Chapter 12 Ventilation

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  Alveolar ventilation ($V_A$) is the movement of air into, and out of, the alveoli. Without continuous $V_A$ there is no alveolar respiration.

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  $V_e$ is the movement of air into, and out of, the lungs. $V_e$ is necessary for $V_A$. Without ventilation ($V_e$), there is no $V_A$.

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  Pulmonary perfusion is based on circulation ($Q$) and must be primarily distributed to alveoli receiving alveolar ventilation ($V_A$). $V/Q$ matching refers to the matching of $V_A$ and pulmonary circulation ($Q$). Both $V_A$ and $Q$ are necessary for alveolar respiration. Without $V_A$ matching with pulmonary $Q$ there is no alveolar respiration.

$V_e$ is the volume of air inspired (breathe in) or expired (breathe out) in a time period. It is most commonly measured in $mL/min$ or $L/min$. As a volume per minute, it is the volume of air per breath times the number of breaths per minute (bpm):

In Equation 12.1, the abbreviation $V_t$ stands for tidal volume. Tidal volume is the volume of air inspired (or expired) with one breath. The underlying assumption for both $V_e$ and $V_t$ is that the volume of air inspired equals the volume of air expired. While this might not be the case breath by breath, it is the case over a minute (or longer) time periods.¹¹1I’ve avoided analogies between ventilation and cardiac output for the sake of space and time. However, for those inclined to look for them, you’ll find them.

Question: Question

If there is an imbalance between $V_t$ in and $V_t$ out, it tends to be limited to transient periods that involve dynamic changes in $V_t$. For example, when $V_t$ increases in the transient periods from rest to exercise, or during exercise when there are variations in $O_2$ needs.
What would happen if the volume inspired did not equal the volume expired over a long period of time? Try this, breathe more in than out, how long can you do that? Now breathe more out than in, how long can you do that?

Not all $V_e$ ends in the alveoli ($V_A$), either per breath ($V_t$), or per minute ($V_e$). And, not all $V_A$ is going to be to alveoli with perfusion (receive capillary circulation). Figure 12.1 depicts the general concept that $V_e$ is going to be greater than $V_A$; and that $V_A$ is going to be greater than the $V/Q$. Pulmonary regulation is largely based on minimizing the discrepancy between $V_e$, $V_A$ and $V/Q$.

The importance of this concept is that the alveolar respiration relies on the match between alveolar ventilation ($V_A$) and perfusion ($Q$). The consequences of all pulmonary (lung), and many cardiovascular conditions, ultimately rest on how they impact the ability to ventilate ($V_e$), the ability to turn as much $V_e$ into alveolar ventilation ($V_A$) as possible, or the ability to have as much $V_A$ perfusion as possible. Take home message: Many cardiopulmonary conditions can be considered based on the impact they have on $V/Q$ matching.

Dead space ventilation is ventilation that does not reach the alveoli (anatomical dead space), or that reaches the alveoli but does not receive perfusion (alveolar dead space). The combination of anatomical and alveolar dead space is called physiological dead space ($V_D$). To understand anatomical dead space ($V_{Dana}$) it is important to understand the structure and function of the airways.

Any air that enters the airways is part of $V_e$, but it is not part of $V_A$ unless it reaches an alveoli. For example, at the end of an inspiration the air remaining in the upper airways (nasal passages, the back of the throat, trachea, bronchi, bronchioles) is part of $V_e$, but not part of $V_A$ (See Figure 12.3).

Air in the airways that does not reach the alveoli (airway conduction zone) is anatomical dead space ($V_{Dana}$). $V_{Dana}$ is a considered fixed volume ($mL$) per breath. For example, if $V_{Dana}=100mL$, and 400 $mL$ is inspired with tidal volume ($V_T$), then 300 ($mL$) reaches alveoli ($V_A$).

