from muscles to a distant sensing site.
Explain the attached figure.
Time 0-4:expired PCO2 doesnt change bc ventilation increased to meet metabolic demands
Time 4-8: Imagine exercising harder: ventilation increases. pt hyperventilates so PCO2 decreases