The air that does reach the alveoli is alveolar ventilation ($V_A$), and is the ventilation minus the anatomical dead space ventilation:

Question: Question

Does $V_A(mL/min)$ change if $V_e(mL/min)$ stays the same but is achieved with different volume ($mL$) per breath at different breathing frequencies (respiratory rates)?
Answer this by figuring out the $V_A(mL/min)$ and $V_e(mL/min)$ if $V_{Dana}=100mL$ per breath, when breathing 24 breaths per minute at 250 $mL/breath$; as compared to breathing 12 breathes per minutes at 500 $mL/breath$; as compared to breathing 6 breaths per minute at 1000 $mL/breath$. With each breathing pattern, $V_{Dana}=100mL$ per breath since this is a fixed volume.
The answer requires using Equation 12.1 ($V_e(mL/min)=V_t(mL)\times RR(bpm)$ and substituting $V_e$ with $V_t(mL)\times RR(bpm)$ and adjust $V_t$ based on $V_{Dana}$ since anatomical dead space occurs with each breath:

$$V_A(mL/min)=(V_t(mL)-V_{Dana}(mL))\times RR(bpm)$$

(12.3)

The upper airways include the nasal passageways, the nasopharynx, and the pharynx. Down to the pharynx the oral passages are also an option for breathing, but mouth (oral) breathing is sub optimal. The nasopharynx passes into the oropharynx which passes into the hypopharynx (also called the laryngopharynx). At this point the epiglottis is the gatekeeper between the larynx (for air) and the esophagus (for food and drink). The larynx is the beginning of the lower airways; it includes the vocal cords and then continues into the trachea.

All airway passages down as far as the terminal bronchioles are lined with epithelial cells that include, in various locations, mucus production cells and cilia. Cilia are small cellular extensions that promote the movement of mucus across the membrane surface. Cilia move continually in a direction that moves mucus toward the pharynx. Mucus and cilia in the airways are combined as a defense mechanism referred to as mucociliary activity. Together they promote the trapping of particles in mucus (including pathogens) and moving the mucus for removal. Cilia movement in the lower airways (trachea and bronchi) is upward, whereas those in the upper airways is downward. Continual cilia movement moves the mucus toward the pharynx. The mucus and its trapped particles are then swallowed or coughed out of the body.

Volumes & capacities are measures of the amount of air that can be ventilated (or that cannot be ventilated in the case of $RV$ which cannot be expired). They are helpful for understanding the functional capabilities of the lungs and describe changes to the lung in various states of disease. For example, with the obstructive pulmonary diseases the $RV$ tends to be higher, which reduces $VC$ (and all other values, except $FRC$). The volumes & capacities also represent a functional measure of the thoracic cavity musculoskeletal range of motion (chest wall mobility) which includes the diaphragm, muscles of the ribs (intercostal muscles), the mobility of the ribs, and the posture of the spine. For example, in situations with diaphragm weakness, reductions in $VC$ are directly related to an inability of the diaphragm to fully descend against the combined resistance of pulmonary elasticity, thoracic muscles and joints, and abdominal contents. In patients with many different neurological conditions there is involvement of ventilatory muscles or spinal posture which greatly influence the ventilatory volume & capacities that further limit activities and result in pulmonary conditions such as pneumonia.

Occasionally the volumes and capacities are utilized as an indication of the chest wall range of motion (ROM), which is referred to as chest wall excursion (CWE). During testing of the strength of inspiratory muscles patients are asked to expire all their air prior to the test because it is best to test those muscles when they are stretched. Those muscles are stretched when they are in the CWE associated with and at the ROM of, $RV$. When doing a forced expiration, or when training someone to improve their cough, they are asked to take in a full breath, they breathe in until they are at the CWE associated with $TLC$. CWE can also be measured as a circumference, but not without limitations. One limitation is that the CWE with a tape measure is measuring circumference in one plane (even if it is an oblique plane, it is only one plane). Whereas the change in thoracic cavity size occurs in all three planes (all three dimensions). If CWE is measured with a tape measure, it is usually recommended that it is measured in more than one place (for example, above, at and below the xiphoid process). CWE is also assessed qualitatively simply by placing the hands on various locations of the chest wall and assessing the symmetry, amount and quality of movement.

Ventilation is certainly part of an intricate set of homeostatic regulation mechanisms. Yet it is also under volitional control. The volitional control allows speech (vocalization), and it also allows the opportunity to use breathing to manipulate (hack) homeostatic systems that cannot otherwise be regulated directly (e.g. the use of deep breathing to increase parasympathetic nervous activity and lower heart rate). Physical therapists contribute uniquely to problems related to breathing and ventilation because of how much these processes rely on the neuromuscular mechanics of the breathing muscles. Like posture, gait and many movements, the breathing muscles and patterns of ventilation are mostly automatic yet are able to be voluntarily controlled, and therefore manipulated, adapted and trained. Emotional states are related to the autonomic nervous system (bi-directional), and the autonomic nervous system (ANS) is related to breathing (bi-directional). The bi-directional connection between ANS and breathing can be used to influence ANS by voluntarily altering breathing (See Figure 12.7). The downside of this is that breathing dysfunction, even when not due to pulmonary disease but rather caused by altered breathing coordination (mechanics) or patterns, can result in altered emotions. Questionnaires to assess whether breathing coordination (mechanics)(including too much mouth breathing) or patterns may be impacting health include a host of signs and symptoms related to the ANS [gilbert_recognizing_2014].

To breathe air into the lungs the ventilatory pump creates negative pressure. For breathing, the terms negative and positive pressure are always being compared with the atmospheric pressure. Negative pressure means less than atmospheric pressure; and positive pressure means greater than atmospheric pressure. When the ventilatory pump generates negative pressure it pulls air into the lungs. It does this by expanding the volume of the thoracic cavity, which lowers the pressure below the atmospheric pressure to establish the necessary pressure gradient for air flow. Based on the familiar equation: $Flow=(P_1-P_2)/R$; the flow is directly proportional to the pressure gradient created, and inversely proportional to the resistance (and the resistance is largely dependent on the radius of the airways).

For breathing air out of the lungs the ventilatory pump is a positive pressure pump. Positive pressure is generated by reducing the volume of the thoracic cavity, which increases the pressure above the atmospheric pressure to establish the necessary pressure gradient for air flow. Air flow is still directly proportional to the pressure gradient, and inversely proportional to resistance. Resistance is still largely dependent on the radius of the airways.

One difference with expiration is that the positive pressure, combined with the fact that during expiration the lungs and airways are getting smaller, it is much more likely that resistance to expiratory flow will impact exhalation (than resistance to inspiratory flow will impact inhalation). The practical implications are that with any condition that impacts airway radius, such as asthma, emphysema and chronic bronchitis, the functional impact is on expiratory flow rates more than inspiratory flow rates. When a limitation is made on expiratory flow rates the term utilized to describe the pattern is obstructive.

Forced expiratory activities - such as airway clearance with sneezing or coughing - requires a rapid increase in positive thoracic pressure. The difference between a sneeze (besides being typically through the nose) and a cough is closure of the epiglottis to allow for a larger build up of positive pressure in the thoracic cavity and a sudden release of that pressure when the epiglottis opens.

Airflow through airways is rapid enough that equilibration can occur at any thoracic cavity volume. Once equilibration occurs, airflow stops. This means that at any thoracic cavity volume, other than $TLC$ or $RV$, changes in volume can cause either inspiration or expiration depending on how the changes in volume change the pressure. At this point it’s helpful to remind readers of the Ideal Gas Law.

The common form of the Ideal Gas Law is:

Where, $P$ is pressure; $V$ is volume, $n$ is the number of moles in the gas (the amount of gas), $R$ is a gas constant, and $T$ is the temperature in Kelvin. For our purposes we can simplify by removing $R$ and $T$ (although there are slight changes during ventilation from the temperature of atmospheric air and the warmed air at body temperature, these are relatively small on the Kelvin scale, and since we are not actually calculating just considering relationships, we’ll be fine).

A simplified version of the Ideal Gas Law, that solves for $P$ is:

An increase in the thoracic cavity $V$ will reduce the $P$. The reduced $P$ results in air flow into the lungs through airways until the amount of air in the lungs $n$ raises $P$ until it equals the atmospheric pressure and air stops flowing into the lungs. At that point, if thoracic cavity $V$ can be increased more then $P$ will drop and more air will flow into the lungs until $n$ increases to the point that $P$ in the lungs equilibrates with the atmospheric pressure. The same process can be considered for exhalation. A reduction in thoracic cavity $V$ increases the $P$, air flows out of the lungs until $n$ is reduced until $P$ equals the atmospheric pressure.

Breathing in, Breathing out is a cyclic variation in the difference between the thoracic (pulmonary) $P$ and the atmospheric pressure, brought on by the cyclic variation in the thoracic (pulmonary) $V$, which is equilibrated by the movement of air into (increase $n$) and out of (decrease $n$) the lungs.

When considering the mechanics of the ventilatory pump during breathing it is useful to understand the conditions surrounding the functional residual capacity ($FRC$). $FRC$ is the resting position (volume) of the thoracic cavity, and therefore the amount of air in the lungs at this position equals the $FRC$. (That’s a nice, intentionally, circular explanation.) $FRC$ is the $V$ of the thoracic cavity when there is no active tension being developed by the breathing muscles. The $V$ of the thoracic cavity can still change based on body position, but it is not changing due to active tension of breathing muscles (either inspiratory or expiratory muscles). If you ”stop breathing” - and there is no airflow or active tension in your inspiratory or expiratory muscles - you are at $FRC$. If you do this in standing and then sit down there may be slightly less $V$ at $FRC$. If you are seated upright and slouch or lean forward then you reduce the $V$ and $FRC$. The $FRC$ is the $V$ in the lungs when there is no active attempt to breath, but it is positionally (supine, prone, sitting, standing) and posturally (spine neutral, flexed, extended) dependent.

$FRC$ is the balance point between an inward elastic recoil force of the lung tissue, and an outward elastic recoil force of the musculoskeletal thoracic cavity and is influenced by other forces such as gravity (and the impact that gravity has on the thoracic cavity) (See Figure 12.9). If the lungs were removed from the body (or detached due to a loss in negative pleural pressure), they would be smaller (less $V$) than at the $FRC$. Without the influence of the lungs, the thoracic cavity would be larger (more $V$) than at the $FRC$.

The balance of forces point of $FRC$ has a large influence on breathing patterns because it has a large influence on optimal breathing volumes. During resting tidal volume ($V_t$) breathing each expiration ends at $FRC$ and therefore is a passive process. Another way to say this is that a resting $V_t$ expiration ends at $FRC$ so that it can be a passive process. Inspiration requires muscles of inspiration to expand the thoracic cavity $V$, working against the passive recoil force of the lung tissue. But then the passive recoil force of the lung returns the $V$ to $FRC$ which promotes expiration. Therefore, with resting $V_t$ breathing only the muscles of inspiration must be utilized.

During resting $V_t$ breathing, initial increases in thoracic cavity $V$ are easier to perform because the thoracic cavity is naturally larger than at $FRC$. However, with increases in thoracic cavity $V$ both the lungs and the thoracic cavity create a passive elastic force that the muscles of inspiration must oppose for continued inspiration. This is one of the reasons that during exercise, breathing patterns typically increase $V_t$ by using more of the $ERV$ as compared to the $IRV$.

Forceful expiration requires a larger and more rapid change in $P$, which requires a larger and more rapid change in $V$, which requires active tension in the muscles of expiration. Increasing the rate of breathing $RR$ alone, or along with an increase in $V_t$, requires active tension of the expiratory muscles so that it occurs more completely (volumes less than $FRC$), and more quickly.

The discussion about the mechanics of ventilation have rightly assumed coherence between the lungs and the thoracic cavity. When the thoracic cavity increases volume, the lungs increase volume which increases the volume of the alveoli. When the thoracic cavity decreases its volume, the lungs decrease volume which decreases the volume of the alveoli. Under all normal circumstances these events are true.

But…. anatomically there is no direct connection between the lungs and the inner wall of the thoracic cavity. There is a space, it’s a small space and it’s filled with fluid, but it’s a space. It is the pleural space and it is filled with pleural fluid. The lungs are lined with a lung pleural membrane and the thoracic cavity is lined with a thoracic pleural membrane. Between them is a thin space with pleural fluid. This arrangement allows the lungs to move within the thoracic cavity with relatively little friction (similar to the pericardial space and the pericardial fluid around the heart).

To keep the lungs inflated and moving along with the thoracic cavity the pleural space is kept at a slightly negative pressure (negative in comparison to the atmosphere, and the atmosphere is taken as 0 cm of water ($cm{H}_{2}O$)³³3In ventilation physiology it is common to simply refer to the atmosphere as 0 which is a relative measurement based on the fact that when not breathing the atmosphere and alveoli pressures equilibrate and that for ventilation it is only differences in these pressures that matter. However, when calculating the partial pressures of gases, we consider the absolute atmospheric pressure which, at sea level, is 760 $mmHg$ (1033 $cm{H}_{2}O$). This is called the intrapleural pressure. The normal intrapleural pressure at the beginning of inspiration is about $-4mmHg$, which is the amount of suction required to hold the lungs at their resting volume. During inspiration the thoracic cavity expands and the intrapleural pressure drops to approximately $-7.5mmHg$. These values are being shared simply to convey that they are slightly negative.

During regular (resting $V_t$) expiration the lungs recoil and pull the thoracic cavity thus maintaining the negative pressure of the pleural space. Due to the movement of the thoracic cavity along with the lungs the intrapleural pressure returns to $-4mmHg$.

During forced expiration the intrapleural pressures become slightly positive as the thoracic cavity pushes on the lungs to reduce their volume. The positive intrapleural pressure can result in a greater degree volume loss in alveoli, and reduction in the size of bronchioles and bronchi than due to the reduction in the volume of the thoracic cavity. In other words, during forced expiration the thoracic cavity directly reduces the lung size and this reduction is further influenced by a positive intrapleural pressure that also decreases lung airways and alveoli volume. This effect is more pronounced with a greater force for forced expiration because there is a higher positive intrapleural pressure.

Warning: Pneumothorax

Pneumothorax is the collapse of a lung which can be precipitated by a loss of negative pleural pressure due to trauma. In certain trauma scenarios air may escape the lung and enter the pleural cavity resulting in positive pleural pressure which collapses the lung. This situation is called a tension pneumothorax and requires the positive pleural pressure to be removed with a tube placed into the chest (chest tube). Chest tubes are commonly used after thoracic surgery (any surgery that opens the thoracic cavity) to prevent the accumulation of edema and also to maintain negative pressure via suction to keep the lungs inflated.

Warning: Pleural Effusion

Pleural Effusion is the accumulation of fluid in the pleural space which then compresses the lung.

Lung Compliance is the change in lung volume for each unit of change in transpulmonary pressure. Transpulmonary pressure is the difference between the alveolar and pleural pressures. For example (and not to memorize), the normal total compliance of both lungs together in a healthy adult is about 200 $mL/cm{H}_{2}O$ (for each 1 $cm{H}_{2}O$ change in pressure there would be a 200 $mL$ change in volume). Lung compliance depends on the elastic recoil forces of the lung. The elastic recoil forces are determined by the elastin and collagen fibers and the surface tension of alveoli. Increased elastic recoil forces (including increased surface tension) decreases compliance. For example, if there is more elastic recoil the compliance may be 100 $mL/cm{H}_{2}O$ which means only 100 $mL$ of volume for a 1 $cm{H}_{2}O$ change in pressure).

As introduced in the Ventilation Overview section, there are three classifications for dead space: anatomical, alveolar and physiological. To summarize:

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  Anatomical dead space ventilation ($V_{Dana}$) is air ventilated but that does not make it into alveoli, $V_{Dana}=V_e-V_A$

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  Alveolar dead space ventilation ($V_{Dalv}$) occurs in alveoli that receive ventilation but do not receive alveolar circulation

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  Physiological dead space ventilation ($V_D$) is the sum of anatomical and physiological dead space, $V_D=V_{Dana}+V_{Dalv}$

Anatomical dead space ventilation ($V{D}_{ana}$) was discussed in the section on Airways, since it is the volume of air that is ventilated but remains in the conductive zone of the airways (does not make it to the alveoli). $V_{Dana}$ is minimized by regulating, and optimizing, the breathing pattern volume and rate. Larger volumes certainly reduce $V_{Dana}$, but if volumes are too large then the work of breathing becomes more difficult for three reasons:

1. 1.

   Inspiratory muscles shorten and it’s more difficult to generate the required active tension based on their length - tension curve.

2. 2.

   The thoracic cavity increases and starts to resist further increases due to passive tension so the muscles must work harder (at a time that it is harder for them to work based on #1)

3. 3.

   Lung compliance starts to decrease because as lungs expand the lung elastic recoil forces (like passive tension) increase (and recall that lung elastic forces are inversely proportional to compliance)

For all of those reasons - optimizing breathing pattern requires a balance between higher volumes and lower rates, which minimize $V_{Dana}$ but increase the word of breathing; and lower volumes and higher rates, which maximize $V_{Dana}$, but lower the work of breathing.

Alveolar dead space ventilation ($V_{Dalv}$) is minimized by the regulation of pulmonary circulation. Pulmonary arterioles dilate in areas with increased $O_2$ and constrict in areas with decreased $O_2$. They also dilate in alveoli receiving fresh ventilation taken in through the nose that has had nitric oxide (NO) since NO is a vasodilator.

Another situation that can result a $V/Q$ mismatch is a right-left (RL) shunt. When alveolar dead space causes a mismatch it is because ventilated alveoli do not receive any (or enough) perfusion. A RL shunt is the opposite situation. Alveoli that do not have ventilation, or are under ventilated, receive blood flow. Because this blood flow does not exchange gases with the alveoli (because the alveoli does not have ventilation), the right sided blood (venous blood) returns unchanged and joins with the left sided blood (arterial blood).

The simplest cause of a RL shunt is not breathing (apnea). With apnea the alveoli still have air. However, since the alveoli equilibrate with blood passing through they quickly, without $V_A$, have the same amount of $O_2$ and $C{O}_2$ as venous blood. This results in elevated $P_{a}C{O}_2$ and reduced $P_a{O}_2$ that worsen with prolonged apnea. While holding your breath is apnea, we should reserve the term apnea for pathological causes of not breathing. Voluntary breath hold to the point of lowering $P_a{O}_2$ is very difficult so is not as good of an example of a RL shunt.

Pathological causes of RL shunts include anything that results in hypoventilation (reduced $V_A$), including conditions that fill the alveoli with something other than ventilated air. For example, pulmonary edema, mucus from pneumonia, inflammation with any pulmonary inflammatory condition such as COVID (which can also cause pneumonia). Chronic pulmonary conditions such as emphysema and bronchitis increase the $RV$ which increases the number of alveoli getting blood flow but not new ventilation, a RL shunt.

$V_D$ & RL Shunt Thought Experiment If all ventilation went to the right lung; and all blood flow went to the left lung the overall $V/Q$ matching would be 0%. The right lung is completely dead space ventilation $V_D$; and the left lung is a complete RL shunt.

The A-a gradient is the drop off that occurs between the partial pressure of $O_2$ from fully ventilated alveoli ($P_A{O}_2$) to the partial pressure of $O_2$ in mixed arterial blood ($P_a{O}_2$). The $P_A{O}_2$, at sea level with a normal fraction of inspired oxygen ($F_i{O}_2=0.21$) is taken as 104 $mmHg$. This blood mixes with blood from other regions of the lung as it travels back to the left atrium. In addition to the venous blood from the bronchial pulmonary circulation, there is blood from normally occurring RL shunts given the normal resting $V/Q$ matching of 80% (20% mismatching). Therefore, we should not be surprised that the normal $P_a{O}_2$ is less than 104 $mmHg$ of $P_A{O}_2$. This difference (approximately 104 - 95 = 9 mmHg) is the A-a gradient. The A-a gradient is proportional to the severity of a RL shunt (See Figure 12.14). In critical care situations the A-a gradient can be elevated even when a patient has a normal blood oxygen level because the $P_A{O}_2$ is elevated. For example, if a patient at sea level is on supplemental oxygen with an $F_i{O}_2=0.6$ (60% oxygen), then the estimated $P_A{O}_2$ is 300 $mmHg$, and the A-a gradient even with a normal $P_a{O}_2$ would be 205, indicating substantial RL shunting.

Neurons that innervate the muscles of the respiratory system are responsible for controlling and regulating pulmonary ventilation. The major brain centers involved in pulmonary ventilation are the medulla oblongata (medullary respiratory center) and the pons (pneumotaxic center). The medullary respiratory center is responsible for the rhythm of breathing and automatic ventilation. The pneumotaxic center controls the rate and depth of ventilation. The cerebral cortex sends impulses directly to the motor neurons of the ventilatory muscles which allows for voluntary control of ventilation.

The medullary respiratory center and the pneumotaxic center adjust $V_t$ and $RR$ in response to afferent input. The overall response patterns are dose-response, negative-feedback. The greater the stimulus, the greater the response. Increasing stimuli results in higher $RR$ and greater volume with $V_t$. These both typically include forced expiration. Multiple factors are involved in stimulating the the centers to adjust. Major factors are the concentration of carbon dioxide in the arterial blood ($P_{a}C{O}_2$), and the pH, as sensed by chemoreceptors. A central chemoreceptor is one of the specialized receptors that are located in the brain and brainstem, and a peripheral chemoreceptor is one of the specialized receptors located in the carotid arteries and aortic arch. Increased $P_{a}C{O}_2$ and decreased pH (acidity), stimulate the respiration centers to increase $V_e$ through some combination of increasing $RR$ and $V_t$, with some combination of muscles (coordination, mechanics). Reduced $P_{a}C{O}_2$ and increased pH (alkaline), reduces stimulation and therefore reduces $V_e$.

There are chemoreceptors for $O_2$, and with hypoxia, $P_a{O}_2$ of less than 60 mmHg, these receptors are activated. The lower the $P_a{O}_2$ the stronger the stimulus. However, under normal circumstances the $P_a{O}_2$ is so far above the threshold for $O_2$ chemoreceptor stimulation they are rarely involved in the regulation of ventilation. If ventilation was reduced enough for hypoxia, then the increase in $P_{a}C{O}_2$ would be substantial enough to have strongly stimulated the $C{O}_2$ chemoreceptors to increase ventilation. To voluntarily allow hypoxia through breath hold, a period of hyperventilation that substantially reduces $P_{a}C{O}_2$ is necessary. This allows prolonged breath holding and enough time for $P_a{O}_2$ to drop. That hyperventilation, hypocarbia (low $P_{a}C{O}_2$) situation, is the underlying principle for what is popularly referred to as ”Wim Hof Breathing.” It can be used to create therapeutic exposures to intermittent hypoxia.

The hypothalamus and other brain regions associated with the limbic system also influence breathing by interacting with the respiratory centers. These regions are responsible for changes in ventilation related in response to fight-or-flight, emotions, pain, and temperature. For example, an increase in body temperature causes an increase in respiratory rate. Feeling excited or the fight-or-flight response results in an increase in $V_e$. These responses, particular the fight-or-flight response act as feed forward regulation. Ventilation increases prior to an increase in $P_{a}C{O}_2$ with exercise because before $P_{a}C{O}_2$ has a chance to increase, ventilation has already increased.

Protective reflexes such as coughing, sneezing, bronchoconstriction, mucus secretion and mucociliary activity respond to irritants such as smoke, dust or larger particles (larger than $O_2$ and $C{O}_2$). These coordinated reflexes work together to capture and expel irritants and potentially harmful pathogens.

Warning: $C{O}_2$ Retainers - $O_2$ Drive for Breathing

The combination of pulmonary diseases classified as chronic obstructive pulmonary disease (COPD) are progressive chronic conditions. In severe to end-stage COPD, among other things, there is chronically elevated $P_{a}C{O}_2$ that creates respiratory acidosis and metabolic compensation. The chronically elevated $C{O}_2$ and reduced pH can result in down regulation of the chemoreceptors to these stimuli. In these situations, $P_a{O}_2$ chemoreceptors are utilized to regulate $V_e$. A consequence of this situation is that $P_a{O}_2$ must be near hypoxia to increase ventilation. If someone in this situation is provided with too much supplemental $O_2$, which increases their $F_i{O}_2$, then their ventilation will decrease and their $P_{a}C{O}_2$ will increase further, to potentially dangerously toxic levels.

The Forced Expiratory Maneuver (FEM) of Pulmonary Function Tests (PFTs) includes a full inspiration (until reaching total lung capacity ($TLC$)), followed by a forced expiration to expire as much air as fast as possible with the goal of expiring air until reaching the residual volume ($RV$). Subjects are usually seated for testing, but they are allowed to extend their spine during the full inspiration and flex their spine during the full, forced expiration. There are several measurements that are made from this single test. But, the two most important measurements for the physical therapist to recognize from an FEM of a PFT are the forced vital capacity ($FVC$) and the forced expiratory volume in 1 second ($FE{V}_1$). They are both measured in liters ($L$). Forced vital capacity ($FVC$) is an estimate of the vital capacity $VC$ and with healthy lungs $FVC=VC$. Forced expiratory volume in 1 second ($FE{V}_1$) is influenced by both expiratory volume and expiratory flow. The ratio of these two measures, the $FE{V}_1/FVC$ considers whether a reduction in $FE{V}_1$ is due to a reduction in $FVC$ (volume) or expiratory flow. When expiratory flow is normal: $FE{V}_1/FVC\approx 0.75$. The lower the $FE{V}_1/FVC$, the more substantial the limitation in expiratory flow.

There are numerous ways to test (and quantify) ventilatory muscle strength and endurance. The most common approach is the maximal inspiratory pressure (MIP) and the maximal expiratory pressure (MEP). MIP and MEP are isometric tests performed when the respective muscles are in their lengthened position. MIP testing is performed at residual volume ($RV$). The subject attempts to breath in as strongly as possible on a tube connected to a device that can measure negative pressure. There can be a small air leak to prevent the use of facial muscles from contributing mouth pressure to the negative pressure generated. MEP testing is performed at total lung capacity ($TLC$). The subject attempts to breath out as strongly as possible on a tube connected to a device that can measure pressure. There can be a small air leak to prevent the use of facial muscles from contributing mouth pressure to the positive pressure. Even though MIP and MEP are isometric tests of pressure they are highly correlated with other approaches to measuring both ventilatory muscle strength and endurance. As with any muscle testing, care must be taken to ensure proper muscle coordination and activation. For example, when being asked to generate a strong inspiratory effort subjects commonly associate what they are being asked to do with a big breath and they associate big breaths with upper chest and accessory muscle use. If the tester wants an estimate of diaphragm strength, care must be taken to prepare the subject, and provide feedback to encourage diaphragm activation as opposed to upper test and accessory muscles. For example, establishing that subjects understand the request to breathe in with their diaphragm even before attempting the test. And then repeating whatever instructions led to a diaphragm activation while doing the test (i.e., ”Breathe in forcefully, starting from deep in your lungs, starting the movement with your abdomen which should move outward while you breathe in.”)

There are two major ventilatory insufficiency patterns.

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  Obstructive pattern: Difficulty getting air out of the lungs during expiration due to airway resistance and bronchiole collapse. This pattern includes increased $RV$, increased $FRC$ and decreased $VC$. PFT’s include reduced $FE{V}_1$ and $FVC$ and a reduced $FE{V}_1/FVC$ ratio, which means $FE{V}_1$ decreases more than $FVC$ because expiratory flow is significantly reduced.

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  Restrictive pattern: Difficulty getting air into the lungs for any reason (intra-pulmonary reasons are within the lungs such as pneumonia or fibrotic changes; extra-pulmonary reasons are outside of the lungs such as pleural effusion, chest wall changes or diaphragm weakness). $FE{V}_1$ and $FVC$ are decreased proportionally, $FE{V}_1/FVC$ ratio is normal, which means ($FE{V}_1$) is reduced because of an overall lower volume, not because of a reduction in expiratory flow.

Chronic pulmonary conditions such as emphysema and bronchitis are termed chronic obstructive pulmonary disease (COPD) because they have an obstructive pattern. The increase in $RV$ eventually changes the anatomy of the thorax, which changes the mechanics of the inspiratory muscles. Therefore, even though there are expiratory flow limitations (reduced $FE{V}_1/FVC$), there is also a reduction in maximal inspiratory pressure (MIP) which contributes to the shortness of breath and activity intolerance. The increased $RV$ also results in substantially under ventilated alveoli (reduced $V_A$), which leads to substantial right-left shunt, which leads to substantial $V/Q$ mismatching, and therefore substantial problems with respiration that include both decreased $P_a{O}_2$ and increased $P_{a}C{O}_2$.

Asthma is a chronic condition that has acute obstructive episodes. Sometimes it is classified as a chronic obstruction, but this should only be the case when there actually is chronic obstruction (chronically reduced $FE{V}_1/FVC$ ratio).